3 immunopathology

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%

3 immunopathology

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