IMMUNOLOGY NOTES

Definition: Study of immunity, that is: the cellular and molecular events following an organism
encountering a microbe or other foreign macromolecule.
#1.THE NATURAL ( INNATE ) IMMUNE SYSTEM AND THE SPECIFIC ( ACUIRED !
ADAPTI"E ) IMMUNE SYSTEM.
THE NATURAL IMMUNE SYSTEM ( INNATE ! NATI"E )
These mechanisms exist prior to exposure. They do not (necessarily)distinguish foreign substances.
(Not functioning completely seperate from specific system the two systems act in concert)
!."#$S%&'( )'**%+*S: s,in, mucous membranes
-..+N+*'( )'**%+*S: fever, p#
/.)%0(0.%&'( )'**%+*S: inflammation, phagocytosis
1.&#+2%&'( )'**%+*S: en3ymatic action, betalysin, interferon, complement
THE SPECIFIC IMMUNE SYSTEM ( ACUIRED ! ADAPTI"E )
!.#420*'( S$ST+2:
)lymphocytes develop into plasma cells. *elease antibodies in blood 5 eg. %n response to bacteria
in circulation (ie. 'n antigen accessible to antibodies).
-.&+((4('* S$ST+2:
Tlymphocytes respond to a cellbound infection ( via Tcell receptor ) eg. %n case of viral infection
or tuberculosis.
(ysis of infected cell re6uired in order to ma,e antigens ( li,e viral proteins) accessible to
circulating antibodies.
7eatures of Specific %mmune *esponse:
Specificity
Specific to an individual antigen.
#ow8 (ymphocytes have surface receptors that recogni3e specific epitopes ( regions on antigen ).
)cells use surface antibodies ( %g2 ) as receptors.
Tcells have T&* ( Tcell *eceptor )
9iversity
Number of specificities of lymphocytes is !:;< ( nr of different antigenic determinants ( epitopes )
that can be recogni3ed.
2emory
primary response: building up of antibodies against a new antigen. That is, sensitization.
Slower response with lower titre ( ablevels ).
secondary response: response to a previously encountered antigen. 7aster response= higher titre :
#ence importance of vaccination.
2emory cells survive long periods. Specific to antigen. *eady for restimulation. &an be activated
by very low antigen concentration.
'fter exposure= proliferation of lymphocytes with same specificity ( clones ) > amplification of
response plus focussing of response to site of entry 5 thus, efficiency.
Selfregulation
%mmune response weans after time.
*easons: 'g eliminated
lymphocyte function stops or changes
special feedbac, mechanism.
Self vs. nonself recognition
Tolerance > nonresponsiveness to selfantigens.
(earned by developing Tlymphos in thymus and by )?s in bone marrow.
%f failure 5 re@ected ( negative selection 5 only nonreactives pass)
'bnormalities result in autoimmune disease.
T$"+S 07 S"+&%7%& %224N%T$
'ctively ac6uired
'rises from exposure to an antigenic stimulus.
%mmune system responds by producing antibodies plus sensiti3ed lymphocytes to inactivate or to
destroy the ag.
(asts years ( eg. Tetanus ) to lifelong (eg. 2easles ).
%nduced by : clinical infection, subclinical infection, or ( artificially ) immuni3ation.
"assively ac6uired
%ntroduction of antibodies to the system.
Naturally: mother to fetus via placenta= to baby via breast mil,.
'rtificially: antibodies administered eg. Sna,e venom ab?s. 'dditional to ab?s produced by patient?s
own immune system. &urtails infection= moderates illness. 9isadvantages: temporary protection
( short lived )= %mmune reaction to in@ection= especially if derived from animals.( sna,e antivenom
produced in sheep better tolerated than that produced in horses. )
S422'*$:
#umoral immunity : extracellular antigens that are accessible to antibodies.
&ellular immunity : intracellular eg. Airuses and T). *e6uires T&*. &ell lysis.
T$"+S 'N9 S4)S+TS 07 ($2"#0&$T+S:
!.Tlymphocytes
&lass that ,ills: T cytotoxic cells ( &9BC )
&ause cytolysis of target cells. N) in defence against cellbourne pathogens.
&lasses that regulate: T helper cells ( &9 1C )
#elp )lymphocytes to ma,e antibodies in response to antigenic challenge ( humoral immunity )
Stimulate cell mediated immunity ( Tcells )
: 'lso T suppressor, Td ( 9elayed hypersensitivity )
-. )lymphocytes
4pon activation by ag, )cells differentiate into cells producing ab of same specificity as their
initial ( surface ab ) receptor. 7orm plasma cells ( main ab producing cells of body ). 7ound in
lymph nodes, spleen, bone marrow.
/.ND cells
mm
##. CELLS OF THE IMMUNE SYSTEM
'll cells arise from pluripotential stem cells.
2ature via one of two lines:
!. L$%&'oi( progenitor gives rise to ) and Tlymphocytes and ND cells.
-. M$e)oi( progenitor gives rise to monocytes ( develop into macrophage cells in tissue )
and to polys ( neutrophils, basophils, eosinophils ) and mast cell precursors.
(ymphocytes
-:E of circulating Fhite )lood &ells.
2emory cells long lived.
Normally Tcells seen in circulation.
"lasma cells ( developed from )cells ) only found in secondary lymphoid organs. Not normally in
circulation. Short lived ( few days ).
2onocytes
!:E of F)&
9evelop in bone marrow G 2igrate through vessel walls into tissues G "hagocytic macrophages.
)inding sites on macrophage: %g., complement, 2#& &lasses % and %%, %g+, &yto,ines: %(!, %7N,
TN7.
"olymorphonuclear granulocytes
H:I:E of F)&
Short lived ( -/ days )
&an diapedese ( migrate through vessel walls ).
No antigenic specificity 5 ie. "art of innate immune system.
N) in inflammation and phagocytosis.
Neutrophils ( HI E of F)& ) > Jfilter cellsK, eosinophils ( -LE ), basophils ( :.-E ) and mast cells
( not in circ., release histamine in allergic reaction )
"latelets
2ost N) function: clotting
'lso involved in immune response, esp. inflammation.
&ome from mega,aryocyte in bone marrow.
#ave 2#& &lass % and %% on surface, and binding site for 7actor A%%%.
"latelets adhere to surface of endothelial cells in tissue damage. 'ggregated platelets release
substances that increase permeability ( for diapedesis ), activate complement, attract F)&.
2onocytes and neutrophils are ma@or phagocytes.
)asophils and eosinophils to lesser extent.
(ymphocytes cannot phagocytose.

mm
#*. LYMPHOID ORGANS
PRIMARY LYMPHOID ORGANS
2a@or site of lymphopoeiesis.
&ells differentiate from stem cells=
2ature into functional cells: Tcells in thymus, )cells in bone marrow.
'ntigen receptors are ac6uired by cells in the primary organs.
&ells are selected when they only recogni3e nonself antigens.
!.Thymus
)ilobed organ overlying heart.
(obes divided into lobules.
%n each lobule the thymocytes ( lymphocytes in the thymus ) are arranged into an outer cortex and
an inner medulla.
&ortex contain immature Tcells. %nner medulla contains more mature Tcells.
'lso epithelial cells throughout.
't @unction between cortex and medulla mainly are found: %9& ( interdigitating dendritic cells ) and
macrophages.
+pithelial cells, %9& and macrophages express MHC molecules 5 vital in education and selection of
Tcells.
-. )one marrow
)cell development in bone marrow, liver in foetus
%slands of haematopoeitic tissue give rise directly to )lymphocyte.
)2 also an N) secondary lymphoid organ.
SECONDARY LYMPHOID ORGANS
&omprises: spleen
lymph nodes
2'(T ( mucosaassociated lymph tissues )
"rovide an environment where lymphocytes interact with:
each other
accessory cells: %9&, macrophages
antigens.
+ncapsulated organs
spleen, lymph nodes.
Spleen responds to antigens in the blood. (ymph nodes respond to antigens via lymphatics and from
the s,in.
*esults in antibody secretion and cellular response.
Nonencapsulated organs
throughout body.
2ost associated with mucosal surfaces.
2'(T protects body by preventing antigens from entering through mucosal cells.
eg. tonsils contain large amounts of lymphoid tissue.
(ymphocyte traffic
(ymphocytes migrate from primary to secondary organs. 9on?t remain= moved to other secondary
organs via blood and lymph circulation.
Traffic ensures an antigen gets exposed to many lymphocytes.
%f reexposure to an antigen occurs, traffic halts for -1 hours.
(ymphocytes tend to home bac, to original organ site.
#+. ANTI,ODIES
)inding of ag and )cell surface ab GG )cell develops into plasma cells G produce ab with same
specificity as the )cell surface ab.
'ntibodies (immunoglobulins ) differ in terms of si3e, charge, amino acids, carbohydrate.
.eneral functions of immunoglobulins
!. 'ntigen binding
-. +ffector functions: binding with: cells of the immune system
some phagocytes
complement
)asic structure
Two identical light chains ( ,appa or lambda )
Two identical heavy chains
(in,ed by disulphide bonds.
&lass of ab determined by its heavy chain type:
eg. %g' 5 alpha chain
%g2 5 mu &#'%N
%g+ 5 epsilom
%g. 5 gamma
subclasses have the same heavy chain but with slight differences, eg. %g.!, %g.-, etc.
I-G MOLECULE SCHEMATIC
FAB REGION
FC REGION
HEAVY
LIGHT
HINGE REGION
CHAINS
V
C
C
C
V: VARIABLE REGION VARIABLE LIGHT AND HEAVY
C
C
C: CONSTANT REGIONS CONSTANT LIGHT AND
HEAVY
CH2 ACTIVATES
COMLEMENT
CH3 MEDIATES
MACROPHAGE
BINDING
L
H
(ight chains either both ,appa or both lambda
#eavy chains in %g. molecule are gamma, hence: .amma globulin ( %mmunoglobulin .amma ).
%g.
2onomer consisting of - either ,appa or lambda light chains and - gamma heavy chains.
2a@or immunoglobulin ( I:ILE ).
2a@or antibody of secondary response.
&rosses placenta.
%g2
"entamer of the %g. monomer, with mu heavy chains.
!:E of total antibodies.
2ostly intravascular.
9oes not cross placenta.
+arly antibody ( primary response ).
%g'
!L-:E
4sually exist as single unit,
S %g' ( secretory %g' > %g'- ) exists as a dimer.
"redominant in secretions 5 saliva, mil,, colostrum, bronchial, genitourinal secretions.
%g9
M!E
(arge 6uantities on )cell surfaces.
*ole possibly lymphocyte differentiation.
%g+
Not usually large amounts in serum.
)ound on surface membrane of basophils and mast cells.
'ssociated with allergies.
'ntibody variations
%sotypic
Aariation between different classes and subclasses of immunoglobulins.
'll the genes responsible for the various isotypic variations are present in all members of a
particular species, eg. .enes for gamma !1, mu, alpha, etc. are all found on the human genome.
'llotypic
.enetic variation of individuals within a species.
+g. %g./ not found in all people.
2ost allotypes are variations of &# domains ( &onstant #eavy ).
%diotypic
Aariation in variable domain ( A# and A( ), especially in hypervariable region, determine antigen
binding specificity.
"rivate idiotypes: specificity for an epitope ( agrecognition region ) uni6ue to one )cell clone.
"ublic idiotypes: epitopespecificity shared by more than one )cell clone.
#ypervariable se6uences ( &omplimentarity 9etermining *egions )
Fithin variable region of molecule. &alled J#ot spotsK.
Short aminoacid se6uences at pos. /:, L:, <L.
%ntervening regions called 7ramewor, regions.
&9* determines antigen binding site.
'ntibody 9iversity can be the result of:
!.*ecombination of genes
-.2ultiple germ line Agenes recombining and mista,es occurring
/.Somatic mutation ( in genomic Aregions )
1.9ifferent heavy and light chains that ma,e up an antibody.
&lass switching
0ccurs during immune response
#.. MHC ( M/0o1 Hi2to3o%&/t/4i)it$ Co%&)e5 )
%9&: %NT+*9%.%T'T%N. 9+N9*%T%& &+(( abundant in lymphoid tissue. 'cts as '"& ( antigen
presenting cell ) carrying ag fragment on 2#& protein. 2#& is a human leucocyte mar,er, called
#(' ( #uman (eucocytic 'ntigen ).
T&*: T&+(( *+&+"T0* ( S4*7'&+ ') )
T-CELL
CYTOTOX. OR
HELPER
T-CELL
(YTOTOXIC OR
HELPER
ID
C
MHC
I / II
ANTIGEN
FRAGMENT
TCR ( T-CELL
AB )
CD /
!"
IDC PROD#CES CYTO$INE
IL-% &HICH ATTRACTS
T-CELL
'"& produces cyto,ine, %nterleu,in!= stimulates Tcell development and production of %(-= T
maturation, prod. (ympho,ines to activate )cells.
CYTOTOXIC
T-CELL
APC
TCR
ANTIGEN FRAG-
MENT
B2
MICRO-
GLOB#LIN
MHC
CLASS I
CD8
C)/22 I MHC : HLA6A7 6,7 6C
#(' is a human white cell mar,er ( #uman (eucocytic 'ntigen ).
S
S
S
S
ALPHA %
CLEFT
ALPHA 2
ALPHA 3
COR$SCRE& HOLDS
HLA ANCHORED
PEPTIDE BINDING
REGION
IMMUNOGLOBULIN -
-LIKE REGION
TRANS-MEMBRANE
REGION
CYTOPLASMIC
REGION
Highly polyo!phi"
C!#$%#& "l#'%
(i)#!&i%y
N'(-)'*+m',)-./
CD" T-/0** 1.(23
-0,0 4.5 CD m5,60,
5(2 TCR
O(*+ 3m5** 5(7.80(
9,58m0(73 /5( 10
),030(702
.( /*097 ( %:-2: 5m.('
5/.23 ); 3'
5(7.80( m<37
10 ),'/03302
.(3.20 /0**.
B075-2 m./,'-
8*'1<*.(
"/= 3: 5m.(' 5/.23
C)/22 II MHC : HLA6DR7 6D7 6DP
S
S
S
S
COR$SCRE& FORMATION
H'*23 MHC 5(/-',02
'( /0** 3<,95/0
PEPTIDE BINDING
REGION
IMMUNOGLOBULIN
-LIKE REGION
TRANS-MEMBRANE
REGION
CYTOPLASMIC
REGION
Alph$ I
Alph$ *
B#%$ +
B#%$ *
H.8-*+ )'*+m',)-./
N'(-)'*+m',)-./
CD!" H0*)0, T-
/0** 1.(23 -0,0
4.5 CD! m5,60,
5(2 TCR
2#& genes
C-,'m'3'm0 >
MHC GENES
C*533 II C*533 III C*533 I
ALSO:
C*533 I : B2 m./,'8*'1<*.( /-5.( 80(0 9'<(2 '( /-,'m.%?
C*533 II : A*)-5 5(2 B075 /-5.(3 /'202 9', 1+ 2.990,0(7 80(03; 5**
(05, /0(7'm0,0.
G0(03 9', D2; DO; DX @ A )30<2'80(03 7-0., ),'70.(3 ('7 +07
2.3/'40,02.
C*533 III : 80(03 107B00( II 5(2 I /'20 9', /'m)*0m0(7 ),'70.(3.
MHC C*533 II 0C),03302 1+ 90B0, /0** 7+)03 7-5( C*533 I
L.(6580 2.30D<5*.1,.<m
S'm07.m03 7B' MHCE3 5,0 9'<(2 7'807-0, m',0 '970( 7-5( .3
3757.37./5**+ 0C)0/702. E8. HLA-A% 5(2 HLA-B .( C5</53.5(
)')<*57.'(.
M5(+ 5<7'-.mm<(0 2.3',20,3 -540 100( 533'/.5702 B.7- 5
)5,7./<*5, HLA 5**0*0.
#8. COMPLEMENT
&lassic "athway
&!6 complement protein binds to &onstant #eavy %% region of 'b.
&1 binds to &!s G &1a ( circulating role in inflammation ) C &1b
( a always smaller fragment, b big )
&- activated by 2gCC attaches to &1b
&- G &-a ( remains attached to &1bcomplex ) C &-b ( goes into circulation )
&/ attaches to &1b-a ( called &/ convertase ) G &/a ( to circulation= role in inflammation ) C &/b
( added to complex )
&L attaches to &1b-a/b ( called &L convertase ) G &La ( to circulation= role in inflammation ) C &Lb
( to common pathway )
2'& ( &ommon "athway )
&Lb C &H G &LbH
&LbH C &I G &LbHI ( inserts into infected cell membrane in doughnut conformation )
&LbHI C &B ( / chains ) C &< ( !-!L chains ) G molecular conformation creates hole in membrane
G cell lysis.
'lternative "athway
No antibody re6uired to initiate 'lternative "athway.
&omplement can bind directly to surface of microbial agent. &oating of antigen by complement
factors is called opsonisation. 2a,es antigen attractive to phagocytes.
&/ G &/a C &/b
&/b C )b ( from factor ) ) forms cleavage complex:
&/b)b acts as &/ covertase which cleaves &/ to produce more &/b ( positive feedbac,
amplification ). &/b responsible for opsonisation.
&L cleaved by &/b)b/b ( &L convertase ) to yield &Lb
&H, I, B and < added on uncleaved > 2'&
7unctions of &omplement
!. 2ediate cytolysis by aggregating on cell surfaces and creating pores.
-. 0psonisation of foreign organisms 5 phagocytes bind to these agcoating complement
components via special receptors. Thus, complement aids phagocytosis.
/. %nflammation activation : some fragments are chemotactic 5 induce migration of
inflammatory cells.
1. Solubilisation of agabcomplexes to ma,e them removable from tissues.
Summary
&omplement components exist as inactive forms.
Fhen activated, proteins are first cleaved.
Se6uences follow formation of cascade.
'mplification occurs : each activated molecule generates multiple active fragments at the next step.
&lassical "athway : agab complexes activate complement.
'lternative "athway : complement binds directly to antigen , opsonisation for phagocytosis.
Re-9)/tion of 3o%&)e%ent /3ti:/tion :
So it doesn?t run amo,.
Soluble serum proteins
&! inhibitor : serine protease inhibitor covalently binds to &!r and &!s to bloc, their role in
complement cascade.
Sprotein : binds to &LbHI ( doughnut ) complex and prevents membrane insertion of 2'&.
S"1:,1: : modulates 2'& formation.
%ntegral membrane proteins
&*! ( &omplement *eceptor Type ! ) : accelerates dissociation of &/ convertases.
: 'cts as cofactor for factor ! mediated cleavage of &/b and
&1b.
#*7 ( #omologous *estriction 7actor ): inhibits lysis of bystander cells ( ie. *eactive lysis ) so that
only target cells are lysed.
: )loc,s &< binding to &B, thus preventing 2'& formation.
&9L< ( 2embrane %nhibitor of *eactive (ysis ) : inhibits reactive lysis by bloc,ing &I and &B from
binding to &LbH.
#;. THE IMMUNE RESPONSE
+xposure to an antigen :
)lymphos proliferate, differentiate into antibodyproducing plasma cells and memory cells.
Tlymphos are stimulated to become effector cells that either directly eliminate, or produce
molecules that help other cells destroy the pathogen ( ie. &hemical signals ).
Type and magnitude of response depends on :
Nature of the antigen
9ose of the antigen
*oute of entry 5 eg. 2ucous G %g'-
.enetic ma,eup of the individual 5 eg. #ypersensitivity to particular antigen
"revious exposure to the antigen ( primary vs. secondary response ).
)cell activation
Surface %g2 triggered on )cell
%ncreased &aCC ions inside cell
%ncreased *N' synthesis ( *eason why plasma cell stain blue with *omaows,i stain )
G increased immunoglobulin production.
This may be all that?s re6uired to destroy the antigen 5 ie. Tcell involvement not re6uired.
'ntigens destroyed in this way called thymusindependant antigens ( ie. 'g?s that stimulate ab
production directly ).
- types :
2itogens : cause )cells to proliferate. Some lectins have mitogen activity (derived from plant
seeds eg. "#', po,eweed ).
(arge molecules : interact directly with )cell%g. 'lso interact with macrophages in secondary
lymphoid tissue. &ause abproduction.
Thymus dependant antigens
2ost ag?s re6uire Tcell mediation.
+pitopes of the antigen bind to surface%g2, but cannot elicit antibody production.
They act li,e haptens ( ag too small to stimulate ab production ).
0ther areas of the antigen stimulate Tcells to provide signals to )cells to differentiate into plasma
cells ( humoral response ).
'ntigen processing and presentation of exogenous molecules (eg. )acteria )
Stage ! : 'ntigen processing and presentation on 2#&
'ntigen is internali3ed ( phagocytosed ) and digested by a phagocytic cell.
Small peptides are generated ( !:-: amino acid fragments ).
2#& class %% molecules are produced by these phagocytes.
The agpeptide fragments associate with the 2#& class %% molecules and transported to the cell
surface.
Stage - : %nterleu,in!
The aforementioned '"& ( 'ntigen "resenting &ell ) produces %(!.
*esting ) and Tcells have a receptor for %(!. Stimulated.
Tcells produce %(- G Tcell stimulation and growth.
Newly activated Tcells produce other lympho,ines which lead to )cell activation, proliferation
and differentiation into plasma cells, or development into effector Tcells.
'g eliminated.
'ntigen processing and presentation of endogenous molecules ( eg. Airuses and T) )
&9BC T ( cytotoxic ) cells recognise antigen expressed on 2#& class %.
Note that all nucleated cells express 2#& class % , thus able to present agfragments to T cytotoxic
cells. %f a virus invades and multiplies inside a host cell, that cell synthesises 2#& class %
molecules. Airal peptides associate with the 2#& class % inside the cell= both moved to cell surface.
Same pathway as with exogenous molecules follow : The infected cell is the '"&. "roduces %(!.
Stimulate resting ) and Tcells ( which have %l! receptor ). Tcells produce %(- G Tcell
stimulation and growth G Tcells produce other lympho,ines G )cells become plasma cells G
produce ab?s to eliminate ag.
N) : Tcells mature, move into circulation. T cytoxic cells lyse virus containing cells by releasing
perforin.
Tcells die after @ob complete.
2emory cells
memory )cells:
http:NNen.wi,ipedia.orgNwi,iN2emoryOcells

memory Tcells:
http:NNen.wi,ipedia.orgNwi,iN2emoryOTOcells
( see summary in bloc, on right )
CONTROL OF THE IMMUNE RESPONSE
*eaction to ag in one of two ways : immunity or tolerance ( ac6uisition of nonreactivity towards an
ag ).
&ontrol of immune response
!.*ole of antigen
"rimary regulator.
0nce ag eliminated, cells not stimulated anymore 5 die= but memory cells formed in case ag
encountered in future ( G secondary immune resp. )
-.*ole of antibodies
'b?s bloc, antigenic sites 5 so no more ab?s made.
7ree ab ( %g. ) competes for antigenbinding more effectively than cell bound ab ( %g2 ).
/.%mmune complexes
Suppress ab production.
1.*egulatory Tcells
#elper factors ( chemical stimulants ) not produced indefinitely.
(ympho,ines inhibit further proliferation > negative feedbac,.
L.%diotypes
'ntiantibodies produced against an idiotype ( a clone ) inhibit response by binding to existing ab?s.
H.Tolerance
Natural or ac6uired.
Natural
Nonresponsiveness to S+(7 molecules.
%f bro,en down G autoimmunity
Natural tolerance induced during foetal development 5 no host recognition involved.
'c6uired
%nduced by a pathogen with a tolerogenic epitope which mimics selfag.
Tolerogenic epitope may be advantageous, eg. %n transplantation.
Sometimes high doses of ag, or repeated exposure to minute doses may induce ac6uired tolerance.
"roteins induce tolerance better when soluble.
Tcell tolerance
'c6uired in thymus.
&91CBC ( double ) thymocytes die.
Negative selection : only Tcells that don?t respond to ownag are passed.
2#& class % and %% on macrophages and other cells J expose Jselfreactive Tcells. &alled veto cells
remove them.
"ostthymic tolerance: some faulty Tcells may escape thymus. "erhaps selfag was not expressed
correctly ( unprofessional '"&?s ), or they have low affinity for them or in too low concentration.
$et, autoimmunity does not occur, because: low affinity for selfag?s = may be removed by spleen
or *+S ( reticuloendothelial system ).
)cell tolerance
Some microorganisms have both foreign and selfli,e epitopes ( tolerogenic epitopes ).
Sometimes )cells re6uire no help ( second signallympho,ines ) from Tcells.
%f a selfreactive )cell escapes bone marrow, it?s not too serious, since )cells die off soon anyway.
'rtificially induced tolerance
&himerism: &oexistence of two or more populations of cells. &an occur if patient is immune
suppressed in transplantation.
.A#9 ( graft vs. host defence ) transplanted tissue may contain mature Tcells. 2ay react to host
(often fatal ).
Treatment : add antiT, eg. 'nti&91C or 'nti&9BC. 0ccupy the Tcells. N administration of
soluble ag to induce tolerance. N attach ag to a naPve )cell ( lac,s Tcell stimulator ). N clonal
exhaustion N antagonists to bloc, 2#& groove N antiab?s to )cell %g.N 'dd Thelper- cells to
suppress Thelper! action.
)rea,down of tolerance
> autoimmunity. #ow8
2#& types:
some 2#& molecules on ? veto cells ?do not remove selfreactive Tcells.
0thers remove the wrong Tcells.
&ross reactivity
+g. microorganisms may have tolerogenic epitopes among other epitopes. &onfuses immune
response.
"reviously inaccessible selfantigens
now exposed to Tcells for first time outside thymus.
&yto,ines
disturbance in cyto,inic production.
%mmune regulation failure
G loss of tolerance.
#;. HYPERSENSITI"ITY
Definition: +xaggerated or inappropriate response of body?s immune system.
&auses inflammatory response and tissue damage. 7our types.
Types %, %%, %%% are antibody mediated.
Type %A is Tcell mediated.
Type % ( %mmediate hypersensitivity )
'llergic reaction. %mmediately follows antigen contact.
The antigen is classified as an allergen.
J'llergyK is synonymous with Type %.
7amily history has a ma@or role.
'topy: asthma, ec3ema, hay fever, food allergy, urticaria ( hives ).
http:NNen.wi,ipedia.orgNwi,iN'topic
(evels of circulating %g+ to an allergen determine whether an anaphylactic reaction will occur upon
reexposure to the same ag. http:NNen.wi,ipedia.orgNwi,iN'naphylaxis
2echanisms:
Nonallergic patient
'g enters body.
%g2 produced ( primary response ).
Second response : %g+ produced by plasma cells. Aery low levels of %g+ produced.
'llergic patient
Aery high levels of %g+ produced by plasma cells.
%g+ associates with two cell types: basophils and mast cells.
These cells have surface receptors for the 7& region of the %g+ molecule. ( 7&: crystalli3able
fragment 5 see schematic of %g. earlier in notes. )
Anti-en 4in(in- 2ite

also see http:NNen.wi,ipedia.orgNwi,iN%g+

Nonallergic patient
2any epitopes ( antigenic determinants ) expressed on cell surfaces in low amounts.
'llergic patient
'lso low levels of many different epitopes ( idiotypes ), but large amount of sites to a particular
epitope.
MAST CELL OR
BASOPHIL
I8E
Note that several %g+?s are anchored on surfaces of mast cells and basophils. %g+ molecules must be
close to one another in order for a response to be generated to antigenic binding. This is the case
with allergic patients due to very high levels of %g+.
2ast cells and basophils release histamine and other factors ( heparin, chemotactic factors, platelet
activating factors ).
#istamine causes: smooth muscle contraction, vasodilation, increased vascular permeability.
Normal response is controlled. %f out of control G anaphylactic response.
%f the allergen is in@ected into circulation ( ie. Not locali3ed ) eg. "enicillin G systemic anaphylaxis
with dyspnoea, bronchospasm, laryngeal edema and vasodilation G sudden drop in )".
%f allergen enters mucous eg pollen, house dust etc. local reaction occurs in respiratory areas.
%f allergen in intestinal mucosa eg nuts, strawberries and fish, a mixed reaction occurs including
s,in rashes and asthma.
The higher individual?s %g+ level, the greater chances of allergy 5 strong family association.
Therapy:
avoid contact with allergen,
small doses of ag continuously given to induce tolerance,
antihistamines to bloc, effects of histamine.
Type %% ( &ytotoxic or '9&& ) hypersensitivity
'9&&: 'ntibodydependant cellmediated
%n Type %% hypersens. , antibodies bind to cells or to an antigen adsorbed onto host cells.
&ells involved: neutrophils, eosinophils, monocytes and ND cells.
+xamples: incompatible blood transfusion, rhesusincompatibility, ab against selfmolecules, eg
thyroid cells ( #ashimoto?s thyroiditis ), ,idney cells ( .oodpasture?s Syndrome ), muscle cells
( 2yesthemia gravis ).
Sedormid is a drug that adsorbs on to platelets. 'b directed at drug destroy platelets.
Some infections eg salmonella or 2ycobacterial infections 5 endotoxins coat patient?s cells, cells
destroyed by antibodies.
Definition T$&e II: production of ab against a selfmolecule or against a foreign ag bound to a cell
surface, an infectious agent or inert material G damaging reactions ( inappropriate host response ).
Type %%% ( %mmune complex ) hypersensitivity
Si3e and form of immune complex depends on how much ag and ab are involved.
(arge complex formation determined by:
class of ab ( eg. %g2 much bigger, with multiple binding sites compared to %g.. )
biding strength of antigen.
Sometimes agab complex comes out of solution.
2onocytes and macrophages remove large complexes, but don?t clear complexes with excess ag
very well.
Neutrophils clear only large complexes.
%f excess ag present G inflammation. This is normal.
%f immune complex persists or become trapped in tissues G Type %%% hypersensitivity :
ischemia develops ( capillary networ,s become bloc,ed )
'rthus? reaction: local reaction. %f an ag is in@ected into circulation of a sensiti3ed patient, agab
complexes deposit in walls of blood vessels G redness, swelling, heat, pain ( ie vasculitis ). *esolves
after -1 hrs.( eg diabetics reacting to animalderived insulin ).
*espiratory type: asthma development 5 approx. B hrs later 'rthus? reaction in respiratory system.
+xamples: farmer?s lung from moldy hay , brewer?s alveolitis from contaminated barley, pigeon
fancier?s lung from dust from pigeon feces.
4sually due to defective wor,ing of macrophages, neutrophils or complement= 0* system
overloaded with complexes due to continuos large presence of the antigen li,e blood sepsis.
Triggers mast cells to degranulate.
Neutrophils attracted 5 release their toxic granules G tissue damage.
&omplement attaches to bystander cells 5 reactive lysis.
"latelet activation factor stimulated G microthrombi.
%f slight ag excess 5 local hypersensitivity in tissues.
%f large excess 5 agab complexes spill over into circulation G serum sic,ness
agab complexes may also deposit in s,in, ,idneys and @oints ( elephantiatis 5 enormous swellings ).
Serum sic,ness also results if patient reacts to diphtheria antitoxin prepared from horses.
'lso can occur in patients sensitive to penicillin and sulphonamide.
'lso streptococcal infection G ,idney damage.
'lso hepatitis ).
note: "enicillin can cause Type %, Type %%% and Type %A hypersensitivity.
Type %A ( &ell mediated or 9elayed ) hypersensitivity
Specifically provo,ed.
Slow to evolve ( -11B hrs )
%nvolves lymphocytes and macrophages.
*ecap on normal reaction to inracell. ag.
Tmemory cells of specific paratope ( recogni3e specific epitope or antigenic determinant ) are long
lived cells remaining a part of immune system after a primary response.
&irculate through body of sensiti3ed individual. 't reexposure to epitope ( presented by '"& on
2#& molecule ).
"roliferation occurs and lympho,ines released G attract macrophages= stimulate Tcytotoxic cells
( &9BC ) G eliminate ag.
N0F, Type %A hypersensitivity occurs when an +Q'..+*'T+9 &+(( 2+9%'T+9 %224N+
*+S"0NS+ occurs.
+xamples:
&hronic infectious diseases eg 2ycobacteria ( T) ) and fungi.
#ost unable to eliminate antigen G continuous release of lympho,ines G continued accumulation of
macrophages G cells fuse together 5 form giant cells.
2acrophages expressing epitope on 2#& release more lympho,ines G tissue damage G granuloma
forms to attempt to isolate ag. http:NNen.wi,ipedia.orgNwi,iN.ranuloma
2ore examples:
.ranulomas form against indigestible inorganic materials li,e silica and talc,
2easles and herpes lesions,
2etals eg nic,el ( in watch straps ),
poison ivy,
potassium dichromate in cement,
penicillin.
These substances on their own may not be antigenic= but when combined with protein eg in s,in :
(angerhans cells ta,e ag to lymph nodes. Tcells return to entry site to release lympho,ines.
*eaction site shows mononuclear infiltrate ( lymphocytes and macrophages ) at approx. 1B hrs.
&linical symptoms : ec3ema 5 redness, swelling, vesicles on s,in, scaling, exudate.
'dditional notes:
7oetal immune response
&91 Th! N Th-
Th! ( interferon gamma ) response > normal response to antigens eg infective agents.
Th- ( interleu,in 1 ) response > allergic response with %g+ production.
The foetal response is s,ewed to Th-.
%nfection in early life is the main immune stimulus helping to restore the balance between Th! and
Th- responses.
%n genetically susceptible infants, early exposure to allergens induces a Th- dominant response
( enhanced by cigarette smo,e exposure )
'lso, increased use of antibiotics may predispose to the persistence of a Th- phenotype in the
infant,
so that early exposure to allergens tend to induce allergic response.
2aternal %g+ does not cross placenta.
(ac, of evidence that manipulation of the maternal diet has a lasting effect on development of food
allergy.
S++ 74*T#+*: ,LOOD TRANSFUSION NOTES
http:NNwww.scribd.comNdocN!-H::!!BN)loodTransfusionNotes