LecLure L03

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l. 8aslc Conslderauons
A. ublqulLy
8. AnaLomlc 8arrlers
ll. lnammauon
A. lever
8. Local 8esponse
C. Slgnals and 8ecepLors
lll. lnnaLe 1argeung of
aLhogens
A. 8evlewlng Lhe 8ud
Cuys
8. AMs
C. CaLegorles of 88s
lv. Cell 1ypes and
luncuons
A. hagocyLosls
8. Cells
v. Summary

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#2#:;A%
2%3%"1%1 4B
#"2 C 9%>>1<
planLs yes no no no
sponges yes yes yes no
arLhropods yes yes yes no
sh yes yes yes yes
repules yes yes yes yes
blrds yes yes yes yes
mammals yes yes yes yes
1able 1: D(''#/* .3 E)1$/)F(;." .3 !''("% 6%1:."1%1
l. 8aslc Conslderauons
An lnnaLe defense ls one LhaL you can produce prlor Lo exposure by a speclc paLhogen.

A. ublqulLy
1. lnsecLs have amoebold cells paLrolllng Lhelr body
cavlues and can make anu-bacLerlal or anu-fungal
pepudes when challenged by speclc paLhogens. (0++
78#&+ 9:
2. lanLs have an even wlder array of paLhogen sensors
Lhan do mammals. (0++ 78#&+ ;:
3. SLem chordaLes, llke Lhe sea squlrLs (LunlcaLes) and
Amphloxus (lanceleLs), have lnnaLe, buL noL adapuve,
defenses. (0++ 78#&+ < => :
G)0(/% HI !"1%9$ G)0(/% -I 5>#"$
G)0(/% JI K#"9%>%$ G)0(/% LI C(")9#$%
8. AnaLomlc 8arrlers

1. Skln. (Leruary lmmune organ)- lew paLhogens
can peneLraLe lnLacL skln, relylng lnsLead on
blLes and abraslons ?0++ 78#&+ @:

a. Lpldermls - Lhln layer of dead cells (keraun) over a Lhlnner
layer of llve regenerauve cells over a basemenL membrane.
b. uermls - deeper Lhlcker layer wlLh blood supply, connecuve
ussue and mesenchymal ussue lmporLanL ln developmenLal
slgnallng.


G)0(/% MI D,)"
2. Mucosa- more vulnerable, Lyplcally slngle layer
of eplLhellal cells over basemenL membrane over
connecuve ussue. ?0++ 78#&+ A:

a. Secreuons: Lears, mucus, lysozyme.
b. Cllla (lungs and reproducuve organs) sweep ouL paLhogens
and debrls Lrapped ln mucus

3. Addluonal Cl defenses: ?0++ 78#&+ B:
a. sLomach acld (vulLures)
b. Lnzymes
c. compeung ora (good bacLerla)

G)0(/% NI O:)$=%>)# G)0(/% PI Q(>$(/%
ll. lnammauon
A. lever
1. PypoLhalamus conLrols Lhe body's LemperaLure seL
polnL.
2. lever provldes overL slgn of lmmune up-regulauon.
3. Plgher body LemperaLure assoclaLed wlLh beuer
survlval raLe, even ln repules.
4. lever lnducuon used wlLh mlxed success Lo LreaL
cancer aL Lhe Lurn of Lhe 20
Lh
cenLury (Coley Loxlns).
8. Local 8esponse: calls ln phagocyuc cells Lo
Lhe slLe of lnfecuon or ln[ury.
1. 8ecognlzed ln 8oman umes (heaL, swelllng, paln,
reddenlng and loss of funcuon). lever provldes overL
slgn of lmmune up-regulauon. (0++ 78#&+0 C = D:
2. SympLoms produced by vascular changes - caplllarles
become more permeable so LhaL plasma (edema) and
cells (exLravasauon) enLer lnfecLed ussue.

3. LeukocyLe exLravasauon ls regulaLed by Lhe changes
ln surface CAM molecules.
G)0(/% RI G)"0%/ G)0(/% SI !"T#''#;."
C. Slgnals and 8ecepLors:
1. WhlLe cells and damaged ussues release chemoklnes, a
Lype of cyLoklne, also generally up-regulaLe lnammauon,
auracung cells Lo Lhe slLe of Lhe lnfecuon. ?0++ 78#&+ 9E:
2. Acuvauon of cells by pauern recepLors also acuvaLes
lnammaLory slgnals.
3. neuLrophlls respond by changlng Lhe conformauon of Lhelr
lnLegrlns, whlch makes Lhem suck Lo Lhe blood vessels
near Lhe problem. ?0++ 78#&+ 99:
a. 8olllng
b. Acuvauon
c. ArresL
d. 1ransendoLhellal mlgrauon
G)0(/% HUI 6.>>)"0 K#F%>%2
G)0(/% HHI V%($/.:=)>
C. Slgnals and 8ecepLors:
4. 1he cyLoklnes produced may also regulaLe Lhe
response so LhaL lL ls mosL eecuve for Lhe parucular
Lype of paLhogen LhaL lnluaLed lL.
3. AcuvaLed macrophages and dendrluc cells Lhen Lravel
Lo Lhe 1
P
cells and presenL anugen, speclcally
acuvaung Lhe adapuve response.

6. 1he 1
P
cells Lhen coordlnaLe an adapuve auack on Lhe
lnfecuons.
lll. lnnaLe 1argeung of aLhogens
A. 8evlew of Lhe 8ad Cuys
(gures 12, 13, 14, 13, 16 & 17)
(Lable 2)

G)0(/% H-I G>( G)0(/% HJI B#9$ D$/(9$(/%1
G)0(/% HLI W#"2)2# G)0(/% HMI X)#/2)#
G)0(/% HNI C/*:#".1.'% G)0(/% HPI C#:%Y./'
5#$=.0%" OZ#':>%1 G#9$.)21 5#8%/" /%9.0");." #>%/$%2 F*I
vlruses

u, small pox, Plv,
pollo, Lbola, rhlnovlrus,
hepauus, measles
Can only reproduce lnslde
cells
lorelgn nuclelc aclds (double
sLranded 8nA, slngle sLranded unA,
forelgn meLhylauon pauerns),
reduced anugen presenLauon by
lnfecLed cells
8acLerla SLrep, sLaph, 18,
anLhrax, leprosy,
bubonlc plague,
perLussls, dlphLherla
8eproduce lnLracellularly
or exLracellularly,
dependlng on Lype

CharacLerlsuc surface
carbohydraLes (pepudoglycan,
mannose repeaLs), agellar proLelns
(agellln), llplds (llpoLecholc acld)
characLerlsuc unA meLhylauon
pauerns
lungl Candlda (Lhrush)
aLhleLe's fooL,
F&'152G2GG#0, rlngworm

Lukaryouc, unlcellular,
mulucellular or
mulunucleaLe
Cell wall: zymosan ( ! 1-3 glucan)
and
chlun (cellulose wlLh n-aceLyl
glucosamlne lnsLead of [usL glucose)
roLozoa

malarla, Chagas,
sleeplng slckness,
ameblc dysenLery,
lelshmanlasls
unlcellular eukaryoLes CharacLerlsuc cell surface proLelns
(prolln) and llplds (glycosylaLed
phosphaudyl lnoslLols - Cl)
Worms
(helmlnLh
paraslLes)
pln worms, hook
worms, hearLworms,
schlsLosomlasls, ukes,
Lapeworms
rlmarlly members of
laLyhelmlnLhes
(aLworms) and
nemaLoda (roundworms)
CharacLerlsuc cell surface proLelns
1able 2: 6%A)%Y .3 B#2 X(*1
8. AMs (aLhogen AssoclaLed Molecular
auerns) 8ecognlzed by 88s - pauern
recognluon recepLors.
1. proLelns - So far, we have ldenued very few proLelns
LhaL we recognlze lnnaLely by Lhelr overall sLrucLure.
1he ones we've found are:
a. llagellln (gure) - bacLerla ?0++ 78#&+ 9C:
b. prolln - surface proLeln of proLozoan (Loxoplasmosls)

2. carbohydraLes and glycopepudes
a. zymosan - componenL of fungal cell walls - a vague
Lerm because lL has noL been exacLly characLerlzed.

b. pepudoglycan - Lhe cell wall componenL of boLh gram
posluve and gram negauve bacLerla, alLhough gram
posluve have a much Lhlcker wall. ?0++ 78#&+ 9D:
G)0(/% HRI G>#0%>># G)0(/% HSI 5%:;2.0>*9#"
3. llplds, especlally auach Lo slgnaLure carbohydraLes or
pepudes. ?0++ 78#&+ ;E:
4. nuclelc aclds
a. unA wlLh speclc meLhylauon pauerns - recall
resLrlcuon endonucleases.
b. wrong sLrandedness" - slngle sLranded unA and
double sLranded 8nA are usually slgns of a poLenual
LhreaL.
c. Mlce can speclcally recognlze Lhe 23s componenL of
bacLerlal rlbosomes.
G)0(/% -UI K):)21
C. CaLegorles of 88s: Speclc recepLors blnd Lo
characLerlsuc paLhogen molecules.
1. LxLracellular
a. Lysozyme (mucus and Lears) - agalnsL pepudoglycans
?0++ 78#&+ ;9:
b. sorlacln (skln) - agalnsL HI G2*4I Can be lnduced by
sunllghL (uv8) vla vlLamln u.
c. AMS - defenslve pepudes LhaL LhaL Lyplcally klll by
dlsrupung bacLerlal membranes.
d. Mannose-blndlng lecun (plasma) - acuvaLes
complemenL.
e. C-reacuve proLeln (C8) (plasma) also recognlzes
mlcrobes and damaged self-cells. ?0++ 78#&+ ;;:
f. Llpopolysaccharlde blndlng proLeln (L8) speclcally
recognlzes gram negauve bacLerla.
G)0(/% -HI K*1.[*'% G)0(/% --I W65
2. CyLoplasmlc
3. Membrane 8ound- Lhe 1oll-llke recepLors
(1L8s) ?0++ 78#&+ ;<:
a. Work slngly or ln palrs. Slngles exLend onLo Lhe
endoplasmlc reuculum lumen, palrs from Lhe plasma
membrane.
b. 8lndlng of a molecule characLerlsuc of a paLhogen on
Lhe ouLslde of Lhe membrane Lrlggers a slgnal on Lhe
opposlLe slde.
c. 1he lnLernal slgnal acuvaLes nl-"8, Lhe ma[or lnLernal
lnammauon regulaLor.
d. nl-"8 Lurns on Lhe producuon of cyLoklnes, alerung a
varleLy of oLher lmmune cells.
e. ldenufy Lhe caLegory of paLhogen and seL of
lnammaLory and adapuve response
G)0(/% -JI CK6 K.9#;."
CK6 /%9.0")[%1 :#$=.0%" '%'F/#"%
1 1rlacyl llpopepudes mycobacLerla plasma
1 & 2 epudoglycan componenL and LrlacylaLed
llpopepudes
llpoLecholc acld
zymosan (!-glucan cell wall componenL)
mucln
Cram+ bacLerla

mycobacLerla
yeasLs and fungl
Lrypanosomes
plasma
2 & 6 llpopepudes Cram+ bacLerla and
mycoplasma
plasma
4 & 4 llpopolysaccharlde (exLerlor membrane)
l-proLeln
8acLerla, nl
8Sv vlrus
plasma
3 (&3?) llagellln llagellaLed bacLerla plasma
6 ulacyl llpopepudes
zymosan
MycobacLerla
?easLs and fungl
plasma
10 (non-funcuonal ln
mlce)
unknown allergens plasma
11 (mlce only) rolln Lukaryouc paraslLes
(also recognlzes bacLerla)
plasma
12 (mlce only)

prolln Lukaryouc paraslLes
(especlally
Lrypanosomes)
plasma
13 mlce only bacLerlal 23s8nA prokaryoLes endomembrane
3 uouble-sLranded 8nA vlruses endomembrane
7 Slngle-sLranded vlral 8nA vlruses (Plv) endomembrane
8 Slngle-sLranded vlral 8nA vlruses endomembrane
9 unA wlLh unmeLhylaLed CpC slgnaLures vlrus and bacLerla endomembrane
1able 3: CK6
?G2.6.#+J:
3. Membrane 8ound- Lhe 1oll-llke recepLors (1L8s)
f. Mechanlsm for endomembrane 1L8s
g. negauve regulauon- you have Lo be able Lo Lurn Lhese
o or you geL excess lnammauon and maybe and
auLolmmune dlsease.
h. lnLeracL wlLh: Mu2 aL surface for blndlng LS (and also
cerLaln vlral and cancer proLelns), Myu88 Lo lnluaLe
lnLernal slgnal sequence.
lv. Cell 1ypes and luncuons
A. hagocyLosls- Macrophages and neuLrophlls -
capLure paLhogens and klll Lhem wlLh a complex
Loxlc brew (0++ 78#&+0 ;>K ;@ = ;A:
1. CapLure paLhogen ln phagosome, promoLed by AM,
complemenL or anubody on surface of paLhogen. -
acuvaLes membrane pump whlch

2. 1rlggers resplraLory bursL (C
2
upLake) by nAuP
phagosome oxldase (phox enzymes) complex. 1hls ls noL
mlLochondrlal resplrauon, buL raLher Lhe dlrecL upLake of
oxygen by enzymes LhaL use lL Lo creaLe Loxlc reacuve
oxygen specles (8CS). ?0++ 78#&+0 ;B = ;C:
a. superoxlde radlcals (C
2
._
)
b. hydrogen peroxlde (P
2
C
2
)
c. PCCL (hypochlorous acld or bleach)
G)0(/% -LI \#9/.:=#0% G)0(/% -MI V%($/.:=)> ]"$=/#Z
G)0(/% -NI 5=#0.9*$.1)1
G)0(/% -PI V]E5^ G)0(/% -RI 5=.Z W.':>%Z
3. Superoxlde radlcals also generaLe reacuve nlLrogen
specles (8nS) lncludlng nC, also Loxlc ?0++ 78#&+ ;D:
4. Cxldauon ls coupled Lo k
+
LransporL, renderlng Lhe
lnLerlor hyperLonlc. k
+
enLers Lo compensaLe for Lhe
negauve charges, resulung ln a rlse ln pP (8.3). Cnce
Lhe pP reaches Lhls, furLher neuLrallzauon ls done by
Lransporung P
+
.
3. Change ln k
+
and LonlclLy dlspersed proLeln granules.
1hese release
a. Pydrolyuc enzymes
b. epudes LhaL poke holes ln Lhe bacLerlal plasma
membrane (8l or defensln) ?0++ 78#&+ <E:
6. MlcrolamenLs package Lhe exLerlor of Lhe vacuole,
prevenung swelllng and malnLalnlng Lhe
concenLrauon of Loxlc compounds lnslde.

G)0(/% -SI 6VD 6_D G)0(/% JUI E%3%"1)"
8. Cells
1. neuLrophlls - Lhe lnfanLry ln Lhe modern sense, and
Lhe rsL on-slLe defenders.

2. Macrophages - Lhe cavalry of Lhe ouulL. hagocyLosls
causes Lhem Lo secreLe lL-1, lL-6 and 1nlo, all
lnammauon acuvaLors.

3. uendrluc cells - Lhe scouLs and paLrols. MosL
lmporLanL lnlual Lrlgger of Lhe adapuve response.
1hey phagocyuze prlmarlly ln order Lo sample
paLhogens and acuvaLe lnammauon on Lhe adapuve
response. ?0++ 78#&+ <9:
4. nk Cells - funcuon by pauern recognluon maklng
Lhem parL of lnnaLe defenses. rlnclpally auack
rogue-self by lnduclng apopLosls.
G)0(/% JHI E%"2/);9 W%>>
v. Summary
W=#/#9$%/)1;9 !""#$% ]2#:;A%
speed response wlLhln mlnuLes rsL response: 2 weeks
second response: 3 days
recognlzes molecules characLerlsuc of
non-self
mosL proLelns, many
carbohydraLes and a few llplds
dlverslLy hundreds of Lypes, soluble and
membrane bound
vAS1 number of Lypes, soluble
and membrane bound
gene rearrangemenL needed no yes
may auack self no yes
memory no yes, prlor exposure speeds
response.
Cells myelold cells, especlally
phagocyLes, nk cells
(lymphocyLes)
8 cells, 1 cells (lnsLrucLed by
myelold anugen-presenung
cells)
found ln all llvlng organlsms (ln varlous
forms)
verLebraLes only
1able 4: !""#$% #"2 ]2#:;A% !''(")$* W.':#/%2