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Burmester, Color Atlas of Immunology © 2003 Thieme


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... Key to Symbols

Membrane,
phospholipid
Antigens layer

Receptors Thymus

Lymph node
TCR

Class I MHC Cellular tissue


molecule

Bacteria and
Class II MHC viruses
molecule

Arrows denoting
Cytokine receptor transportation,
effect, and
direction

Positive effect
Antibody (Ab)

Negative effect

Auto-Ab Inhibition

Blockade

Complement Signal

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
... Key to Symbols

Stem cell Plasma cell

Antigen-
presenting cell
B cell (APC)

Natural killer cell


(NK cell)
T cell

Erythrocyte Macrophage

Monocyte Megakaryocyte

Neutrophil
granulocyte Thrombocytes

Basophil ,
granulocyte Langerhans cell

Eosinophil Interdigitating
granulocyte dendritic cell

Basophil mast cell Mature


dendritic cell

Burmester, Color Atlas of Immunology © 2003 Thieme


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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
CD34+ Pluripotent stem cell
#?+$?%+@
!
Myeloid Lymphoid
progenitor progenitor

T-cell B-cell
Mega- pre- Thymus pre-
karyocyte Myeloblast Monoblast cursor cursor

Erythroblast

;2'<91+'.9, :$%'8%=,+-
Platelets
B
P lympho-
h cytes
Erythrocytes a
g o e s
c y t
T lympho-
cytes

"
Basophils

Eosinophils Dendritic Natural


Neutrophils Monocytes cells killer cells
A. Origin of cells of the immune system

Innate immunity Adaptive immunity


Infectious
Phagocytes agents

Generation of
Natural killer cells specific receptors

Blood
components

Hours Days, weeks

B. Defense mechanisms against infections

Hematopoietic
CD34+ stem cell

!
Hepatocytes
Cardio-
Neurons myocytes
Smooth Endothelial Skeletal
muscle cells cells muscle cells
C. Plasticity of stem cells
A

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Ontogenesis Primary lymphoid organs Secondary
7=(%=1(>
!
lymphoid organs
Progenitor cell
Medulla
Epithelium
IL-1
IL-2
Dendritic IL-6 Spleen
cells IL-7

Cortex Macro-
phages T lymphocytes

Fetal liver

9&6:0.(6$05 ;%16'1/5(2
Thymus T lymphocytes

Myelopoietic
progenitor cell
Pluripotent
stem cell
?

"
Bone marrow B lymphocytes Lymph nodes
Lymphatic
progenitor cell
Progenitor cell

Sinus
IL-1
IL-6
IL-7
Erythron Stroma

Mucosa-associated
B lymphocyte
lymphoid tissue
A. Structure of the lymphoid system

Liver

Lung Spleen

Skin

B. Lymphatic recirculation
Mesenteric
lymph nodes
Peyer´s
patches

Efferent lymphatics
Peripheral
lymph nodes

!
?

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Thyroid gland
Large
10('23
!
vessels 40

Lung 30

Weight (g)
Heart 20 Cortex Fat and
connective tissue

10

Medulla
0
Diaphragm 0 5 10 10 20 30 40 90

;2#)$'+#%$- <58#98.-+3
Age/months Age/years
1. Position of the thymus 2. Growth curve

Hassall’s
body Fat
Hassall’s
body

Inter- Thymic
lobular

"
parenchyma
connective
tissue
(trabecula) Inter-
lobular
connective
tissue

Cortex

Medulla

3. Thymus of a newborn 4. Thymus of an adult

Thymo-
Thymo- cytes
cytes Cortex Medulla
Epithelial
cells

Epithelial
cells

Inter-

!
lobular
connective
tissue
Hassall’s Hassall’s
5. Histology body body
A. Anatomy and development of the thymus
>

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Red pulp Germinal center White pulp Sinus
A(%:,+(%8- >%?8.5
!
Lymphoid
follicle
Arteriole
Follicular mantle Marginal zone
Mantle zone Marginal zone
B
B
B
T T
Periarterial B T
lymphatic sheath Germinal center T

@&.482(.$8- A%:.':,-(5
1. Anatomic structure 2. Cross-section through arteriole and
follicle; lymphocyte circulation
A. Structure of the spleen

Capsule Secondary follicle

Marginal sinus Paracortex

"
Inter-
follicular
sinus
Afferent
Medullary sinus lymphatic

Primary follicle Efferent lymphatic

1. Inactive lymph node 2. Active lymph node


B. Structure of the lymph node

Follicle center M cells Follicle-associated


epithelial cells
Mantle zone Dome region

T-cell zone

Postcapillary venule

Muscular mucosa

1. GALT: Gut-associated1.
Efferent lymphatic

lymphoid tissue; Peyer’s patch


C. Mucosa-associated lymphoid tissue
2. BALT: Bronchus-associated
2. lymphoid tissue
!
C

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
3. Branchial pouch Thymus
,:9.// 6.7./)85.*%

Thymic epithelial cell


!
1. Epithelial
– thymulin
component
Thymic – thymosin "1
2. hormone – thymopoietin
– etc.

3.

Circulation
4.

Progenitor cell (pre-thymocytes)


Thymocytes Mature T cells
(bone marrow, fetal liver)

A. Maturation of T cells

=&*<$5.*%$/ 2'(*-(8/.0
Location

Fetal liver
Thymus
Bone marrow
Pre- Early General Mature thymocyte
thymocytes thymocyte thymocyte CD4
CD4 CD8 TCR
CD2 CD2
TCR CD3
CD5 CD7
Cell

CD3
CD8

"
CD7
CD1 CD7
TCR
(CD1) CD2 CD5 CD2 CD3
CD5 CD7
Rearrangement Transcription Cell surface Mainly expression
of TCR! of TCR! expression of TCR",#
TCR

rearrangement of TCR!,", #
of TCR#
TdT enzyme TdT, CD2, CD7 TdT, CD1, CD2, CD3, TH: CD2, CD5,
CD5, CD4 and CD8 CD7, CD3, CD4
Marker

(CD1) TC: CD2, CD5,


CD7, CD3, CD8
Double negative Double positive Single positive
B. Phases of thymocyte development

CD3
CD8 CD3
CD4 Naive
Cytotoxic T cell
CD45RA
T cell
CD2, 5, 7, TCR",# CD2, 5, 7, TCR",#
CD3
CD4
CD3
CD4 Memory

!
CD45RO T cell
T-helper cell
CD29
CD2, 5, 7, TCR",# CD2, 5, 7, TCR",#
Thymus
(see B) Mature T cell in blood and lymphoid system
C. Development of mature T cells
>>

Burmester, Color Atlas of Immunology © 2003 Thieme


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! ./64+7&,%43$ 8$9$1,7+$(3 '(: 8)--$;$(3)'3),(

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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Pre-
./0$11 2$1$%3),(
!
thymocytes

<5(:'+$(3'1 =;)(%)71$*
Thymic
epithelial cells
MHC molecule

TCR

A B

Dendritic

C
cell

D
"
(No
Autoantigen binding)

Thymus with
maturing thymic cells

Thymocyte Self-MHC Autoantigen Fate


(type) binding recognition

Missing or _
A Cell death
weak

B Strong _ Cell death

!
C Moderate Yes Cell death
Mature
Complete
immuno-
D Moderate No
maturation competent
T cell

A. Mechanisms of T-cell selection in the thymus


>@

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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8"2*<".(/@ 5;-+"" 0+-+#,20 -$%.(/ $%D+ )%$+%-."
$"!+,#* %() /,#*'%#' $"!+,#*9 J( ,$+ " -$%.(@
,$+ 6;,+01.(%" +()/ 2= ,$+ P 0+8.2( &".(E *+;
,A++( ,$+ P %() 6 0+8.2(/' %0+ +(-2)+) *3
F %() G 8+(+/9 5$+ P 0+8.2(/ 2= ,$+ ! %() "
-$%.(/ $%D+ >KQL>>R %1.(2 %-.)/ %() -2(,%.(
,A2 -3/,+.(+ -21#2<()/ ,$%, #+01., ,$+ =20;
1%,.2( 2= % )./<"=.)+ *0.)8+9
5$+ 6 0+8.2(/ 2= ,$+ ! %() " -$%.(/ -2(,%.(
>STL>BR %1.(2 %-.)/ %() $%D+ =2<0 =<(-,.2(%"
)21%.(/@ A$.-$ %0+ (201%""3 +(-2)+) *3 ).=;
=+0+(, +42(/9
5$+ %1.(2;,+01.(%" 6 )21%.( -2(,%.(/ ,A2
-3/,+.(+ -21#2<()/ A.,$ )./<"=.)+ *0.)8+/

!
A.,$.( ,$+ -$%.(U $+(-+@ ,$+ ,+0,.%03 /,0<-,<0+
#0+/<1%*"3 -200+/#2()/ ,2 ,$%, 2= ,$+ -2(/,%(,
0+8.2( 2= ,$+ .11<(28"2*<".( 12"+-<"+9 5$+
,0%(/1+1*0%(+ )21%.( -21#0./+/ QKLQ? #0.;
1%0."3 $3)02#$2*.- %1.(2 %-.)/9
CD

Burmester, Color Atlas of Immunology © 2003 Thieme


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!, " (Chromosome 14)
#$%&'' (&)&*+,-4
!
V!1 V!2 V!n V"n D" J C" V J! segments C!
"

# (Chromosome 7q)
V#1 V#2 V#3 V#n D#1 J#1 C#1 D#2 C#2 V#14

$ (Chromosome 7p)
V$I V$II V$III V$IV Jp1 Jp J1 C$1 C$2

V1.1 V1.3 V1.5 V1.6 V1.8 VA VB VII


V1.2 V1.4 V1.5P V1.7

08/?12&/+1' <-3/)3*'&4
Pseudogene (Reversed direction of transcription)

A. T-cell receptor gene families

I
II

II

Deletion
B. T-cell receptor rearrangement
I
II
Unequal chromosome switch Inversion
"
! (") # ($) Gene segments !-chain #-chain
V 100 100
Extra- V! S S
V D 0 2
cellular S S
region J 100 13
CHO
V x D x J-combinations 104 2 x103
C! S S
C N-sequences 104 104
S S
SS Total number
Trans- of !/# combinations 1015
membrane
region D. Possible combinations of the T-cell
Cyto- receptor (!/#)
plasmic-
!/# $/"
region Total:
248 282 95 % 5%

Marker: CD4+ CD8– 66 % <1%


! chain = V - J - C
# chain= V - D - J - C
" chain = V - D - J - C
$ chain = V - J - C
C. Configuration of the T-cell receptor
CD4–
CD4–
CD4+
CD8+
CD8–
CD8+
33 %
<1 %
<1 %

E. Distribution of !/# and $/" T cells


25 %
70 %
<12 %
Weak

!
CE

Burmester, Color Atlas of Immunology © 2003 Thieme


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! ()67%892471+ -+:+,28%+'1 &'; -.//+0+'1.&1.2'

!" #$$%&%'" &' &() *+,)-- .),)/&'.0 "12).'13


()-/). 2'-),1-)3 #.) #-3' "))$)$ 4'. &()
$)5)-'/2)"&0 $%44).)"&%#&%'"0 #,&%5#&%'"0 #"$
%" ,-#33 !! KL> 2'-),1-) 9%"$%"6 #"$ %"&).#,&3
:%&( /NV-,J &8.'3%") J%"#3)7 !& #-3' 3).5)3 #3 &()
9%"$%"6 /.'&)%" 4'. &() (12#" %221"'$)4%+
#"&%6)" .),'6"%&%'" '4 * ,)--37 *()3) 2'-),1-)3 ,%)",8 5%.13 ;L!W<7 *() >?U #"&%6)" ,'..)+
/-#8 #" %2/'.&#"& .'-) %" &() 9%"$%"6 '4 * ,)--3 3/'"$3 &' &() >?O 2'-),1-)0 :(%,( ,'"3%3&3
:%&( #"&%6)"+/.)3)"&%"6 ,)--3 ;#,,)33'.8 2'-)+ '4 &:' ,(#%"3 #"$ %3 ,(#.#,&).%3&%, '4 ,8&'&'A%,
,1-)3<7 ='2) '4 &()3) 2'-),1-)30 31,( #3 &() * ,)--37 !& %3 #-3' -',#&)$ '" %22#&1.) &(82'+
>?@ #"&%6)"30 ',,1. )A,-13%5)-8 '" ,)--3 '4 &() ,8&)3 #"$ %3 :)#J-8 ,(#.#,&).%3&%, '4 "#&1.#- J%--+
*+,)-- -%")0 :().)#3 '&().3 ',,1. '" B ,)--3 #"$ ). ,)--37 !& %3 .)3/'"3%9-) 4'. 9%"$%"6 &' ,-#33 !
#,,)33'.8 ,)--37 *()3) 2'-),1-)3 ,#" 9) .),'6+ KL> 2'-),1-)3 #"$ %"&).#,&3 :%&( /NV-,J &8.'+
"%C)$ #"$ #"#-8C)$ :%&( &() ()-/ '4 2'"',-'+ 3%") J%"#3)7
"#- #"&%9'$%)37 *(%3 2)&('$ (#3 "'& '"-8 6.)#&-8 *() >?N #"&%6)" #"$ >?T #"&%6)" #.) #-3'
%",.)#3)$ &() 1"$).3&#"$%"6 '4 -82/(#&%, ,)-- ,(#.#,&).%3&%, '4 * ,)--37 >?N %3 %"5'-5)$ %" 3%6"#-
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<$';&%+'1&, =0.'4.8,+5

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!& %3 &() 2)&('$ 13)$ &' $)&).2%") &() *+,)-- 2#.J).X %&3 2'$) '4 #,&%'" %3 3&%-- -#.6)-8
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'4 2#-%6"#"& -82/(#&%, &12'.37 D& ,'"3)"313 # 319/'/1-#&%'" '4 B -82/(',8&)37
,'"4).)",)30 #"&%6)"3 %$)"&%4%)$ 13%"6 2'"'+ >?MO #"$ >?GNM ;>*ID+U< 2'-),1-)3 %"&).+
,-'"#- #"&%9'$%)3 (#5) 9))" ;#"$ :%-- ,'"&%"1) #,& :%&( >?OY #"$ >?OV 2'-),1-)3 '" #"&%+
&' 9)< 6%5)" %"&)."#&%'"#--8 5#-%$ $)3%6"#&%'"3 6)"+/.)3)"&%"6 ,)--37 !"&).#,&%'" 9)&:))"
3&#.&%"6 :%&( E>?F ;,-13&). '4 $%44).)"&%#&%'"< >?MO #"$ >?OYZ>?OV 6)").#&)3 #" %2/'.&#"&
#"$ # ,'..)3/'"$%"6 "129).7 ,'+3&%21-#&'.8 3%6"#- 4'. *+,)-- #,&%5#&%'" #"$
/.'-%4).#&%'"7 *() 9%"$%"6 '4 >*ID+U &' &(%3 2'+
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3%6"#- 4'. &() * ,)--7

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*() >?G #"&%6)" (#3 4%5) %3'4'.23 ;#0 90 ,0 $0 )<
#"$ %3 )A/.)33)$ '" ,'.&%,#- &(82',8&)3 #"$
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3%2%-#. &' ,-#33 ! 2#H'. (%3&','2/#&%9%-%&8 #"&%+
6)"37 I%J) &() KL> #"&%6)"30 &()8 4'.2 ,'2+
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#.) &('16(& &' 9) %"5'-5)$ %" &() /.)3)"&#&%'"
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&).%#- -%/%$%, #"&%6)"3 #.) #-3' /.)3)"&)$ 98 >?G7
*() >?M 2'-),1-) 3).5)3 #3 # .),)/&'. 4'.
&() >?NO #"&%6)"0 )7670 &() -82/(',8&) 41",+
&%'"#- #"&%6)" ;IPD<+G7 >?M %3 #" %2/'.&#"& 4#,+
&'. %" #-&)."#&%5) *+,)-- #,&%5#&%'"7 !& %3 #" )#.-8
*+,)-- 2#.J). &(#& %3 )",'$)$ 98 #-- * -82/('+
,8&)3 #"$ "#&1.#- J%--). ;QR< ,)--37
*() >?@ ,-13&). ,'"3%3&3 '4 # "129). '4 %2+
/'.&#"& 2)29.#")+9#3)$ 2'-),1-)3 &(#& #.)
,-'3)-8 #33',%#&)$ :%&( *+,)-- .),)/&'.37 *()3)
2'-),1-)30 )3/),%#--8 &()%. C)&# ;"< #"$ )&#
;#< ,(#%"30 #.) .)S1%.)$ 4'. 3%6"#- &.#"3$1,&%'"
'",) ,'"&#,& :%&( KL> 2'-),1-)3 (#3 9))" )3+
&#9-%3()$7 KL> 2'-),1-)3 #.) $%.),&-8 .)3/'"+
3%9-) 4'. *+,)-- #,&%5#&%'"7 D" )A#,& $)3,.%/&%'"

!
'4 (': &()3) 2'-),1-)3 41",&%'" ,#" 9) 4'1"$
'" /7 GT7
*() >?U 2'-),1-) %3 ,(#.#,&).%3&%, '4 *+()-/+
). ,)--37 D/#.& 4.'2 %22#&1.) &(82',8&)30 %& %3
#-3' )A/.)33)$ 98 #,,)33'.8 ,)--3 #"$ )'3%"'+
>? /(%-%, 6.#"1-',8&)37 !& /-#83 #" %2/'.&#"& .'-)

Burmester, Color Atlas of Immunology © 2003 Thieme


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Molecule Molecular
weight (kDa)
Gene
locus
Cell expression
()*+,, !'1.@+'5

Function
!
# 43 – 49 1q22-23 Thymocytes, Antigen-
dendritic cells, presentation
CD1a few B cells (CD1c) (glycolipids)
$ 2m b,c,d,e

50 1p13 Thymocytes, Receptor for CD58


all T cells, (LFA-1), T-cell acti-
CD2 NK cells vation

%
CD3g 25 11q23 Maturing Signal-
& CD3d 20 11q23 thymocytes, transduction
!/" CD3e 20 11q23 T cells after MHC-TCR

<$';&%+'1&, =0.'4.8,+5
#(&)
!-chain 16 1q22 contact
"-chain 22 1q22
$(%)
'
CD3/TCR

55 12p12 Thymocytes, Binding to


T-helper cells, mono- MHC class II
cytes/macrophages, MHC
dendritic cells,
eosinophilic
CD4 granulocytes

CD5
67

40
11q13

17q25
Thymocytes,
all maturing T cells,
few B cells

All cells of
T-cell lineage
Signal transduction

Not known
"
CD7

# CD8# 33 2p12 Thymocytes, cyto- Binding


$ CD8$ 33 2p1 toxic T-cells, NK to class I MHC
cells (weak, CD8a) molecules
CD8

33 Xq26.3- CD4+ T cells Binds to CD40,


27.1 (after activation), activates B cells
CD8+ T cells and dendritic
(subpopulation), cells
CD154
basophils
(CD40L)

40 2q33 Thymocytes Ligand for CD80,


CD4+T cells, CD86 (“co-stimula-

CD8+T cells, tory signal )
CD28 (subpopulation)

!
33 2q33 Activated T cells Ligand for CD80,
CD86 (negative
regulator of
CD152
T-cell activation)
(CTLA–4)

A. Human T-cell differentiation molecules


>A

Burmester, Color Atlas of Immunology © 2003 Thieme


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! #$>?8=7-(?)& @&+&'-=8&.) ,./ @*99&2&.)*,)*-.

!" #$%&'' !()*+,)*-. ,./ 0*1.,'


#2,.3/4()*-.
> #$33) 4YZT>9 =<+2 &'$ 5<$$A%)&%"; =+<2 &+ &'$
(#&%I$ =+<2 *. ?(. += 5'+)5'+<.3(&%+" 53(.) (
-$#%)%I$ <+3$ %" &'$ 5<+#$))6 YZT> 2%;<(&$) &+
!"#$ %& '() *$$" *+,"- *. /01 ! ("- " &'$ ",#3$,): *%"-) &+ &'$ )5$#%=%# UX@M 5<+2+&$<
2+3$#,3$) 4)$$ 56 789: &'$ ("&%;$"%# 5$5&%-$ %) <$;%+": ("- #++5$<(&$) ?%&' ("+&'$< ",#3$(<
5<$)$"&$- &+ &'$ )5$#%=%# > #$33: ?'%#' =%<)& *%"-%"; =(#&+< 4TN@8 #+253$A9 %" )&(<&%"; UX@M
=+<2) ( *+"- ?%&' ! ("- " #'(%") &+ =+<2 ( &<%@ ;$"$ &<(")#<%5&%+" I%( KYT 5+3.2$<()$ UU6
2+3$#,3(< #+253$A 4)$$ 56 B796 >'$ *+"- %) )&(@
*%3%C$- *. &'$ 1DEF1DG 2+3$#,3$6 >'$ (#&,(3 5" #$%&'' !()*+,)*-.6 #7& #*8& %-423&
)%;"(3 &<(")-,#&%+" 5<+#$)) =%"(33. &(H$) 53(#$ -9 :&.& ;<=2&33*-.
2(%"3. I%( &'$ # ("- $ 2+3$#,3$) += &'$ 1DB
#+253$A6 1DE ("- 1DG 4! #'(%"9 #$33) (<$ %"@ T -%)&%"#&%+" %) 2(-$ *$&?$$" %22$-%(&$:
I+3I$- %" )%;"(3 &<(")-,#&%+" I%( 57J3#H &.<+)%"$ $(<3.: ("- 3(&$ >@#$33 (#&%I(&%+" 5<+#$))$)6 N<+@
H%"()$: *,& &'$ 1DE7 ("&%;$" 53(.) ( I$<. &+@+"#+;$"$) 4#@1&0 ("- #@'*#9: ",#3$(< *%"-@
%"; 5<+&$%") 4)$$ )$#&%+" !9: ("- #.&+H%"$ ;$"$)
A4./,8&.),' B2*.(*='&3

%25+<&("& <+3$6 >'$ 3(&&$< +##,<) %" )$I$<(3


%)+2$<%# =+<2) ("- $A'%*%&) %"&<(#$33,3(< &.<+@ *$#+2$ %"I+3I$- %" &'%) +<-$< += ),##$))%+"6
)%"$ 5'+)5'(&()$ (#&%I%&.6 0$"#$: 5'+)5'+<.3(@ >'$ %"#<$()$- $A5<$))%+" += /01 -$&$<2%"("&)
&%+" (#&%I%&. 2$-%(&$- *. 5'+)5'+&.<+)%"$ H%@ 4+" #$<&(%" #$33 ).)&$2)9 ("- (-'$)%+" 2+3$@
"()$ %) &'$ =%<)& )&$5 &+?(<- >@#$33 (#&%I(&%+" #,3$) +##,<) +"3. )$I$<(3 -(.) 3(&$<6
(=&$< &'$ 3%;("- *%"-) &+ &'$ >1K 2+3$#,3$6
>'%) 5<+#$)) 5$<2%&) +&'$< 5<+&$%") ?%&' )5$#%@
=%# &.<+)%"$@*%"-%"; 5<+5$<&%$) &+ #+2*%"$ ?%&'
5'+)5'+<.3(&$- 5<+&$%")6 >'$)$ )&<,#&,<(33.
5<$)$<I$- *%"-%"; 2+&%=) (<$ <$=$<<$- &+ ()
!"#$%&'&(&)*$+ ,&'-./0 4L0M -+2(%")9 *$@
#(,)$ &'$. ?$<$ =%<)& %-$"&%=%$- %" &'$ L<# 5<+@

"
&$%"6
N'+)5'+<.3(&%+" += &.<+)%"$ (2%"+ (#%-) +"
&'$ #.&+53()2%# 5(<& += ( 2$2*<("$@*()$- 5<+@
&$%" 3$(-) &+ &'$ *%"-%"; += L0M@#+"&(%"%"; 5<+@
&$%") (& &'%) *%"-%"; )%&$6 O$)%-$) 1DE7: 57P=.":
("- 57J3#H: C$&(@())+#%(&$- 5<+&$%" 4QR HD(9 ("-
C$&(@())+#%(&$- 5<+&$%" H%"()$) 4STN H%"()$9
(3)+ 53(. (" %25+<&("& <+3$6
N'+)5'(&%-.3%"+)%&+3 5'+)5'+3%5()$ 4NUN9
$"C.2$ %) )&%2,3(&$- -,<%"; &'$ (#&%I(&%+" 5<+@
#$))6 >'%) &<%;;$<) +&'$< 5<+#$))$) &'(& ,3&%@
2(&$3. 3$(- &+ (" %"#<$()$ %" &'$ #+"#$"&<(&%+")
+= %"+)%&+3 &<%)5'+)5'(&$ 4UNB9 ("- -%(#.3;3.#$<@
+3 4DTV9 %" #.&+53()26 >'%): %" &,<": #(,)$) (
#+")%-$<(*3$ %"#<$()$ %" #$33,3(< #(3#%,2 3$I$3)
-,$ &+ &'$ 2+*%3%C(&%+" += 2$2*<("$@*()$-
%"&<(#$33,3(< #(3#%,2 -$5+)%&)6 >'%) %"=3,A +=
DTV ("- #(3#%,2 =%<)& (#&%I(&$) 5<+&$%" H%"()$
1 4NW19: ( )$<%"$F&'<$+"%"$ 5'+)5'+H%"()$:
&'$" &'$ 5<+&+@+"#+;$"$ 5<+-,#& K()6 >'%) %"@
%&%(&$) ( )5$#%=%# )%;"(3 &<(")-,#&%+" #()#(-$
&'(& 3$(-) &+ &'$ (#&%I(&%+" += &<(")#<%5&%+" (#@
&%I(&+<): ),#' () TNF8 4)$$ *$3+?96 1(32+-,3%"

! CD
("- #(3#%"$,<%" (<$ (3)+ %"I+3I$- %" &'%) (#&%I%&.6
>'$)$ $I$"&) ,3&%2(&$3. 3$(- &+ ;$"$ (#&%I(@
&%+" ("- &'$ <$;,3(&%+" += ;$"$ &<(")#<%5&%+"6
>'$ %"%&%(&%+" += %"&$<3$,H%"@M 4UX@M9 ;$"$ &<("@
)#<%5&%+" %) ( H$. =(#&+< %" >@#$33 (#&%I(&%+"6 >'$
&<(")=+<2(&%+" += &'$ ",#3$(< =(#&+< += (#&%I(&$-

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
APC MHC
#$%&'' !()*+,)*-.
!
$ # CD4(CD8)

CD3 Ag
CD45 $ #
% '
! !(") & %
! !

PIP2
PLC

A4./,8&.),' B2*.(*='&3
DAG
TCR
IP3
p56Ick PKC
p59fyn

Ca2+
Tyrosine kinases
T cell Ca-dependent
kinases

"
Phosphorylated proteins
Cytoplasm

Gene activation
Nucleus regulation of transcription Phosphorylated
proteins
A. T-cell activation: Signal transduction
Immediate

Proto-oncogenes c-fos c-myc


Nuclear binding proteins NFAT-1 NF(B
Minutes 15 30

Cytokines IFN-' TGF-# IL-4 GM-CSF


IL-2 IL-3 IL-5
IL-6
Receptors Insulin-R IL-2R Transferrin-R
Activating CD69
Early antigens
Enzymes,
intracellular ODC Actin Cyclin Transferrin Histones
proteins
Hours 1 2 3 4 5 6 12 18 24 48

!
MHC HLA-DR
Late Cytokines Rantes
Adhesion proteins VLA-4 VLA-1
Days 2 4 6 8 10
B. T-cell activation: Time course of gene expression
CE

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! ,=><?@A+1<)& #&B&2+@?&() *(/ #$%%&'&()$*)$+(

!" #$%%&'&()$*)$+( $()+ ,-. *(/ ,-0 1&223


!"#$%&"#'( ) *"((+ *', -$.."#",/$'/" $,/0 ,'$1" )
*"((+ ',- 2"20#3 ) *"((+ 4+"" %'5" 6!78 9./"#
+:%%#"++$0,8 )&" *&'#'*/"#$+/$* *3/0>$,"+; 0,
/&" 0/&"# &',-; &'1" ' %0+$/$1"; $,/",+$.3$,5 ".B
."*/ 0, /&" #"+%"*/$1" +:=%0%:('/$0,8 GHBA; .0#
"N'2%("; '*/+ 0, )?@ *"((+ ',- GHBX 0, )?A *"((+8
.:#/&"# ',/$5", *0,/'*/; /&"3 .0#2 /<0 -$+/$,*/
\" 2:+/ +/#"++; &0<"1"#; /&'/ /&"#" '#" 0./",
+:=%0%:('/$0,+ >,0<, '+ /&" )?@ ',- )?A +:=B
,0 +/#$*/ ($,"+ ="/<"", /&" +:=%0%:('/$0,+ $,
5#0:%+8
/&" &:2', -".",+" +3+/"28 ], /&" *0,/#'#3;
9./"# /&" $,$/$'( *0,/'*/ <$/& 1'#$0:+ ',/$B
$/ $+ %0++$=(" /0 &'1" +200/&; %'/&05",B-"%",B
5",+ 4"858; ='*/"#$'; .:,5$; %#0/0C0',+; 5#'++ %0(B
-",/ /#',+$/$0,+ ="/<"", /&" +:=%0%:('/$0,+8
(",+7; 20+/ )? *"((+ ",*0:,/"# "("2",/+ 0. /&"
,0,+%"*$.$* $22:," +3+/"2; "+%"*$'((3 2'*#0B 4" 5&672*)$+( +% 869 :'+/71)$+(
%&'5"+; ,'/:#'( >$(("# *"((+; ',- 2'+/ *"((+8 )&"
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+%0,-$,5 ',/$5", #"+%0,+" '#" +:=D"*/ /0 /&" :('/$0, 0. G5^ %#0-:*/$0,8 9*/$1'/$0, 0. /&" O
*"(( /'>"+ %('*" 2'$,(3 1$' /&" FRXTQFRXT ($B
C7(/*?&()*2 :'$(1$@2&3

5","/$* +:+*"%/$=$($/3 4%#"-$+%0+$/$0,7 0. /&"


&0+/; <&$*& $+ -"/"#2$,"- =3 E?F *02%0B 5',- +3+/"28 )&"#" 0**:#+ ' #"("'+" 0. GHBX;
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*$+$1" ".."*/ 0, /&" .:#/&"# *0:#+" 0. /&" $2B @Z $,-:*"+ /&" .0#2'/$0, 0. G5VX ',- G5V^ ',/$B
2:," #"+%0,+"8 G,/"#(":>$, 4GH7B@A; <&$*& $+ +"B =0-$"+8
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"
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,"#+ 0. ',/$5", %#"+",/'/$0,; /&" 0#$5$,'((3 1'#$0:+ ':/0$22:," -$+"'+"+ $, 2$*"8 )&"3
:,-"/"#2$,"- )B&"(%"# ,:(( *"(( 4)?T7 /#',+B '(+0 +""2 /0 %('3 ' #0(" $, %#"1",/$,5 ".."*/$1"
.0#2+ $,/0 "$/&"# ' )?@ 0# )?A *"((8 $22:,0+:#1"$((',*" $, %'/$",/+ <$/& *',*"#
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%&'5" '*/$1'/$0, ',- ("'-+ /0 2'#>"- $22:,0B

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Antigens
,-. *(/ ,-0 ;&223
!
Protozoans
Bacteria Fungi (e.g. helminths) Pollen

Genetic susceptibility (e.g. MHC, TCR etc.)

C7(/*?&()*2 :'$(1$@2&3
NK cell !/" T cell Basophils, ?
Macrophage mast cell
IL-12 IFN-! IL-4

Cytokine milieu
IL-12 IFN-! IL-4

Dendritic
cell
MHC II

B7-1
(CD80)
TCR

CD28

TH0
TCR

CD28
MHC II

B7-1
(CD80)
Dendritic
cell
"
IFN-! IL-4

IL-2 TH1 TH2


IFN-! 0 IL-5
IFN- IL-1
Intracellular TNF-# ! IL-4 IL-4 Antibody
killing

Macro-
phage B cell

A. Differentiation into TH1 and TH2 cells

IL-13 IL-4R
IL-10 IL-4 Ag

IL-4R IL-4R sIgM

!
IL-4
TCR MHC + Ag
IgE
CD40 CD40
TH2 ligand B cell
B. Regulation of IgE production
0.

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! -6./)(0'1/+$ #$%$&'()$*+ 7*8 #9,,$:$*+97+9'*

!" #$%$&'()$*+ ', - ./)(0'1/+$2


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42'$ %"52.%')*/) +)*$ (*""+ ./ 2*1().'/ )' +.67
./1" $1)521).'/ '4 ! (*""+ ./)' %"1+$1 (*""+ )&*/
'((52+ ./ )&* 0'/* $122'3 '2 ./ )&* $5('+1 '4
)&* 61+)2'./)*+)./1" )21()=
S'$* '4 )&* 1/).6*/7+).$5"1)*, ! (*""+ $.7
/1"+ 42'$ +)2'$1" (*""+ 8+'"50"* (#)'9./*+:
621)* )' )&* $126./1" ?'/* '4 )&* %*2.%&*21" '27
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61/+ 1/, ,.44*2*/).1)* ./)' J6C7/*61).-*P BCID7
>&* %2'6*/.)'2 ! (*"" 8%2'7! (*""< .+ )&* 4.2+)
/*61).-*P 1/, BCDH7%'+.).-* (*""+ 8*A)214'"".(57
2*('6/.?10"* +)16* '4 !7(*"" ,*-*"'%$*/)= @2'7!
"12 ! (*""+<= J/ ('/)21+) )' $'+) ')&*2 ! (*""+P
(*""+ 12* +*"472*%"*/.+&./6 (*""+ )&1) *A%2*++
)&*+* (*""+ (1/ 1"+' 2*1() )' (120'&#,21)* 1/).7
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6*/+ 8>7(*""7./,*%*/,*/) 2*+%'/+*<P 05) '/"#
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>&* /*A) +)16* '4 ,.44*2*/).1).'/ .+ (1""*, )&* >&*+* ! (*""+ 8!FV !7(*"" 421().'/< 12* 0*".*-*,
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"#$%& /',*+ '2 ./ $5('+171++'(.1)*, "#$7
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/'6"'05"./ +3.)(&< 1/, '4 &.6&*2 144./.)#= >*2$7

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
CD34 CD19 CD38
-63$&& ?*+'@$*$292

CD19 CD20 CD38


!
CD10
CD117

CD22 CD10
Pro-B Plasma cell Intestinal Pro-plasma cell
submucosa

Follicle Marginal
zone
Pro-PC

;<*87)$*+7& =:9*19(&$2
Pro-B Plasma cell
Antigens

Circulating
follicular
Circulating B cell
follicular Extra-
T-cell zone follicular
B cell
B cell

Apoptosis
Pre-B

Bone marrow : primary


B-cell production

CD20
CD19
CD22
CD19
CD20
„Virgin”-B

Peripheral blood

CD21
CD22 CD19
CD20 CD21
Virgin-B

Secondary lymphatic organs:


antigen-induced B-cell proliferation

CD22 CD19
CD20 CD21
CD22
"
CD23
CD37 CD39
cyt-µ
slgM slgM slgM
slgD CD11c
Circulating Extra-
Pre-B Virgin-B follicular B cell follicular B cell

A. Development of B lymphocytes

Pleural space CD5+ B cells


– T-independent
– Secrete low-affinity
lgM-autoantibodies
Bone marrow – Can renew themselves
CD5+
– No hypermutations
slgM+

CD5 CD45R
CD20

Early ontogenesis
B. CD5+ B cells
Peritoneal cavity slgM
CD11a

!
>A

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! #$@<3?0-(<)& 8&+&'-?3&.) ,./ 8*77&2&.)*,)*-.

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"
23,& $0* #3;1)((*+ )*+,- %&'( 32 $0* -*,&%")( /,3+'1* 0%-0;)22%"%$. )"$%-*";)+)/$*+ )"$%>3;
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BC 2*,*"$%)$* )-)%" %"$3 1*"$,3>()#$#C >'$ &). )(#3

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
= Follicular
dendritic
Follicle
mantle
1&23*.,' %&.)&2 4&,()*-.
!
cells (FDC)
Primary
B-blasts Phase 1
of follicle
Primary lymphoid reaction
follicle (3-4 days)
Follicle
Follicle mantle
mantle – Centrocytes
– FDC Light zone
Secondary
– T-helper cells
B-blasts
– Macrophages
Phase 3 Phase 2
of follicle of follicle
reaction reaction

A9./,3&.),' 62*.(*?'&>
(months) – Centroblasts Dark zone (3 weeks)

A. B-cell activation: the germinal center reaction

Follicular Primary Centroblast Centrocyte


B cell B-blast
– CD19 – CD19 – CD19 – CD10
– CD20 – CD20 – CD20 – CD19 Circulating Apoptosis
– CD21 – CD22 – CD22 – CD20 memory cell

"
Antigen – CD22 – CD40 – CD38 – CD22 Plasmablast
profile – CD23 – slgM – CD77 – CD37
– CD39 – CD40 – CD38
– CD40 – slg± – CD40
– CD76 – slgM/A/G/E Intestinal Bone
– slgM/D mucosa- marrow
plasma cell plasma cell
B. Antigen profile of B cells during germinal center reaction

Antigen-specific B cell FDC FDC

Apoptosis

Apoptosis

Repeated cycles
Dark zone Light zone
of germinal center of germinal center
– Proliferation Mutated immunoglobulin with higher affinity
– Point mutation in binds antigen-presenting FDC and survives
– V-region of H/L-chains

A A C T G C

T T G A C G
A A C C G C

T T G G C G
= Amino acid switch = 10-fold increase in affinity

C. Selection of high-affinity antibodies through hypermutation in the germinal center


!
BD

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! 1>?6$3@'/6-0 90;0)'3$0&- 5&A 9+440.0&-+5-+'&

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($+)J$36

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
CDR Variable Constant Domain
#$$%&'()'*%)+&=
!
C1q binding site
Light chain

S
S
Heavy chain

S S
S S
CH1

SSSS
COOH CH1
CH2 CH3
VH S
S VH CH2 CH3 CH4
COOH
CL CL Only at
NH2 IgE
VL VL and IgM
NH2 Fab Fc Antigen
Antigen binding Effector function binding

B%&A5$0&-5) C.+&/+3)0=
CDR = complementarity-determining region VH = variable domain of heavy chains
Fab = antigen-binding fragment VL = variable domain of light chains
Fc = crystallizable fragment CH/L = constant domain of heavy / light chains
A. Immunoglobulin structure
N N N
N
N
N
N
N N
NN

"
! # #
(") ($) NN

!2m # !

C C CC C CC C C C C C C C
IgG TCR I/II MHC MHC CD4 CD8 Poly-IgR CD19 CD22 N-CAM/
class I class II CD 56
B. Immunglobulin-“superfamily”

CDR
L3 -N-terminal end
90-95
SSSS

CDR
L1
26-32
CDR
L2
49-55
CDR CDR CDR
H3 H1 H2
Variable domain of light chain 95-101 30-35 49-64
with the 3 hypervariable
complementarity determinants

C. Hypervariable regions determine the antigen specificity


CDR
L2
49-55
A n
t i g
e n - E p i t o p
CDR
L1
26-32
e
CDR
L3
90-95 !
DF

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme


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Albumin Globulins
5667)%8+%97+() :+<//'/

Breast
milk
!
! 1 !2 " #

Fc
receptors

1. Circulating Ig 2. Membrane- 3. Secretory Ig 4. Cell-bound Ig


IgM IgD IgA IgG 2. bound Ig
A. Protein electrophoresis B. Different immunoglobulin types

V IgG IgA IgM IgD IgE


Serum: Serum: lgM Serum: lgD

>7)=<6')&<+ #$(),(-+'/
VL Monomeric lgA
CL
SS
SS

SS

IgG1 65%
SS SS

SS
SS

SS

SS
SS

SS
SS
SS
SS

IgG2 23%

"
Secretory Membrane- Membrane-
lgA; dimer bound lgM bound lgD
SS
SS
SS
SS
Hinge
SS SS
SS SS SS
SS
region SS
SS
SS
SS

J
IgG3 8%
S
S chain SS

SS
SS
SS

Mature Mature Basophil


B lymphocyte B lymphocyte granulocyte
IgG4 4%

Serum lg 80% 13% 6% 0.1% 0.002%

Half-life 23 6 5 3 2.5 days

C. Immunglobulin structure and features

Lumen Fc#R Binding at pH <7.0 Secretory component Lumen

pH 7.4 Release at pH 7.4

D. IgG transport through intestinal epithelium


lgA
E. Secretion of IgA
J chain
!
CE

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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&(.#9'.-(8 8#-($/ .6- ! 6-'%8 )6'#" ,2 .6- 3&(#"/4 \%-+ .6- ),&+/- ,2 .#9-@ .6- +-'++'"7-$
#99&",7(,3&(#"4 56- .,.'( ,2 )'4 B1 C 7-"-/@ CGI /-Q&-")-/ '+- *,/#.#,"-$ $#+-).(8 '$A')-".
01EF1 G 7-"-/@ '"$ H I 7-"-/ 8#-($/ ' +-),93#: ., ,.6-+ K 7-"-/4 O%-+8 K 7-"- #/ *+-)-$-$ 38 '
"'.#," *,.-".#'( ,2 '+,&"$ F!01F ., D!01F 2,+ /,:)'((-$ /S#.)6#"7 ;]= /-Q&-")- .6'. ),".+,(/
.6- '9#", ')#$ /-Q&-")-/ ,2 .6- %'+#'3(- +-7#," .6- +-'++'"7-9-". *+,)-// 38 +-),93#"#"7
,2 6-'%8 )6'#"/4 56#/ *+,)-// #/ +-2-++-$ ., '/ S#.6 ,.6-+ ] /-Q&-")-/ $&- ., .6- 6#76 (-%-(
!"#$%&' ()'"#*&+$%&"+4 ,2 6,9,(,784 56- K! /-Q&-")-/ (,)'.-$ 3-:
.S--" .6- CGI /-Q&-")-/ '"$ .6- "-S K 7-"-/
8" #$%&'()&*(+' +0 ! 9(%:* ;:&(' 2.'.3 '+- $-(-.-$ #" .6- *+,)-//4
56- 7-"-/ 2,+ # (#76. )6'#"/ '+- (,)'.-$ ," )6+,:
9,/,9- J4 !+,&"$ FBE>1 2&").#,"'((8 ').#%- C
7-"-/ ;.,7-.6-+ S#.6 .6- ),++-/*,"$#"7 P
7-"-/= ),$- 2,+ '9#", ')#$/ 0 ., DB ,2 .6- %'+#:

!
'3(- +-7#," ,2 # (#76. )6'#"/X B I 7-"-/ ),$- 2,+
'9#", ')#$/ DH ., 0014 C 7-"-/ '+- 3+,&76. "-W.
., I 7-"-/ $&+#"7 .6- *+,)-// ,2 GT! +-'++'"7-:
9-".4 ! *+-)&+/,+ 9UT! #/ .+'"/)+#3-$ 2+,9 '
CI /-Q&-")-@ .,7-.6-+ S#.6 .6- /-Q&-")- 2+,9
FG .6- ),"/.'". +-7#," ,2 .6- # (#76. )6'#" ;K#=4 56-
P /-Q&-")- .6-" /*(#./ ,22 2+,9 .6- *+,.-#"4

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
n = ~50
4//5'+%6+756(' 2.'. #$%&'()&*(+'

Chromosome 14
!


VH1 VH2 VH3 Vn

5' 3'
L1 L2 L3 Ln D1 D2 D 3 D 4 Dn J1 J2 J3 J4 J5 J6 Cµ C% C#3 C#1 C&1 C#2 C#4 C' C&2

DJ rearrangement Deletion Germline DNA

VH1 VH2 VH3 Vn C#4


5' 3'
L1 L2 L3 Ln D1 D2 D3 J5 J6 Cµ C% C#3 C#1 C&1 C#2 C' C&2

Deletion Transcription

D5',&/.'*&6 E$('@(B6.3
VDJ-rearrangement DJ-Cµ mRNA DJ-Cµ protein
VH1 VH2
Cleavage
5' 3' of L-coded
L1 L 2 D3 J 5 J6 Cµ C% C#3 C#1 C&1 C#2 C#4 C( C&2 sequence

VDJ-Cµ coding mRNA µ heavy


A. Organization and rearrangement of immunoglobulin H genes chains

"
n = ~35
V$1 V$2 V$3 V$n
5' 3' Chromosome 2
L1 L2 L3 Ln J$1 J$2 J$3 J$4 J$5 C$

B. Organization of ! light chain genes

V"1 V"x V"n


5' 3' Chromosome 22
L1 Lx VpreB Ln J"2 C"2 J"4 C"4 J"x C"x

C. Organization of " light chain genes


C%
µ

#3
C

VDJ
s Cµ C% s C#3 s C#1 Maturation V D J s s C& 1
C# 1

!
mRNA mRNA
µ #1

lgM-expressing B cell lgG1 -expressing B cell


D. Immunoglobulin class-switching
FH

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! #$:;3<2/1;-& (&=&'/<3&,- .,9 ()**&+&,-).-)/,

!" #$%&'' ()**&+&,-).-)/, 012&3&


!"#$%&' '(")*' %+ ,-.*// 0$++*#*1($"($%1 ."1 2*
0*+$1*0 3$(4 (4* 4*/5 %+ "1($2%0$*' 0$#*.(*0
B#*-,-OO .*//' 4"N* "/#*"0? #*"##"1)*0
!V-9V-WV "10 '?1(4*'$Y* " !9W-8" 5#%(*$1
.%##*'5%10$1) (% " .%=5/*(* " .4"$16 74$' .4"$1
FV"H $' *@5#*''*0 %1 (4* .*// =*=2#"1* (%-
")"$1'( '&#+".* "1($)*1'6 74* "1($)*1' 89:;
)*(4*# 3$(4 (4* !5#*,G!U '&##%)"(* .4"$1A
"10 89<< "#* (4* *"#/$*'( '5*.$+$. ,-.*// ="#-
34$.4 +&1.($%1' "' (4* '$)1"/ (% '("#( #*"##"1-
>*#'6 89<< $' $1$($"//? *@5#*''*0 %1/? $1 .?(%-
)$1) (4* /$)4( .4"$16 O=="(&#* , .*//' "#* 0*-
5/"'= 2&(A "' (4* ="(&#"($%1 5#%.*'' .%1($1&*'A
+$1*0 2? (4* '$=&/("1*%&' *@5#*''$%1 %+ (4*
$( $' "/'% *@5#*''*0 %1 (4* .*// '&#+".*6 B#%)*1$-
" 4*"N? .4"$1' $1 "''%.$"($%1 3$(4 !5#*,G!U
(%# , .*//' "/'% *@5#*'' '(*= .*//-"''%.$"(*0
'&##%)"(* .4"$1' FV"G!5#*,H "10 3$(4 1%#="/
"1($)*1'A '&.4 "' 89CD "10 89::E F.->$(G'(*=
>"55" %# /"=20" /$)4( .4"$1' F.%=5/*(*
.*// )#%3(4 +".(%# #*.*5(%#H "10 89:I6 J$1.*
O)MG# ZV"GL"[ %# O)MG! ZV"GL"[ $==&1%-
89:I 3"' +$#'( 0*(*.(*0 $1 (4* .*//' %+ /*&>*=$"
)/%2&/$1'H6 O+ #*"##"1)*=*1( "( " /$)4( .4"$1
5"($*1('A $( $' #*+*##*0 (% "' .%==%1 ".&(* /?=-
/%.&' $' '&..*''+&/ "10 " /$)4( .4"$1 $' '?1-
>5,9.3&,-.' ?+),1)<'&@

54%2/"'($. /*&>*=$"-"''%.$"(*0 F8KLLKH "1($-


(4*'$Y*0A +&#(4*# #*"##"1)*=*1( "( (4* L /%.$
)*16 M"(&#* .$#.&/"($1) .*//' "#* 89:I-1*)"($N*A
3$// 2* '&55#*''*06 O+ " .*// 4"' &10*#)%1* 5#%-
2&( 89:I $' *@5#*''*0 %1 )*#=$1"/ .*1(*# .*//'6
0&.($N* #*"##"1)*=*1( "( (4* # /%.&'A +%# *@"=-
74* *@5#*''$%1 %+ 89<I '("#(' "55#%@$="(*/? "(
5/*A #*"##"1)*=*1( "( (4* ! /%.&' 3$// 2* '&5-
(4* /*N*/ %+ 5#*-,-OO .*//'6
5#*''*0 "10 N$.* N*#'"6 X*"##"1)*=*1( "( (4* !
89<C F/%3 "++$1$(? P.-O)Q #*.*5(%#H "10 89<:
/%.&' $' '($// 5%''$2/*A 4%3*N*#A $+ #*"##"1)*=*1(
"#* ="#>*#' %+ ="(&#* , .*//'6 89<: $' "/'% " #*-
"( (4* # /%.&' 3"' "2%#(*06 74$' =*.4"1$'=
.*5(%# +%# (4* Q5'(*$1R,"## N$#&' "10 +%# (4*
*1'&#*' (4* 5#%0&.($%1 %+ %1/? %1* (?5* %+ /$)4(
8C0 +#")=*1( %+ .%=5/*=*1(6
.4"$1 2? (4* , .*// F!"#$% &$'"( )*+%)"&%",(H6
#" 4335,/6'/75'), 8/95'.-)/, 95+),6
#$%&'' ()**&+&,-).-)/,

" O==&1%)/%2&/$1' "#* *@5#*''*0 %1 (4* '&#+".*


%+ ="(&#* , .*//' "10 "#* '*.#*(*0 $1 /"#)*
"=%&1(' 2? 5/"'=" .*//'6 74* "=$1% ".$0 '*-
S&*1.*' +%# (4* 0$++*#*1( 5"#(' %+ (4* .%=5/*(*
$==&1%)/%2&/$1 "#* 0*(*#=$1*0 $1 (4* 5#*.&#-
'%# .*//' 0&#$1) (4* .%&#'* %+ ,-.*// %1(%)*1?6
O1 5#%)*1$(%# , .*//' F5#%-, .*//'HA '($// &1=%-
0$+$*0 9TK $' +%&10 "( 4*"N? "10 /$)4( .4"$1 /%.$
$1 (4* '%-."//*0 )*#=/$1* .%1+$)&#"($%16 O1 "0-
0$($%1 (% )*1*' +%# (4* /"=20" /$)4( .4"$1A (3%
%(4*# )*1*' F!5#*, "10 !UH (4"( .%0* +%# (4*
.%##*'5%10$1) /$)4( .4"$1-/$>* 5#%(*$1' F'&##%-
)"(* /$)4( .4"$1'H "#* "/'% /%."(*0 %1 .4#%=%-
'%=* <<6 74* '&##%)"(* /$)4( .4"$1' "#* +$#'( *@-
5#*''*0 %1 (4* .*// =*=2#"1* (%)*(4*# 3$(4 "
:CI >9" )/?.%5#%(*$1 .%=5/*@6 74*? 5#*'&=-
"2/? 2$10 (% .*//&/"# %# '%/&2/* /$)"10' "10
(#"1'5%#( (4* '$)1"/' +%# +&#(4*# ,-.*// 0*N*/%5-
=*1( (% (4* .*// $1(*#$%#6
M%#* 0$++*#*1($"(*0 , .*//' F5#*-,-O .*//'H
4"N* #*"##"1)*0 9V "10 WV )*1*' "( (4* V /%.&'
%+ .4#%=%'%=* :D6 K 9W-8" 5#%(*$1 $' .%0*0

!
0&#$1) (4* 5#%.*'' %+ 9W-8" =XTK (#"1'.#$5($%1
F'** 56 CIH6 74* 5#%(*$1 (#"1'=$(' " 1*)"($N*
+**02".> '$)1"/ (% '(%5 (4* +&#(4*# '?1(4*'$'
%+ 9W-8" 5#%(*$1'6 !5#*,G!U .4"$1' ."1 "''%.$"(*
2%(4 3$(4 5:CI )/?.%5#%(*$1' "' 3*// "' 3$(4
AB 9W-8" 5#%(*$1' %1 (4* .*// =*=2#"1*6

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
pro-B pre-B-I pre-B-II
4335,/6'/75'), C&,& ?+/951- DE<+&@@)/,

Immature B Mature B Plasma cell


!
HL A -class II
(HL A -DR)
CD34
CD10
Surface
lg-!/lg-"
Surface
VpreB/#5
cyt-µ slgM/slgD
Immunoglobulins
CD22
CD19
CD20

>5,9.3&,-.' ?+),1)<'&@
CD21
CD23
A. B-cell differentiation scheme Cytoplasmic

CD34 CD19 CD19


IL-7R CD22cyt IL-7R CD22cyt
H L$ H L$
CD10
DJ-rearrangement
L# L#

Pro-B
VpreB/#5

CD19
CD22cyt
pre-B-I

DJ-Cµ
VpreB/#5

transcription
CD19
CD22cyt
"
H L$ H L$
CD10 VDJ-rearrangement CD10

L# L#

Pre-B-II Pre-B-I Prot.


VpreB/#5
DJ-Cµ
Hµ/VpreB/#5

VL-JL- Rearrangement HµL$

Hµ/L$ (slgM) CD19 CD19


CD22cyt CD22s
CD20 CD20

or or

!
CD21
Immature B Mature B CD23
slgM+
Hµ/L#(slgM)
Hµ/VpreB/#5 HµL# (slgM)

B. Immunoglobulin modulation during B-cell differentiation


AA

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! !"#$%&'()$*+ ,+-+.(&%+/* 0/1 ,233+4+/*20*2(/

!"# $%&'%&( )* +& +&,%(#& ,) -./*+0# %11.&)2


(3)$.3%&- ,/%((#/- + 0+-0+'# )* $%)0"#1%0+3 -%(2
&+3- 4%,"%& + 5 0#336 7%&0# %11.&)(3)$.3%&-
+.,)0/%&#T:+/+0/%&# 520#33 (/)4," *+0,)/ )00./-
+- + 03#+8+(# :/)'.0, )* <=M>6
!"($ %- 1+%&39 #?:/#--#' $9 5 0#33-; $., +3-)
"+8# )&39 + 8#/9 -")/, %&,/+209,):3+-1%0 ,+%3; $9 '#&'/%,%0 0#33- A=<D; *)33%0.3+/ '#&'/%,%0 0#33-
,"#9 +/# '#:#&'#&, )& +00#--)/9 1)3#0.3#-; -%2 AS=<D; "#1+,):)%#,%0 :/)(#&%,)/ 0#33-; #:%,"#3%+3
1%3+/ ,) ,"# <=> 0)1:3#? )* ,"# !20#33 /#0#:,)/6 0#33-; +&' 0+/0%&)1+ 0#33-6 <=UJ %- + 1#1$#/ )*
@(2! A<=BC+D +&' @(2" A<=BC$D 0"+%&- +--.1# ,"# !VS /#0#:,)/ *+1%396 F !VS2/#3+,#' (390)2
,"%- *.&0,%)&6 !"#-# 0"+%&- +/# -,/.0,./+339 -%2 :/),#%& ,"+, %- 1+%&39 #?:/#--#' )& +0,%8+,#'
1%3+/ ,) !<E #; $; +&' % 0"+%&- +&' ,"#9 *)/1; <=U ! ! 0#33- A<=UJ 3%(+&'; <=IWUD :/)8%'#-
,)(#,"#/ 4%," ,"# %11.&)(3)$.3%&-; ,"# 52 +& %1:)/,+&, -./8%8+3 -%(&+3 *)/ 5 0#33-6 !"#
0#33 /#0#:,)/ A5<ED 0)1:3#?6 (#/1%&+3 0#&,#/- 0+&&), '#8#3): 0)1:3#,#39
!"#$ %- /#*#//#' ,) +- !"##"$ %!&'( %* <=UJT<=UJ 3%(+&' %&,#/+0,%)& %- '#*#0,%8#6 @*
)*#+,"-)%.'/! )(&0(#/%1%.."!/%'(2 A<FGGFD ,"%- %- ,"# 0+-#; @(X %- ,"# )&39 %11.&)(3)$.3%&
%$'/3($ $#0+.-# %, 4+- *%/-, *).&' )& 391:")2 ,"# 5 0#33- 0+& :/)'.0# $#0+.-# )* + $3)0H#'
56/10%+/*0. 742/)2&.+8

$3+-,- )* :+,%#&,- 4%," ,"# 0)11)& 8+/%+&, )* %11.&)(3)$.3%& 03+--2-4%,0"%&( A"9:#/2@(X


+0.,# 391:"+,%0 3#.H#1%+ A0)11)& FGGD6 -9&'/)1#D6
<=IJ %- +& #?,/+0#33.3+/ K%&02$%&'%&( 1#,+33)2 !")&; 3%H# <=M>; %- + 1#1$#/ )* ,"# %./%)"1
:/),#%&+-# ,"+, 0+& 0+,+39K# ,"# 03#+8+(# )* 8+/2 3)*!"+5"'(/$ /#0#:,)/ *+1%396 G%H# <=IC; %, %- +
%).- :#:,%'#-; -.0" +- -.$-,+&0# L; #&'),"#3%&; $/)+' 520#33 1+/H#/; $., %,- *.&0,%)& %- &),
)?9,)0%&; $/+'9H%&%&; +&' +&(%),#&-%&- @ +&' @@6 9#, .&'#/-,))'6 Q+/3%#/ #8%'#&0# ,"+, <=BM
@, %- #?:/#--#' )& -,/)1+3 0#33-; )& %11+,./# *.&0,%)&- +- + 3%(+&' *)/ <=W "+- &), 9#,
! +&' 5 0#33- %& ,"# $)&# 1+//)4; +&' )& $##& 0)&*%/1#'6
(#/1%&+3 0#&,#/ 0#33- %& -#0)&'+/9 391:")%' !"*$ +&' !"*+ +/# &), 520#33 3%&#+(#2-:#0%2
)/(+&-6 *%06 !"#9 +/# #?:/#--#' )& ),"#/ +&,%(#&2:/#2
!"#% %- #?:/#--#' )& ,"# 1#1$/+&# )* +33 5 -#&,%&( 0#33-; -.0" +- 1)&)09,#- +&' '#&'/%,%0
391:")09,#- +&' %- ,".- + 1+/H#/ )* ,"# #&,%/# 0#33-6 !"# %&,#/+0,%)& )* <=NJT<=NY 4%," ,"#%/

" 5 0#33 -#/%#-6 <=IC .&%,#- 4%," <=MI; <=NI; +&'


G#.2I> ,) *)/1 + 0)2/#0#:,)/ ,"+, 1)'.3+,#-
,"# -%(&+3- ,/+&-'.0#' $9 ,"# 5<E 0)1:3#?6
!"%- +0,%8%,9 %- #-:#0%+339 %1:)/,+&, %& %11+2
,./# 5 0#33-6
!"&$; + O:+&2520#33 1+/H#/P #?:/#--#' )& +33
3%(+&'- )& ! 0#33- A<=MN +&' <!GF2UD %- 0/.0%+3
*)/ ,"# 0)1:3#,# +0,%8+,%)& )/ '#+0,%8+,%)& )*
! 0#33- A-## :6 >YD6

5 0#33- #?0#:, :/)(#&%,)/ 5 0#33-; %- -,/.0,./+339


-%1%3+/ ,) +& %)& 0"+&&#36 @,- ,/+&-1#1$/+&#
-#(1#&, 0/)--#- ,"# 0#33 1#1$/+&# *)./ ,%1#-
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,)&6
!"&# %- + 3)42+**%&%,9 /#0#:,)/ *)/ ,"# 0)12
:3#1#&, 03#+8+(# :/)'.0,- %<>$ +&' <>'6 @, +3-)
-#/8#- +- ,"# Q:-,#%&R5+// 8%/.- /#0#:,)/6 !)2
(#,"#/ 4%," <=IC; <=NI; +&' G#.2I>; <=MI %-
*.&0,%)&+339 +--)0%+,#' 4%," ,"# 520#33 /#0#:,)/6
!"&&; 3%H# <=> )& ! 0#33-; #?"%$%,- $%1)'+3
#?:/#--%)&6 <=MM %- #?:/#--#' )& ,"# 0#33 1#12
$/+&# )&39 %& 1+,./# 5 0#33-; $., %- :/#-#&,
4%,"%& ,"# 09,):3+-1 )* +33 5 0#33-6 @, *.&0,%)&-
+- +& +'"#-%)& 1)3#0.3# ,"+, %&,#/+0,- 4%,"
./%)*)3)*!"!"$4&3%'(.6 G%(+,%)& )* <=MM 3#+'-

!
,) ,"# ')4&/#(.3+,%)& )* -%(&+3 ,/+&-1%--%)&
$9 5<E 0)1:3#?#-; 1#'%+,%&( +& %&"%$%,)/9
#**#0,6
!"&' %- ,"# 520#332+--)0%+,#' /#0#:,)/ *)/ ,"#
S0 */+(1#&, )* @(Q6 !"# $%&'%&( )* <=M> ,) @(Q
9: )/ ,) %11.&# 0)1:3#?#- 0)&,+%&%&( @(Q %&2
'.0#- *##'$+0H %&"%$%,%)& )* @(Q -9&,"#-%-6 F&
Burmester, Color Atlas of Immunology © 2003 Thieme
All rights reserved. Usage subject to terms and conditions of license.
Molecule Molecular Gene locus
weight(kDa) (chromosome)
Cell expression
;%&(4*0/* !"<+.. =/*2>+/8

Function
!
slg 150–900 14 (!-chains) Mature B cells Antigen binding
2 ("-chain) part of B-cell antigen
22 (#-chain) receptor (BCR)

Ig-$(CD79a) 34 19q132 Pre-B cells sIg-associated molecules


Ig-%(CD79b) 39 17q23 Mature B cells signal transducing
part of BCR
100 3q21-q27 Pre-B cells Neutral endopeptidase
B cells of

56/10%+/*0. 742/)2&.+8
germinal center
NH

CD10 (CALLA) Granulocytes

95 16p11.2 All B cells With CD21-, CD81-


incl. progenitor Leu-13 co-receptor
B cells
COOH

for BCR
CD19

35–37 11q-q13 Pre-B cells Ion channel


NH2 COOH

Mature B cells subunit


CD20

140 1q32 Mature B-cells


Follicular
dendritic
C3d/EBV-receptor
(CR2)
BCR-association,
"
COO

CD21 cells (FDC) signal transduction

135 19q13.1 All B cells B-cell adhesion


(cytoplasm) molecule (B-B and B-T
Mature B cells interaction)
COOH

CD22 (surface) modulation of BCR

45 19p13.3 Mature B cells Low-affinity Fc&


FDC receptor (Fc&RII)
NH2

Act. monocytes cleavage product = B-cell


CD23 eosinophils growth factor

48 20q12- Pre-B cells Interaction with CD40


q13.2 Mature B cells ligand (T cell)
COO

Dendritic Anti-apoptosis signal


CD40 cells (DC)

43–39 9p All cells of Adhesion molecule


B-cell lineage
NH2

CD72 Macrophages

!
B cells, T-APC interaction
act. monocytes (ligands for
60 3q21 CD28/CTLA-4)
COOH

Dendritic
CD80/86 cells (DC)
A. Important B-cell antigens
9?

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! 5&%%A5&%% *+/&01'/.$+)

!" #$%&'(%&) *+,$%,&- .+ *+/&01'/.$+)


2&/3&&+ 4 5&%%) 1+- !65)
3",3 )3*/0&0) +4 -.3+3+K*- 5 &./1(+-.3") 8;5A)<
%,' ,%30$%& B*&&"$ -"&& 8[]< 40,-3*+,@ GD[2! )3*2
/0&%3") %,3*/*-$+E*%& %,' 1$+*,4&%//%3+$.
!"#"$%& %'(")*+, %,' %--"))+$. /+&"-0&") 1$+2 %-3*#*3. +4 /%-$+1(%7") %,' ",(%,-") 3(" %-3*2
/+3" 3(" *,3"$%-3*+, +4 5-"&&) 6*3( %,3*7",21$"2 #%3*+, +4 ;5A)@
)",3*,7 -"&&) 89:;)<= )0-( %) > -"&&)= '",'$*3*-
-"&&) 8?;)<= %,' /+,+-.3")@ 5" *5=8 .+ 4<5&%% !'/.,1/.$+
A"0B+-.3" 40,-3*+,2%))+-*%3"' %,3*7",2C
8AD92C<= % 0E*F0*3+0) %,3*7",= E*,') 3+ *,3"$-"&2 ^,&*B" ;?IS= 3(" ;?IS (+/+&+7+0) *,'0-*E&"
&0&%$ %'(")*+, /+&"-0&"2C 8G;9H2C<@ ;?I E*,') 52-"&& -+2)3*/0&%3+$ 8G;W!< *) ,+3 -+,)3*303*#"&.
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%,' 1$+'0-" &%$7" F0%,3*3*") +4 GA2CI@ 5(" %'("2 -%, *,'0-" E+3( 5ZC %,' 5ZI '*44"$",3*%3*+,@
)*+, +4 > -"&&) 3+ 5 -"&&) *) 40$3("$ )3%E*&*O"' E. G;W! *,3"$%-3) 6*3( 3(" G;W! &*7%,' G;W!A=
*,3"$%-3*+,) +4 3(" ;?CMP %,3*7",= +$ !%)-0&%$ 6(*-( *) %&)+ B,+6, %) >V(= >VU:2C= %,' >V2
""&& #'(")*+, $+&"-0&"2C 8Q;9H2C<= 6(*-( *) ZI@ G;W!A *) "K1$"))"' -+,)3*303*#"&. +, > -"&&)=
%&)+ "K1$"))"' +, ",'+3("&*%& -"&&)= 6*3( 3(" ?;)= /%-$+1(%7")= %,' ",'+3("&*%& -"&&)= %,' *3
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"
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9,3*7", $"-+7,*3*+, E. 3(" 52-"&& $"-"13+$ 85;U< +4 3(" 1$+-"))"' 1"13*'" "/E"''"' *, 3("
1$+#*'") % 4*$)3 %-3*#%3*,7 )*7,%& 4+$ % 5 -"&&= E03 HZ; -+/1&"K 6*3( 3(" " %,' # -(%*, +4 3("
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;?SPX *3 -+/1"3") 6*3( ;?IS %,' *,(*E*3) -"&& "44"-3) *, 3(" (+)3@
-.-&" 1$+7$"))*+,@ 5(*) ,"7%3*#" )*7,%& *) 1$+E2
%E&. "/*33"' E. ;5A92L 3+ ",' 52-"&& %-3*#%3*+,
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$")1+,)"@ 9 40$3("$ *,(*E*3+$. $"-"13+$ *) B,+6,
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!
*,3"$%-3 6*3( 36+ >V 4%/*&. /"/E"$)Y :?2AC +$
>V2ZG %,' :?2AI +$ >V2?;@
5"$/*,%&&. '*44"$",3*%3"' ?;) -%, 1$+'0-"
&%$7" F0%,3*3*") +4 GA2CI +, ;?LMN;?LM2&*7%,'
*,3"$%-3*+,= *,'0-*,7 3(" $"&"%)" +4 *,3"$4"$2
CD +,2! 8GD[2!< %,' 3(" '*44"$",3*%3*+, +4 ;?L\
-"&&) *,3+ 5ZC -"&&)@ GA2CI *) %&)+ % '*$"-3 %,' 1+2
Burmester, Color Atlas of Immunology © 2003 Thieme
All rights reserved. Usage subject to terms and conditions of license.
CD 11a/18
*+/&01'/.$+) 2&/3&&+ 4 5&%%) 1+- !+/.9&+<?0&)&+/.+9 5&%%)

CD54 CD40 CD40L


!
(LFA-1) (ICAM-1)
CD54 CD11a/18
CD2 CD58
(LFA-3) CD58 CD2

APC = dendritic cell


CD3 CD8 or CD4
MHC

APC = B cell
T cell

MHC class I TCR


class II (or

T cell
TCR
(or class II)
class I) CD3
CD4 or CD8
ICOS B7h/ICOSL ICOSL/B7h ICOS

CD28/CTLA-4 CD80/CD86 CD80/CD86


(B7.1/B7.2) CD28/CTLA-4
(B7.1/B7.2)
CD106 CD49d

B(+-1@&+/1% 60.+'.?%&)
CD40L CD40 (VCAM)
A. Molecules involved in T cell – APC interaction

APC APC

Non APC CD80/ CD80/ CD80/


CD86 CD86 CD86
APC
CD28 CD152 CD28 CD152

T T

"
MHC I CD80/
MHC I Upregulation of
antigen CD86
TCR CD152/CTLA-4
CD28 3. Self-limitation/downregulation
CD28

APC
T T
CD80/ CD40
CD86 IL12
Anergy/Tolerance T-cell activation
CD28 CD154
TH1 CTL
T IFN-#
1. Signal 1 only 2. Co-stimulation Upregulation of
via CD28 CD154/CD40L
B. Several signals needed for T-cell activation 4. Effector cell induction

APC B cell

IL-6
CD80/ MHC II AgR B7RP-1/ " ! Superantigen
CD86 ICOSL
TCR
CD28 ICOS Variable region

!
IL-4 of ! chain (V!)
T H1
T IL-13
Upregulation
of ICOS IL-2
T H2
C. ICOS in T-cell activation D. Superantigen stimulation
CE

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! -'*0($78,87 #$,$*0$ /$&&0

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!(&&)% -)&& "//$21>&1:$&(2=&(') #)-)0#1%. *+EY.,
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21# "##"-' -)&&. #8"# )@0%).. 21%/"& &)A)&. 17 12&9 12 !+ -)&&. "23 12 " .$:>%1$0 17 < -)&&.F
BCD -&".. E /1&)-$&).F :$# #8)9 '(&& -)&&. EJ<.LJEY. "%) "&.1 )@0%)..)3 12 /121-9#).F 3)2=
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#8) S- %)-)0#1% 12 " !+ -)&& *DM4T, "-#(A"#).
B"29 %)-)0#1%. "%) (2A1&A)3 (2 #8) %)-1>2(=
#8) -9#1&9#(- 0%1>%"/ 17 +2#(:139=,)0)23)2#
#(12 17 -&"..(-"& BCD /1&)-$&).; E2 -12#%".# #1
-)&&=/)3("#)3 -9#1#1@(-(#9 *VMDD, :9 (23$-(2>
"2#(>)2=.0)-(7(- < -)&&.F #8).) %)-)0#1%. $.$"&&9
#8) %)&)".) 17 0%1#)1&9#(- )2I9/). *'(.,;
%)-1>2(I) " G81&) .)# 17 3(77)%)2# CJV -&".. E
AB "&&)&). :$# 21# #8) 0)0#(3)LBCD -1/0&)@;
<8)9 -"2 :) >%1$0)3 (2 #G1 &"%>) 7"/(&().]

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
T progenitor cell CD34+
CD33-
-3+>43& .8&&$4 /$&&0
!
CD2+
TCR CD7+ Further
rearrangement CD5+ T-cell development
CD1+
Thymus CytCD3+
IL-7
CD34
CD33
T/NK-progenitor cell
CD7
NK progenitor cell Mature NK cell
CD2+/- CD34- CD34-
CD5+/- CD33- CD7+
Bone marrow
IL-5 CD7+ CD2+/-
CytCD3 CD2+/- CD5-
CD5- CD1-

=>*?3)$*+3& @48*78(&$0
CD1- CD16+/-
CD16- CD56+
Fetal liver T/NK CD56-

A. Development of NK cells

Target CD95 APO-1 NK cell


cell Fas
Unknown NKp30,44,46 ligand
carbo-
hydrate?

"
NKG2D DNA-
fragmentation
MICA
Activation
MICB
NKR-P1
Apoptosis
Inhibition
1. Nonsecretory lysis
MHC I
KIR3DL1 Target Formation of pores Degranulation
cell Granzyme
Perforin

B. Target recognition by NK cells


DNA-
fragmentation

Cw2,4,5,6 KIR2DL1
Apoptosis +necrosis
2. Secretory lysis
Cw1,3,7,8 KIR2DL2
Target Perforin NK cell
cell Granzyme
Bw4
KIR3DL1

A3, A11
KIR3DL2 DNA Antibody
fragmentation against

HLA-E

C. Inhibitory receptors of
C. NK cells
CD94
+
NKG2A
Apoptosis + necrosis

D. of NK cells
target
antigen
Fc-receptor

3. ADCC (antibody-dependent cellular cytotoxicity)


D. Cytolytic mechanisms
!
AC

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! 1)2)*+,%. '26 :%26=3,3* 7%>>.

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%&'()*+ ('&'$)A,*0.%&#*0$8 :#(*'" 1!A3BC4 7"'A B+6+"#& "+(+7*'", (#$ 90$/ *5+ C( 7'"*0'$ ':
.'*+, *5+ /0::+"+$*0#*0'$ 0$*' 8"#$%&'()*+,- 0..%$'8&'9%&0$, 1,++ 7> GP4> Y+(+7*'", :'"
<50&+ 8"#$%&'()*+A.#("'75#8+ ('&'$)A,*0.%A E8!- E8N- #$/ E8Z #"+ (#&&+/ C(#Y- C(!Y- #$/
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:#(*'"A! 1?HCA!4 7"'.'*+ /0::+"+$*0#*0'$ 0$*' *5"'%85 0..%$"+(+7*'" *)"',0$+A9#,+/ #(*06#A
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Stem cell
Flt3L IL-3
#$% &$'()*+,% -+.,%/
!
IL-3
SCF Thymic DC
Lymphoid DC
M-SCF
in lymph nodes
IL-3 Promyelocyte
Promonocyte IDC
Granulocytes SF
GM-C
F
G-CS
M-CSF Langerhans cell
IL-3 Dendritic cell in skin/mucosa
Monocyte precursor
GMCSF GCDC
IL-4

8?26'/%2,'> &=32*3<>%.
Dermis/
Interstitial DC

Mesangial Tissue LN/spleen Alveolar Serosa


Kupffer cells cell Microglia macrophage monocyte macrophage macrophage
A. The phagocyte system
0.5 µm

Clathrin
Coated pit Actin
H2O

polymerization
"
1. Pinocytosis 2. Phagocytosis 3. Coiling phagocytosis
B. Mechanism of endocytosis

IgG opsonized particle

Mannose
or fucose C3bi
Fc#RIIA Fc#RI Fc#RIII
i CR4
C3b
C4b C3b CR3
I y I y
T P T P
I
T
y P A y A y Actin CR1
M P M P
A y P Myosin
M
k

k
Sy

Sy
k
Sy

Binding

!
IL-12
– Cytoskeleton – Internalization
IL-1!
rearragement – Actin, vinculin, paxillin
IL-6
– Release of – No inflammatory
TNF-"
inflammatory mediators released
mediators
E. Complement receptor-
C. Fc-mediated phagocytosis D. Mannose receptor mediated phagocytosis
@B

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme
All rights reserved. Usage subject to terms and conditions of license.
1. Activation 2. Chemotaxis, tissue inflammation
+)%)&,'- #$%&'()% /%0 !%'(4-%.

3. Phagocytosis, scavenger
!
Bacteria, LPS TNF-$ IL-8 function, tissue repair
IL-1
TNF-$
IL-1 NO Elastase
IL-6
Collagenase
IFN-# – fibrogenic stim-factor
Acute phase – angiogenic factors
proteins

IL10 – NO
GM-CSF – H2O2
IL12 – O2
TH2 – Toxic factors – Lysozyme
T H1 TNF-$ – TNF proteases – Hydrolase
4. Effector function

#$%0/9-%'/8 :1(%&(28-.
6. Immunomodulation 5. Antigen presentation
A. Function of monocytes/macrophages
Molecule Molecular- Gene locus Cell expression Function
weight (kDa) (chromosome)
CD11a CD11a: 180 16p11-13.1 Monocytes, !", Cell–cell and cell–matrix
CD18: 95 21q22.3 lymphocytes (T-B), adhesion,
LFA-1 granulocytes ligand for ICAM-1, ICAM-2
CD18

CD11b CD11b: 170 16p11-13.1 Myeloid cells, Cell–cell and


CD18: 95 21q22.3 NK cells cell–matrix adhesion,
CR3 ligand for iC3b,
C4b, ICAM-1

"
CD18
CD11c CD11c: 150 16p11-13.1 Macrophages, Cell–cell adhesion,
CD18: 95 21q22.3 myeloid cells ligand for iC3b, C4b,
CR4 ICAM-1, LPS,
fibrinogen
CD18
55 5q31 Monocytes, !", Receptor for LPS
CD14
granulocytes, (B cells) and LPS/LPB complex

50–80 1q23 Monocytes, !", Low-affinity


or CD16 NK cells, Fc-lgG receptor
(FcRIII) granulocytes (GPI)

40 1q23-24 Phagocytes, B cells, Intermediate-


CD32 (FcRII) platelets affinity Fc-lgG receptor

72 1q21 Monocytes, High affinity Fc-lgG


CD64 (FcRI) !" receptor

48 20q12- Pre-B cells, Interaction with


COOH

q13.2 mature B cells CD40 ligand (T cell),


CD40 dendritic cells (DC) anti-apoptosis signal
CD80/86 60 3q21 B cells, act. macrophages, T-APC interaction
COOH

dendritic cells (DC) (ligands for CD28/CTLA-4)

CD83 45 6p23 Mature dendritic cells, Adhesion receptor


some B cells and T cells
Phagocytes, Pattern recognition
180 10p13
Mannose receptors lymphoid endothelium receptor

!
CD1a 43–49 1q22-23 Thymocytes, DC Antigen presentation
(glycolipids)
110 17p13 Monocytes, !", Lysosomal
granulocytes, basophils, and endosomal
CD68 LGL lymphocytes glycoprotein

B: Monocytes and DC antigens


;=

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
CD34+cell
#&(*'$)$+ ,&-- ./01-2)$/(3
!
Flt3L, IL-3
Thymic
DC
TNF-! M-CSF GM-CSF
GM-CSF IL-4
TNF-!
IL-3
CD11c+
CD11c+ CD1c+ CD123+
CD13+ BDCA3+ CD2/5/7 (+)
CD1a+ CD33+ CD11c+ BDCA2+
CD14+ CD13+ BDCA2+
CD1c+ Pre-DC-1 BDCA4+
Monocyte Pre-DC-2 TLR9+
Langerhans cell LPS CD40 ligation
Endothelium transmigration CD40 ligation viral infection

;1(*28&()2- .'$(+$0-&3
Ag
uptake HEV “Lymphoid”
DC2
IDC Interstitial DC GCDC Myeloid DC 1

– LPS CD83+
– Bacterial
products
A. Different DC populations

Langerhans- Veiled Interdigitating DC

Antigen
cell cell

HLA-DR CD40
CD40L

T
"
CD80/
Eosinophils CD86 CD28

Macrophages IL-2
T cells NK cells IFN-"

B. Life cycle of a dendritic cell Activated T cell

Epithelium (Tonsil, gut) SLC


CCR7
MIP-3! MIP-3!
CCR6 MIP-3#
Mature DC

Immature
DC
CCR7

Lymphatic vessel

1. Migration to and from inflamed tissue


SLC

C. Recruitment of dentritic cell precursors/DC migration


2. Lymph node homing !
<=

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme
All rights reserved. Usage subject to terms and conditions of license.
Immature DC Mature DC
#+ -.)/'.)(0%1 +2.%3$4 (% 52$%0)67$ .%& 8/%*)(0%

Resting DC
Low level of MHC:
Activated DC
High level of MHC:
!
High turnover Extended long life
CD13, CD33, CD14 ++ (+)
CD40, CD80, CD86 (+) +++ Foreign Antigen
antigen + LPS, TNF
CD83 - ++
LAMP - ++
CCR1, CCR5, CCR6 ++ - Recycling
CCR7 - +
Phagocytosis +++ (+)
AG presentation + +++
IL-12 secretion + ++++

A. DC maturation: changes in phenotype and function

8/%&.G$%)., 5'(%*(7,$4
CD34+ CD34+
Myeloid CD11c+
Lymphoid
CD11-
progenitor CD13/33/14+ CD2/7/5(+) progenitor
GMCSF FLT3L TCR-!+
TNF-! IL-3
IL-4
BDCA3+ CD123+
Mannose rec+ BDCA2+ Pre-
Pre- CD1a/b/c+ BDCA4+
DC-1 TLR2+ TLR7+ DC-2
TLR4+ CD40L IL-3 TLR9+
LPS CD40L Viral infection

"
High phagocytic capacity Low phagocytic capacity
DC-1 High IL-12 secretion Low IL-12 secretion DC-2
High costimulation Secretes IFN-!/#(IPC)

High IL-12 Low IL-12


TH TH2
IFN-" High IL-12 Low IL-12 IL-4
IL-10
IFN-"
– Unmethylated
CTL CpG oligo-
nucleotides – IL-10
– CD40 ligation – TGF#
– LPS – PGE2
– IFN-" – Ox40L
$ High DC/T ratio signalling
Both DC-2 and DC-1
B. Polarization of TH responses by DCs: lineage duality vs. plasticity

TH IFN-" – low costimulation


Mucosa – low IL-12 secretion
High – IL-10 secretion
+ IL-12
pre-DC-1 DC-1 TH1
Skin
Low

!
- IL-12 Antigen-
Immature
DC specific
pre-DC-2 DC-2
TH2 IL-4 T-cell
Tumors tolerance

C. Feedback regulation of DC-1/2 D. Tolerogenic potential of immature DCs


HJ

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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()", +% *+0+*,* +$(2 # $).9," 2: ,-2$% (1#(
:2". (1, 0#"+2)% *2.#+$%7 !1, 3,$,% (1#(
42*, :2" 42.&',.,$( :#4(2"% >RH >TH #$* L:
#", '24#(,* 9,(8,,$ (1, <=> 4'#%% K #$* KK

Burmester, Color Atlas of Immunology © 2003 Thieme


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1. 21B C4B long 21A C4A
#$%&'() *+,-%(.-/(&% &0 /1$ 23! 4&'56$7

Chromosome 6
!
p
Short
21B C4B short 21A C4A
arm

21B C4B short

21B C4A

21A C4A
q
21B C4B short 21A C4B short 21A C4A

21B C4B short 21B C4B short 21A C4A

>?%@-'$%/-6 A+(%)(56$:
21A C4B long 21A C4B long 21A C4B long 21A C4A

C4/CYP21 gene organization (haplotypes)

2. MHC class II TNF MHC class I


D-region C4B C4A Bf C2 !" B C A

CYP 21 CYP 21P LTB

Direction of transcription

DPB2

3.
DPA2
DPB1
DPA1
DNA
DMA
DMB
DOB
DQB2
DQA2
DQB3
DQB1
DQA1
DRB1
DRB2
DRB3
DRB9
DRA
"
4. B1 B6 B9
DR1, 10, 103 (DR1 group)
B1 B6 B5 B9
DR15, 16, (DR51 group)
B1 B2 B3 B9
DR3, 11, 12, 13, 14, 1403, 1404 (DR52 group)
B1 B7 B8 B4 B9
DR4, 7, 9 (DR53 group)
B1 B9
DR8 (DR8 group)
DRB gene organization (haplotypes)

5. Exon 1 Exon 2 Exon 3 Exons 4, 5, 6


DRB1 gene

1 4 9 13 25 38 57 60 67
Amino acids

A. Genomic organization of the HLA complex


74 94
DRB1 polypeptide
First domain

!
BD

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! #$! ,A50(. +%#: ,A50(.7

!" #$! %&'()*'(


+,)-(./01) 2(34(5(60/01&67
./02,>+ 0/1->/"10,/"( /,+-/#("1.>- 2,> 1$-+
<") 0/1>,8.#-8@ A$- /-< 8-)0;/"10,/ 2,> %&'
#(")) * +,(-#.(-) #,/)0)1) ,2 " #,8- 2,> 1$-
!"#$ %&' #(")) * +,(-#.(- #,/)0)1) ,2 " 33 45" ;-/- >-;0,/ "/8 "/ 08-/1020#"10,/ /.+?->D )-=
$-"67 #$"0/ "/8 " 9: 45" (0;$1 #$"0/ 4/,</ ") B">"1-8 ?7 "/ ")1->0)4@ '(( #.>>-/1(7 4/,</
!:=+0#>,;(,?.(0/@ A$- " #$"0/ 0) " 1>"/)+-+= "/8 1>"8010,/"((7 8-20/-8 "((-(-) ">- (0)1-8 0/
?>"/- B>,1-0/ #,/)0)10/; ,2 1$>-- 8,+"0/) C"9D 1$- 1"?(-@
":D "/8 "ED <01$ FG "+0/, "#08) -"#$HD B(.) "
1>"/)+-+?>"/- 2>";+-/1 C:I ''H "/8 "/ 0/1>"= #$! <2= <>= /6? <@ !''('(5 16 0-(
#-((.("> 2>";+-/1 CEG ''H@ A$- " #$"0/) 2,>+ #$! ,A50(. +0/B'(5 &6 33" CD= CE7
/,/#,6"(-/1 ?,/8) <01$ 1$- -J1>"#-((.("> !:=
+0#>,;(,?.(0/@ A$-)- 1"?(-) #,/1"0/ "/"(,;,.) #("))020#"10,/)
!"#$ #(")) ** %&' +,(-#.(- #,/)0)1) ,2 1<, ,2 1$- #(")) ** "/10;-/)@ A$- /,+-/#("1.>- 0) )10((
#$"0/)D /"+-(7D " EEKEI 45" " #$"0/ "/8 " >"1$-> #,+B(0#"1-8 ,<0/; 1, 1$- B,(7+,>B$0#
/"1.>- ,2 1$- " "/8 ! #$"0/)@ A$- ).?>-;0,/
F*6?/.(60/' @416)13'(5

:LK:M 45" ! #$"0/@ N,1$ #$"0/) $"6- 1<, -J1>"=


#-((.("> 8,+"0/) <-0;$0/; FGK9GG 45" -"#$ %&'=5TD 2,> -J"+B(-D #,/1"0/) " ;-/- 2,> 1$-
C8-)0;/"1-8 "9D ": "/8 !9D !:H <$0#$ ./01- " #$"0/ C5T'9H "/8 2,> )-6->"( ! #$"0/)
<01$ " 1>"/)+-+?>"/- 2>";+-/1 #,/1"0/0/; C5TN9D 5TN:D 5TNED 5TN3D 5TNID 5TNLD "/8
:GK:I "+0/, "#08) "/8 <01$ "/ 0/1>"#-((.("> 5TNFHD <$0#$ 8, /,1 "(( ,##.> )0+.(1"/-,.)(7
2>";+-/1 #,/)0)10/; ,2 MK9I "+0/, "#08)@ A$- C)-- " ,/ B@ 3IH@ A$- ).?>-;0,/ %&'=5U #,/1"0/)
": "/8 !: 8,+"0/) ">- B>-)->6-8D <$->-") 1$- #,80/; ;-/-) 5U'9 "/8 5UN9D "/8 1$- ).?=
1$- "9 "/8 !9 8,+"0/) ">- $0;$(7 B,(7+,>B$0#@ >-;0,/ %&'=5V #,/1"0/) 1$- #,80/; ;-/-)
A$- ("11-> 8,+"0/) #,/)0)1 ,2 " O?")- B("1-P 5V'9 "/8 5VN9@ A$- 8-)0;/"10,/ 2,> 1$-
+"8- ,2 ?-1"=B(-"1-8 )$--1)D 1, 1$- )08- ,2 ;-/- ,> ).?>-;0,/ 0) 2,((,<-8 ?7 "/ ")1->0)4D
<$0#$ "(B$" $-(0#-) ?0/8@ A$0)D "(1,;-1$->D 1$-/ 1$- 08-/1020#"10,/ /.+?-> ,2 1$- "((-(-D 0+=
70-(8) " ?")4-1(04- )1>.#1.>- 2,> "/10;-/ "##,+= +-80"1-(7 2,((,<-8 ?7 1$- /.+?-> ,2 1$- ).?=

"
+,8"10,/ C)-- "(), !H@ 17B-@ %&'=5TN9WG9G9 1$->-2,>- +-"/)X 5TN9
(,#.) C#,8-8 2,> ! #$"0/ 9HD "((-(- G9D ).?17B-
8" ,04*)0*4( &9 #$! :'/55 ; %&'()*'(5 G9@ A$- 1"?(- ,/ B@ I: (0)1) 1$- 1>"8010,/"( /,=
+-/#("1.>- C-@;@D 5T3H 2,((,<-8 ?7 1$- #-((.(">
A$- )B"10"( )1>.#1.>- ,2 %&' "/10;-/) #"/ ?- 8-=
17B- 8-)0;/"10,/ "/8 ,1$-> #,8-) 2,> ,(0;,/.=
+,/)1>"1-8 ?7 +-"/) ,2 J=>"7 )1>.#1.>"( "/"(7=
#(-,108- 17B0/;@
)0)D ") 0) )#$-+"10#"((7 )$,</ 2,> " #(")) * +,=
(-#.(-@ !"#$ ,2 1$- "9 "/8 ": 8,+"0/) #,/)0)1)
,2 2,.> "/10B">"((-( ?-1"=B(-"1-8 )$--1)D 1$-
Q=1->+0/"( -/8) ,2 <$0#$ ?0/8 1, "(B$" $-(0#-)@
A$0) 0/8.#-) 1$- 8-6-(,B+-/1 ,2 "/ "/10;-/=
#,+?0/0/; )1>.#1.>- 1$"1 #,>>-)B,/8) 1, " B-B=
108-=#,+?0/0/; ;>,,6- C)-- 20;.>-H@ A$- A=#-((
>-#-B1,> /,< >-#,;/0R-) 01) +"1#$0/; %&'
"/10;-/ CS%Q >-#-B1,>H ") <-(( ") 1$- B-B108-
#,/1"0/-8 0/ 01) ;>,,6- C!"#$%&'()&*" (%$+&',H@
A$- ?,/8 ?-1<--/ 1$- "/10;-/=?-">0/; #-((
"/8 1$- A #-(( 0) )1"?0(0R-8 ?7 O$-(B-> +,(-=
#.(-)DP ).#$ ") Q5M 0/ 1$- #")- ,2 #71,1,J0#
A #-(()@

:" #$! :'/55 ; !''('(5


A$- %&' "/10;-/) <->- 1>"8010,/"((7 /"+-8 0/

!
1$- ,>8-> ,2 1$-0> 80)#,6->7 ") 'D ND "/8 Q C#("))
*H "/10;-/) "/8 5 "/10;-/) "/8 "))0;/-8 /.+=
?->) <01$0/ 1$- 0/80608."( ;>,.B)@ ') " >-).(1D
1$- 8-)0;/"10,/) ?-#"+- 1,, 6">0-8 "/8 #,/2.)=
0/;@ '21-> 1$- -J"#1 )1>.#1.>- ,2 1$- ;-/-) <")
CG 08-/1020-8 ?7 +,(-#.("> ?0,(,;0#"( +-1$,8)D "

Burmester, Color Atlas of Immunology © 2003 Thieme


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Class II !1 NH2
"1
#$! %&'()*'( ,04*)0*4( /6? :'/55 ; !''('(5

T-cell receptor
!
Antigenic peptide
CHO !1 !2
CHO

!2 "2

CHO !1 N

!2 !3
NH2
COOH COOH
NH2
CHO C Antigen
COOH CD8
"2m C
!3 "2 m N

F*6?/.(60/' @416)13'(5
CD8 HVIII
Exosol
View from above
on antigen-binding
part
COOH Class I Cytosol
A. HLA molecules (schematic) B. Structure of an HLA class I molecules

HLA-A alleles HLA-B alleles HLA-C alleles


New Old New Old New Old
nomen- nomen- nomen- nomen- nomen- nomen-
clature clature clature clature clature clature
A*0101
A*0201
A*0202
A*0203
A*0204
A*0205
A*0206
A*0207
A1
A2, A2.1
A2, A2.2F
A2, A2.3
A2
A2, A2.2Y
A2, A2.4a
A2, A2.4b
B*0701
B*0702
B*0801
B*1301
B*1302
B*1401
B*1402
B*1501
B7, B7.1
B7, B7.2
B8
B13, B13.1
B13, B13.2
B14
Bw65 (14)
Bw62 (15)
Cw*0101
Cw*0201
Cw*02021
Cw*02022
Cw*0301
Cw*0501
Cw*0601
Cw*0701
Cw1
Cw2, Cw2.1
Cw2, Cw2.2
Cw2, Cw2.2
Cw3
Cw5
Cw6
Cw7
"
A*0208 A2, A2.4c B*1801 B18 Cw*0702 Cw7, JY328
A*0209 A2, A2-ZB B*2701 B27, 27f Cw*1101 Cw11
A*0210 A2, A2-LEE B*2702 B27, 27e, 27K, B27.2 Cw*1201 Cx52
A*0301 A3, A3.1 B*2703 B27, 27d, 27J Cw*1202 Cb-2
A*0302 A3, A3.2 B*2704 B27, 27b, 27C, B27.3 Cw*1301 CwBL18
A*1101 A11, A11E B*2705 B27, 27a, 27W, B27.1 Cw*1401 Cb-1
A*1102 A11, A11K B*2706 B27, 27D, B27.4
A*2401 A24 (9) B*3501 B35
A*2501 A25 (10) B*3502 B35
A*2601 A26 (10) B*3701 B37
A*2901 A29 (w19) B*3801 B38 (16), B16.1
A*3001 A30 (w19), A30.3 B*3901 B39 (16), B16.2
A*3101 A31 (w19) B*4001 Bw60 (40)
A*3201 A32 (w19) B*4002 B40, B40*
A*3301 Aw333 (w19), Aw33.1 B*4101 Bw41
A*6801 Aw68 (28), Aw68.1 B*4201 Bw42
A*6802 Aw68 (28), Aw68.2 B*4401 B44 (12), B44.1
A*6901 Aw69 (28) B*4402 B44 (12), B44.2
B*4601 Bw46
B*4701 Bw47
B*4901 B49 (21)

!
B*5101 B51 (5)
B*5201 Bw52 (5)
B*5301 Bw53
B*5701 Bw57 (17)
B*5801 Bw58 (17)
B*7801 B'SNA'
C. HLA class I alleles
CH

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! !"# $%&'()&'*+ ,&-** .. #&&'&'* /.0

New
nomenclature
Old
nomenclature
New Old
nomenclature nomenclature

DRB1-alleles DRB1-alleles

DRB1*0101 DR1, Dw1 DRB1*1304 DRw6, DRw13


DRB1*0102 DR1, Dw20 DRB1*1305 DRw6, DRw13
DRB1*0103 DR' BR', Dw' BON' DRB1*1401 DRw6, DRw14, Dw9, Drw6b
DRB1*1501 DR2, DRw15, Dw2 DRB1*1402 DRw6, DRw14, Dw16
DRB1*1502 DR2, DRw15, Dw12 DRB1*1403 DRw6, DRw14
DRB1*1601 DR2, DRw16, Dw21 DRB1*1404 DRw6, DRw6b.2
1)23-4'25-& 6782(89&'*

DRB1*1602 DR2, DRw16, Dw22 DRB1*1405 DRw6, DRw14


DRB1*0301 DR3, DRw17, Dw3 DRB1*0701 DR7, Dw17
DRB1*0302 DR3, DRw18, DRB1*0702 DR7, Dw'DB1'
DRB1*0401 DR4, Dw4 DRB1*0801 DRw8, Dw8.1
DRB1*0402 DR4, Dw10 DRB1*08021 DRw8, Dw8.2
DRB1*0403 DR4, Dw13, 13.1 DRB1*08022 DRw8, Dw8.2
DRB1*0404 DR4, Dw14, 14.1 DRB1*08031 DRw8, Dw8.3
DRB1*0405 DR4, Dw15 DRB1*08032 DRw8, Dw8.3

" DRB1*0406
DRB1*0407
DRB1*0408
DRB1*0409
DR4, Dw'KT2'
DR4, Dw13, 13.2
DR4, Dw14, Dw14.2
DR4
DRB1*0804
DRB1*09011
DRB1*09012
DRB1*1001
DRw8
DR9, Dw23
DR9, Dw23
DRw10
DRB1*0410 DR4
DRB1*0411 DR4
DRB1*1101 DR5, DRw11, Dw5, DRw11.1 Other DRB alleles

DRB1*1102 DR5, DRw11, DRw11.2 DRB3*0101 DRw52a, DW24


DRB1*1103 DR5, DRw11, DRw11.3 DRB3*0201 DRw52b, Dw25
DRB1*1104 DR5, DRw11 DRB3*0202 DRw52b, Dw25
DRB1*1201 DR5, DRw12, Dw'DB6' DRB3*0301 DRw52c, Dw26
DRB1*1202 DR5, DRw12, DRw12b DRB4*0101 DRw53
DRB1*1301 DRw6, DRw13, Dw18, DRw6a DRB5*0101 DR2, DRw15, Dw2
DRB1*1302 DRw6, DRw13, Dw19, DRw6c DRB5*0102 DR2, DRw15, Dw12
DRB1*1303 DRw6, DRw13, Dw'HAG' DRB5*0201 DR2, DRw16, Dw21

! :;
DRB1*1304 DRw6, DRw13 DRB5*0202 DR2, DRw16, Dw22

A. HLA-DR, HLA-DQ, and HLA-DP alleles in the HLA system (class II alleles)

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New Old
nomenclature nomenclature
New
!"# $%&'()&'*+ ,&-** .. #&&'&'* /..0

Old
nomenclature nomenclature
!
DQA1 alleles DPA1 alleles

DQA1*0101 DQA 1.1, 1.9 DPA1*0101 LB14/LB24, DPA1


DQA1*0102 DQA 1.2, 1.19, 1.AZH DPA1*0102 pSBa-318
DQA1*0103 DQA 1.3, 1.18, DRw8-Dqw1 DPA1*0103 DPw4a1
DQA1*0201 DQA 2, 3.7 DPA1*0201 DPA2, pDAa13B
DQA1*03011 DQA 3, 3.1, 3.2
DQA1*03012 DQA 3, 3.1, 3.2, DR9-DQw3 DPB1 alleles

1)23-4'25-& 6782(89&'*
DQA1*0302 DQA 3, 3.1, 3.2, DR9-DQw3 DPB1*0101 DPw1, DPB1, DPw1a
DQA1*0401 DQA 4.2, 3.8 DPB1*0201 DPw2, DPB2.1
DQA1*0501 DQA 4.1, 2 DPB1*02011 DPw2, DPB2.1
DQA1*05011 DQA 4.1, 2 DPB1*02012 DPw2, DPB2.1
DQA1*05012 DQA 4.1, 2 DPB1*0202 DPw2, DPB2.2
DQA1*05013 DQA 4.1, 2 DPB1*0301 DPw3, DPB3
DQA1*0601 DQA 4.3 DPB1*0401 DPw4, DPB4.1, DPw4a
DPB1*0402 DPw4, DPB4.2, DPw4b
DQB1 alleles
DQB1*0501
DQB1*0502
DQB1*05031
DQw5 (w1), DQB 1.1, DRw10-DQw1.1
DQw5 (w1), DQB 1.2, 1.21
DQw5 (w1), DQB 1.3, 1.9, 13.1
DQw5 (w1), DQB 1.3, 1.9, 13.2
DPB1*0501
DPB1*0601
DPB1*0801
DPB1*0901
DPw5, DPB5
DPw6, DPB6
DPB8
DPB9
"
DQB1*05032 DPB1*1001 DPB10
DQB1*0504 DQB 1.9 DPB1*1101 DPB11
DQB1*0601 DQw6 (w1), DQB 1.4, 1.12 DPB1*1301 DPB13
DQB1*0602 DQw6 (w1), DQB 1.5, 1.2 DPB1*1401 DPB14
DQB1*0603 DQw6 (w1), DQB 1.6, 1.18 DPB1*1501 DPB15
DQB1*0604 DQw6 (w1), DQB 1.7, 1.19 DPB1*1601 DPB16
DQB1*0605 DQw6 (w1), DQB 1.8, 1.19b DPB1*1701 DPB17
DQB1*0201 DQw2, DQB 2 DPB1*1801 DPB18
DQB1*0301 DQw7 (w3), DQB 3.1 DPB1*1901 DPB19
DQB1*0302 DQw8 (w3), DQB 3.2
DW4 DRB1*0401
DQB1*03031 DQw9 (w3), DQB 3.3 DW10 DRB1*0402
DQB1*03032 DQw9 (w3), DQB 3.3 DW13 DRB1*0403

!
DW14 DRB1*0407
DQB1*1401 DQw4, DQB 4.1, Wa DR4
DW15 DRB1*0404
DQB1*0402 DQw4, DQB 4.2, Wa DW"KT2" DRB1*0408
DRB1*0405
DRB1*0406

B. HLA-DR, DQ, and DP alleles in the HLA system (continued)


:<

Burmester, Color Atlas of Immunology © 2003 Thieme


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! $<! =>(0,9 ?#$% =>(0,9@

!" #$% %&'(( ))*+,-,./,.0 !.012,.


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7" !.6854 !91.5 !61/( 1. #$% )) 3,-01/,("
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*7% 6%6*+/%34+&/+&$ $1##8% #0 9:; 2#.%-'.%( GG 2#.%-'.% +&*%1)-* F+*7 *7% (+/% -7)+&( #0 *7%
4%0#1% )&*+$%&3(6%-+0+- ;<=> ? -%..( 1%-#$&+5% 6%6*+/% )&/ /%*%12+&% 4+&/+&$ )00+&+*A@ !)-7
*7%2@ ?71#'$7 1%-%6*#132%/+)*%/ %&/#-A*#(+( -.)(( GG )..%.% 7)( /+00%1%&* (+/% -7)+& -#&*)-*(,
#1 67)$#-A*#(+( B(%% 6@ =CD, %"#$%&#'( )&*+$%&( )..#F+&$ #&.A 6%6*+/%( F+*7 -%1*)+& )2+&#
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AB./'9,.0'& 341.61-&,(

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)1% /+$%(*%/ 4A -A(*%+& 61#*%)(%( -)..%/ -)*7%3 +26#1*)&*, ).*7#'$7 .%(( -1+*+-). )&-7#1(, )1%
6(+&(@ ?7% %&/#(#2%( *7%& 0'(% F+*7 8%(+-.%( *7% )2+&# )-+/( )* 6%6*+/% 6#(+*+#& =, N, )&/
-#&*)+&+&$ 9:; -.)(( GG 2#.%-'.%(@ H%-%&*.A Z@ Y& *7% #*7%1 7)&/, (+/% -7)+&( #0 -%1*)+& )2+3
(A&*7%(+5%/ *1)&(2%241)&% 61#*%+&(, ('-7 )( &# )-+/( -)& +&*%10%1% F+*7 6%6*+/% 4+&/+&$ B+&3
9:; 2#.%-'.%(, )1% *1)&(.#-)*%/ 01#2 *7% 7+4+*#1A )2+&# )-+/(D@ I&-7#1 6#(+*+#&( )1% *7%
-A*#(#. *# *7% %&/#6.)(2+- 1%*+-'.'2 B!HD, 2#(* +26#1*)&* -#&*)-* (+*%( #0 *7% 6%6*+/%
F7%1% *7%A )1% 0#./%/ )&/ )((%24.%/ -#11%-*.A@ F+*7 *7% 9:; GG 2#.%-'.%, (# +* +( &#* ('161+(+&$
?7%A 0+1(* #--'1 )( /+2%1( #0 ! )&/ " -7)+&(@ *7)* *7% ()2% L%A 6#(+*+#&( )1% -1+*+-). 0#1 4+&/3
I *7+1/ -7)+&, *7% $)22) #1 J+&8)1+)&*K -7)+& +&$ +&7+4+*+#&@ I2+&# )-+/( *7)* 0)8#1 #1 +&7+4+*
B!"3-7)+&D, 4+&/( &#&-#8).%&*.A *# )& 9:; GG 6%6*+/% 4+&/+&$ *# :QI3<HVT[C=CT )1% (7#F&
!3" 7%*%1#/+2%1 4.#-L+&$ +*( 4+&/+&$ (+*%@ +& &@ ?7% ;QGR 6%6*+/% #0 *7% +&8)1+)&* -7)+& -)&

"
?7+( 61%8%&*( *7% 4+&/+&$ #0 %&/#$%&#'(.A 4+&/ 61#2+(-'#'(.A *# /+00%1%&* 9:; GG )..%.%(\
(A&*7%(+5%/ 6%6*+/%(, F7+-7 )1% )4'&/)&* +& +* 7)( 2%*7+#&+&% )* 6#(+*+#& T )&/ (+/% -7)+&(
*7% !H B(%% ).(# 6@ MND@ ?7% 6)1* #0 *7% +&8)1+)&* *7)* )1% )--%6*%/ 4A ).. <H )..%.%( +& 6#(+*+#&( U3
-7)+& *7)* 4.#-L( *7% $1##8% #0 *7% !3" 7%*%1#3 Z@ ;#26'*%1 61#$1)2( -)& &#F 61%/+-* 4+&/+&$
/+2%1 +( -)..%/ #$)((3GG )((#-+)*%/ "&8)1+)&* 2#*+0( 0#1 ) 6)1*+-'.)1 :QI3<H )..%.% 01#2 *7%
-7)+& %%6*+/% B&'!(D@ ?7% 61#*%+& #)$*+,"* 1%3 61#*%+& (%]'%&-%@
*)+&( *7% -#26.%" F+*7+& *7% !H '&*+. )((%24.A
+( -#11%-*, *7%& /+((#-+)*%( )&/ )..#F( *7% -#23 +" :*%,&& !601;'015. ;1' #$% ))
6.%" #0 9:; GGOG+ *# .%)8% *7% !H 8+) (2).. -#)*3 ?7% 6%6*+/%O9:; -.)(( GG -#26.%" -)& )-*+8)*%
#2%13-#)*%/ 8%(+-.%(@ ?7%(% 0'(% F+*7 *7% P#.$+ ;<=> ? -%..( )&/ +&/'-% *7% 61#.+0%1)*+#& )&/ (%3
)66)1)*'( #& /+((#-+)*+#& #0 *7% -#)*#2%13 -1%*+#& #0 8)1+#'( -A*#L+&%(@ ?'2#1 &%-1#(+(
-#)*%/ 61#*%+&@ ?7% +&8)1+)&* -7)+& *)1$%*( 0)-*#13! B?WS3!D 1%.%)(%/ 4A *7% )&*+$%& 61%3
*7% 9:; -#26.%"%( *# *1)&(6#1* 8%(+-.%( #0 (%&*+&$ -%.. 6.)A( )& +26#1*)&* 1#.% +& *7+( 61#3
*7% J*1)&(3P#.$+ &%*F#1L,K F7+-7 *1)00+- *# %&3 -%((@ G* .%)/( *# *7% 0#12)*+#& #0 #"A$%& 1)/+-).(
/#(#2). 8%(+-.%(@ ?7% +&8)1+)&* -7)+& +( -.%)8%/, *7)* )1% )4.% *# L+.. +&*1)-%..'.)1 2+-1##1$)&3
.%)8+&$ #&.A *7% (2).. ;QGR 01)$2%&* 4#'&/ *# +(2(@ S'1*7%12#1%, )-*+8)*%/ ;<=> ? -%..( -)&
*7% 4+&/+&$ (+*% #0 *7% 9:; GG 7%*%1#/+2%1@ ?7% (*+2'.)*% )&*+4#/A 0#12)*+#& +& V -%..(@ V#*7
-#26)1*2%&* F7%1% 0'(+#& #0 *7% *1)&(6#1* 8%3 2%-7)&+(2( )1% /+1%-*%/ )* *7% %.+2+&)*+#&
(+-.%( F+*7 *7% %&/#(#2%( #--'1( +( -)..%/ -:; #0 %"*1)-%..'.)1 6)*7#$%&(@
-.)(( !! ##26)1*2%&* B-!!&D@ I& 9:; -.)(( GG3
.+L% 2#.%-'.%, -)..%/ :QI3<9, +&/'-%( 1%.%)(%
#0 *7% ;QGR 6%6*+/% 01#2 *7% 4+&/+&$ $1##8%
#0 *7% 9:; )&/ (*)4+.+5%( *7% %26*A 9:; GG

! CD
7%*%1#/+2%1 '&*+. )& )661#61+)*% %"#$%&#'(
6%6*+/% +( 4#'&/@ S+&)..A, :QI3<9 /+((#-+)*%(
)&/ *7% 6%6*+/%O9:; GG -#26.%" +( *1)&(6#1*%/
*# *7% -%.. 2%241)&%@ R%6*+/%( *7)* F%1% '&3
)4.% *# 4+&/ *# 9:; 2#.%-'.%( )1% /%$1)/%/
+& .A(#(#2%(@

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Extracellular protein
#$% %&'(( ))*/,-,./,.0 !.012,. 34,(,.0'015.
!
Coat proteins

Endocytosis

Early
endosome Golgi

MHC class II Transport


compartment vesicles
Calnexin
Terminal Ii
lysosome

AB./'9,.0'& 341.61-&,(
Endogenous
proteins
mRNA
ER HLA-DM

A. MHC class II-dependant antigen processing

Anchor AA Inhibitory AA

P1 Phe, Ile, Leu, Met, Val, Trp, Tyr

P1

N
P4 P6 P9

HVIII
P4

P6
Asp, Met, Gln, Ser Gly, Lys, Pro, Arg, Trp, Tyr

Ser, Thr, Val Gln, Phe, Gly, His, Lys, Leu, Met, Tyr
"
P9 Ser Asp, Gln, Leu, Asn, Pro

C. Allele-specific motifs in DRB1*0401-binding


B. Anchor AA in MHC II peptides peptides

IL-2
CD4
CD4 B
IL-4
IFN-! IL-6

TNF-"

NO
H2O2
O2

D. T-cell activation via MHC II


Antibody
production
!
CC

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All rights reserved. Usage subject to terms and conditions of license. "
! 23! 45(.'6 7829 45(.'6:

!" #$%&'(()*+ ,*- #$'('*.,.)%*


%/ 0*-%+'*%1( !*.)+'*(
85, +,'.+0$.03-' /0$.&.,/ =6 .5, &-$53+ +,'0)
/:,' &+, +,'*3-'0=%, 23+ .5, 2&$. .5&. 3:. 32 &
953%, *+3.,0- 3-%6 & '4&%% -:4=,+ 32 *,*.0/,'
!"# $%&'' ()*+,',-.,/ *,*.0/,' /,+01, 2+34 =0-/ 90.5 50;5 &220-0.6 .3 & *&+.0$:%&+ "YX)&%)
*+3.,0-' .5&. &+, *+,',-. 0- .5, $6.3*%&'47 %,%, @(B7 "39,1,+> '0-$, ,&$5 0-/010/:&% 4&6
850' &%%39' .5, 044:-, '6'.,4 .3 +,$3;-0<, 5&1, :* .3 '0E /022,+,-. "YX &%%,%,' @4&.,+-&%
$,%%' .5&. 5&1, =,,- 0-2,$.,/ =6 10+:',' 3+ =6 &-/ *&.,+-&% &%%,%,' 32 "YX)X> )Z> &-/ )#B> &
0-.+&$,%%:%&+ =&$.,+0&7 85,3+,.0$&%%6> .50' &%'3 &%) =+3&/ '*,$.+:4 32 *,*.0/,' $&- '.0%% =, *+,)
%39' +,$3;-0.03- 32 4:.&.,/ *+3.,0-' 32 $&-$,+ ',-.,/7 #34*:.,+ *+3;+&4' &1&0%&=%, .5+3:;5
$,%%'7 .5, (-.,+-,. $&- *+,/0$. =0-/0-; ,*0.3*,' 32 &
(- 3+/,+ .3 *+,',+1, $,%% 10&=0%0.6> /&4&;,/> ;01,- *+3.,0- 23+ .5, 43'. $3443- "YX 5&*)
/,-&.:+,/> :-&'',4=%,/> 3+ 40'23%/,/ *+3.,0-' %3.6*,'7
4:'. =, ,%040-&.,/7 ?3+4&% *+3.,0-' &%'3 -,,/
Y64*530/ .0'':, &-/ $,%%' ,E*3',/ .3 ([?)#
.3 =, $3-'.&-.%6 /,;+&/,/ &-/ +,*%&$,/ @90.5 5&1, & '%0;5.%6 /022,+,-. *+3.,&'34, $34*%,E &'
;1*-,6'*.,< #$)*&)=<'(

5&%2)%01,' +&-;0-; 2+34 & 2,9 40-:.,' .3 ',1) '34, 32 .5, ! ':=:-0.' &+, ':='.0.:.,/ =6 ':=)
,+&% /&6' 3+ 9,,A'B7 C+3.,0-' &+, .&;;,/ 23+ :-0.' 90.5 /022,+,-. ':='.+&., *+,2,+,-$,'> ':$5
/,'.+:$.03- =6 .5, *+3.,0- :=0D:0.0-7 !:%.0) &' Y!CF> Y!CN> &-/ !S#YL @044:-3*+3.,&)
:=0D:0.0-&.,/ *+3.,0-' &+, +,$3;-0<,/ =6 .5,
'34,> )B7 85, *+3.,3%6.0$ &$.010.6 32 .5, 044:)
*+3.,&'34,> & %&+;, *+3.,&', $34*%,E 90.5 & -3*+3.,&'34, &**,&+' .3 =, ,-5&-$,/ $34)
43%,$:%&+ 9,0;5. 32 FGGG AH&7 (. 0' =&++,%) *&+,/ 90.5 .5, $3-'.0.:.01, *+3.,&'34,>
'5&*,/ &-/ 4&/, 32 & $3+, :-0. 32 FGI @JKG 950$5 0' 0- &$$3+/&-$, 90.5 .5, 50;5,+ &-.0)
AH&B &' 9,%% &' 32 .93 &//0.03-&% 3:.,+ +0-;' ;,-)*+3$,''0-; +,D:0+,4,-.' 32 &-.0;,-)*+,)
32 LMI @,&$5 NGG AH& 0- '0<,B7 85, 23:+ +0-;'
',-.0-; $,%%' &-/ 32 10+:')0-2,$.,/ $,%%' ,E*3',/
32 .5, FGI *+3.,&'34, $3-'0'. 32 .93 0--,+ ! .3 ([?)#7 C+3.,0-' *+3$,'',/ =6 .5, 044:-3)
:-0.' &-/ .93 " :-0.'> &%% 32 .5,4 $3-'0'.0-; *+3.,&'34, $&- ;,-,+&., & 953%, /022,+,-.
32 ',1,- /022,+,-. ':=:-0.'> 950$5 ':++3:-/ & ',. 32 *,*.0/,'7

"
$,-.+&% $5&4=,+ 95,+, *+3.,3%6'0' 3$$:+'7 8)$,%% +,$3;-0.03- $&- =, *+,1,-.,/ =6 V04)
85, 4&O3+0.6 32 *,*.0/,' *+3$,'',/ =6 .5,
4:-, ,'$&*,W 4,$5&-0'4' @*B\ /,2,$.'],7;7>
*+3.,&'34, &+, D:0$A%6 /,;+&/,/ 0-.3 '0-;%, 4:.&.03-'> 0- .5, ',D:,-$, 32 8XC *+3)
&40-3 &$0/' =6 $6.3'3%0$ 3+ -:$%,&+ ,-<64,'7 .,0-']$&- *+,1,-. .5, .+&-'*3+. 32 *,*.0/,'
P-%6 & 2,9 *,*.0/,' @43'.%6 90.5 & '0<, 32 0-.3 .5, ST '3 .5&. ,4*.6 !"# ( 43%,$:%,'
QRLG &40-3 &$0/'B &+, .+&-'*3+.,/ 0-.3 .5, &+, ;,-,+&.,/ .5&. &+, :-'.&=%, &-/ /0''3$0&.,
,-/3*%&'40$ +,.0$:%:4 @STB =6 & 5,.,+3) D:0$A%6 2+34 .5, $,%% 4,4=+&-,7 ^0+&% *+3.,0-'>
/04,+U*+3.,0- $34*%,E $&%%,/ !+&-'*3+.,+ &''3) ':$5 &' .5, ",+*,' ^0+:' *+3.,0-' _IF &-/ _ILL>
$0&.,/ 90.5 "-.0;,- #+3$,''0-; @$%&B7 (- .5, ST> $&- 0-/:$, &$.01, ,E*3+. 32 !"# 43%,$:%,'
*,*.0/,' =0-/ .3 .5, *,*.0/,)=0-/0-; ;+331, 32 2+34 .5, ST> *+,1,-.0-; %3&/0-; 32 10+&% *,*)
!"# $%&'' ( *+3.,0-' 02 .5, '0/, $5&0-' 32 .5,0+ .0/,' 0- .5, !"# 43%,$:%,'7 (-/,,/> %39 %,1,%'
&40-3 &$0/' 20. *+3*,+%6 90.5 .5, &40-3 &$0/' 32 !"# ( &+, 2+,D:,-.%6 23:-/ 0- 10+&% 0-2,$.03-'7
32 .5, =0-/0-; ;+331, 32 .5, !"# ( " $5&0-7 I0-$, 4&-6 ,-/3;,-3:' V',%2W *,*.0/,' &+,
(-0.0&%%6> .5, " $5&0- 0' =3:-/ =6 V$5&*,+3-W *+,',-.,/ .3 8 $,%%' =6 !"# ( 43%,$:%,'> .93
*+3.,0-'> ':$5 &' $&%-,E0-> $&%+,.0$:%0-> S+*KN> 4&O3+ 4,$5&-0'4' ,E0'. .3 *+,1,-. &:.3+,&$)
950$5 +,;:%&., *,*.0/, =0-/0-;7 8&*&+0- =+0/;,' .010.67 (- .5, .564:'> *+,',-.&.03- 32 ',%2)&-.0)
.5, " $5&0- .3 8XC7 893 3+ .5+,, *3$A,.' 0- ,&$5 ;,-' =6 .5640$ ,*0.5,%0& 3+ /,-/+0.0$ $,%%' $&-
!"# 43%,$:%, &$$,*. 3-%6 *&+.0$:%&+ &40-3 %,&/ .3 $%3-&% /,%,.03- 32 &-.0;,-)'*,$020$ 8 $,%%'
&$0/' @,7;7> &%0*5&.0$ &40-3 &$0/'> =&'0$ &40-3 @$,-.+&% .3%,+&-$, =6 .5640$ /,%,.03-> + &-/ *7
&$0/'B7 85,', &+, $&%%,/ &-$53+ +,'0/:,'7 85,6 LFB7 (- .5, *,+0*5,+6> +,$3;-0.03- 32 ',%2)&-.0)
/022,+ 23+ /022,+,-. !"# ( &%%,%,'> '0-$, ,&$5 ;,-' =6 &-.0;,-)'*,$020$ 8 $,%%' .5&. 4&6 5&1,
&%%,%, 5&' & /022,+,-. ',D:,-$, 32 .5, " $5&0-7 ':+101,/ .5640$ ',%,$.03- %,&/' .3 &=3+.01, &$)
(- 43'. $&','> .5, &40-3 &$0/' 0- *3'0.03- F

!
.01&.03- 3+ &*3*.3'0' =,$&:', 32 & %&$A 32 $3)'.0)
&-/ M &+, $+:$0&% 23+ =0-/0-;7 X-$53+ +,'0/:,' 4:%&.3+6 43%,$:%,' @*,+0*5,+&% .3%,+&-$,> ,B7
32 *,*.0/,' .5&. =0-/ 90.5 50;5 &220-0.6 .3 .5+,,
2+,D:,-. "YX &%%,%,' &+, '539- 0- '7 C,*.0/,'
90.5 & /022,+,-. &40-3 &$0/ 0- .5,', *3'0.03-'
4&6 =0-/> =:. 90.5 & %39,+ &220-0.67
>?

Burmester, Color Atlas of Immunology © 2003 Thieme


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829 9<,(( @A-'='*-'*. !*.)+'* #$'('*.,.)%*
!
Subunits Exocytosis
Ubiquitinated ! " " ! via Golgi
protein
Ubiquitin
TAP
Erp57

19S 19S
20S
"2m
26S proteasome Tapasin

;1*-,6'*.,< #$)*&)=<'(
Enzymatic
digestion

Single AA Unfolded MHC I chain Calreticulin

A. Processing and presentation of endogenous antigens

HLA-A*0201 P2=Leucine MAPPQVLAFGLLLAAATATFAAAQEECVLENY


P9=Valine, KLAVNCFVNNNRQCQCTSVGAQNTVICSKL
Tyrosine AAKCLVMKAEMNGSKLGRRAKPEGALQNND
NH3+

COO

P2 P9 GLYDPDCDESGLFKAKQCNGTSTCWCVNTA

"
GVRRTDKDTEITCSERVRTYWIIIELKHKAREK
HLA-A3: P2=Leucine
P9=Lysine PYDSKSLRTALQKEITTRYGLDPKFITSILYENN
VITIDLVQNSQQKTQNDVDIADVAYYVEKDV
Pockets
KGESLFSHKKMDLTVNGEQLDLDPGQTLIYY
in ! chain
HLA-B7: P2=Leucine VDEKAPEFSMQGLKAGVIAVIVVVVIAVVAGI
P9=Proline
of MHC I VVLVISRKKRMAKIEKAEIKEMGEMHRELNA
C. HLA-A2-binding epitopes of a 314 AA
B. Binding motifs protein
VPYGSFKHV
Non-APC cells Lack of presentation

••TGSTA US2
VPYGSFKHV KHVDTRLQ US11
DTRLQ••• Virus infected cells
– tumor cells

APC, IFN-#-treated cells


D. Immunoproteasome E. Immune escape mechanisms

Thymic medulla Non-APC


dendritic cell cell Apoptosis/
Self antigen Self-antigen anergy

CD4+/CD8+
Thymocyte
Apoptosis

F. Central tolerance to self antigens


Clonal deletion
Lack of
co-stimulation
G. Peripheral tolerance to self-antigens
!
>B

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! 27( #$%&'(%()* 418*(%

!" #$%&'(%()* !+*,-.*,$)


!"# $%&'()#'#*+,-./ ,%+010+. &2 3#-4' 03 -#5
640-#7 2&- +"# ).303 &2 %#))3 &- 8,%+#-0, 8. ,*+05
/" 01*,+ 2(3%,).' 4(56()+(
!>& (-&+#&).+0% ?L %&*1#-+,3#3 ,-# +"# +#-'0*,)
(-&74%+3 &2 +"# %),330%,) ,*7 ,)+#-*,+01# %&'5
8&70#39 : *4'8#- &2 (-&+#,3#3 -#2#--#7 +& ,3 ()#'#*+ ,%+01,+0&* (,+">,.39 P* #,%" (,+">,.<
!"#$%&#&'( !"#$"'&'() ,-# -#3(&*308)# 2&- ?B8 3#-1#3 ,3 +"# 80*70*= 30+# 2&- +"# ?L 3#-4'
+"03 3#-4' ,%+010+.9 ;03+&-0%,)).< +"#3# (-&+#0*3 (-&+#0*< >"0%" 03 3()0+ 0*+& ?L, ,*7 ?L8 2-,=5
,-# 7#30=*,+#7 >0+" +"# )#++#- $?/ 2&))&>#7 '#*+3 8. (-&+#&).3039 ?L8 03 %,(,8)# &2 80*70*=
8. , *4'8#-9 !"# ',@&-0+. &2 %&'()#'#*+ (-&5 %&'()#'#*+ (-&+#0*3 ?Q ,*7 ?R9 ?L8QR 03 , ".5
+#0*3 ,-# *+#",&')< 09#9< 0*,%+01# (-&#*A.'#3 7-&("&80% +-0'&)#%4),- %&'()#H +",+ 8#%&'#3
+",+ 8#%&'# ,%+01,+#7 ,2+#- (-&+#&).3039 !"# >#)) ,*%"&-#7 0* +"# )0(07 7&48)# ),.#- &2 +"#
%)#,1,=# (-&74%+3 ,-# ),8#)#7 >0+" ,* ,7705 %#)) '#'8-,*#9 ?&'()#'#*+ (-&+#0*3 ?S ,*7
+0&*,) )&>#-5%,3# )#++#-9 ?T %,* 80*7 +& ?L8QR< .0#)70*= , ?L8QRST &-
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96):.%()*.' ;3,)+,&'(8

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+& ,3 -. !"'/&0(1)&9 ",1# , 34-2,%# (-&+#0*5'#70,+#7 (-&+#%+01# '#5
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34%" ,3 +"&3# 0* 0''4*# %&'()#H#3 ",1# , '#'8-,*# 8. =).%&3.)("&3(",+07.)0*&30+&)
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80*70*= ?C (-&+#0*9 ?C6 80*70*= 0*74%#3 , %&*5 -#',0* $3&)48)#/ 0* +"# )0(070% %#)) '#'8-,*#<
2&-',+0&*,) %",*=# 0* ?C9 !"03 )#,73 +& +"# ,%5 +"#. ",1# , "0=" )#1#) &2 $),+#-,) '&80)0+.9/
+01,+0&* &2 ?C- ,*7 ?C3< >"0%" %,+,).A#3 +"# ?NLT '&)#%4)#3 0*"080+ +"# 0*3#-+0&* ,*7 (&).5

"
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'#*+< 80*73 +& %&'()#'#*+ (-&+#0* ?J< >"0%" 080)0+. &2 #-.+"-&%.+#3 +& ).303 8. ,4+&)&=&43
03 +"#* 8-&K#* 7&>* 8. ?C3 0*+& ?J, ,*7 ?J8 %&'()#'#*+ 0* 703#,3#3 34%" ,3 (,-&H.3',)
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(2/& !"#$%&#&'( $1(341+ %,* 8# ,%+01,+#7
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03'9 N4# +& 0*+#-,%+0&* >0+" ?B8< (),3', 2,%+&-3
G ,*7 N %,+,).A# +"# %)#,1,=# &2 2,%+&- G 0*+& G,
,*7 G8 2-,%+0&*39 !&=#+"#- >0+" ?B8< 2,%+&- G8
2&-'3 +"# ?B8G8 %&'()#H< ,*&+"#- ?B %&*1#-5
+,3#9 G0*70*= >0+" (-&(#-70* E2,%+&- OF 3+,805
)0A#3 +"# ?B8G8 %&'()#H9 !"# 3+,80)0A#7 %&'5
()#H %,+,).A#3 +"# %&*+0*4#7 ,*7 %&'()#+#
(-&+#&).303 &2 ?B E,'()020%,+0&*F9 ?B8G8 80*73

! <=
&+"#- ?B8 2-,='#*+3< 4)+0',+#). (-&74%0*=
?B8G8B8< +"# ?L %&*1#-+,3# &2 +"# ,)+#-*,+01#
%&'()#'#*+ (,+">,.9

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Antigen
!+*,-.*,$) .): >??(+*$38

C3
!
Immune C1r
C1s Spontaneous hydrolysis Contact with
complex
microorganisms
C1q
C1s C1s
C4 C4b C2a C2
C3a
C3b

C4a C2b
Factor D Factor B

96):.%()*.' ;3,)+,&'(8
Amplification Ba
C4b2a = loop
C3 convertase of the C3b Bb
classical pathway Properdin
C3bBb =
P C3 convertase
of the alternative
C3 C3b pathway
C3a
C3bBbP

C4b2a3b =
C5 convertase
of the classical pathway

1. Classical pathway

A. Complement activation
C3b
C4b

Cell
C2a
C3bBb3b =
C5 convertase of the
alternative pathway

2. Alternative
pathway
Cell
C3b
C3bBb
"
C5 C5a C6 C7 C8

C5
convertase

C5b C5b67 C5b678

C9 C9 (Up to 14 molecules) Inhibition of the stable


C9 bond by CD59
(MAC-inhibitor)

Unstable
C9 bond

B. Lytic terminal sequence


Stable
C9 bond
Poly-C9
membrane attack complex (MAC)
CD59

!
<@

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
" =>' 0%56-'5'*& ?2/&'5

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:)*0#*-+,1 :; -*"-.-+)% =#/-(-#*(2 1#,=$ +) +,*+ %)1# -* +"# #1-'-*,+-)* )/ -''&*)()'6
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+-)*> ?"-(" ',*-/#$+$ ,$ $#4#%# ,*= %#(&%%#*+ ()'31#F#$ ,%# +%,*$3)%+#= +) +"# 1-4#% ,*=
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!"#%# ,%# ,1$) , *&'.#% )/ ()'31#'#*+6 .)+" :C; ,*= B( %#(#3+)%$ (,* %#')4#
()*+%)11-*0 3%)+#-*$> $&(" ,$ !"#$%&$##"'"($)*+,
+"#' /%)' +"# $&%/,(# )/ +"# #%2+"%)(2+#$7
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$%"> ?"-(" -$ #F3%#$$#= ,$ :@D;> 3%-',%-12
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'#*+$ 9:J, ,*= :K,< +",+ -*=&(# +"# =#0%,*&6 -*=&(#= .2 ()'31#'#*+ %#(#3+)%6.#,%-*0 (#11$7
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-$ '#=-,+#= .2 %#(#3+)%$ +",+ -*=&(# $'))+"6 (#11$ 9&<7
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,*= ',$+ (#11$7 !"-$ ,(+-4-+2 ,1$) -*=&(#$ ("#6
')+,F-$ ,*= ,(+-4,+-)* )/ 0%,*&1)(2+#$> %#$&1+6
-*0 -* +"# %#1#,$# )/ 3%)+#)12+-( #*H2'#$ ,*=
+"# 3%)=&(+-)* )/ /%## %,=-(,1$7

0" 8)%-%.)(4- 9++'(&/ %+ 0%56-'5'*&;


<55,*%-%.)(4- 9++'(&/
!"# +#%'-*,1 $#M&#*(# )/ ()'31#'#*+ 1#,=$ +)
=-%#(+ 12$-$ )/ .,(+#%-, .2 '#,*$ )/ 3)%# /)%',6

" AB
+-)* 9!<7 !"# 3%)(#$$ )/ (),+-*0 '-(%))%0,*-$'$
?-+" ()'31#'#*+ -*+#%'#=-,+#$ 9.04.+*5$)*.+<
1#,=$ +) -*(%#,$#= 3",0)(2+)$-$ )/ +"# '-(%))%6
0,*-$'$7 !"-$ ,(+-4-+2 ,1$) 3%#4#*+$ +"# ,((&6
'&1,+-)* )/ , =,*0#%)&$ #F(#$$ )/ ,*+-.)=26
%-(" -''&*# ()'31#F#$7

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
C2 C2a
3'.,-4&)%* 4*@ 9++'(&/
"
C2a
C4b C4b C4b C4b FI C3b FI C3c
DAF
CR1 CR1 C3dg

1. Blockage 2. Dissociation of C2a and C4b, 3. Cleavage of C4b and C3b by CR1/FI
of binding 2. enhanced by DAF or CR 1
A. Regulation of complement effects: protection of autologous cells

:,*@45'*&4- #$)*()6-'/
1. Contraction of 2. Increased 3. Degranulation 4. Chemotaxis, release
1. smooth muscles permeability of 3. of basophils 4. of O2-radicals and
blood vessles 4. lysosomal enzymes
Anaphylatoxins

C3a + + + -
C4a (+) (+) (+) -
C5a ++++ ++++
B. Biological effects of complement factors: inflammatory effects

C3b/C3d/iC3b
receptor
+ ++++

#
1. Antimicrobial effects 2. Clearing of immune complexes

APC Killer cell FDC


FcR

C3b C3d FcR B


CR1 CR2
MHC C3b B

"
CR1

T cell Target cell B cell B


CR2 C3d
3. Cell adhesion 4. B-cell stimulation Memory B cell
C. Biological effects of complement: immunological effects
AC

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. #
! =**$%) =??2*.%@

!" #$%&'()*+!,,'-.$%)/ 0'1)-21$3 #$%%)3*,


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+.()$+()%* .&#+$#/ DU5 ("# ("),6 .%0?%*#*( %1
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!+("%3#*2"//%.)+(#6 #%&#.'&+, !+((#,*/ 0#6)+(# ("# '?(+F# +*6 (,+*/?%,( (% &-/%/%0#/
789:8/;5 <")." +,# ")3"&- .%*/#,$#6 +0%*3 7');@ 91(#, &-/%/%0+& 6#3,+6+()%* +*6 +*()3#*
0).,%%,3+*)/0/ ='( *%( #>?,#//#6 =- "%/( ()/2 ?,%.#//)*35 ("# 0).,%=)+& ?#?()6#/ .+* =# ?,#2
/'#/@ !"#- +,# ,#.%3*)4#6 =- /?#.)1). !+((#,* $#2 /#*(#6 (% ! .#&&/ $)+ :YD .&+// JJ 0%&#.'&#/
.%3*)()%* $#.#?(%,/ 7%&&;5 <")." +,# #>?,#//#6 7+6+?()$# )00'*)(-;@ !"# 0+**%/# ,#.#?(%,
0%/(&- %* ?"+3%.-(#/@ +*6 /.+$#*3#, ,#.#?(%,/ =#&%*3 (% ("# .&+//
9 (-?).+& 89:8 )/ =+.(#,)+& AB95 <")." %1 #*6%.-(). ?+((#,* ,#.%3*)()%* ,#.#?(%,/@
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A2*/$?)*%$1 #3.*-.51),

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%1 .#&& <+&&/ %1 E,+02*#3+()$# =+.(#,)+@ H8L2 ?+("<+- )/ ("# %*# 0#6)+(#6 =- !HIK +1(#, ,#2
=)*6)*3 ?,%(#)* 7HN8; ?&+-/ + ,%&# +/ +* %?/%*)* .%3*)()%* %1 H8L@ :A2P )/ + 0%&#.'&# ("+( =)*6/
7)@#@5 (+33)*3 ("# 0%&#.'&# 1%, =#((#, .&#+,+*.#;5 (% ("# #>(,+.#&&'&+, 6%0+)* %1 !HIK +*6 )/ ,#2
+*6 DAOK )/ +* %?/%*). ,#.#?(%, 1%, .%0?&#>#/ C'),#6 1%, !HIK /)3*+&)*3@ !HIK "+/ + .-(%?&+/2
%1 H8L +*6 HN8@ J1 ("# 6%/# %1 H8L #>.##6/ ?"-2 0). 6%0+)* /)0)&+, (% ("+( %1 ("# JH2O ,#.#?(%,@
/)%&%3).+& &#$#&/5 H8L .+* +&/% =# (+F#* '? =- J*6##65 .%00%* /)3*+&)*3 /(#?/ )*.&'6# =)*62
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"
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(#,)+ (-?).+&&- #>?%/# ?#?()6%3&-.+*/ +( ("# .#&& +*6 %1 ("# +6+?(#, 0%&#.'&# !B\ ,#.#?(%,2+//%2
/',1+.#5 <")." +,# ,#.%3*)4#6 =- !HIP@ Q("#, .)+(#6 1+.(%, ] 7!I9\];5 ("# )*$%&$#0#*( %1 0)2
&)3+*6/ 1%, !HIP +,# &)?%?,%(#)*/5 &)?%?#?()6#/5 (%3#*2+.()$+(#6 ?,%(#)* F)*+/#/ 7:98[;5 +*6
?#?()6%3&-.+*/5 +*6 &)?%+,+=)*%0+**+*@ !"# ("# 1)*+& ,#&#+/# %1 ("# (,+*/.,)?()%* 1+.(%,
&+((#, )/ + 3&-.%&)?)6 ("+( )/ ?,#/#*( )* 0-.%=+.2 B\!N 1,%0 )(/ )*")=)(%,- ?,%(#)* J!N (% )*6'.#
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("+( 0#6)+(# ?"+3%.-(%/)/@ !")/ ?,%.#// )/ 1+2 $*/ !/$5%.>) =??2*.%@
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6" #$%%)3* 4)-'(*.%.'* 4)-)5%'3, +/ /.+$#*3#, ,#.#?(%,/@ !HI/ /#*/# H8L +/
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8+((#,* ,#.%3*)()%* ,#.#?(%,/ .+* =# 6)$)6#6
+*6 0#6)+(# /)3*+&)*3 ("+( ,#/'&(/ )* ("# /#.,#2
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F)*#/@ !"# )**+(# )00'*# ,#/?%*/# )/ +.()$+(#6
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<)(")* "%',/@ !",%'3" /.+$#*3#, ,#.#?(%,/5
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=+.(#,)+ +,# ?"+3%.-(%/#6 +*6 6#/(,%-#6@ J* +62
(+3 ("#0 1%, 6#3,+6+()%* =- ("# .%0?&#0#*(
6)()%*5 !HI/ )*6'.# AD 0+(',+()%* +*6 '?,#3'2
/-/(#0 %, =- ?"+3%.-(#/ 7'(;@ !"# =#/(2F*%<*
&+()%* %1 .%2/()0'&+(%,- 0%&#.'&#/5 /'." +/
,#.#?(%, %1 (")/ .&+// )/ 0+**%/#2=)*6)*3 &#.()*5
DAW^_DAW]5 <")." ?,%0%(# ("# ?,#/#*(+()%*

!
<")." )/ /#.,#(#6 =- ("# &)$#, +/ +* S+.'(#2
%1 0).,%=)+& ?#?()6#/@ 91(#, U2V 6+-/5 /()0'&+2
?"+/#T ?,%(#)*@ J( ,#.%3*)4#/ .+,=%"-6,+(#/
()%* =- AD/ ,#/'&(/ )* /'11).)#*( *'0=#,/ %1
%* =+.(#,)+5 -#+/(5 +*6 /%0# ?+,+/)(#/ +*6
.&%*+&&- #>?+*6#6 +*()3#*2/?#.)1). !2#11#.(%,
$),'/#/@ :+**%/#2=)*6)*3 &#.()* .%*(+)*/ (<%
+*6 !2"#&?#, .#&&/5 ("# .%0?%*#*(/ %1 +6+?()$#
0+**+*2=)*6)*3 &#.()*2+//%.)+(#6 ?,%(#+/#/
)00'*)(-@
BC 7:9L8 O +*6 P; ("+( +,# ,#&+(#6 (% DO, +*6
DO/ %1 ("# .&+//). .%0?&#0#*( ?+("<+-@ !"#),
Burmester, Color Atlas of Immunology © 2003 Thieme
All rights reserved. Usage subject to terms and conditions of license.
Bacterial DNA
#$%&'()*+$,,'-.$%)/ 0'1)-21$3 #$%%)3*, $*/ #$%%)3* 4)-'(*.%.'* 4)-)5%'3,

PAMPs PRR
!
– CpG Toll-like-receptor 9
Mycobacteria Scavenger receptors, LBP,
– LPS CD14, Toll-like receptors 4
– Lipoproteins Toll-like-receptor 2
Gram +ve bacteria
– Peptidoglycans CD14, Toll-like-receptor 2
– Lipoarabinomannan CD1, Toll-like-receptor 2
Gram -ve bacteria
Mannose receptor
– Mannan Mannose-binding protein

Yeasts Mannose receptor, !-glucan


– Zymosan receptors, Toll-like receptor 2

A. Pathogen-Associated Molecular Patterns and Pattern Recognition Receptors

A2*/$?)*%$1 #3.*-.51),
Bacteria

Mannose- C3 C3b
“Acute phase”
binding
lectin Complement C3a
MASP1 MASP2 activation
1. Secreted pattern recognition receptors

"
Mannose receptor
MHC II

Scavenger receptor Lysosome Presentation

2. Endocytic pattern recognition receptors

MD-2 P I"B Nucleus


MyD88
TLR4 IRAK
Bacterial MAPK
lipopoly- Adapter TRAF 6 NF"B Activation of
saccharide CD14 proteins inflammatory
and immune
3. Signaling pattern recognition receptors
response genes
B. Pattern recognition receptors

LPS IL-1, IL-12


Toll-like receptor
MHC II TCR Clonal
expansion

Endocytic
PRR CD80/86 CD28

C. Dendritic cells as a link between innate and adaptive immunity


Quiescent
T cell

Help
!
BD

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! #$%&'()*$ :.;30*.'/

!" #$%&'()*$ !+,$-.'/ 0/+ 12*3040-0*.'/


!"#$%&'"()* +),-) (%) './'0+,(.&1 2" $,**.13
(%/&03% (%) )14&(%)+.0#5 61 (%) $&*(',$.++,/"
C ')++* )F$/)** (%) '%)#&@.1) /)')$(&/ OOXK: ,
/)')$(&/ 7&/ W!O ,14 7&/ (%) %$*().1YZ,// -./0*<
.140')4 /)')$(&/ *.3,14 7%)#&@.1) =G!O>:
?%.'% .* ,+*& /)7)//)4 (& ,* 6,'/&$%,3) ?17+,#<
-)10+)* &7 +"#$% 1&4)* ,14 8)")/9* $,('%)*:
#,(&/" 0/&().1<[" =8@'/A">5 C<')++ #.3/,(.&1 .*
, *$)'.,+.;)4 )14&(%)+.0# #,4) 0$ 2" 010<
4/.-)1 2" W!O $/&40')4 2" *(/&#,+ ')++* ,14
*0,++" %.3% )14&(%)+.,+ ')++*: ',++)4 !.3%<"1<
G!O #,4) 2" 4)14/.(.' ')++* ,14 #,'/&$%,3)*
4&(%)+.,+ #)10+)* =$%&>: ,++&?* #.3/,(.&1 &7
.1 (%) +"#$% 1&4) C ;&1)5 A)#&/" C ')++*
/)*(.13 +)0@&'"()*5 A.3/,(.&1 .* )1%,1')4 .1
%,-) , +&? )F$/)**.&1 &7 OOXK '&#$,/)4
.17+,#)4 (.**0)*5 B* , 7./*( *()$: (%) './'0+,(.13
?.(% 1,.-) C ')++*: ?%.'% #," '&1(/.20() (&
+)0@&'"()* )13,3) ,4%)*.&1 #&+)'0+)* .1 &/4)/
(%)./ /)40')4 (/,77.'@.13 (%/&03% +"#$% 1&4)*5
(& *+&? 4&?15 C%.* *()$ .* ',++)4 D()(%)/.13E ,14
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(%) C<')++ ;&1) &7 *)'&14,/" +"#$%&.4 &/3,1*5 C<')++ ,/),*5

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
#$%&'()*$ !+,$-.'/ 0/+ :.;30*.'/
!
Endothelium

Tethering Rolling Activation Arrest

Glycoprotein !4"7 !4"1 7TMR ! L" 2 ! M" 2 !4"7 !4"1


PSGL-1 L-selectin integrin integrin integrin integrin integrin* integrin*

@%/+0?$/*09 A3./(.B9$-
Chemokines

P-selectin PNAd MAdCAM-1 VCAM-1 ICAM-2 ICAM-1 MAdCAM-1 VCAM-1


E-selectin
*activated
A. Leukocyte adhesion and extravasation

T cell

"
CCR 7
HEV SLC CXCR5
Lymphoid BLC
follicle
T cell

B cell
CCR 7 FDC,
ELC c stromal cells
DC, MØ
B. T-cell migration C. B-cell migration

RANTES
IL-8 MCP-1

MIP-1!

TNF-!
CCR1
CCR2
CCR5
(CCR6)
Immature DC CXCR1
D. DC migration into inflamed tissue
Mature DC
CCR7
CXCR4
Migration to
lymph nodes !
CE

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! 31.4(5(6-215 7889,& :&241,-'8' 1,; #(5&+1,2&

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*(#/ =9 50.1)*%$9 4#1)$$4%-# %*/ $#*%.
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==

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
*$%&+'&,'-.-/-.$ 0&12.-(,'

Mucus secretion
!
Antigen

Reexposure to antigen
Second
antigen
Insect venom Food Pollen Dust mite

constriction
contact

Bronchial
Increased
Urticaria
permeability
Antigen Fc!R of blood
vessels
IgE

Basophil/mast cell Degranulation,


Type I: Immediate hypersensitivity mediator release

<9,;18&,.15 3+-,2-%5&'
Penicillin Mother
RhD-
Antigen

Fetus
RhD+ Complement
Anti-BM
R' S CH3 antibodies
CH3 1st pregnancy
C N Immune
O COO complex

Immune
Post
partum
anti-
RhD

Pulmonary
bleeding
complex
deposit C3a
C5a
"
Enzyme
release,
2nd pregnancy cell
Lysis Nephritis damage

Type II : Cytotoxic antibody reactions Type III: Immune complex reaction

Hapten Hapten – Langer- Hapten/antigen


carrier hans reexposure
complex cell Lymph nodes

Epidermis

Dermis

Lymphatic

A. Types of hypersensitivity reactions


Induction of
antigen-specific
T cells
Type IV: Delayed type hypersensitivity (DTH ) !
=>

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! :2(;*0*5)'20 #==&$/ </';2$)7=7 2$% ,*0/12$'/

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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Adult mouse, strain A
#$%&'()*$ 2$% :1/7/1A2()*$ *+ ,*0/12$'/

Embryonic mouse, strain B


!
Embryonic
Spleen thymus with
immature
thymocytes
Dendritic
cell + antigen

>&$%2=/$(20 :1)$')60/7
Mature T cells Tolerance
of strain B to A

T cell activation against A

A. Induction of T-cell tolerance by antigen-presenting dendritic cells

Mature T cell

Auto-peptide/MHC Foreign antigens/recognizable


not accessible autoantigens

"
T -cell receptor
Co-receptor
Elimination,
deletion, TCR/
Ignorance loss by co-receptor Regulatory
innocence consumption Anergy modulation cells
B. Peripheral mechanisms of tolerance induction

Fertilized Microinjection Own gene


egg of foreign gene product
Foreign gene
product
Implantation of egg
in syngenic mouse

C. Transgenic mice
Transgenic
offspring
Tolerance

!
?B

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
B-'>5$)/,/ *+ !&(*),,&$)(2 F#G
!
TC

Resting
T cells
Islet cell

LCM Antigenic peptide Cyto-


virus toxicity

<&$%5,-$(56 A4)$')06-/
TH APC
Signal Signal Activated T cells
A. Induction of an autoimmune response by virally induced T-cell activation

Antigen Surface Autologous cell


Foreign part immuno-
Autoantigenic globulin
part Virus

Processing
Auto
antigen
T cell

C. Induction of an autoimmune reaction


Viral
antigen
"
C. by molecular mimicry
B cell Autoantibodies
Target cell T cell that
HLA class II and virus recognizes
antigen Viral viral Ag
presentation antigen
Help

T-cell IFN-!
receptor

HLA class II
antigen

Auto-
antigen T cell that

!
T cell
recognizes
Cell damage auto-Ag
B. Induction of autoantibodies by T-cell D. Induction of an autoimmune response
help after autoantibody-mediated after viral infection by aberrant
antigen presentation MHC class II antigens
DH

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Antigen Antibody
(anti-idiotypes)
Organ-specific
diseases
71'.6$)3,3 *+ !&(*),,&$)(- I##J

Non-organ-
specific diseases
"
Brain
MS Brain
SLE
Cartilage
Polychondritis Nose
APC TH Wegener’s
B
Thyroid gland granulomatosis
T-helper/ Hashimoto’s
thyroiditis,
inducer primary myxedema, Lung
cell thyrotoxicosis Scleroderma,
(Graves’ disease) MCTD,
Macrophage Wegeners’
Stomach granulomatosis
Pernicious
TR TZ anemia

F&$%6,1$(65 D/)$')<513
Muscle/skin
Presentation Autoaggressive Liver Dermato-
Regulatory PBC, myositis
of effector autoimmune
autoantigens cell functions hepatitis
Pancreas Kidney
A. Induction of autoimmunity by loss Juvenile diabetes SLE,
A. of regulatory mechanisms Wegeners’
Intestine granulomatosis
Crohn’s disease,
d ulcerative colitis
Lens er e Joints
es t Rheumatoid
qu Bone marrow
Se Autoimmune hemolytic arthritis
Hidden
antigens anemia, ITP

#
Skin
An Skin Scleroderma,
tig
Cartilage en Pemphigus SLE
s Testes
B. Organ-specific and non-organ-
C. Sequestered antigens B. specific autoimmune diseases
Frequency (%)
Disease Allele*
Patients Controls Relative risk
Behçet’s disease B5 41 10 6,3
Ankylosing spondylitis B27 90 9 87,4
Reiter’s syndrome B27 79 9 37,0
Acute anterior uveitis B27 52 9 10,4
Subacute thyroiditis B35 70 15 13,7
Psoriasis vulgaris Cw6 87 33 13,3
Dermatitis herpetiformis DR3 85 26 15,4
Celiac sprue DR3 79 26 10,8
Graves’ disease DR3 56 26 3,7
Diabetes mellitus type I DR3 and/or DR4 91 57 7,9
Myasthenia gravis DR3 50 26 2,5
Systemic lupus erythematosus DR3 70 26 5,8
Idiopathic membr. nephropathy DR3 75 26 12,0
Narcolepsy DR2 100 25 N.D.
Multiple sclerosis DR2 59 25 4,1
Rheumatoid arthritis
Hashimoto’s thyroiditis
Pernicious anemia
Juvenile chronic arthritis
DR4
DR5
DR5
DRw8
D. Associations between diseases and the HLA system (*old nomenclature)
50
19
25
23
19
6
6
8
4,2
3,2
5,4
3,6 "
GK

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. #
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'&/* +('.1+'"$ -)6*$'/"+% (+$2+$"$ G +*- \; /">
$&(0 +$ +*'.4"* /"("2')/ 5.*-.*49 :0.$ '+B"$
$&#'.*4 .* IP? 3/+4%"*'+'.)* +*- +2)2')$.$9
2#+("; 3)/ "A+%2#"; 60"* '0" $'.%&#&$ )((&/$
!+$2+$"$ (+* 5" .*0.5.'"- 5, C?L$ 7.*0.5.')/$
6.'0)&' '0" +(("$$)/, $.4*+#$ 7$"" 29 GH89
)3 +2)2')$.$ 2/)'".*$89
D&/3+(" %)#"(&#"$; $&(0 +$ !IJK 7?LM>N
)/ O+$ +*'.4"*8; +/" .%2)/'+*' %"-.+')/$ )3
#" =<05/):,/*$* /% !2/2,/,$) 8&77*
+2)2')$.$9 !IJK .$ + %"%5"/ )3 '0" '&%)/
*"(/)$.$ 3+(')/ 7:PO8Q*"/1" 4/)6'0 3+(')/ I&/.*4 +2)2')$.$; 20)$20+'.-,#$"/.*" 7LD8 .$
7PRO8 3+%.#, )3 /"("2')/ 2/)'".*$9 S0"* +('.> "A2)$"- +' '0" ("## $&/3+("9 D(+1"*4"/ /"("2')/$
1+'"- 5, ?LM>NQO+$ #.4+*-$; !IJK '/.44"/$ +* ? +*- "*-)')A.* /"("2')/ !IN] (+* 5.*- ') LD9
+2)2')'.( $.4*+# .* + *&%5"/ )3 ("##$9 ?2)2')$.$ :0" 1.'/)*"('.* /"("2')/ ())2"/+'"$ 6.'0 '0"
'0/)%5)$2)*-.* 7:DL8 /"("2')/ !IGH ') 5.*-

!
(+* 5" '/.44"/"- 5, '0" #)$$ )3 ("##T("## ()*'+('
7'1"(2(%8 )/ '0" 6.'0-/+6+# )3 4/)6'0 3+(')/$ 5, :DL9 :/.44"/.*4 )3 '0"$" /"("2')/$ .*-&("$ +('.*
4#&()()/'.().-$; 0,2"/'0"/%.+; +*- 4/+*E,%" /"+//+*4"%"*'; #"+-.*4 ') .*'"/*+#.E+'.)* )3
7$"" 29 GU89 ? ()%%)* .*'/+("##&#+/ %"-.+')/ +2)2')'.( ("##$9 :0" /"#"+$" )3 2/).*3#+%%+')/,
%+, 5" )A.-+'.1" $'/"$$; 60.(0 (+&$"$ *&(#"+$" (,')B.*"$ )/ (0"%)B.*"$ .$ -)6*/"4&#+'"-9
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.*') 3/+4%"*'$9 C* IP? "#"('/)20)/"$.$; '0.$

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
– Ischemia Necrosis
Inflammation
!2/2,/*$*
!
– Hyperthermia
– Hypothermia
– Physical
or chemical
damage
– Trauma Swelling
of the cell, Lysis –
Apoptosis damage to organelles destroyed
signal organelles chromatin destroyed

>6(10?&(,07 ='$()$27&*
Chromatin Cell shrinkage, Chromatin Segmentation Apoptotic Phagocytosis:
condensation zeiosis margination of the nucleus, bodies no
DNA fragmentation inflammation
A. Differences between necrosis and apoptosis

Oxidants Bax Calcium


Apo-1/FAS antigen
Ceramide Active
CD95 caspases
Glucocorticoid T/B-

"
receptor antigen receptor Mitochondrion
Cytochrome c
O2, H2O2 release
i

DNA
OH, NO damage
(UV light, Apaf-1
Loss of cell- irradiation) pro-caspase 9
cell contact
Granzyme
Deprivation of Activation of further caspases, apoptosis
Hyperthermia growth factor

Effector genes C. Caspase activation by mitochondria


-p53 Apoptotic
-nur 77
cell
-c-myc
-ICE
Apoptosis- Apoptosis TSP
inhibiting promoting Vitronectin
genes genes receptor
-bcl-2 -bax CD36
-bcl-xL -bad PS
-Rb -bcl-xS
Scavenger
CD14 receptor-A

Actin

!
polymerization Actin
Anti-inflammatory response
Actin
TNF-" IL-1! MCP-1 IL-8
Survival Apoptosis
B. Regulation of apoptosis D. Phagocytosis of apoptotic cells
@B

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! !1.%*$1B!1.%(0&C =1.$)/,.%017

!" #$%&$'($)*$) +)$,%-%./.%01 23)4$


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)* '+# "#($'%)* &"%*$%&7# )6 %00-*# $)0&7#>
$(* 2# &#"6)"0#/ %* .)7%/ &+(.# 8"(/%(7 %00-9
6)"0('%)* /-# ') (*'%1#*I(*'%2)/3 %*'#"($'%)*4
*)/%66-.%)*: %00-*)#7#$'")&+)"#.%.; )" 7%,-%/
5+# $-B#''# %. %""(/%('#/ <%'+ 7(.#" 7%1+': <+%$+
&+(.# .3.'#0. 8'-"2%/%0#'"3: *#&+#7)0#'"3;4
.$(''#". 6")0 '+# %00-*# $)0&7#>#.4 J#*.#.
5+# !"#$"%&"'("' )'"*#)#+,+#-. */'0" $(* 2#
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/#.$"%2#/ (. 6)77)<.4 =)7-27# %00-*# $)09
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$)*$#*'"('%)* %* '+# (.$#*/%*1 &("' )6 '+# .,-("# )6 '+# /%(0#'#" 8$L; )6 '+# "%*1 )6 &"#$%9
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6)"0 /-# ') %*'#"($'%)* 2#'<##* (* (*'%2)/3
(*/ 0)7#$-7(" (*'%1#*.4 E* %00-*# &"#$%&%'(9
'%)*: '+# (*'%1#* %. /%7-'#/ 23 /%66-.%)* %* (
.(0&7# <%'+ ( D*)<* (*'%2)/3 $)*$#*'"('%)*
-*'%7 '+# &)%*' )6 &"#$%&%'('%)* )$$-".: %4#4: -*'%7
'+# (*'%1#*A(*'%2)/3 "('%) "#($+#. '+# #,-%B(9
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2)/3 (*/ &("'%$-7('# (*'%1#*.4 @ /%.'%*$'%)* %.
0(/# 2#'<##* /%"#$' (117-'%*('%)* 8#414: +#9
0(117-'%*('%)* '#.' 6)" /#'#"0%*('%)* )6 27))/
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(*/ %*/%"#$' (117-'%*('%)* '#.'. 8#414: 7('#> (19
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10"2%3%4#'"5, @* (*'%1#* .(0&7# %. &7($#/ %* (

!
$-B#''# (*/ (77)<#/ ') "#($' <%'+ (* #>$#.. )6
(* (*'%.#"-0 $)*'(%*%*1 '+# $)""#.&)*/%*1
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5+# $+(*1# %* '-"2%/%'3 %* '+# $-B#''# %. 0#(9
.-"#/ 23 &+)')0#'"34 5) /#'#"0%*# '+# #*/
EF &)%*': '+# %*$"#(.# %* (2.)"&'%)* <%'+%* ( $#"9

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
:$>%1%.%017 /1& +)$,%-%./.%01 G$,91%H3$7
!
Size of Immune complex
immune formation with
complexes molecular
(precipitate antigens
mass)

Precipitation
Ag : Ab ratio
Ag surplus Equivalence range Ab surplus
Immune complex
formation with
Ag Ab antigenic particles
(e g. erythrocytes,

D/(0)/.0)C !--'%,/.%017
latex particles)

Agglutination

A. Heidelberg curve B. Precipitation and agglutination

Turbidimetry
(Extraction measurement)

Laser/
quartz lamp
Cuvette
Photodetector

Scattered light detector


"
Nephelometry
(Scattered light measurement)

C. Precipitation techniques in fluid phase

Gel with antibodies


Ag-concentration C

in solution
!
Spot for antigen C ~ d2
to be tested 4
Standard
curve
Precipitate rings

!
(equivalence range)

d d
Relationship between diameter d of
precipitate ring and antigen concentration
D. Simple radial immunodiffusion (RID) according to Mancini
EE

Burmester, Color Atlas of Immunology © 2003 Thieme


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! !/6&A,/C!/6&+)%8 -/6,7$46&)/1

!" #$%&$' ()*+', -..*/)%&00*1&)/


23*456,7')/8 9,65)%:
(" #)4?,6 <',467)>5)7,1&1 2<',467)>5)7@
,1&1 &/ !/6&+)%8@4)/6$&/&/A B,':
!" #$%& #'&#( )*#$ +"#%,'" +"- +"#%)*-. -%//0&' !" #$%& #'4$"%50'( +"#%,'"& 9%,1+#' #$1*0,$ +
1+-%+22. #*3+1- '+4$ *#$'1 %" +50'*0& +,+1*&' ,'2 4*"#+%"%", +" +"#%)*-. #*3+1- +" +"*-'6
,'26 7%&%)2' )+"-& */ 81'4%8%#+#%*" /*19 +# #$' :$%& 2'+-& #* #$' /*19+#%*" */ 2*",( 1*4<'#?
&%#'& 3$'1' #$' +"#%,'" +"- +"#%)*-. 9''#6 &$+8'- 81'4%8%#+#'& =1*4<'#&> #$+# 4+" )' ;%&0+?
:$%& 9'#$*- %& + ;'1. '//'4#%;' 3+. #* #'&# 2%K'- ). &#+%"%",6 :$%& 9'#$*- 8'19%#& 50+"#%?
#$' %-'"#%#. */ 0"<"*3" +"#%,'"& )+&'- *" #+#%*" */ #$' +"#%,'" 4*"4'"#1+#%*" ). 4*98+1?
#$' &.99'#1. */ 81'4%8%#+#%*" 8+##'1"&6 !-'"#%#. %", #$' #'&# &8'4%9'" #* + &%902#+"'*0&2.
*/ #3* +"#%&'1+ =3%#$ 1'&8'4# #* #$' 0"<"*3" 9'+&01'- &#+"-+1-6
+"#%,'"> *4401& 3$'" #$' #3* )+"-& */ 81'4%8%?
#+#%*" /0&' #* /*19 + &%",2' 2%"'6 :$' )+"-& 41*&&
3$'" #$'1' %& "*"%-'"#%#.( +"- + &*?4+22'- &801
D$+)7$6)78 !>>'&4$6&)/1

/*19& %" 8+1#%+2 %-'"#%#.6

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2=)*/6,74*77,/6 <',467)>5)7,1&1:
@$'" + &+982' %& +-A0&#'- #* + ,%;'" 8B ='6,6(
8B C6D /*1 #$' #'&# +"#%,'"E 'F#1+4#+)2' "042'+1
+"#%,'"&( GHI>( #$' +"#%,'" +"- +"#%)*-. 9%?
,1+#' %" *88*&%#' -%1'4#%*"& #$1*0,$ #$' ,'2
-0' #* -%//'1'"4'& %" #$'%1 '2'4#1%4 4$+1,'&6
!990"' 4*982'F'& /*19 -01%", #$' #1+"&9%?
,1+#%*" 81*4'&& %/ #$' 4*11'&8*"-%", +"#%)*-.

"
%& 81'&'"# %" #$' 8+#%'"#J& &'1096 :$' %990"'
4*982'F'& /*19 2%"'& */ 81'4%8%#+#%*" #$+# 4+"
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!990"*'2'4#1*8$*1'&%& %& + 4*9)%"+#%*" */
81*#'%" '2'4#1*8$*1'&%& +"- %990"*81'4%8%#+?
#%*"6 :$' #'&# +"- 1'/'1'"4' &+982'& +1' /%1&#
&'8+1+#'- ). '2'4#1*8$*1'&%&6 :$' +"#%&'109
-%//0&'& 8'18'"-%402+12. #* #$' -%1'4#%*" */ &'?
8+1+#%*"6 L0' #* #$' /*19+#%*" */ 81'4%8%#+#%",
%990"' 4*982'F'&( &$+182. -'/%"'- 2%"'& */
81'4%8%#+#%*" /*19 %" #$' 1+",' */ '50%;+2'"4'6
M1*#'%"& 4+" )' %-'"#%/%'- )+&'- *" #$' %"#'"?
&%#.( &$+8'( +"- 8*&%#%*" */ #$' 81'4%8%#+#%*"
2%"'&6
!990"*'2'4#1*8$*1'&%& %& 0&'- %" 8+#%'"#&
3%#$ &0&8'4#'- 9*"*42*"+2 +"- 8*2.42*"+2
,+99*8+#$%'&6 M*2.42*"+2 %990"*,2*)02%"&
+1' 0"%/*192. -%&#1%)0#'- #$1*0,$*0# #$' ,+9?
9+?,2*)02%" /1+4#%*" +/#'1 '2'4#1*8$*1'#%4 &'?
8+1+#%*"6 N*"*42*"+2 %990"*,2*)02%"& /*19
+ 2*4+2 ,1+-%'"# %" #$' ,+99+?,2*)02%" /1+4#%*"

! EF
=N ,1+-%'"#>( 2'+-%", #* #$' /*19+#%*" */ + -%&?
#%"4#%;' %"-'"#+#%*" 8+##'1"6

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Possible
G,45/&H*,1 )0 <',467)>5)7,1&1
!
precipitation Anti-!, " Anti-!, " Anti-!, "
patterns
of anti-!, "-
antiserum with x y x y x y
mixtures of the
antigens !, "
in spots x and y x y x y x y

Antigen ! ! ! " ! !"


or: !" !"
or: " "

D$+)7$6)78 !>>'&4$6&)/1
Identity No identity Partial identity
x=y x#y x y
A. Radial double diffusion (Ouchterlony)

Principle

Anode Cathode

Ab Ag Anti-ENA ENA
(anti-ENA) (ENA)

"
B. Transmigration electrophoresis ( countercurrent electrophoresis )

Start Serum
Anode Cathode

Electrophoresis

Alb !1 !2 " $

Antiserum/diffusion in gel

A n t i s e r u m
Precipitation
Immunoelectrophoresis

C. Immunoelectrophoresis (time course of procedure )

Cathode
Ag

Ag
Anode
Precipitation
line
D. Electrophoresis in antibody-containing gel (rocket electrophoresis)
!
EI

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! !(&'#,(;!(&'6*7< =(&,>)-&'*(0

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&(+ *($&/'"&#0 &( * 0#1-2 0*23,#4 !"#$%&'&
%#,,0 %'*$#" C&$5 $#0$ *($&/'"&#0 :&22-(#
%'23,#=#0; *1# -0#" *0 $5# &("&%*$'1 090$#24
J5#( $5# $#0$ &0 3'0&$&F#D (' %'23,#2#($.
()'*+",*&- *1# &22-('+,'/-,&(0 ') $5# 6+7 2#"&*$#" 5#2',90&0 ') $5# &("&%*$'1 090$#2
%,*004 85#9 /&(" $' $5# *($&+#( "#$#12&(*($0 '%%-10 0&(%# $5# %'23,#2#($ C*0 %'(0-2#"4
') 1#" /,''" %#,,0 *0 3#($*2#10 *(" &("-%# 6) $5# $#0$ &0 (#+*$&F#D %'23,#2#($ &0 0$&,, *F*&,.
*++,-$&(*$&'( ') $5# *($&+#(04 85#9 *1# %*,,#" */,# $' &("-%# ,90&0 ') $5# $#0$ ?@A0 ') $5# &("&.
%'23,#$# :(*$-1*,; *($&/'"&#0 /#%*-0# $5#9 %*$'1 090$#24
%*( &("-%# *++,-$&(*$&'( "-# $' $5#&1 3#($*. K(# ') $5# "1*C/*%G0 ') $5&0 2#$5'" &0 )*,0#.
2#1&% 0$1-%$-1#4 <($&/'"&#0 *+*&(0$ /,''" 3'0&$&F# 1#0-,$0 "-#D )'1 #=*23,#D $' 0#,).&(5&/&.
+1'-3 *($&+#(0 *1# * $93# ') %'23,#$# *($&. $&'( ') 0#1-2 "-# $' 15#-2*$'&" )*%$'10D &2.
/'"&#04 2-(# %'23,#=#0D #$%4 85&0 &0 1#),#%$#" *0 * 3'.
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?)6*>)&*>< !44$'-)&'*(0

"&#0;4 85#0# *($&/'"&#0 /&(" $' $5# *($&+#(


"#$#12&(*($ ') ?@A0 /-$ %*(('$ &("-%# *+. K$5#1 2*$#1&*,0 2*9 *,0' %'($*2&(*$# $5#
+,-$&(*$&'(4 B#2*++,-$&(*$&'( '%%-10 C5#( *($&+#( *(" )'12 &22-(# %'23,#=#0 C&$5
$5# "&0$*(%# /#$C##( 1#" /,''" %#,,0 &0 1#. $5# $*1+#$ *($&/'"9 &( $5# 3*$&#($H0 0#1-2D
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*,,'C&(+ $5# 6+> *($&/'"9 :&(%'23,#$# *($&. $1', *($&+#(4
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+",2 ,&'&/'*") :3*,(% #&'4",;! @*%$#1&*, 0-0.
3#(0&'(0 &(%-/*$#" &( 0#1&*, "&,-$&'(0 ') $5#
3*$&#($H0 0#1-2 0#1F# *0 $5# *($&+#(4 <++,-$&(*.
$&'( '%%-10 &) $5# *($&/'"9 %'11#03'("&(+ $'
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
!##$%&'()&'*( +,-.('/%,0B2*34$,3,(&56'(7'(# 8,)-&'*(

Before: chemical
!
Agglutination of binding
Sheep
Ag-loaded test erythrocytes
Ag erythrocyte
in the presence of specific
antibodies in patient serum

1. Hemagglutination

RF
(IgM anti-IgG)

IgG

?)6*>)&*>< !44$'-)&'*(0
Agglutination =
positive test reaction
Latex IgM-RF in
particle patient serum

2. Latex agglutination in rheumatoid factor screening


A. Agglutination techniques

Principle: competition between test system(Ag + Ab) and indicator system


(erythrocytes loaded with test Ab) for complement

Complement

Ag
Ab
Pre-incubation

Test system
+

Test system
Indicator system
(test erythrocytes,
loaded with test Ab)
"
Complement Positive
Ag (exogenously added) result No
Ab (patient serum) (complement hemolysis
bound by antigen-
antibody complex)

Negative
result
(complement Hemolysis
available for lysis
of test erythrocytes

Complement

Test system
(no specific
Ab present)
B. Complement-binding reaction (CBR)
+

Test system Indicator system


!
@C

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Indicator (no color)
+ substrate
Indicator-H (colored)
+ H2O
#*.7!J @.!J 5$- .''/$03=044+$D
!
(H2O2)
Color reaction

E E
E E Anti-mouse
antibody
Monoclonal Ig
E E
Antigen
Polyclonal Ig
(e.g. rabbit-
anti- xy)

*53025402& !GG=+A54+0$1
Detection of specific antibodies directed Sandwich ELISA
against an antigen by enzyme-labeled for sensitive antigen detection
secondary antibodies ( conjugate ) (e.g. cytokines)
E

Antibody Antigen Secondary antibody, enzyme linked

A. Enzyme-linked immunosorbent assay (ELISA)

High titer: Low titer:


low high
radioactivity radioactivity

* * *
"
Test Ab Measurement of radioactivity
Serum + tracer

E Patient

C1q
Ig
antibodies
* * *
Anti-human Ig
Antigen at solid phase
with subsequent
color reaction Principle: antibody in patient serum competes with radioactively
labeled test antibody
B. C1q solid-phase ELISA C. Radioimmunoassay (classical method)
1. SDS-PAGE 2. Transfer 3. Staining
PAG NC
MW (kDa)
100
AP
80

50
41
31

10

Mouse Ab against human Ig

Human Ab against B. burgdorferi

D. Immunoblotting (Western blot)


AP Alkaline phosphatase

B. burgdorferi proteins Immunoblot !


HK

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
UV radiation
Fluorescing FITC FITC Exciter
/,,%+&0$%&'()*(+*(
!
substrate excitation fluorescence filter
365 450- 520-
(Invisible) 490 nm 560 nm
400
Energy Band-
Energy (nm)

pass
decrease
500 filter
Green
555 Dichroic
(visible)
600 mirror
Fluorescence Light >510 nm

700
300 400 500 600
![nm]
1. Generation 2. Absorption/emission- 3. Fluorescence microscope

<8:&'84&'3 !==$-*84-&+)
2. spectrum of FITC
A. Fluorescence

Fluorescing FITC- PE-conjugated


antibody antibody

1. Direct immunofluorescence 2. Double fluorescence


Fluorescing
Primary antibody anti-Ig antibody
(mouse anti-human) (anti-mouse)

"
4. Intracytoplasmic
3. Indirect immunofluorescence 4. fluorescence
B. Immunfluorescence

Cells in Side Photomultiplier


suspension scatter
530 – 550 nm Granulocytes Monocytes
(green)
Side scatter

560 – 580 nm (red) Light-


sensitive Lymphocytes
diode
Forward scatter
1. Principle Forward scatter
C. Flow cytometry 2. Separation of cell fractions

Negative control 75% positive CD3+ CD3+


No fluorescing cells CD4- CD4+
cells
Anti-CD3
antibody
CD3-FlTC

Negative Positive
Cell count

Cell count

1. Histograms
Fluorescence intensity

D. Flow cytometry: Histograms


Fluorescence intensity
CD3-
CD4-
CD4-PE
2. Dot plot, two-color analysis
CD3-
CD4+

!
>@

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
#$$%&'()*+','-7
!
E.g.
lymph node
or spleen or N2
tumor tissue – Heat Rupture of
Surgical specimen Shock freeze – Formamidase H-bonds:
– Alkaline solutions single-strand DNA

Hybridization

Thin sections ( 4-8 µm) on Cryostat


microscope slides sections Fluorochrome-

E/8'3/+'37 !>>,)./+)'&*
labeled
1. Preparation of samples complementary
1. With DNA probes DNA-probe
3 Streptavidin/peroxidase
2 Antibody + Comple-
B S POX
(rabbit mentary
anti-mouse, + RNA RNA probe,
Chromogenic
biotin- substrate digoxigenin-
conjugated ) (DAB: diamino- labeled Hybridization
1 Antibody benzidine)
(murine) Mild fixation

Section with antigen F

"
F F F F

2. Biotin–avidin/peroxidase staining
+ FITC-labeled
anti-
Alkaline digoxigenin
phosphatase RNA-specific fluorescence Ab
3 AP–AAP + Chromo-
complex genic 2. With RNA probes
(mouse Ab) substrate B. Fluorescence in-situ hybridization
1 Primary 2 Bridging B. methods
antibody antibody
(mouse) (rabbit) Chromosome 8 Chromosome 8q-
Chromosome 21 Chromosome 21q+

3. APAAP staining

ETO gene AML 1 gene

t(8:21)

4. Detection of
tumor cells in
the bone marrow
5. Staining of the
follicle mantle
with CD22 Abs
A. Immunohistological staining
Normal cell
Interphase cytogenetics
C. Example of FISH staining in 8:21
C. translocation
t(8:21) cell

!
@G

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Centrifuge
1/&& #$%&'()%* 9/.5*)E-/$
!
Mononuclear
cell fraction
Ficoll

Diluted Ficoll Granulocytes,


blood (density: 1.077) erythrocytes,
platelets
A. Isolation of mononuclear cells from peripheral blood

Non-T fraction
Sheep (B lymphocytes,

:'@%0'(%0; !44&).'()%*$
erythrocytes monocytes
T lymphocytes,
Centrifuge Ficoll sheep
erythrocytes
Mononuclear cells Binding of sheep erythrocytes
to T cells: rosette formation
B. Separation of T and B lymphocytes: Rosette formation

Plastic surface Antibody


coated with labeled with
antibodies iron beads

Antigen-
bearing
Antigen-
negative
Antigen-
bearing Antigen-
"
Magnet

cells cells cells negative


adhere attracted by cells
magnet
1. Panning method 2. Immunomagnetic separation
C. Antibody-mediated separation of cell fractions

Cells in suspension Photomultiplier


Vibrating cuvette for side-scattered Photomultiplier for
light light
530–550 nm (green)

Bandpass filter Photomultiplier


for light
560–580 nm (red)

Laser Dichroic mirrors


Light-sensitive
photodiode
– + Forward scatter

Positive cells
+
+ –

D. Cell separation by flow cytometry


Negative cells
!
DF

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Stimulus Stimulus
*+,$, (1 *B2+00 34)#$%()

T0 4 12 24 h
!
CD69

CD71

[Ca2+]i
CD25
GM-CSF
IL-2, IL-4 HLA-DR
IFN-! 0 2 4 6 8 10 min
1. Cytokine measurement 2. Flow cytometry [Ca2+]i 3. Expression of
1. (ELISA) 3. activation antigens
A. Activation assays

='>(/'$(/< !??0%#'$%(),
Dist. Glass fiber filter
3 H2O
H-thymidine = Radioactive captures cells

16 h, 37 ˚C, 5%CO2
48 h
Scintillation
37˚C
5% CO2

– Mononuclear cells
– Stimulus (lectins, antigens)
Cell division: DNA synthesis
incorporation of 3H-thymidine
in new DNA strands
Vacuum
fluid

"-counter "
– Growth factors cpm (counts
Waste
B. Proliferation assay per minute)

Proximal
Proteus 8 1 Tetanus
Trichophyton 7 2 Diphtheria
Candida 6 3 Streptococcus
Control 5 4 Tuberculin
(glycerin)
Distal

C. T-cell function in vivo: Mérieux multitest


!
@C

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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?'@*&'(*&6 !//2)0'()*%4

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:",;#$"<%4%< = <"))# $("#",& %, &'" #&0(&%,: 4%(#& <-)&-("1 %, &'" $("#",<" *4 &(%&%-.;)0/")"1
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%, 0 )0(:" .0F*(%&3 *4 ,*,;0,&%:",;#$"<%4%< *4 &'" <"))#@ Z'", <"))# 1%" 1-" &* 0$*$&*#%# 2#""
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:(*+&' 2#*." *4 &'" $(*)%4"(0&%,: <"))# 4*(. 0-&*.0&"1 <")) '0(?"#&"(@ ='" '%:';.*)"<-)0(;
'-:" <")) 0::(":0&"#8@ G# 0 ("#-)&9 #*." *4 &'" +"%:'& !JG *4 %,&0<& <"))# %# <0-:'& %, &'" 4%)&"(9
<0?%&%"# %, &'" <-)&-(" $)0&" <*,&0%, *,)3 0 #%,:)" +'"("0# &'" )*+;.*)"<-)0(;+"%:'& !JG *4
= <"))@ H)*,0) ">$0,#%*, *4 &'" 0,&%:",;#$"<%4%< = 0$*$&*&%< <"))# %# (".*?"1 +%&' &'" +0#'%,:
<"))# %, &'"#" +"))# %# 0<'%"?"1 /3 011%,: AB;C 4)-%1@ ='" (0&" *4 )3#%# <0, /" <0)<-)0&"1 -#%,:
0,1 &'" &0(:"& 0,&%:",@ 0, 0$$(*$(%0&" 4*(.-)0@

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:", %, &'"%( IBG .*)"<-)"#@ J0&-(0) D%))"( 2JK8
<"))#9 *, &'" *&'"( '0,19 D%)) <"))# &'0& "%&'"( 1*
,*& ">$("## LIH .*)"<-)"# *( ">$("## 4*("%:,
*( 0/"((0,& LIH .*)"<-)"# 2#"" $@ MN8@ ='"
*+,)#"(# ,-!-./- .//.0 %# &'" <)0##%<0) &"#& *4
JK <")) 4-,<&%*, 0,1 H=B 4-,<&%*,@ ='" &"#& %#
$"(4*(."1 /3 )0/")%,: &'" &0(:"& <"))# +%&'
(01%*0<&%?" <'(*.%-. 2O5H(89 +'%<' /%,1# &*
<3&*$)0#.%< $(*&"%,#@ P,)3 0 #.0)) 4(0<&%*, *4
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&'" <"))# 2#$*,&0,"*-# )3#%#9 /0<D:(*-,1 )3#%#8@
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&%*,# 4*( RSN '*-(#9 +'%<' )"01# &* )3#%# *4
&'" &0(:"& <"))#@ T-$&-(%,: *4 &'" <")) .".;
/(0,"9 +'%<' %# %,1-<"1 /3 $"(4*(%,# 0,1 :(0,;
U3."# 2#"" $@ MV!89 )"01# &* &'" (")"0#" *4 (01%*;
0<&%?" <'(*.%-.9 +'%<' <0, /" ."0#-("1 %,

!
&'" #-$"(,0&0,&@ ='%# &3$" *4 )3#%# %# 0)#*
("4"(("1 &* 0# WD%))%,:@X ='" .*(" "44"<&%?" &'"
)3#%#9 &'" '%:'"( &'" 0.*-,& *4 <'(*.%-. (";
)"0#"1@ L0>%.0) <'(*.%-. (")"0#" %# 0<'%"?"1
/3 )3#%,: 0)) *4 &'" <"))# %, 0 #-%&0/)" 1"&"(:",&
AB 2"@:@9 =(%&*,8@ ='" "44%<0<3 *4 <")) )3#%# %# $0(&%0))3
1"$",1",& *, &'" (0&%* *4 "44"<&*( <"))# &* &0(:"&
Burmester, Color Atlas of Immunology © 2003 Thieme
All rights reserved. Usage subject to terms and conditions of license.
+ Irradiated
autologous MNC
!%(),$%-4/$0)+)0 1$4(4

Limiting dilution
!
Cell 1000 cells/well
+ Antigen growth 100 cells/well
+IL-2 10 cells/well
1 cell/well
4-7 days 7 days 0.3 cell/well
37°C 37°C
5% CO2 5% CO2
Repeat 3 – 4x
– Mononuclear cells (MNC)
– Antigen + Antigen
– Human AB serum + IL-2
A. Generatiion of antigen-specific T cell clones

?'@*&'(*&6 !//2)0'()*%4
No
Medium effector cells =
background
Effector/target
ratio1 : 1

Washing Effector/target
ratio 5 : 1
Binds to
intracellular
proteins Effector/target
ratio 20 : 1

+ Triton
Maximal cell lysis

cpm probe – cpm background


cpm maximum – cpm background
x 100
"
B. Cytotoxicity assay: Chromium release assay

Target cell Effector Target cell


+ 3H-thymidine cell apoptosis

Labeled
DNA
1. 2. Fragmented DNA

Dist. !-counter
H2O
Lysis in %

cpm without cpm probe


effector cell
Only x 100

3.
Filter

C. Cytotoxicity assay: Jam test


waste
intact
DNA
sticks
to
filter 4.
cpm without effector cells

cpm = counts per min


!
AC

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! 63445410 #>>5.:/7

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:;99#7+6A

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;+3 ! ?#006 ;7# :0;?#3 95@#9"#7 1+ ; D#00 *5= ; !"# ;+91853- 1+191;00- 81+36 95 JRHUC ; 481>41/
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! ?#006C 9"# 1+97;?#0040;7 69;1+1+@ 9#?"+1>4#
?;+ ;065 :7#?16#0- 13#+91=- 9"# 9-:# 5= ;?91K;9#3
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5= 647=;?# .;72#76 16 ;?"1#K#3 461+@ .4091:0#

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=547 =0457#6?#+?#6 ;+3 .;2#6 19 :566180# 95

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Coating Ab Over night
!<<17 *0823C503< D80 6E1012/30:F:.; !./:;3.&<@32:D:2 , 2344<

24–28 h
!
Wash
Antigen-presenting
cells, antigen, T cells
Detection Ab 1h
E E

Wash E Wash

Chromogenic substrate
E

(1?801/807 !@@4:21/:8.<
A. IFN-" ELISPOT
?
!-CD4- !-CD8-
PerCP AP 2

Surface staining
Intracellular
cytokines
Wash + Permeabilize
fixate with PFA

!-IL-4-
PE

Intracellular
!-IFN-"
FITC
with saponin

CD-8-APC IL-4-PE
"
staining
CD4-PerCP IFN-"-FITC
B. Intracellular IFN-" staining

CD45

Bispecific Ab, Restimulation,


!-CD45 ˜!-IFN-" IFN-" production
for 45 min

PE
FACS sorting

!-IFN-"-Ab PE PE

!-PE bead

C. Cytokine secretion assay PE


MACS sorting

!
AG

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! 89:-0,' ;::9.*)6

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',-.,/%.)'0 .#&2 (, 84,007.)'?&-# ,5 ("# )++%7
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',-.,/%.)' +,.#8%.#0< ("#4#/1 )+)(&()'- 3"17
+)(1 (, ("# &'()/,2170#84#()'- 8#..0 &4#
0),.,-)8&. 0()+%.&(),' 2%# (, &'()-#'09 @)'8#
.10#29 !"# '%+/#4 ,5 "#+,.1()8 3.&$%#0 8,47
("# /)'2)'- ,5 )++%',-.,/%.)'0 (, A8 4#8#3(,40
4#03,'20 (, ("# '%+/#4 ,5 (#4+)'&..1 2)55#47
"&0 &' )'")/)(,41 #55#8(< A&/ 54&-+#'(0 54,+
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&4# %0#2H< ("# 6 8#..0 0,+#()+#0 34,2%8# &%(,7
84)'# -4,;(" 5&8(,40< +&?)'- ("# %0# ,5 5%4("#4
#=,-#',%0 0()+%.) %''#8#00&419

%" #$%&'' 2*11&0&.)*,)*-.3 !.)*4-56


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!
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8#..0 ("&( 34,2%8# &'()/,2)#09 Y&4),%0 "#+,.17
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Antigen Stimulus
A&>)> -1 #$%&'' B9.()*-.

Marker T0 4 24 h
!
CD69

CD71

[Ca2+]i
CD25 ( )

CD23 ( ) ( )

0 2 4 6 8 Min
Anti-IgM Cross-linkage Activated Increase in Expression of activation
antibody, of slg B cell intracytoplasmic calcium antigen
SAC

<,4-0,)-06 !=='*(,)*-.>
A. B-cell activation

IL-2 40
H-thymidine incorporation (cpm)

IL-14 (BCGF)
30
IL-4
20
sCD 23

10
Activated CD40 ligand,

"
B cell anti-CD40
antibody
3

Anti-IgM IL-14 SAC Anti-IgM Anti-IgM +


+ IL-14 anti-CD40
B. B-cell proliferation

Sheep erythrocytes
coated with anti-Ig
serum
+ Complement
Hemolytic
plaques
B
+

Agarose gel

1. Inverse plaque-forming cell assay

Antigen- E E E E EE EE
E E
coated EE EE
E

Petri dish
Washing Washing
+ +

!
E E E

Ab-producing Enzyme-linked Gel with chromogenic


B cells anti-Ig antibodies substrate
2. ELISPOT test
C. B-cell differentiation: Antibody secretion
?C

Burmester, Color Atlas of Immunology © 2003 Thieme


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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Slot
!*4,2&-74, C(7'*-;%(5
!
15.8 kb
13.1 kb
9.0 kb
7.1 kb
6.5 kb
2.9 kb
1.0 kb
a b c
Agarose gel after DNA transfer filter Autoradiography film or
gel electrophoresis labeled enzymatic color reaction
75 V; 60 mA DNA probe xy
A. Southern blotting

>4?$)4&$)2 !@@,-74&-$*5
28S

18S

12S

5S

a b c

"
Agarose gel after RNA transfer filter Autoradiography film or
gel electrophoresis labeled enzyme color reaction
75 V; 60 mA cDNA-probe xy
B. Northern blotting

Region to amplify !-gt-11 !-gt-11


left arm right arm
Denaturation to DNA Insert
single strands
Hybridization with strand-
specific primers Biotin-conjugated
PCR mit primers
Nonconjugated
primers
Second heat denaturation,
hybridization with primers
and synthesis of comple-
Streptavidin- Separation of single strands
mentary strands
coated by streptavidin-linked
particle magnetic beads

A C G T
3'ddTACGGAGCTGATTA....
3'ddACGGAGCTGATTA....
3'ddCGGAGCTGATTA....
Sequence analysis

3'ddGGAGCTGATTA....

!
Direction 5'-3'

3'ddGAGCTGATTA....
Primer PCR cycle repeated 3'ddAGCTGATTA....
sequence 20–35 times 3'ddGCTGATTA....
3'ddCTGATTA....
3'ddTGATTA....
Millions of copies of DNA product
C. Polymerase chain reaction D. DNA sequencing
AA

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Pyoderma Meningitis
=0-.7,% 8--0'.*)9&:&)':&)4

Albumin
"
Infections
Xq21 of upper
and lower ! 1 !2 " #-fraction
airways is missing
X-linked Sepsis
recessive

A. Bruton’s agammaglobulinemia Serum protein electrophoresis

Bacterium Monocyte Opsonization, S. pneumoniae, Produced from


phagocytosis, H. influenzae, 2nd year or life on;
Ab-mediated N. meningitidis Ab against bacterial
cellular polysaccharides,

5%&'&:,% 8--0'.%.+3
cytotoxicity teichoic acid
Fc# receptor Absence increased Absence increased
susceptibility to susceptibility
IgG1 + IgG3 bacterial infections IgG2 to infections

Not able to Half life (t 1 2 ):


activate
C1q of IgG1 = 23 days
Ag complement
t1
2 ~12 days
Complement Dangerous when Dangerous when IgG1

IgG4
cascade other subclasses
are absent

1. Selective IgG subclass defects/properties of IgG subclasses

Mutations
in the gene for
TCR
IgG3

Ag
MHC
is absent because of
short half-life of IgG3

IgM or IgD
#
CD40 ligand

Xq26 Class switch


CD40 CD40
ligand IgG or IgA
2. Hyper-IgM syndrome
B. Dysgammaglobulinemia

Pro-B pre-B Virgin-B Recurrent


pneumonia
Arrest in Circulating Auto-Ab
pre-B B cell
phase Association
with HLA-A1,
Impaired
B8, DR3, see
TH regulation
SLE-association
Defective Bronchiectasis

"
glycosylation of Ig Plasma
cell Gastrointestinal
symptoms:
spruelike celiac
disease,
diarrhea,
C. CVID: Common variable immunodeficiency – possible causes malabsorption
;<;

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. #
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+," 7& : %"<< +"-)%)"*%)"/= U5%)5< +./'&$96)/'D '5<;
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
V+D+J+C VDJ+C!
'$;;/;8& .))/,(-$0+1+$,1+$<
"
# " !
Recombinase Point
mutationXq13
IgG, heavy
TCR, " chain RAG I, II-genes chain
X-linked IL-2-receptor
A. Forms of SCID recessive

Clinical
1. Eustachian tube Facial
picture
abnormalities Thymic
22q11 Pharyngeal tonsil hypoplasia
2. Hypopara-
Thymus thyroidism
Frequent
3. Parathormone infections

';+,+18; .))/,(;(62
Embryonic Lower
4. Parathyroid
developemental cCa2+ cp Aortic
disorder Upper glands i arch
of 3rd and 4th
5. malformation
Ultimobranchial
pharyngeal body (C cells)
pouches Hypo-
Lateral pharynx calcemic seizures
B. Di George syndrome

Autos. recessive, Ionizing

#
heterogenous 1. Oculo-1. radiation
group cutaneous #, ", !, X
1. telangi-
1. ectasia
Impossible
Chromosomal 2. Cerebellar Thymidine to repair
instability 2. ataxia dimer DNA
3. Dys- damage
morphism
Breakages and
translocations
in chromosome 14
(gene loci for Caution during
TCR and Ig)
Clinical triad radiodiagnostics!

C. Ataxia telangiectasia

Xp11.22
1.Frequent infections

2. Eczema
Thrombo-
2. constitution
cytes
3. Thrombo-
3. cytopenic
3. purpura: 1
3. epistaxis;

"
CD43 T cells 3. petechial
(Sialoglyco- 2
3. skin bleeding;
proteins) Bundle formation
3. melena
of actin filaments Impaired
in cytoskeleton function
Clinical triad
D. Wiskott – Aldrich syndrome
ABD

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. #
! #<<0$17*%(-(*$-(*3

!" #$%&$'()* +*,'(- ./&$0)1-2'13(3


!"#$"%&'( )(*%&+ ,-$".'/+0%/)&) 1!234 &) +5$-$+%(-&6(7
80 %5( &"%-$+(''.'$- 9&''&", /# 8$+%(-&$ 80 :&+-/8&+&;
5" =*081-2'* !76*/*$-* >/1'*($ ?*%*-'3
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%(-&$' 8&"7&", $"7 *5$,/+0%/)&)= >5( 7(#(+% &) *-())&/" /# ICS@N %5( !;+5$&" /# %5( $75(-("+(
+$.)(7 80 $ '$+9 /# +0%/+5-/:( !??@ &" %5( *5$,/; ).-#$+( *-/%(&" RTB;SN +/:*'(:("% -(+(*%/- UN
)/:$' :(:8-$"( /# ,-$".'/+0%()= ABCDE &) ."$8'( $"7 %5( IU7, -(+(*%/-= >0*( H &) +5$-$+%(-&6(7 80
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$"7 %-$")#(- %5(: %/ GH :/'(+.'()= I0%/+5-/:( .'/+0%() #-/: -/''&", /" %5( K())(' M$'') $"7 :&;
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%5( ,-$".'/+0%( $+%&K&%0N &:*$&-:("% /# "$%.-$'
9&''(- +('') $"7 $ -(7.+%&/" &" $"%&8/70;7(*("7("%
+(''.'$- +0%/%/<&+&%0 1BCII4 +$" $')/ 8( /8)(-K(7=
>5( :$&" +'&"&+$' :$"&#()%$%&/") /# I5(7&$9PE&,$;
)5& )0"7-/:( $-( *$-%&$' /+.'/+.%$"(/.) $'8&"&):
$))/+&$%(7 M&%5 *5/%/*5/8&$ $"7 K$-&/.) "(.-/;

!
'/,&+$' )0:*%/:)= D$%&("%) M&%5 %5&) 7(#(+% $-(
*$-%&+.'$-'0 ).)+(*%&8'( %/ &"#(+%&/") +$.)(7 80 +$%;
$'$)(;"(,$%&K( 8$+%(-&$= I5/'&"(-,&+ $,("%) $-(
%5(-$*(.%&+$''0 (##(+%&K( 8(+$.)( %5(0 *-/:/%(
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BCD '(K(') /# +3QD=

Burmester, Color Atlas of Immunology © 2003 Thieme


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Glucose-6- P -dehydrogenase
./&$0)1-2'(- ?*%(-(*$-(*3

Hexose monophosphate pathway


!
Glucose-6- P Ribulose-6- P + CO2
Xp21 NADP+ NADPH + H+
NADPH oxidase
e-
g1
22
Defect
Staphylo-
e- coccus,
Cytochrome b558 O2 O2 (radical) Klebsiella,
Serratia

5)($(-&) #<<0$1)1;2
Pronasal Septic abscesses in lung, intestine, bones, liver Abscesses in
pyoderma lymph nodes
A. Infantile septic granulocytosis

Streptococcus, Neurological

"
Pneumococcus, symptoms
H. influenzae

Intracellular Partial
Chemotaxis bactericidal function oculocutaneous
(degranulation) Clinical albinism
B. Chediak – Higashi syndrome outcome

CD18-expression Homo- a Mannose Fucose Endothelium


logies
with WF
Granulocyte
and FB
granulocyte
Trans-
surface
migration Adhesion
CD18 CD11a CD18 CD11b CD18 CD11c
Rolling
! " ! " ! "

Sgp50
L-selectin
LFA-1 CR-3 C3dg-R
Type 1 Type 2 E-selectin LewisX ligand
C. Leukocyte adhesion deficiency

H2O2 + Cl- OCl- + H2O

!
17q21 MPO

defect Bactericidal activity C. albicans


D. Myeloperoxidase deficiency
BCE

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
! F669&*@-.%/%-&/%-5

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022-.# 4,4/#27 < 4#&(.6 /,*# "%4 401.4 %.6 0./+%8%4&-$%+ %.6 #I/+%8%4&-$%+ "#2($,404E /"# &$0.3
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$%/#6 *"(4*"%/06,$0.(40/($ @MJDA7 H#&%,3%&&#$#+%/3 (. /"# 6#1+## () 02*%0+#6 4-+)%&# #I*+#440(. ()
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&#$$ &$(.#4 ;0/" 2#25+%.#35(-.6 *+(/#0. 6#)03

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3-)3/3

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
C1 inhibitor
#*6C7-6-&) ,-.%/%-&/%-5 3&@ ,-.-/)5
!
C1 Plasminogen
XI

C4 C2 Pre-
kallikrein Plasmin
C1qrs
XII
C4b C2b

#7%&%/37 F669&*7*;0
Complement activation Coagulation Kallikrein Fibrinolysis

“Kinin-like” High molecular Bradykinin


C2b-fragment kininogen

"
Local permeability of blood vessels , edema

A. C1 inhibitor deficiency

Protein E.g. DAF


C-terminal z.B. LFA-3 C3 H P
z.B. N-CAM
P z.B. erythr.
Carbohydrate chain

G z.B. AChE
G M C3b

G G M M C4b C2b Bb
C
I
Ba
C3a
GPI-anchor

P
H2C CH CH2 C3b
Phosphatidylinositol

C
O O C3b B
C O C O
C3b B

B. Paroxysmal nocturnal
B. hemoglobinuria (PNH)
C3c C3dg

C. Positive feedback loop dysfunction


!
$GI

Burmester, Color Atlas of Immunology © 2003 Thieme


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! >..&-)0(*2'2(-'2(6

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7" 9(:82'/$2)- 7;'8( 2- $+( 5)6$ 7(88
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',-+"++ ",$(/',&6 6,0 ?6"')&@) )6#2'/6 A 4.' 4#6,)2#&8$ 45$ OP! &, 0'(8*$3)4#6,0$0 FP!< =5$
2',0&4&',) 4564 560 8$$, #6#$ (,4&* 45$,< B&/&*6# !"# D*',> 4$#/&,6* #$"$64)G ', 8'45 $,0) '1 45$
26)$) '1 62C(&#$0 &//(,'0$1&2&$,2+ )+,0#'/$ #$4#'%&#()I 4'>$45$# .&45 45$ $,N+/$ &,4$>#6)$I
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Nucleocapsid
nuclear
Increases
infectiosity
Enables
budding
Viral surface proteins
mediate CD4 binding
5>1 #$%&'$&%( /-0 9(:82'/$2)-
!
proteins and membrane fusion
nef
gag vif vpu env
LTR pol vpr tat LTR
rev
Reverse
Long transcriptase Weak, strong Regulator of
terminal Protease transcription expression of
repeats Ribonuclease activator structural proteins

gp 120
gp 41
Structural proteins
RNA
Enzymes p7-nucleocapsid
Regulatory proteins Lipid membran

782-2'/8 >..&-)8)4;
Other proteins p24-capsid
p17-matrix

A. Structure of the genome and the virion

gp 41 HIV Hemato-
poietic
2. stem cell ?
Change in
gp 120 conformation

"
(V3-loop)

1. Binding Chemokine
1. to CD4 receptor Monocyte
1. molecule CXCR-4
or CCR-5

CD4+ Langerhans Macro-


CD4+ T cell cell phage
T cell
B. Binding to the host cell D. Cells susceptible to HIV

Reverse Viral DNA Production of viral


transcriptase RNA and proteins
transforms RNA
HIV into DNA Integration in
cell genome

Protease
Integrase

Binding
to CD4,
membrane
fusion
Release of
virion contents
into the cell

C. Replication cycle of HIV in the host cell


Production of integral
membrane proteins
(gp 41, gp 120)
RER
Budding of
virus
particles !
?@B

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme


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Acute phase Symptom-free interval ARC
#$%&'( $) *+, +.)(/0-$.

AIDS
!
Helper T cells
Cytotoxic T cells

Anti-HIV antibodies
HIV particles

1 2 3 4 5 6 7 8 9 10 11 12
Months Time (years)
A.Time course of HIV Infection

#:-.-/;: +55%.$:$<7
Infection Immune response
– Sexual intercourse – Anti-HIV antibodies
– Blood products – Acute infection, – Immune cells
– Mother child often unapparent that recognize HIV
– Infected needles – Symptom-free – Cellular cytotoxicity
carrier
– Viral suppression
– Viral mutation – New immune response
– Viral replication – Humoral and cellular
adjustment to new

"
– Virus activated by epitopes
- other infections ?
– Migration into brain ? – Viral suppression

– Loss of immune cells – Insufficient-


- CD4+ T-cells <400/µL immune response
– New mutations
– Increased
viral replication – Viral remains active

ARC
B. Immune response

AIDS

Opportunistic infections Neurological complications HIV-associated tumors


Pneumocystis carinii Acute meningo- Vacuolar Kaposi’s sarcoma
Toxoplasmosis encephalitis myelopathy Malignant lymphomas: NHL
Mycobacteria
Herpes viruses: HSV, CMV, EBV

Chronic
AIDS-

!
Peripheral encephalo-
neuropathy pathy

Pneumocystis carinii infection Kaposi’s sarcoma

C. AIDS
===

Burmester, Color Atlas of Immunology © 2003 Thieme


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Burmester, Color Atlas of Immunology © 2003 Thieme


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Patient Anti-human-Ig
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!
serum + enzyme substrate

Well coated with HIV Substrate is enzymatically


processed Photometric
antigen determination
A. Diagnosis of HIV infection by ELISA

RNA a) Blocking of H3C


H O Nevirapin
catalytic center N

N N N

89$'$/%9 ,446'(9(&:
Produced DNA b) Incorporation HO Azidothymidine
of wrong N3 O H (AZT)
Reverse O
Translation nucleoside, N
transcriptase N O
strand breakage
CH3

c) Blocking of catalytic center because of


similarity with cleavage site H
H O

Viral proteins
1. Antiviral drugs
Protease
Saquinavir

Binding to MHC I molecules


N
O
N

O
NH2
N
H OH O
N

MHC I–peptide
complex
N
H
H

"
RER
Cellular
Immune response
Endogenous
processing Humoral
Translation
Plasmid

2. Pure DNA as vaccine Free proteins

Antigen, HIV-provirus Signal transduction


mitogen
IL-16 ?

Infected CD4+ T cell Virus production


TCR

Activated
CD8+ T cell

3. Interleukins
B. Treatment strategies
MIP-1!/",
RANTES
Chemokine
receptor

CD4
Non-
infected
!
;;=

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme


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Blood group A: ~ 42% Blood group B: ~ 14% Blood group AB: ~ 6%
!#$ #-++. ?@+<0 %&'()*

Blood group O: ~ 38%


!
Antibodies Antibodies No Antibodies
against B against A antibodies against
against A A and B
or B

A antigen B antigen A antigen No A


or B
B antigen antigens

A. The ABO blood group system

Deletion of
Bacteria, Rich in A, B clones producing
antigens antibodies against
pollen own erythrocyte

8-121:6- ;**<2+-+3&
IgM-antibodies antigens
Newborn
against A, B, AB
B. Development of A and B antibodies

Ceramide Glu Gal GlcNAc Gal


Precursor substance (paragloboside)
Erythrocyte GPD-
L-fucosyltransferase

"
fucose
(H-gene active in 99.9% of population)

Chromosome 9 Fuc

Ceramide Glu Gal GlcNAc Gal

H-antigen
B
A
0
O gene Active A gene Active B gene Both A and B
(silent allele) (galactosaminyl- (galactosyl- genes active
transferase) transferase)

Unmodified N-Acetyl- Galactose A antigen + B antigen


H antigen galactosamine
A antigen

B antigen

Blood group O Blood group A


C. Development of the ABO antigens
Blood group B Blood group AB !
==A

Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license. "
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Burmester, Color Atlas of Immunology © 2003 Thieme


All rights reserved. Usage subject to terms and conditions of license.
Chromo-
#$%&'& 207 5*$%6 ,-..7 ?6.'; ()&*%+&

Most common Fre- Pheno- Immuno-


!
some 1
genotypes quency type genicity
Locus 1 Locus 2 +++
DCe/DCe 18% D
2 possible 4 possible
alleles: alleles: DCe/dce 35%
c
D or Ce, cE, DCe/DcE 13%
d (inactive) CE, ce Rh+
DcE/dce 12% E
cE
CE Ce
DcE/DcE 2% C
ce D
Dce/dce 2%
e
dce/dce 15% Rh- (+)

A.