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8/11/2019 3 Immunopathology
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3 Immunopathology
Cells of the Immune System
Table 3-1. Types of Immune Cells
Cell Type Derivation Location Function
T cells CD4 (helper)CD8(cytotoxic/suppressor)
Bone marrowlymphocyte stemcells mature inthymus
Peripheral blood andbone marrow,thymus, paracortexo lymph nodes,Peyer!s patches
CD4 cells" secrete cyto#ines($%&' prolieration oCD4/CD8 T cells &intereronacti*ation o macropha+es)help B cells become antibody&producin+ plasma cellsCD8 cells" #ill *irus&inected,neoplastic, and donor +ratcells
B cells Bone marrowstem cells
Peripheral blood andbone marrow,+erminal ollicles in
lymph nodes,Peyer!s patches
Dierentiate into plasma cellsthat produce immuno+lobulinsto #ill encapsulated bacteria
(e+, Streptococcuspneumoniae)-ct as -PCs that interact withCD4 cells
.atural #iller cells Bone marrowstem cells
Peripheral blood(lar+e +ranularlymphocytes)
ill *irus&inected andneoplastic cells
0acropha+es Con*ersion omonocytes intomacropha+es inconnecti*e tissue
Connecti*e tissueor+ans (e+, al*eolarmacropha+es, lymphnode sinuses)
$n*ol*ed in pha+ocytosis andcyto#ine production
-ct as -PCs
Dendritic cells Bone marrowstem cells
1#in (%an+erhans!cells), +erminalollicles
-ct as -PCs
Cells of the Immune System
Table 3-1. Types of Immune Cells
Cell Type Derivation Location FunctionT cells CD4 (helper)CD8(cytotoxic/suppressor)
Bone marrowlymphocyte stemcells mature inthymus
Peripheral blood andbone marrow,thymus, paracortexo lymph nodes,Peyer!s patches
CD4 cells" secrete cyto#ines($%&' prolieration oCD4/CD8 T cells &intereronacti*ation o macropha+es)help B cells become antibody&producin+ plasma cellsCD8 cells" #ill *irus&inected,neoplastic, and donor +ratcells
B cells Bone marrowstem cells
Peripheral blood andbone marrow,+erminal ollicles inlymph nodes,Peyer!s patches
Dierentiate into plasma cellsthat produce immuno+lobulinsto #ill encapsulated bacteria(e+, Streptococcus
pneumoniae)-ct as -PCs that interact withCD4 cells
.atural #iller cells Bone marrowstem cells
Peripheral blood(lar+e +ranularlymphocytes)
ill *irus&inected andneoplastic cells
0acropha+es Con*ersion omonocytes intomacropha+es inconnecti*e tissue
Connecti*e tissueor+ans (e+, al*eolarmacropha+es, lymphnode sinuses)
$n*ol*ed in pha+ocytosis andcyto#ine production
-ct as -PCs
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Dendritic cells Bone marrowstem cells
1#in (%an+erhans!cells), +erminalollicles
-ct as -PCs
$nnate (natural, nonspeciic) immunity
2 -nti+en&independent cells pro*idin+ irst deense a+ainst patho+ens' Types o cells
a Pha+ocytic cells (e+, neutrophils, macropha+es)
b .atural #iller cells
-c3uired (speciic) immunity
2 -nti+en&dependent acti*ation and expansion o lymphocytes
' B lymphocytes produce antibodies (ie, humoral immune response)a $+0 synthesis be+ins at birth Presence o $+0 at birth may indicate con+enital inection
(e+, cytome+alo*irus)b $+ synthesis be+ins at ' months
Presence o $+ at birth is maternally deri*ed $+
5 T cells are in*ol*ed in cell&mediated immune responses
a!or "istocompatibility Comple# $"C%
%ocation
1hort arm o chromosome 6
%ocation
1hort arm o chromosome 6
7uman leu#ocyte anti+en (7%-) +enes
Code or 7%- proteins that are uni3ue to each indi*idual
Class $ 07C molecules
2 Coded by 7%-&-, &B, and &C +enes' Present on the membranes o all nucleated cells
o Notpresent on mature BCs present on platelets
5 eco+ni9ed by CD8 T cells and natural #iller cells
Class $$ 07C molecules
2 Coded by 7%-&DP, &D:, and &D +enes' Present on anti+en&presentin+ cells (-PCs)
o B cells, macropha+es, dendritic cells
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5 eco+ni9ed by CD4 T cells
7%- association with disease
2 7%-&B'; with an#ylosin+ spondylitis' 7%-&D' with multiple sclerosis
5 7%-&D5 and &D4 with type 2 diabetes mellitus
7%- testin+
2 Transplantation wor#upo Close matches o 7%-&-, &B, and &D loci in both the donor and +rat
recipient increase the chance o +rat sur*i*al' Determinin+ disease ris#
o ection
Pha+ocytosis" warm ($+) autoimmune hemolyticanemia, -B= and h hemolytic disease o newborn
Complement&independent reactions
-ntibody ($+, $+ections o increasin+ly
+reater amounts o aller+en, resultin+ in production o $+antibodies that attach to aller+ens and pre*ent them rom bindin+ tomast cells
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$+< antibody&mediated acti*ation o mast cells (eector cells) produces an
inlammatory reaction
2 $+< antibody production (sensiti9ation)a -ller+ens (e+, pollen, dru+s) are irst processed by -PCs
(macropha+es or dendritic cells)b -PCs interact with CD4 T7' cells, causin+ interleu#ins ($%s) to
stimulate B&cell maturationc $%&4 causes plasma cells to switch rom $+0 to $+< synthesisd $%&A stimulates the production and acti*ation o eosinophils
' 0ast cell acti*ation (reexposure)a -ller+en&speciic $+< antibodies are bound to mast cellsb -ller+ens cross&lin# $+< antibodies speciic or the aller+en on mast
cell membranesc $+< tri++erin+ causes mast cell release o preormed mediators
i
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4 Clinical examples o type $$ hypersensiti*ity (see
Type $$$ (immunocomplex) hypersensiti*itypa+e 4A
pa+e 46
-cti*ation o the complement system by circulatin+ anti+en&antibody
complexes (e+, D.-&anti&D.- complexes)
2 ?irst exposure to anti+eno 1ynthesis o antibodies
' 1econd exposure to anti+en
a. Deposition o anti+en&antibody complexes
b. Complement acti*ation, producin+ CAa, which attracts neutrophils
that dama+e tissue' -rthus reaction
a. %ocali9ed immunocomplex reaction
b.
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anti&7%- cytotoxic antibodies
5 Close matches o 7%-&-, &B, and &D loci between recipients and donors
?actors enhancin+ +rat *iability
2 -B= blood +roup compatibility between recipients and donors' -bsence o preormed anti&7%- cytotoxic antibodies in recipients
o People must ha*e pre*ious exposure to blood products to de*elop
anti&7%- cytotoxic antibodies
5 Close matches o 7%-&-, &B, and &D loci between recipients and donors
Types o +rats
The etus is an allo+rat that is notre>ected by the motherTrophoblastic tissue may pre*ent maternal T cells rom enterin+etus
2 -uto+rat (ie, sel to sel)o -ssociated with the best sur*i*al rate
' 1yn+eneic +rat (iso+rat)o Between identical twins
5 -llo+rato Between +enetically dierent indi*iduals o the same species
4 eno+rat
a. Between two species
b. ectionpa+e 46
pa+e 4;
-cute re>ection is potentially re*ersible with immunosuppressi*ea+ents, such as cyclosporine (bloc#s CD4 T&cell release o $%&'),=T5 (monoclonal antibody a+ainst T&cell anti+en reco+nition site),and corticosteroids (lymphotoxic) $mmunosuppressi*e therapy is
associated with an increased ris# o cer*ical s3uamous cell cancer,mali+nant lymphoma, and s3uamous cell carcinoma o the s#in(most common)
Transplantation re>ection in*ol*es a humoral or cell&mediated host response
a+ainst 07C anti+ens in the donor +rat
2 7yperacute re>ectiona $rre*ersible reaction occurs within minutesb Patho+enesis
i -B= incompatibility or action o preormed anti&7%-antibodies in the recipient directed a+ainst donor anti+ens in
*ascular endotheliumii Type $$ hypersensiti*ity reaction
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c Patholo+ic indin+
@essel thrombosisb ection
a 0ost common transplant re>ectionb e*ersible reaction that occurs within days to wee#s
i Type $@ cell&mediated hypersensiti*ity CD4 T cells release cyto#ines, resultin+ in acti*ation
o host macropha+es, prolieration o CD8 T cells,and destruction o donor +rat cells
uryii -ntibody&mediated type $$ hypersensiti*ity reaction
Cyto#ines rom CD4 T cells promote B&cell
dierentiation into plasma cells, producin+ anti&7%-
antibodies that attac# *essels in the donor +rat @asculitis with intra*ascular thrombosis in recent
+rats $ntimal thic#enin+ with obliteration o *essel lumens
in older +rats
' Chronic re>ection
b $rre*ersible reaction that occurs o*er months to yearsc Patho+enesis
i .ot well characteri9edii $n*ol*es continued *ascular in>ury with ischemia to tissue
d Blood *essel dama+e with intimal thic#enin+ and ibrosis
rat&*ersus&host (@7) reaction
2 Causesa Potential complication in bone marrow and li*er transplantsb Potential complication in blood transusions +i*en to patients with a T&
cell immunodeiciency and newborns' Patho+enesis
o Donor T cells reco+ni9e host tissue as orei+n and acti*ate host CD4
and CD8 T cells2. Clinical indin+s
a Bile duct necrosis (>aundice)b astrointestinal mucosa ulceration (bloody diarrhea)
c Dermatitis
Types o transplants
Table 3-3. Some Types of Transplants
Type of Transplant Comments
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Cornea Best allo+rat sur*i*al rateDan+er o transmission o Creut9eldt&a#ob disease
idney Better sur*i*al with #idney rom li*in+ donor than rom cada*er
Bone marrow rat contains pluripotential cells that repopulate host stem cells7ost assumes donor -B= +roupDan+er o +rat&*ersus&host reaction and cytome+alo*irus inection
*utoimmune Diseases
-utoimmune dysunction is associated with a loss o sel&tolerance, resultin+
in immune reactions directed a+ainst host tissue
0echanisms o autoimmunity
2 elease o normally se3uestered anti+ens (e+, sperm)' 1harin+ o anti+ens between host and patho+en
5 Deects in unctions o helper or suppressor T cells4 Persistence o autoreacti*e T and B cells
A Presence o speciic autoantibodies
Table 3-+. *utoantibo,ies in *utoimmune Disease
*utoantibo,ies DiseaseTest Sensitivity$%
-ntiacetylcholine receptor 0yasthenia +ra*is E
-nti&basement membrane oodpasture syndrome FE
-nticentromere C
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Connecti*e tissue disease that mainly aects the blood, >oints, s#in, and
#idneys
2 =ccurs predominantly in women o childbearin+ a+e' Patho+enesis
o Polyclonal B&cell acti*ation, sustained estro+en acti*ity,
en*ironmental tri++ers (e+, sun, procainamide)5 Clinical indin+s
a. 7ematolo+ic
-utoimmune hemolytic anemia, thrombocytopenia,
leu#openiab. %ymphatic
22 enerali9ed painul lymphadenopathy
222 1plenome+aly
b. 0usculos#eletal
1mall&>oint inlammation (e+, hands) with absence o >oint
deormity22 1#in
22 $mmunocomplex deposition alon+ basement membrane
Produces li3ueacti*e de+eneration
222 0alar butterly rash
b. enal
Diuse prolierati*e +lomerulonephritis (most common+lomerulonephritis)
22 Cardio*ascular
22 ?ibrinous pericarditis with or without eusion
222 %ibman&1ac#s endocarditis (sterile *e+etations on mitral
*al*e)c. espiratory
22 $nterstitial ibrosis o lun+s
222 Pleural eusion with riction rub
d. Pre+nancy&related
22 Complete heart bloc# in newborns
Caused by $+ anti&11&- (o) antibodies crossin+the placenta
222 ecurrent spontaneous abortions
Caused by antiphospholipid antibodies
' Dru+&induced lupus erythematosusa. -ssociated dru+s
Procainamide, hydrala9ine
22 ?eatures that distin+uish dru+&induced lupus rom 1%