Ch 19: Inflammation & the Immune

Response
I. Introduction
protection from harmful microorganisms and cells
recovery after injury/ tissue damage
critical to maintaining health/ preventing disease
immunocompetent: when all different parts of in‡ammation &
immunity are working well
function of immunity reduced by disease, injury, medical therapy
temporary or permanent reduction
endangers person÷s health
loss of protection r/ t poor function of any or all parts of
in‡ammation & immunity
overfunctions/ inappropriate time functioning
II. Over view
composed of cell functions that protect people against invasion or
effects of injury
defenses to prevent organisms from getting into internal
environment
intact skin
mucous membranes
skin surface ‡ora
natural chemicals (inhibit bacterial growth)
invasions occur often, more often than disease (due to proper
immune function)
Purpose of Inflammation & Immunity
meet human need for protection by neutralizing, eliminating, &
destroying organisms that invade the internal environment
meet protection needs without harming the body by only
 attacking non-self proteins & cells
Self vs. Non-Self
non-self proteins & cells include infected body cells, cancer cells &
all invading cells & organisms
self-tolerance: the ability to recognize self vs non self
immune system cells are only cell capable of this
p o s s ib le b e c a u s e o f p ro t e in o n c e ll m e m b ra n e s
each cell is surrounded by a plasma membrane
proteins protrude through the membrane
the AA sequence of each protein differs from all others
proteins are unique to the person
o n ly s h a re d w it h id e n t ic a l t w in
s e rv e a s UPC o r ”c e llu la r fln g e rp rin t ‘
re c o g n iz e d a s fo re ig n o r n o n -s e lf t o a n o t h e r p e rs o n ÷s
im m u n e s y s t e m
t h e r e f o r e t h e y a r e a n t ig e n s ( p r o t e in s c a p a b le o f
s t im u la t in g a n im m u n e r e s p o n s e )
human leukocyte antigens (HLAs): the unique UPC for each person
also present on the surface of nearly all body cells (not just
leukocytes)
d e t e rm in e t is s u e t y p e s o f a p e rs o n
they are antigens only if they enter another person÷s body
40 major HLAs, unknown # of minor HLAs
m a jo r HLAs d e t e rm in e d b y s e t o f g e n e s c a lle d t h e m ajo r
h is t o c o m p at ab ilit y c o m p le x ( s p e c iflc a n t ig e n s d e t e rm in e d b y
g e n e t ic s )
key for recognition & self confldence
at each encounter immune system cells compare the surface
protein HLAs to determine if cell is self or non-self
s e lf = n o t a t t a c ke d
n o n s e lf = n e u t ra liz e , d e s t ro y , e lim in a t e fo re ig n in v a d e r
immune function changes during life according to:
nutritional status
environmental condition
drugs
disease
age (most efflcient in 20÷s & 30÷s then declines, older adults
not in any one organ/ body area
in‡uenced by many body systems, especially:
n e rv o u s
e n d o c rin e
GI
most immune system cells come from bone marrow
some mature in bone marrow
others leave bone marrow in mature elsewhere
when mature they are released into the blood where they
circulate & have speciflc effects
bone marrow is a source of all blood cells (even immune cells)
produces stem cells (immature, undifferentiated cells)
p lu rip o t e n t : e a c h c e ll h a s m o re t h a n o n e p o s s ib le o u t c o m e
w h e n 1 s t c re a t e d it is u n d if f e re n t iat e d ( n o t y e t c o m m it t e d
t o m a t u rin g in t o a s p e c iflc b lo o d c e ll t y p e ) t h e re fo re it is
‡ e xib le ( c o u ld b e c o m e a n y o n e o f m a n y m a t u re b lo o d c e lls o r
p lu rip o t e n t )
t y p e o f m a t u r e s t e m c e ll it b e c o m e s d e p e n d s o n t h e
p a t h w a y it f o llo w s
m a t u r a t io n a l p a t h w a y d e p e n d s o n :
b o d y n e e d s a t t im e
p r e s e n c e o f s p e c ifl c c h e m ic a ls ( g r o w t h f a c t o r s )
WBCs/ leukocytes protect the body from invasion effects
aka immune system cells
provide protection through defensive actions
re c o g n it io n o f s e lf v s . n o n -s e lf
d e s t ru c t io n o f fo re ig n in v a d e rs , c e llu la r d e b ris & u n h e a lt h y o r
a b n o rm a l s e lf c e lls
p ro d u c t io n o f a n t ib o d ie s d ire c t e d a g a in s t in v a d e rs
c o m p le m e n t a c t iv a t io n
p ro d u c t io n o f c y t o kin e s t h a t s t im u la t e in c re a s e d fo rm a t io n
o f le u ko c y t e s in b o n e m a rro w & in c re a s e s p e c iflc le u ko c y t e
a c t iv it y
3 processes needed for human protection through immunity
1. in‡ammation
2. antibody mediated immunity (AMI) ”humoral immunity‘
3. cell mediated immunity (CMI) ”cellular immunity‘
each process uses different defensive actions but also requires
assistance from the other two
full immunity (immunocompetence) requires the function and
III. Inflammation “natural immunity”
immediate protection against effects of tissue injury & invading
foreign proteins
in‡ammatory response critical to health & well-being
differs from immunity (AMI & CMI) in 2 ways
immediate but short term, no ”true immunity‘ on repeated
exposure
non-speciflc defense to invasion or injury & can be started
quickly by almost anything regardless of where it occurs & what
causes it
how widespread in‡ammation is depends on:
1. intensity of exposure
2. severity of exposure
3. duration of exposure
Purpose
start tissue actions that cause visible & uncomfortable symptoms
rid body of organisms
in‡ammation in excess = tissue damage
start AMI & CMI actions to activate full immune response
Infection
in‡ammation occurs in response to tissue injury or invasion by
microorganisms
in‡ammation does not mean that an infection is present!
infection is usually accompanied by in‡ammation
in‡ammation can occur without infection
s p ra in s , MI, s u rg ic a l in c is io n s , b lis t e rs , t h ro m b o p h le b it is
in‡ammation with invasion of noninfectious foreign objects
a lle rg ic rh in it is , c o n t a c t d e rm a t it is , o t h e r a lle rg ic re a c t io n s
in‡ammation with infection
o t it is m e d ia , a p p e n d ic it is , p e rit o n it is , v ira l h e p a t it is e t c .
Cell types involved in inflammation
Neutrophils - use phagocytosis to destroy & eliminate invaders
Description & Origin
5 5 -7 0 % o f t o t a l n o rm a l WBC
c o m e fro m s t e m c e lls , m a t u re in b o n e m a rro w
 a ka ”g ra n u lo c y t e s ‘ , ”s e g s ‘ , ”s e g m e n t e d n e u t ro p h ils ‘ , o r
”p o ly m o rp h o n u c le a r c e lls ‘ , ”p o ly s ‘ , & le s s m a t u re n e u t ro p h ils
a re kn o w n a s ”b a n d s ‘
1 2 -1 4 d a y s t o m a t u re n o rm a lly
s h o r t e n e d b y c o n d it io n s t h a t t r ig g e r g r o w t h f a c t o r
p r o d u c t io n ( c y t o k in e s )
i. e . g r a n u lo c y t e - m a c r o p h a g e c o lo n y s t im u la t in g f a c t o r
( GM-C S F)
1 0 0 b illio n n e w , m a t u re n e u t ro p h ils re le a s e d fro m b o n e
m a rro w t o c irc u la t io n d a ily
lif e s p a n = 1 2 - 1 8 h o u r s
Function
la rg e s t g ro u p o f c irc u la t in g le u ko c y t e s b u t e a c h c e ll is s m a ll
p ro t e c t io n a ft e r in v a d e rs e n t e r b o d y
d e s t ro y b y p h a g o c y t o s is o r e n z y m a t ic d ig e s t io n
s m a ll e n e rg y s u p p ly ( c a n t re p le n is h ) & n o w a y t o re p le n is h
e n z y m e s u s e d in p h a g o c y t o s is
1 e p is o d e o f p h a g o c y t o s is p e r n e u t r o p h il
m a t u re n e u t ro p h ils a re t h e o n ly o n e s t h a t c a n p e rfo rm
p h a g o c y t o s is
% & # o f a c t u a l m a t u r e c ir c u la t in g n e u t r o p h ils = A N C
( a b s o lu t e n e u t r o p h il c o u n t ) / a b s o lu t e o r t o t a l g r a n u lo c y t e
count
in c r e a s e d A N C = g r e a t e r r is k f o r in f e c t io n
WBC d iffe re n t ia l s h o w s t h e # & % o f d iffe re n t t y p e s o f
c irc u la t in g le u ko c y t e s
m o s t a r e s e g s , s m a ll p e r c e n t a r e b a n d s
b a n d s s h o u ld n o t b e in b lo o d
c a u s e s s e p s is
s e g s c h a n g e t o b a n d s ( ” le f t s h if t ‘ / b a n d e m ia )
p a t ie n t ÷s b o n e m a r r o w c a n n o t m a k e e n o u g h
m a t u r e n e u t r o p h ils t o k e e p p a c e w it h c o n t in u in g
in f e c t io n a n d is r e le a s in g im m a t u r e n e u t r o p h ils in t o
t h e b lo o d
Macrophages - use phagocytosis to destroy & eliminate invaders
Description & Origin
o rig in a t e in m y e lo id s t e m c e lls in b o n e m a rro w
fo rm t h e m o n o n u c le a r p h a g o c y t e s y s t e m
s t e m c e lls t u rn t o m o n o c y t e s 1 s t ( re le a s e d in t o b lo o d )
lim it e d a c t iv it y - m o v e f r o m b lo o d in t o t is s u e s & m a t u r e t o
m a c ro p h a g e s
” fl x e d ‘ w it h in t is s u e s o r m o v e b e t w e e n / w it h in t is s u e s
in d if f e r e n t t is s u e s t h e y ÷r e c a lle d d if f e r e n t t h in g s
in la r g e # s in liv e r , s p le e n & in t e s t in a l t r a c t
Function
im p o rt a n t in im m e d ia t e in ‡ a m m a t o ry re s p o n s e s , a n d
s t im u la t e AMI/ CMI im m u n it y
 Description & Origin
o rig in a t e in m y e lo id s t e m c e lls
1 % WBC c o u n t
c a u s e m a n ife s t a t io n s o f in ‡ a m m a t io n
Function
h a v e g ra n u le s w it h m a n y c h e m ic a ls ( v a s o a c t iv e a m in e s ) t h a t
a c t o n b lo o d v e s s e ls
h e p a r in , h is t a m in e , s e r o t o n in , k in in , le u k o c t r ie n e s
a c t o n s m o o t h m u s c le & b lo o d v e s s e l w a lls
h e p a r in : in h ib it s b lo o d & p r o t e in c lo t t in g
h is t a m in e : c o n s t r ic t s s m a ll v e in s & r e s p ir a t o r y s m o o t h
m u s c le
n a r r o w s a ir w a y & r e s t r ic t s b r e a t h in g
in h ib it s b lo o d ‡ o w ( v e in c o n s t r ic t io n )
d e c re a s e d v e n o u s re t u rn
b lo o d c o lle c t s in c a p illa r ie s / a r t e r io le s a n d in c r e a s e d
c a p illa r y p e r m e a b ilit y & t h is c a n le a d t o v a s c u la r
le a k s y n d r o m e ( w h e r e b lo o d le a k s in t o in t e r s t it ia l
space)
Eosinophils - release chemicals that act on blood vessels to cause
tissue-level responses
Description & Origin
m y e lo id o rig in
m a n y v a s o a c t iv e c h e m ic a ls
1 -2 % WBC c o u n t
Function
a c t a g a in s t in fe c t io n s o f p a ra s it ic la rv a e
g ra n u le s c o n t a in m a n y d iffe re n t s u b s t a n c e s
s o m e in d u c e in ‡ a m m a t io n
e n z y m e s re le a s e d b y e o s in o p h ils d e g ra d e t h e v a s o a c t iv e
c h e m ic a ls re le a s e d b y o t h e r le u ko c y t e s & c a n lim it t h e
in ‡ a m m a t o ry re a c t io n s
e o s in o p h ils in c r e a s e d u r in g a lle r g ic r e s p o n s e
Phagocytosis
engulflng/ destructing of invaders
also rids the body of debris after tissue injury
most efflcient: neutrophils & macrophages
1. exposure & invasion: must be exposed to organism in blood
& ECF (foreign protein, debris, damage tissue), phagocytosis
is triggered
2. attraction: second step, substances attract neutrophils and
macrophages (chemotaxins) which are create/ secreted by
damaged tissues & blood vessels
 coating cell (antigen or organism) - many cells can act as
opsonins (particles from dead neutrophils, antibodies,
activated/ flxated complement components)
3. recognition: phagocytic cell sticks to surface of target cell
and recognizes it as non-self
m a d e e a s ie r b y o p s o n in s
n o n s e lf = p h a g o c y t o s is b e g in s
4. cellular ingestion: target cell brought inside the phagocytic
cell by phagocytosis (engulfment) by bending membrane
around target cell and form a vacuole
5. phagosome formation: occurs when granules are inside
vacuole (break & release enzymes that attack the ingested
target)
6. degradation: flnal step, enzymes digest engulfed target,
broken to smaller pieces, only small particle of debris remain
Sequence of Inflammatory Response
3 stages regardless of trigger, timing of stages may overlap
responses @ tissue level cause 5 cardinal manifestations of
in‡ammation
1. warmth
2. redness
3. swelling
4. pain
5. decreased function
Stage 1: vascular
changes in blood vessels
injured tissues and leukocytes secrete histamine, serotonin,
kinins
c o n s t ric t s m a ll v e in s , d ila t e a rt e rio le s
r e d n e s s & w a r m t h o f t is s u e s ( in c r e a s e d b lo o d ‡ o w o r
h y p e r e m ia , in c r e a s e d d e liv e r y o f n u t r ie n t s ) c a u s e s e d e m a
( p r o t e c t s & d ilu t e s ) , le a d s t o c a p illa r y le a k s y n d r o m e
( b lo o d p la s m a m o v e s in t o t is s u e s a n d is a c c o m p a n ie d b y
s w e llin g & p a in [ o c c u r s in 2 4 t o 7 2 h o u r s ]
macrophage is major cell
ra p id a c t io n ( a lre a d y in p la c e a t s it e o f in ju ry o r in v a s io n )
lim it e d b e c a u s e n u m b e r o f m a c ro p h a g e s is s m a ll
t o e n h a n c e in ‡ a m m a t o r y r e s p o n s e t h e o t h e r t is s u e
 p r o d u c e W B C s ( u s u a lly 1 4 d a y s t o h o u r s )
s o m e c y t o k in e s in c r e a s e r e le a s e o f n e u t r o p h ils f r o m t h e
b o n e m a r r o w a n d a t t r a c t t h e m t o t h e s it e o f in ju r y o r
in v a s io n w h ic h le a d s t o t h e n e x t s t a g e o f in ‡ a m m a t io n
Stage 2: cellular exudate
neutrophilia (an increased # of circulating neutrophils occurs)
e xu d a t e / p u s fo rm s
c o n t a in s d e a d W B C s , n e c r o t ic t is s u e a n d ‡ u id s t h a t c a n
e s c a p e f r o m d a m a g e d c e lls
neutrophil is main cell
u n d e r in ‡ u e n c e o f c y t o kin e s t h e n e u t ro p h il c o u n t c a n
in c re a s e u p t o flv e t im e s w it h in t w e lv e h o u rs o f o n s e t o f
in ‡ a m m a t io n
n e u t r o p h ils a t t a c k a n d d e s t r o y o r g a n is m s a n d r e m o v e
d e a d t is s u e t h r o u g h p h a g o c y t o s is
acute in‡ammation - healthy person produces enough mature
neutrophils to keep pace with invasion and prevent the
organism from growing
b e g in s s lo w ly b u t is lo n g -la s t in g
WBCs a n d in ‡ a m e d t is s u e s e c re t e c y t o kin e s
c y t o k in e s a llo w t is s u e m a c r o p h a g e s t o in c r e a s e a n d
t r ig g e r b o n e m a r r o w p r o d u c t io n o f m o n o c y t e s
arachidonic acid (AA) cascade increases in‡ammatory response
c o n v e rs io n o f fa t t y a c id s in p la s m a m e m b ra n e s in t o AA
e n z y m e s ( c y c lo o x y g e n a s e ) c o n v e r t A A in t o c h e m ic a ls
c h e m ic a ls f u r t h e r p r o c e s s e d in t o s u b s t a n c e s t h a t c o n t in u e
in ‡ a m m a t o r y r e s p o n s e in t h e t is s u e s ( h is t a m in e s ,
le u k o t r ie n e s , p r o s t a g la n d in s , s e r o t o n in , k in in s )
a n t i-in ‡ a m m a t o ry d ru g s c a n s t o p t h is c a s c a d e b y p re v e n t in g
a n e n z y m e fro m c o n v e rt in g AA in t o c h e m ic a ls m e n t io n e d
when an infection stimulating in‡ammation lasts longer than a
few days, bone marrow cannot produce and release enough
mature neutrophils (decreased number of circulating mature
neutrophils)
b o n e m a rro w re le a s e s im m a t u re n e u t ro p h ils
lim it s h e lp f u l e f f e c t s o f in ‡ a m m a t io n
in c r e a s e d r is k o f s e p s is
Stage 3: tissue repair & replacement
last completed stage but begins at the time of injury
critical
s o m e WBCs in d u c e h e a lt h y c e lls t o d iv id e
t rig g e rs n e w b lo o d v e s s e l g ro w t h ( a n g io g e n e s is ) a n d s c a r
t is s u e fo rm a t io n
s c a r t is s u e d o e s n o t b e h a v e lik e n o r m a l t is s u e
 im m u n it y
lo n g la s t in g im m u n e a c t io n s d e v e lo p t h r o u g h A M I & C M I

IV. Antibody-Mediated Immunity (AMI)

“humoral immunity”
antigen-antibody interactions neutralize, eliminate &destroy foreign
proteins
Purpose
main purposes of B cells are to become sensitized to a speciflc
foreign protein (antigen) and to produce antibodies directed
speciflcally against that protein
the antibody (not the actual T-cell) causes one of several
actions to neutralize, eliminate & destroy
B cells have the most direct role in AMI
macrophages & T-lymphocytes work with B cells to start and
complete antigen-antibody interactions
optimal AMI - entire immune system must function adequately
originate in bone marrow (primary lymphoid tissue) then
commit to lymphocyte pathway and are then restricted in
development
re le a s e d in t o b lo o d
m ig ra t e in t o s e c o n d a ry ly m p h t is s u e s ( m a t u ra t io n is
c o m p le t e ) - s p le e n , p a rt s o f ly m p h n o d e s , t o n s ils , in t e s t in a l
m ucosa
Antigen-Antibody Interactions
body learns to make enough of any speciflc antibody to provide
long lasting immunity and protection
7 steps to produce a speciflc antibody directed at a speciflc
antigen (whenever exposed)
1.) exposure or invasion:
a n t ig e n m u s t e n t e r b o d y
m u s t o c c u r in la rg e n u m b e rs t h a t s o m e o f t h e a n t ig e n is n o t
d e t e c t e d b y b o d y ÷s d e fe n s e s o r o v e rw h e lm s t h e
in ‡ a m m a t o ry re s p o n s e
a s a v iru s g ro w s , WBCs t a ke p a rt in a n t ib o d y -a n t ig e n
re a c t io n s t o p re v e n t h im / h e r fro m h a v in g a d is e a s e m o re
t han once
 r e c o g n it io n s t a r t e d b y m a c r o p h a g e s
a lt e r e d s u r f a c e b y o p s o n iz a t io n ( r e c o g n iz e d a s n o n s e lf
t h e n p h y s ic a lly a t t a c h e s it s e lf
p r e s e n t s a n t ig e n t o h e lp e r T c e ll
b o t h m a c r o & T c e ll p r o c e s s a n t ig e n t o e x p o s e r e c o g n it io n
s it e s ( U P C )
T c e ll b r in g s a n t ig e n t o B c e ll
B c e ll r e c o g n iz e s a s n o n s e lf
3.) lymphocyte sensitization:
B c e ll re c o g n iz e s a n t ig e n a s n o n s e lf & n o w is ”s e n s it iz e d ‘
c a n o n ly b e s e n s it iz e d o n e t im e ( s o c a n o n ly b e s e n s it iz e d
t o o n e t y p e o f a n t ig e n )
w ill r e s p o n d t o a n y s u b s t a n c e t h a t c a r r ie s t h e s a m e
a n t ig e n
a lw a y s r e m a in s s e n s it iz e d
a ll c e lls p r o d u c e d b y t h a t B c e ll a r e a ls o s e n s it iz e d t o t h a t
a n t ig e n
im m e d ia t e ly f o r m s 2 c e lls b y d iv is io n
1. p la s m a c e ll: s t a r t s im m e d ia t e ly t o p r o d u c e a n t ib o d ie s
a g a in s t s p e c ifl c a n t ig e n - s h o r t lif e s p a n
2. m e m o r y c e ll: s e n s it iz e d b u t d o e s n o t s t a r t f u n c t io n
u n t il t h e n e x t e x p o s u r e t o t h e s a m e a n t ig e n
4.) antibody production & release:
a llo w t h e a n t ib o d ie s t o s e a rc h o u t s p e c iflc a n t ig e n s
a n t ib o d ie s p r o d u c e d b y p la s m a c e lls
w it h f u ll s t im u la t io n , e a c h p la s m a c e ll c a n m a k e 3 0 0
m o le c u le s o f a n t ib o d y / s e c o n d
e a c h p la s m a c e ll p r o d u c e s a n t ib o d y - s p e c ifl c o n ly t o t h e
a n t ig e n t h a t o r ig in a lly s e n s it iz e d
t h e a n t ib o d y c la s s ( Ig G , Ig M , e t c ) m a y v a r y b u t a n t ib o d y
c a n o n ly b e d ir e c t e d a g a in s t t h a t s p e c ifl c a n t ig e n
m a d e b y p la s m a a n d t h e n r e le a s e d in t o b lo o d a n d o t h e r
‡ u id s a s a f r e e a n t ib o d y ( r e m a in in b lo o d 3 - 3 0 d a y s )
b e c a u s e it is s e p a r a t e f r o m B - c e lls a n d f o u n d in b o d y ‡ u id s
s o m e t im e s c a lle d ” h u m o r a l im m u n it y
c irc u la t in g a n t ib o d ie s c a n b e t ra n s fe rre d fro m p e rs o n t o
p e rs o n t o p ro v id e t h e re c e iv in g p e rs o n w it h im m e d ia t e
im m u n it y o f s h o rt d u ra t io n
5.) antibody-antigen binding:
n e e d e d fo r a n t i a n t ig e n a c t io n s
a n t ib o d ie s a re y s h a p e d m o le c u le s
t ip s o f s h o r t a r m s o f t h e Y r e c o g n iz e t h e s p e c ifl c a n t ig e n
& b in d t o it
t h e r e f o r e e a c h a n t ib o d y c a n b in d t o t w o a n t ig e n s o r t o
t w o a r e a s o f t h e s a m e a n t ig e n
s t e m o f Y is t h e ” F c f r a g m e n t ‘ a n d c a n b in d t o F c
r e c e p t o r s it e s o n W B C s
t h e W B C c a n t h e n a t t a c k a n t ig e n s a n d a ls o a d d s u r f a c e
a n t ib o d ie s t h a t s t ic k t o t h e a n t ig e n
n o t n e c e s s a r ily le t h a l b u t b e g in s t h e o t h e r s t e p s t h a t
n e u t r a liz e , e lim in a t e a n d d e s t r o y t h e a n t ig e n
6.) antibody-binding actions:
 im m u n e c o m p le x
u s u a lly b a c t e r ia a n d v ir u s e s a r e t h e n o n s e lf c e lls t h a t
a r e d a m a g e d t h r o u g h m o s t t h r u ly s is
c . ) c o m p le m e n t a c t iv a t io n & fl x a t io n
a c t io n s t r ig g e r e d b y s o m e c la s s e s o f a n t ib o d ie s t h a t
c a n r e m o v e o r d e s t r o y a n t ig e n
t h e t w o c la s s e s o f a n t ib o d y t h a t c a n a c t iv a t e t h e
c o m p le m e n t s y s t e m a r e Ig G & Ig M
b in d in g o f a n t ib o d y f r o m e it h e r o f t h e s e c la s s e s t o
a n t ig e n p r o v id e s a b in d in g s it e f o r t h e 1 s t c o m p o n e n t
o f c o m p le m e n t
o n c e t h e 1 s t c o m p le m e n t m o le c u le is a c t iv a t e d , o t h e r
p r o t e in s o f t h e c o m p le m e n t s y s t e m a r e a c t iv a t e d in a
cascade
d . ) p r e c ip it a t io n
s im ila r t o a g g lu t in a t io n w it h a la r g e r r e s p o n s e
a n t ib o d y m o le c u le s b in d s o m u c h a n t ig e n , t h a t la r g e ,
in s o lu b le , a n t ig e n - a n t ib o d y c o m p le x e s a r e f o r m e d
c a n ÷t s t a y s u s p e n d e d in t h e b lo o d in s t e a d t h e y f o r m a
la r g e p r e c ip it a t e w h ic h c a n b e a c t e d o n a n d r e m o v e d b y
n e u t r o p h ils & m a c r o p h a g e s
e . ) in a c t iv a t io n ( n e u t r a liz a t io n )
t h e p r o c e s s o f m a k in g a n a n t ig e n h a r m le s s w it h o u t
d e s t r o y in g it
u s u a lly a s m a ll a r e a o f t h e a n t ig e n ” t h e a c t iv e s it e ‘
c a u s e s t h e h a r m f u l e f f e c t s , r e s t o f t h e a n t ig e n n o t
h a rm fu l
w h e n a n a n t ib o d y b in d s t o t h e a n t ig e n a n d c o v e r s u p
t h e a n t ig e n ÷s a c t iv e s it e , t h e a n t ig e n is m a d e u n h a r m f u l
w it h o u t d e s t r o y in g it
7.) sustained immunity (memory):
lo n g la s t in g im m u n it y t o a s p e c iflc a n t ig e n
re s u lt s fro m m e m o ry B c e lls m a d e d u rin g t h e ly m p h o c y t e
s e n s it iz a t io n s t a g e
re m a in s e n s it iz e d t o t h e s p e c iflc a n t ig e n t h e y w e re o rig in a lly
e xp o s e d t o
o n re -e xp o s u re , t h e y ra p id ly re s p o n d
flrs t m e m o ry c e lls d iv id e a n d fo rm n e w s e n s it iz e d b la s t c e lls
a n d n e w s e n s it iz e d p la s m a c e lls
b la s t c e lls c o n t in u e t o d iv id e p ro d u c in g m a n y m o re s e n s it iz e d
p la s m a c e lls
t h e s e n e w p la s m a c e lls ra p id ly m a ke la rg e a m o u n t s o f t h e
a n t ib o fy , s p e c iflc fo r t h e s e n s it iz in g a n t ig e n
t h is a llo w s a ra p id a n d la rg e im m u n e ( a n a m n e s t ic ) re s p o n s e
t o t h e a n t ig e n
b e c a u s e s o m u c h a n t ib o d y is m a d e , u s u a lly t h e in v a d in g
o rg a n is m s a re c o m p le t e ly re m o v e d a n d t h e p e rs o n d o e s n o t
b e c o m e s ic k
b e c a u s e o f t h is , m o s t p e o p le d o n o t b e c o m e ill w it h c h ic ke n
p o x o r o t h e r in fe c t io u s d is e a s e s m o re t h a n o n c e e v e n t h o u g h
 in the gamma fraction of plasma proteins during electrophoresis
5 antibody types classifled by differences in size and timing
on 1st exposure to an antigen, the newly sensitized B-cell
produces the IgMantibody against the antigen
IgMforms itself in a 5 member group
each IgMgroup then has 10 antigen binding sites
even though slow at flrst exposure, antibody production
produces very efflcient antibody type at antigen binding
ensures initial illness lasts only 5-10 days
on reesposure the already sensitized B cell makes large
amounts of IgG type of antibody against that antigen
IgG does not form groups of 5 but enormous amount produced
efflcient at clearing the antigen and protecting the person from
becoming ill with the disease again
Acquiring Antibody-Mediated Immunity
innate native immunity/ ”natural immunity‘ & adaptive acquired
immunity
natural protective feature
barrier to prevent organisms from entering the body or can be
an attacking force that eliminates organisms that have already
entered the body
cannot be developed or transferred from one person to another
and is not an adaptive response to exposure or invasion by
foreign proteins
in‡ammatory response is a part
other parts = skin, mucosa, antimicrobial chemicals on the skin,
complement and natural killer cells
adaptive immunity - immunity that a person÷s body learns to make
(or can receive) as an adaptive response to invasion to organism
or foreign particle
i.e. antibody mediated immunity
occurs naturally or artiflcially through lymphocyte responses
and can be active or passive
n a t u ra l - m o s t e ffe c t iv e & lo n g la s t in g
a rt iflc ia l - v a c c in a t io n / im m u n iz a t io n
 a c t iv e - a n t ig e n s e n t e r t h e b o d y a n d re s p o n d s b y m a kin g
s p e c iflc a n t ib o d ie s a g a in s t t h e a n t ig e n
a c t iv e b e c a u s e t h e b o d y t a k e s a n a c t iv e p a r t in m a k in g
t h e a n t ib o d ie s
n a t u r a l a c t iv e - o c c u r s w h e n t h e a n t ig e n e n t e r s t h e b o d y
a n d t h e b o d y r e s p o n d s b y a c t iv e ly m a k in g a n t ig e n s
u s u a lly t h e in v a s io n t h a t t r ig g e r s a n t ib o d y p r o d u c t io n ,
a ls o c a u s e s t h e d is e a s e
p r o c e s s e s o c c u r in g in t h e b o d y a t t h e s a m e t im e a s
in f e c t io n c r e a t e im m u n it y t o t h a t a n t ig e n ( w ill n o t
b e c o m e ill a f t e r a 2 n d e x p o s u r e t o s a m m e a n t ig e n )
m o s t e f f e c t iv e , lo n g e s t la s t in g
a r t ifl c ia l a c t iv e im m u n it y is p r o t e c t io n d e v e lo p e d b y
v a c c in a t io n o r im m u n iz a t io n
u s e d t o p r e v e n t in f e c t io n s o r illn e s s e s ( t e t a n u s ,
d ip t h e r ia , p o lio ) t h a t h a v e s u c h s e r io u s c o n s e q u e n c e s
t h a t a v o id in g t h e d is e a s e a lt o g e t h e r is t h e m o s t
d e s ir a b le
s m a ll a m o u n t s o f a s p e c ifl c a n t ig e n a r e p la c e d a s a
v a c c in a t io n in t o t h a t p e r s o n
im m u n e r e s p o n s e a c t iv e ly m a k e s a n t ib o d ie s
e x p o s u r e d o e s n o t c a u s e d is e a s e b e c a u s e t h e a n t ig e n s
h a v e b e e n a t t e n u a t e d ( s p e c ifl c a lly p r o c e s s t h e m t o b e
le s s lik e ly t o g r o w in t h e b o d y )
la s t s m a n y y e a r s a lt h o u g h r e p e a t e d b y s m a lle r d o s e s o f
o r ig in a l a n t ig e n r e q u ir e d a s a ” b o o s t e r ‘ t o r e t a in t h e
p r o t e c t io n
p a s s iv e im m u n it y o c c u rs w h e n n t ib o d ie s a g a in s t a n a n t ig e n
a re in a p e rs o n ÷s b o d y b u t w e re n o t c re a t e d t h e re
a n t ib o d ie s t r a n s f e r r e d t o t h e p e r s o n ÷s b o d y a f t e r b e in g
m a d e in t h e b o d y o f a n o t h e r p e r s o n o r a n im a l
b e c a u s e t h e y ÷r e f o r e ig n , t h e y ÷r e r e c o g n iz e d a s n o n s e lf
a n d a r e e lim in a t e d q u ic k ly
p r o v id e s o n ly im m e d ia t e , s h o r t t e r m p r o t e c t io n a g a in s t a
s p e c ifl c a n t ig e n
n a t u r a l p a s s iv e im m u n it y - a n t ib o d ie s a r e p a s s e d f r o m
m o t h e r t o f e t u s v ia p la c e n t a o r t h r o u g h c o lo s t r u m / b r e a s t
m ilk
a r t ifl c ia l p a s s iv e - in v o lv e s in je c t in g a p e r s o n w it h
a n t ib o d ie s t h a t w e r e p r o d u c e d in a n o t h e r p e r s o n o r a n im a l
u s e d w h e n a p e r s o n is e x p o s e d t o a s e r io u s d is e a s e f o r
w h ic h t h e y h a v e lit t le / n o a c t iv e ly a c q u ir e d im m u n it y
a c t iv e a n t ib o d ie s e x p e c t e d t o in a c t iv a t e a n t ig e n
t e m p o ra ry ( fe w d a y s t o w e e ks )
c a n b e u s e d t o p r e v e n t d is e a s e o r d e a t h f o r p a t ie n t s
e x p o s e d t o r a b ie s , t e t a n u s , s n a k e b it e s
AMI works with in‡ammation to protect against infection
AMI can provide the most effective, long lasting immunity when
combined with CMI
V. Cell-Mediated Immunity (CMI) “cellular
immunity”
producing and releasing cytokines
for total immunocompetence CMI must function optimally
Cell types involved in CMI
the WBCs with the most important roles in CMI include several
speciflc T-lymphocytes (T-cells) along with a special population of
cells known as natural killer (NK) cells
T cells have a variety of subsets each of which has a speciflc
function
ID T-c e ll s u b s t s is t o e xa m in e ”m a rke r p ro t e in s ‘ ( a n t ig e n s )
o n t h e c e ll m e m b ra n e ÷s s u rfa c e
> 2 0 0 d iffe re n t T c e ll p ro t e in s h a v e b e e n IDe d o n c e ll
m e m b ra n e s a n d 1 1 o f t h e s e ( T1 -T1 1 ) a re u s e d t o c lin ic a lly
ID c e lls
An t ib o d ie s h a v e b e e n m a d e a g a in s t e a c h o f t h e s e
t h e re fo re e a c h T c e ll s u b s e t c a n b e IDe d b y it s re a c t io n t o
c o m m e rc ia l a n t ib o d ie s
m o s t T c e lls h a v e m o r e t h a n o n e a n t ig e n o n t h e ir c e ll
m e m b ra n e
i. e . a ll m a t u r e T c e lls c o n t a in T 1 , T 3 , T 1 0 , T 1 1
c e r t a in T c e lls a ls o c o n t a in o t h e r s p e c ifl c T c e ll m e m b r a n e
a n t ig e n s
n a m e s u s e d t o id e n t ify s p e c iflc T c e ll s u b s e t s in c lu d e t h e
s p e c iflc m e m b ra n e a n t ig e n a n d t h e o v e ra ll a c t io n s o f t h e
c e lls in a s u b s e t
3 T-c e ll s u b s e t s c rit ic a lly im p o rt a n t fo r t h e d e v e lo p m e n t a n d
c o n t in u a t io n o f CMI a re :
1 . ) h e lp e r / in d u c e r T c e lls
h a v e T 4 p r o t e in s o n t h e ir m e m b r a n e
t h e s e c e lls a r e u s u a lly c a lle d T 4 + c e lls o r T h c e lls - m o s t
c o r r e c t n a m e is C D 4 + ( c lu s t e r o f d if f e r e n t ia t io n 4 ) -
a ls o r e f e r r e d t o a s O K T 4 p o s it iv e o r L e u - 3 p o s it iv e
b e c a u s e o f t h e s p e c ifl c a n t ig e n s o n t h e m e m b r a n e
s u rg a c e
e a s ily r e c o g n iz e a s s e lf o r n o n s e lf c e lls
in r e s p o n s e t o r e c o g n it io n o f n o n s e lf ( a n t ig e n ) ,
h e lp e r / in d u c e r T c e lls s e c r e t e ly m p h o k in e s t h a t c a n
e n h a n c e a c t iv it y o f o t h e r W B C s
m o s t ly m p h o k in e s s e c r e t e d in c r e a s e im m u n e f u n c t io n ,
in c r e a s e b o n e m a r r o w p r o d u c t io n o f s t e m c e lls a n d
s p e e d u p t h e ir m a t u r a t io n
t h u s h e lp e r / in d u c e r T c e lls a c t a s o r g a n iz e r s in
” c a llin g t o a r m s ‘ v a r io u s s q u a d s o f W B C s in v o lv e d in
in ‡ a m m a t o r y , a n t ib o d y a n d c e llu la r p r o t e c t iv e a c t io n s
t o d e s t r o y o r n e u t r a liz e a n t ig e n s
2 . ) s u p p r e s s o r T c e lls
c a n h e lp r e g u la t e C M I
h a v e t h e T 8 ly m p h o c y t e a n t ig e n o n t h e ir m e m b r a n e
 b a la n c e is 2 : 1 r a t io o f h e lp e r / in d u c e r s u p p r e s s o r c e lls
w h e n r a t io in c r e a s e s ( h e lp e r v a s t ly o u t # s u p p r e s s o r )
o v e r r e a c t io n s c a n o c c u r ( s o m e a r e t is s u e d a m a g in g a s
w e ll a s u n p le a s a n t )
w h e n r a t io d e c r e a s e s ( f e w e r t h a n n o r m a l h e lp e r / in d u c e r
T c e lls ) im m u n e f u n c t io n is s u p p r e s s e d a n d t h e p e r s o n ÷s
r is k f o r in f e c t io n s in c r e a s e s
3 . ) c y t o x ic / c y t o ly t ic T c e lls a k a ” T c c e lls ‘
s u b s e t o f s u p p r e s s o r c e lls b e c a u s e t h e y h a v e t h e T 8
p r o t e in p r e s e n t o n t h e ir s u r f a c e s
d e s t r o y c e lls t h a t c o n t a in a p r o c e s s e d a n t ig e n s m a jo r
h is t o c o m p a t a b ilit y c o m p le x ( M H C )
m o s t e f f e c t iv e a g a in s t s e lf c e lls in f e c t e d b y
p a r a s it e s , s u c h a s v ir u s e s o r p r o t o z o
p a r a s it e in f e c t e d c e lls h a v e b o t h s e lf M H C p r o t e in s
( U P C ) a n d t h e p a r a s it e ÷s a n t ig e n s o n t h e c e ll s u r f a c e
t h is a llo w s t h e p e r s o n ÷s im m m u n e s y s t e m c e lls t o
r e c o g n iz e t h e in f e c t e d s e lf c e lls a s a b n o r m a l a n d t h e
c y t o x ic / c y t o ly t ic T c e ll c a n b in d t o it
w h e n t h e c y t o x ic / c y t o ly t ic T c e ll b in d s t o t h e
in f e c t e d c e lls M H C , t h e c y t o x ic / c y t o ly t ic T c e ll m a k e s
h o le s in t h e m e m b r a n e o f t h e in f e c t e d c e ll, c a u s in g it
t o ly s e a n d d ie
o n c e t h e le t h a l h it h a s b e e n d e liv e r e d , t h e
c y t o x ic / c y t o ly t ic T c e ll r e le a s e s t h e d y in g , in f e c t e d c e ll
a n d c a n t h e n d e s t r o y a n d a t t a c k o t h e r in f e c t e d c e lls
c a r r y in g t h e s a m e a n t ig e n M H C c o m p le x
+ n a t u r a l k ille r c e ll - n o t a t r u e T c e ll b u t c o n t r ib u t e s t o C M I
( a ka ”CD1 6 + ‘ )
v e r y im p o r t a n t in p r o v id in g C M I
a c t u a l s it e o f d if f e r e n t ia t io n a n d m a t u r a t io n u n k n o w n
h a s s o m e T c e ll f e a t u r e s , b u t n o t a t r u e T c e ll s u b s e t
d ir e c t c y t o x ic e f f e c t s o n s o m e n o n s e lf c e lls w it h o u t
b e in g s e n s it iz e d
t h e c e ll k illin g a c t io n s a r e in d e p e n d e n t o f t h e in t e r a c t io n
o f o t h e r W BCs
” s e e k & d e s t r o y ‘ m is s io n s in t h e b o d y t o e lim in a t e n o n
s e lf c e lls
m o s t e f f e c t iv e in d e s t r o y in g u n h e a lt h y o r a b n o r m a l s e lf
c e lls
m o s t o f t e n c a n c e r c e lls a n d v ir a lly in f e c t e d b o d y c e lls
Cytokines
CMI regulates the immune system by production & activation of
cytokines (small protein hormones produced by many WBCs and
some other tissues)
cytokines made by the macrophages, neutrophils, eosinophils and
monocytes = monokines
cytokines produced by T-cells are lymphokines
works like other types of hormones
one cell produces a cytokine
which in turn exerts its effects on other cells of the immune
 c y t o kin e s c o n t ro l m a n y in ‡ a m m a t o ry a n d im m u n e re s p o n s e s
a n d a re c o n t ro lle d b y in t e ra c t io n s w it h o t h e r s y s t e m s ( e s p .
t h e n e rv o u s s y s t e m )
s o m e c y t o kin e s a re p le io t o p ic ( e ffe c t s a re w id e s p re a d w it h in
t h e im m u n e s y s t e m ) a n d s e n t in t o m o t io n m a n y d iffe re n t
im m u n e a c t io n s
o t h e r c y t o kin e s h a v e s p e c iflc a c t io n s lim it e d t o o n ly o n e t y p e
o f c e ll
c y t o kin e s in c lu d e in t e rle u kin s ( la rg e s t g ro u p ) , in t e rfe ro n s ,
c o lo n y s t im u la t in g fa c t o rs a n d t u m o r n e c ro s is fa c t o
Protection provided by CMI
CMI helps protect the body through the ability to differentiate self
vs. non self
the non self cells most easily recognized by CMI are cancer cells
and those infected by organisms that live within host cells
watches for and rids body of self cells that might potentially harm
the body
important in preventing the development of cancer and
metastasis after exposure to carcinogens
Transplant rejection
NK cells and cytoxic/ cytolytic T cells also destroy cells from other
people or animals
usually helpful but responsible for rejection of tissue grafts and
transplanted organs
because seldom protect identical match of human leukocyte
antigens the immune system recognize organ as non-self and
starts in‡ammatory and immunologic actions to destroy or
eliminate these non self cells
t h is c a u s e s o rg a n re je c t io n
r e s u lt o f a c o m p le x s e r ie s o f r e s p o n s e s t h a t c h a n g e o v e r
t im e a n d in v o lv e d if f e r e n t c o m p o n e n t s o f t h e im m u n e
system
3 types of rejection
1.) Hyperacute rejection
b e g in s im m e d ia t e ly o n t ra n s p la n t a t io n
a n t ib o d y -m e d ia t e d re s p o n s e
a n t ig e n -a n t ib o d y c o m p le xe s fo rm in t h e b lo o d v e s s e ls o f t h e
t ra n s p la n t e d o rg a n
t h e h o s t ÷s b lo o d h a s p re -e xis t in g a n t ib o d ie s t o o n e o r m o re
 fo rm t h ro u g h o u t t h e o rg a n
o c c lu d e s b lo o d v e s s e ls a n d le a d s t o is c h e m ic n e c r o s is ,
in ‡ a m m a t io n w it h p h a g o c y t o s is o f t h e n e c r o t ic b lo o d
v e s s e ls a n d r e le a s e o f ly t ic e n z y m e s in t o t h e n e w o r g a n
t h e s e e n z y m e s c a u s e m a s s iv e c e llu la r d e s t r u c t io n a n d
g r a f t lo s s
o c c u r s m o s t ly in t r a n s p la n t e d k id n e y s b u t le s s c o m m o n
r e la t e d t o g r e a t e r e f f o r t s in H L A m a t c h in g
t h o s e a t g r e a t e s t r is k a r e t h o s e w h o h a v e r e c e iv e d
d o n a t e d o r g a n s o f a n A B O b lo o d t y p e d if f e r e n t t h a n t h e ir
o w n , h a v e r e c e iv e d m u lt ip le b lo o d t r a n s f u s io n s a t a n y t im e
in lif e b e f o r e t r a n s p la n t a t io n , h a v e a h is t o r y o f m u lt ip le
p r e g n a n c ie s o r h a v e r e c e iv e d a p r e v io u s t r a n s p la n t
m a n ife s t a t io n s a re a p p a re n t in m in u t e s o f a t t a c h m e n t o f
d o n a t e d o rg a n t o t h e h o s t s b lo o d s u p p ly
p ro c e s s c a n n o t b e s t o p p e d o n c e it h a s b e e n s t a rt e d a n d t h e
re je c t e d o rg a n is re m o v e d a s s o o n a s t h e h y p e ra c u t e
re je c t io n is d ia g n o s e d
2.) Acute rejection
o c c u rs 1 w e e k t o 3 m o n t h s a ft e r t ra n s p la n t a t io n
2 m e c h a n is m s re s p o n s ib le
1 . ) a n t ib o d y m e d ia t e d a n d r e s u lt s in v a s c u lit is in
t r a n s p la n t e d o r g a n ( b lo o d v e s s e l n e c r o s is le a d s t o t h e
o r g a n ÷s d e s t r u c t io n )
2 . ) c e llu la r h o s t c y t o x ic / c y t o ly t ic T c e lls a n d N K c e lls
e n t e r t h e t r a n s p la n t e d o r g a n t h r o u g h t h e b lo o d , p e n e t r a t e
t h e o r g a n c e lls , s t a r t a n in ‡ a m m a t o r y r e s p o n s e a n d c a u s e
t h e ly s is o f t h e o r g a n c e lls
d ia g n o s e d w it h la b t e s t s t h a t s h o w t h e im p a ire d fu n c t io n o f
t h e d o n a t e d o rg a n a n d b y a b io p s y o f t h e d o n a t e d o rg a n
s y m p t o m s v a ry w it h e a c h p a t ie n t a n d t h e s p e c iflc o rg a n
t ra n s p la n t e d
i. e . k id n e y - s o m e t e n d e r n e s s in k id n e y a r e a a n d g e n e r a l
s y m p t o m s o f in ‡ a m m a t io n
a n e p is o d e d o e s n o t a u t o m a t ic a lly m e a n t h e p a t ie n t w ill lo s e
t h e n e w o rg a n
d ru g m a n a g e m e n t o f h o s t im m u n e re s p o n s e s a t t h is t im e
m a y lim it t h e d a m a g e t o t h e o rg a n a n d a llo w t h e g ra ft t o b e
m a in t a in e d
3.) Chronic rejection
u n c le a r o rig in
s im ila r t o c h ro n ic in ‡ a m m a t io n & s c a rrin g
s m o o t h m u s c le s o f b lo o d v e s s e ls o v e rg ro w a n d o c c lu d e t h e
v e s s e ls
t h e d o n a t e d o rg a n t is s u e s a re re p la c e d w it h flb ro t ic , s c a r like
t is s u e
fl b r o t ic t is s u e is n o t o r g a n t is s u e - t r a n s p la n t e d o r g a n s
f u n c t io n is r e d u c e d in p r o p o r t io n t o t h e a m o u n t o f n o r m a l
 w h e n flb ro s is in c re a s e s t o t h e e xt e n t t h a t t h e t ra n s p la n t e d
o rg a n c a n n o lo n g e r fu n c t io n , t h e o n ly c o u rs e is
re t ra n s p la n t a t io n
Treatment of transplant rejection
re je c t io n in v o lv e s a ll 3 c o m p o n e n t s o f im m u n it y a lt h o u g h CMI
c o n t rib u t e s t h e m o s t
m a in t e n a n c e t h e ra p y : c o n t in u o u s im m u n e s u p re s s io n
c o m b o o f s p e c ifl c im m u n e s u p p r e s a n t s
c y c lo s p o r in e ( s a n d im u n e , N e o r a l, G e n g r a f )
in c lu d e s s p e c ifl c a n d e f f e c t iv e s u p p r e s s io n b u t w it h
m a jo r lo n g t e r m s id e e f f e c t s , & e x p e n s iv e
le s s s p e c ifl c im m u n o s u p p r e s s io n s
a z a t h io p r in e ( Im u r a n )
m y c o p h e n o la t e ( C e ll- c e p t , M y f o r t ic )
a n d o n e o f t h e c o r t ic o s t e r o id s
p r e d n is o n e ( D e lt a - c o r t e f )
n e w d r u g - g u s p e r im u s ( S p a n d in )
d o s a g e o f a ll is a d ju s t e d t o t h e im m u n e re s p o n s e o f e a c h
p a t ie n t
t re a t m e n t w it h t h e s e a g e n t s in c re a s e ris k fo r b a c t e ria l a n d
fu n g a l in fe c t io n s a n d fo r c a n c e r d e v e lo p m e n t
T c e ll s u p p re s s io n : t a c ro lim u s ( Pro g ra t ) is s im ila r t o
e ry t h ro m y c in a n d s p e c iflc a lly s u p p re s s e s T c e ll a c t io n s
in c lu d in g IL-2 p ro d u c t io n
w it h o u t IL - 2 , h e lp e r T c e lls a n d c y t o x ic a n d c y t o ly t ic T
c e lls a r e s lo w t o r e p r o d u c e a n d d o n o t p e r f o r m t h e ir u s u a l
f u n c t io n s
s u p p r e s s io n a llo w s d o n a t e d o r g a n t o n o t b e d e s t r o y e d
g e n e r a l im m u n o s u p p r e s s io n is n o t a s p r o f o u n d a n d t h e
h o s t ÷s r is k f o r in f e c t io n is n o t g r e a t ly in c r e a s e d
a ls o p r e v e n t s a c t iv a t io n o f u n s e n s it iz e d c y t o x ic / c y t o ly t ic
T c e lls
o t h e r d r u g s w it h s im ila r a c t io n s in c lu d e s ir o lim u s
( R a p a m u n e ) a n d e v e r o lim u s ( C e r t ic a n )
u s e o f m o n o c lo n a l a n t ib o d ie s d ire c t e d a t IL-2 re c e p t o r s it e s
o n a c t iv a t e d T-c e lls ( e s p e c ia lly h e lp e r/ in d u c e r)
t h e s e a n t ib o d ie s
b a s ilix im a b ( S im u le c t )
d a c liz u m a b ( Z e n a p a x )
a r e g iv e n w it h in 2 h o u r s IV b e f o r e t h e t r a n s p la n t
s u rg e ry
r e d u c e s T c e ll g r o w t h a n d a c t iv a t io n f o r m o n t h s
re s c u e t h e ra p y : u s e d t o t re a t a c u t e re je c t io n e p is o d e s
m a y b e u s e d in a d d it io n t o o r in p la c e o f t h e m a in t e n a n c e
d r u g s in t h e h o s t s n o r m a l t r e a t m e n t r e g im e n
a n t ily m p h o c y t e g lo b u lin ( ALG) is a n a n t ib o d y p ro d u c e d a ft e r
t h e a n im a l h a s b e e n e xp o s e d t o h u m a n ly m p h o c y t e s
c a n b e m a d e m o r e s p e c ifl c b y e x p o s in g t h e a n im a l t o
h u m a n T - c e lls
w h e n t h e s e a n t ih u m a n ly m p h o c y t e s a r e g iv e n t o h u m a n s
 e f f e c t iv e n e s s in c o m b a t t in g g r a f t r e je c t io n d e c r e a s e
w it h e a c h u s e
o n ly g iv e n f o r s h o r t t im e t o c o m b a t a c u t e r e je c t io n
e p is o d e b e c a u s e o f im m u n o lo g ic s id e e f f e c t s w h ic h
in c r e a s e in in t e n s it y o n r e p e a t e d e x p o s u r e
a n t ib o d ie s m a d e in o t h e r a n im a ls ( e s p . m ic e ) c a u s e s / e in
h u m a n s b e c a u s e a n im a l p r o t e in s a r e r e c o g n iz e d a s f o r e ig n
b y h u m a n im m u n e s y s t e m
in c id e n c e o f s id e e f f e c t s is d e c r e a s e d b e c a u s e
a n t ib o d ie s h a v e b e e n ” h u m a n iz e d ‘
r e m o v e s m o u s e s p e c ifl c p r o t e in s a n d r e p la c e s w it h
h u m a n s p e c ifl c p r o t e in s