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 marrow
lymphocyte stem
cells mature in
thymus
Peripheral blood and
bone marrow,
thymus, paracortex
o lymph nodes,
Peyer!s patches
CD4 cells" secrete cyto#ines
($%&' prolieration o
CD4/CD8 T cells( )&intereron
acti*ation o macropha+es)(
help B cells become antibody&
producin+ plasma cells
CD8 cells" #ill *irus&inected,
neoplastic, and donor +rat
cells
B cells Bone marrow
stem cells
Peripheral blood and
bone marrow,
+erminal ollicles in
lymph nodes,
Peyer!s patches
Dierentiate into plasma cells
that produce immuno+lobulins
to #ill encapsulated bacteria
(e,+,, Streptococcus
pneumoniae)
-ct as -PCs that interact with
CD4 cells
.atural #iller cells Bone marrow
stem cells
Peripheral blood
(lar+e +ranular
lymphocytes)
/ill *irus&inected and
neoplastic cells
0acropha+es Con*ersion o
monocytes into
macropha+es in
connecti*e tissue
Connecti*e tissue(
or+ans (e,+,, al*eolar
macropha+es, lymph
node sinuses)
$n*ol*ed in pha+ocytosis and
cyto#ine production
-ct as -PCs
Dendritic cells Bone marrow
stem cells
1#in (%an+erhans!
cells), +erminal
ollicles
-ct as -PCs
Cells of the Immune System
Table 3-1. Types of Immune Cells
Cell Type Derivation Location Function
T cells CD4 (helper)
CD8
(cytotoxic/suppressor)
Bone marrow
lymphocyte stem
cells mature in
thymus
Peripheral blood and
bone marrow,
thymus, paracortex
o lymph nodes,
Peyer!s patches
CD4 cells" secrete cyto#ines
($%&' prolieration o
CD4/CD8 T cells( )&intereron
acti*ation o macropha+es)(
help B cells become antibody&
producin+ plasma cells
CD8 cells" #ill *irus&inected,
neoplastic, and donor +rat
cells
B cells Bone marrow
stem cells
Peripheral blood and
bone marrow,
+erminal ollicles in
lymph nodes,
Peyer!s patches
Dierentiate into plasma cells
that produce immuno+lobulins
to #ill encapsulated bacteria
(e,+,, Streptococcus
pneumoniae)
-ct as -PCs that interact with
CD4 cells
.atural #iller cells Bone marrow
stem cells
Peripheral blood
(lar+e +ranular
lymphocytes)
/ill *irus&inected and
neoplastic cells
0acropha+es Con*ersion o
monocytes into
macropha+es in
connecti*e tissue
Connecti*e tissue(
or+ans (e,+,, al*eolar
macropha+es, lymph
node sinuses)
$n*ol*ed in pha+ocytosis and
cyto#ine production
-ct as -PCs
Dendritic cells Bone marrow
stem cells
1#in (%an+erhans!
cells), +erminal
ollicles
-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 (i,e,, 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, $+4 synthesis be+ins at ' months,
Presence o $+4 at birth is maternally deri*ed $+4,
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 Not present on mature 8BCs( present on platelets
5, 8eco+ni9ed by CD8 T cells and natural #iller cells
Class $$ 07C molecules
2, Coded by 7%-&DP, &D:, and &D8 +enes
', Present on anti+en&presentin+ cells (-PCs)
o B cells, macropha+es, dendritic cells
5, 8eco+ni9ed by CD4 T cells
7%- association with disease
2, 7%-&B'; with an#ylosin+ spondylitis
', 7%-&D8' with multiple sclerosis
5, 7%-&D85 and &D84 with type 2 diabetes mellitus
7%- testin+
2, Transplantation wor#up
o Close matches o 7%-&-, &B, and &D loci in both the donor and +rat
recipient increase the chance o +rat sur*i*al,
', Determinin+ disease ris#
o <xample&7%-&B';&positi*e indi*iduals ha*e an increased ris# o
an#ylosin+ spondylitis,
"ypersensitivity &eactions
Table 3-'. "ypersensitivity &eactions
&eaction(athogenesis )#amples
Type $ $+<&dependent acti*ation
o mast cells
-topic disorders" hay e*er, ec9ema, hi*es, asthma,
reaction to bee stin+
Dru+ hypersensiti*ity" penicillin rash or anaphylaxis
Type $$ -ntibody&dependent
reaction
Complement&dependent reactions
%ysis" -B= mismatch, 4oodpasture!s syndrome,
hyperacute transplantation re>ection
Pha+ocytosis" warm ($+4) autoimmune hemolytic
anemia, -B= and 8h hemolytic disease o newborn
Complement&independent reactions
-ntibody ($+4, $+<)&dependent cell&mediated
cytotoxicity" natural #iller cell destruction o neoplastic
and *irus&inected cells( helminth destruction by
eosinophils
-ntibodies directed a+ainst cell surace receptors"
myasthenia +ra*is, 4ra*es! disease
Type $$$ Deposition o anti+en&
antibody complexes
1ystemic lupus erythematosus (D.-&anti&D.-)
8heumatoid arthritis ($+0&?c receptor $+4)
1erum sic#ness (horse antithymocyte +lobulin&antibody)
Type $@ -ntibody&independent T
cell&mediated reactions
Delayed type" contact dermatitis (e,+,, poison i*y),
tuberculous +ranuloma
Cell&mediated cytotoxicity" #illin+ o tumor cells and *irus&
inected cells
Type $ (immediate) hypersensiti*ity
pa+e 44
pa+e 4A
Desensiti9ation therapy in*ol*es repeated in>ections o increasin+ly
+reater amounts o aller+en, resultin+ in production o $+4
antibodies that attach to aller+ens and pre*ent them rom bindin+ to
mast cells,
$+< 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 maturation,
c, $%&4 causes plasma cells to switch rom $+0 to $+< synthesis,
d, $%&A stimulates the production and acti*ation o eosinophils,
', 0ast cell acti*ation (reexposure)
a, -ller+en&speciic $+< antibodies are bound to mast cells,
b, -ller+ens cross&lin# $+< antibodies speciic or the aller+en on mast
cell membranes,
c, $+< tri++erin+ causes mast cell release o preormed mediators,
i, <arly phase reaction with release o histamine, chemotactic
actors or eosinophils, proteases
ii, Produces tissue swellin+ and bronchoconstriction
d, %ate&phase reaction
i, 0ast cells synthesi9e and release prosta+landins and
leu#otrienes,
ii, <nhances and prolon+s acute inlammatory reaction
5, Tests used to e*aluate type $ hypersensiti*ity
a, 1cratch test (best o*erall sensiti*ity)
Positi*e response is a histamine&mediated wheal&and&lare
reaction ater introduction o an aller+en into the s#in,
b, 8adioimmunosorbent test
Detects speciic $+< antibodies in serum that are a+ainst
speciic aller+ens
22 Clinical examples o type $ hypersensiti*ity (see
Type $$ (cytotoxic) hypersensiti*ity
-ntibody&dependent cytotoxic reactions
2, Complement&dependent reactions
a, %ysis
-ntibody ($+4 or $+0) directed a+ainst anti+en on the cell
membrane acti*ates the complement system, leadin+ to lysis
by the membrane attac# complex,
b, Pha+ocytosis
?ixed macropha+es (e,+,, in spleen) pha+ocytose
hematopoietic cells (e,+,, 8BCs) coated by $+4 antibodies
and/or complement (C5b),
', Complement&independent reactions
a, -ntibody ($+4, $+<)&dependent cell&mediated cytotoxicity
%eu#ocytes with receptors or $+4 or $+< lyse but do not
pha+ocytose cells coated by antibodies,
b, $+4 autoantibodies directed a+ainst cell surace receptors
5, Tests used to e*aluate type $$ hypersensiti*ity
a, Direct Coombs! test detects $+4 and/or C5b attached to 8BCs,
b, $ndirect Coombs! test detects antibodies in serum (e,+,, anti&D),
4, Clinical examples o type $$ hypersensiti*ity (see
Type $$$ (immunocomplex) hypersensiti*ity
pa+e 4A
pa+e 46
-cti*ation o the complement system by circulatin+ anti+en&antibody
complexes (e,+,, D.-&anti&D.- complexes)
2, ?irst exposure to anti+en
o 1ynthesis o antibodies
', 1econd exposure to anti+en
a. Deposition o anti+en&antibody complexes
b. Complement acti*ation, producin+ CAa, which attracts neutrophils
that dama+e tissue
', -rthus reaction
a. %ocali9ed immunocomplex reaction
b. <xample&armer!s lun+ rom exposure to thermophilic actinomycetes,
or anti+ens, in air
5, Test used to e*aluate type $$$ hypersensiti*ity
a. $mmunoluorescent stainin+ o tissue biopsies
b. <xample&+lomeruli in +lomerulonephritis
4, Clinical examples o type $$$ hypersensiti*ity (see
Type $@ hypersensiti*ity
-ntibody&independent T cell&mediated reactions (cellular immunity)
2, Delayed reaction hypersensiti*ity
o CD4 cells interact with macropha+es (-PCs with 07C class $$
anti+ens), resultin+ in cyto#ine in>ury to tissue,
', Cell&mediated cytotoxicity
o CD8 T cells interact with altered 07C class $ anti+ens on neoplastic,
*irus&inected, or donor +rat cells, causin+ cell lysis,
5, Test used to e*aluate type $@ hypersensiti*ity
a. Patch test to conirm contact dermatitis
<xample&suspected aller+en (e,+,, nic#el) placed on an
adhesi*e patch is applied to the s#in to see i a s#in reaction
occurs,
b. 1#in reaction to Candida
', Clinical examples o type $@ hypersensiti*ity (see
Transplantation Immunology
?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
?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 not re>ected by the mother,
Trophoblastic tissue may pre*ent maternal T cells rom enterin+
etus,
2, -uto+rat (i,e,, sel to sel)
o -ssociated with the best sur*i*al rate
', 1yn+eneic +rat (iso+rat)
o Between identical twins
5, -llo+rat
o Between +enetically dierent indi*iduals o the same species
4, Beno+rat
a. Between two species
b. <xample&transplant o heart *al*e rom pi+ to human
Types o re>ection
pa+e 46
pa+e 4;
-cute re>ection is potentially re*ersible with immunosuppressi*e
a+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>ection
a, $rre*ersible reaction occurs within minutes,
b, Patho+enesis
i, -B= incompatibility or action o preormed anti&7%-
antibodies in the recipient directed a+ainst donor anti+ens in
*ascular endothelium
ii, Type $$ hypersensiti*ity reaction
c, Patholo+ic indin+
@essel thrombosis
b, <xample&blood +roup - person recei*es a blood +roup B heart,
22 -cute re>ection
a, 0ost common transplant re>ection
b, 8e*ersible reaction that occurs within days to wee#s
i, Type $@ cell&mediated hypersensiti*ity
CD4 T cells release cyto#ines, resultin+ in acti*ation
o host macropha+es, prolieration o CD8 T cells,
and destruction o donor +rat cells,
<xtensi*e interstitial round cell lymphocytic iniltrate
in the +rat, edema, and endothelial cell in>ury
ii, -ntibody&mediated type $$ 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 years
c, Patho+enesis
i, .ot well characteri9ed
ii, $n*ol*es continued *ascular in>ury with ischemia to tissue
d, Blood *essel dama+e with intimal thic#enin+ and ibrosis
4rat&*ersus&host (4@7) reaction
2, Causes
a, Potential complication in bone marrow and li*er transplants
b, 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 cells,
2. Clinical indin+s
a, Bile duct necrosis (>aundice)
b, 4astrointestinal mucosa ulceration (bloody diarrhea)
c, Dermatitis
Types o transplants
Table 3-3. Some Types of Transplants
Type of Transplant Comments
Cornea Best allo+rat sur*i*al rate
Dan+er o transmission o Creut9eldt&Ca#ob disease
/idney Better sur*i*al with #idney rom li*in+ donor than rom cada*er
Bone marrow 4rat contains pluripotential cells that repopulate host stem cells
7ost assumes donor -B= +roup
Dan+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, 8elease 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 cells
4, Persistence o autoreacti*e T and B cells
A, Presence o speciic autoantibodies
Table 3-+. *utoantibo,ies in *utoimmune Disease
*utoantibo,ies Disease
Test Sensitivity
$-%
-ntiacetylcholine receptor 0yasthenia +ra*is DE
-nti&basement membrane 4oodpasture syndrome FDE
-nticentromere C8<1T syndrome 5E
-ntiendomysial and anti+liadin Celiac disease DA
-nti&insulin Type 2 diabetes AE
-nti&islet cell ;A
-nti&intrinsic actor Pernicious anemia 6E
-nti&parietal cell DE
-ntimicrosomal 7ashimoto!s thyroiditis D;
-ntithyro+lobulin 8A
-ntimitochondrial Primary biliary cirrhosis DE&2EE
-ntimyeloperoxidase 0icroscopic polyan+iitis 8E (p&-.C-)
-ntiproteinase 5 Ge+ener!s +ranulomatosis FDE (c&-.C-)
-ntiribonucleoprotein 0ixed connecti*e tissue
disease
2EE
-nti&thyroid&stimulatin+ hormone
receptor
4ra*es! disease 8A
c&-.C-, cytoplasmic antineutrophil cytoplasmic antibody( p&-.C-, perinuclear antineutrophilic cytoplasmic
antibody,
1ystemic lupus erythematosus (1%<)
pa+e 4D
pa+e AE
-nticardiolipin antibodies may produce a alse&positi*e syphilis
serolo+ic test by cross&reactin+ with cardiolipin in the rapid plasma
rea+in (8P8) and @enereal Disease 8esearch %aboratory (@D8%)
tests,
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#openia
b. %ymphatic
22 4enerali9ed painul lymphadenopathy
222 1plenome+aly
b. 0usculos#eletal
1mall&>oint inlammation (e,+,, hands) with absence o >oint
deormity
22 1#in
22 $mmunocomplex deposition alon+ basement membrane
Produces li3ueacti*e de+eneration
222 0alar butterly rash
b. 8enal
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. 8espiratory
22 $nterstitial ibrosis o lun+s
222 Pleural eusion with riction rub
d. Pre+nancy&related
22 Complete heart bloc# in newborns
Caused by $+4 anti&11&- (8o) antibodies crossin+
the placenta
222 8ecurrent spontaneous abortions
Caused by antiphospholipid antibodies
', Dru+&induced lupus erythematosus
a. -ssociated dru+s
Procainamide, hydrala9ine
22 ?eatures that distin+uish dru+&induced lupus rom 1%<
22 -ntihistone antibodies
222 %ow incidence o renal and central ner*ous system (C.1)
in*ol*ement
2222 Disappearance o symptoms when the dru+ is discontinued
5, %aboratory indin+s in 1%<
a. Positi*e serum antinuclear antibody (-.-) (almost all cases)
22 -nti&double&stranded D.- antibodies and anti&1m antibodies
Hsed to conirm the dia+nosis o 1%<, because they
are hi+hly speciic or the disease (i,e,, ew alse&
positi*e results)
222 -nti&8o antibodies are positi*e in 'AI to AEI o cases,
b. -ntiphospholipid antibodies
22 %upus anticoa+ulant and anticardiolipin antibodies
222 Dama+e *essel endothelium, producin+ *essel thrombosis
2222 $ncreased incidence o stro#es and recurrent spontaneous
abortions
c. %upus erythematosus cell
22 .eutrophil containin+ pha+ocytosed altered D.-
222 Not speciic or 1%<
d. Decreased serum complement
Hsed up with acti*ation o complement system
22 $mmunocomplexes at the dermal&epidermal >unction in s#in biopsies
$mmunoluorescent studies identiy complexes in a band&li#e
distribution alon+ the dermal&epidermal >unction,
1ystemic sclerosis (scleroderma)
pa+e A'
<xcessi*e production o colla+en that primarily tar+ets the s#in (scleroderma),
+astrointestinal tract, lun+s, and #idneys
2, =ccurs predominantly in women o childbearin+ a+e
', Patho+enesis
a, 1mall&*essel endothelial cell dama+e produces blood *essel ibrosis
and ischemic in>ury,
b, T&cell release o cyto#ines results in excessi*e colla+en synthesis,
5, Clinical indin+s
a, 8aynaud!s phenomenon
i, 1e3uential color chan+es (normal to blue to red) caused by
di+ital *essel *asculitis and ibrosis
ii, Di+ital inarcts
b, 1#in
i, 1#in atrophy and tissue swellin+ be+innin+ in the in+ers and
extendin+ proximally
ii, Parchment&li#e appearance
iii, <xtensi*e dystrophic calciication in subcutaneous tissue
i*, Ti+htened acial eatures (e,+,, radial urrowin+ around the
lips)
c, 4astrointestinal
i, Dyspha+ia or solids and li3uids
.o peristalsis in the lower two thirds o the
esopha+us (smooth muscle replaced by colla+en)
%ower esopha+eal sphincter relaxation with relux
ii, 1mall bowel
%oss o *illi (malabsorption)
Gide&mouthed di*erticula (bacterial o*er+rowth)
d, 8espiratory
i, $nterstitial ibrosis o lun+s
ii, 8espiratory ailure (most common cause o death)
e, 8enal
i, @asculitis in*ol*in+ arterioles (i,e,, hyperplastic
arteriolosclerosis) and +lomeruli
ii, $narctions, mali+nant hypertension
4, %aboratory indin+s in systemic sclerosis
a, 1erum -.- is positi*e in ;EI to DEI o cases,
b, -ntitopoisomerase antibody is positi*e in 2AI to 4EI o cases,
A, C8<1T syndrome
o %imited sclerosis
a, Clinical indin+s
i, C&calciication, centromere antibody
ii, 8&8aynaud!s phenomenon
iii, <&<sopha+eal dysmotility
i*, 1&sclerodactyly (i,e,, tapered, claw&li#e in+ers)
*, T&telan+iectasis (i,e,, multiple punctate blood *essel dilations)
b, %aboratory indin+s
-nticentromere antibodies in 5EI o cases
Dermatomyositis (D0( with s#in in*ol*ement) and polymyositis (P0( no
s#in in*ol*ement)
2, =ccurs predominantly in women 4E to 6E years o a+e
', -ssociated with ris# o mali+nant neoplasms (2A&'EI o cases), particularly
lun+ cancer
5, Patho+enesis
a, D0 is associated with antibody&mediated dama+e,
b, P0 is associated with T cell&mediated dama+e,
4, Clinical indin+s
a, 0uscle pain and atrophy
1houlders are commonly in*ol*ed,
b, 7eliotrope eyelids or Jraccoon eyesJ (purple&red eyelid discoloration)
A, %aboratory indin+s
a, 1erum -.- is positi*e in ewer than 5EI o cases,
b, $ncreased serum creatine #inase
c, 0uscle biopsy shows a lymphocytic iniltrate,
0ixed connecti*e tissue disease (0CTD)
2, 1i+ns and symptoms similar to 1%<, systemic sclerosis, and P0
', 8enal disease is uncommon,
5, -ntiribonucleoprotein antibodies are positi*e in almost 2EEI o cases,
Immuno,eficiency Disor,ers
Deects in B cells, T cells, complement, or pha+ocytic cells
8is# actors or immune disorders
pa+e A'
pa+e A5
2, Prematurity
', -utoimmune diseases (e,+,, systemic lupus erythematosus)
5, %ymphoprolierati*e disorders (e,+,, mali+nant lymphoma)
4, $nections (e,+,, human immunodeiciency *irus K7$@L)
A, $mmunosuppressi*e dru+s (e,+,, corticosteroids)
Con+enital immunodeiciency disorders
Table 3-.. Congenital Immuno,eficiency Disor,ers
Disease Defect$s% Clinical Features
/-Cell Disor,ers
Bruton!s
a+amma+lobulinemia
?ailure o pre&B cells to become
mature B cells
0utated tyrosine #inase
B&lin#ed recessi*e disorder
1inopulmonary inections
0aternal antibodies protecti*e
rom birth to a+e 6 months
$mmuno+lobulins
$+- deiciency ?ailure o $+- B cells to mature into
plasma cells
1inopulmonary inections,
+iardiasis
-naphylaxis i exposed to blood
products that contain $+-
$+- and secretory $+-
Common *ariable
immunodeiciency
Deect in B&cell maturation to plasma
cells
-dult immunodeiciency disorder
1inopulmonary inections, 4$
inections (e,+,, Giardia),
pneumonia, autoimmune disease
$mmuno+lobulins
T-Cell Disor,er
Di4eor+e syndrome ?ailure o third and ourth pharyn+eal
pouches to de*elop
Thymus and parathyroids ail to
de*elop
7ypoparathyroidism (tetany)(
absent thymic shadow on
radio+raph( PCP
Dan+er o 4@7 reaction
Combine, /- an, T-
Cell Disor,ers

1e*ere combined
immunodeiciency
(1C$D)
-denosine deaminase deiciency(
adenine toxic to B and T cells,
deoxynucleoside triphosphate
precursors or D.- synthesis
-utosomal recessi*e disorder
Deecti*e C0$
$mmuno+lobulins
Treatment" +ene therapy, bone
marrow transplant (patients with
1C$D do not re>ect allo+rats)
Gis#ott&-ldrich
syndrome
Pro+ressi*e deletion o B and T cells
B&lin#ed recessi*e disorder
1ymptom triad" ec9ema,
thrombocytopenia,
sinopulmonary inections
-ssociated ris# o mali+nant
lymphoma
Deecti*e C0$
$+0, normal $+4, $+- and $+<
-taxia&telan+iectasia 0utation in D.- repair en9ymes
Thymic hypoplasia
-utosomal recessi*e disorder
Cerebellar ataxia, telan+iectasias
o eyes and s#in
8is# o lymphoma and/or
leu#emia
1erum M&etoprotein
C0$, cell&mediated immunity( 4@7, +rat&*ersus&host( PCP, Pneumocystis jiroveci pneumonia,
2, B&cell disorders
o 8ecurrent encapsulated bacterial inections (e,+,, Streptococcus
pneumoniae)
', T&cell disorders
o 8ecurrent inections caused by intracellular patho+ens (un+i, *iruses,
proto9oa)
5, Combined B& and T&cell disorders
-c3uired immunodeiciency syndrome (-$D1)
pa+e A5
pa+e A4
pa+e A4
pa+e AA
Table 3-0. Laboratory Tests 1se, in "I2 an, *IDS
Test 1se Comments
<%$1- 1creenin+ test Detects anti&+p2'E antibodies
1ensiti*ity 2EEI
Positi*e within 6&2E wee#s
Gestern
blot
Conirmatory test Hsed i <%$1- is positi*e or indeterminate
Positi*e test" presence o p'4 anti+en and +p42 antibodies
and either +p2'E or +p26E antibodies
2EEI speciicity
p'4 -nti+en $ndicator o acti*e *iral
replication
Present beore anti&
+p2'E antibodies
Positi*e prior to serocon*ersion and when -$D1 is
dia+nosed (two distinct pea#s)
CD4 T&cell
count
0onitorin+ immune
status
Hseul in determinin+ when to initiate 7$@ treatment and
when to administer prophylaxis a+ainst opportunistic
inections
7$@ *iral
load
Detection o acti*ely
di*idin+ *irus
0ar#er o disease
pro+ression
0ost sensiti*e test or dia+nosis o acute 7$@ beore
serocon*ersion
-$D1, ac3uired immunodeiciency syndrome( <%$1-, en9yme&lin#ed immunoabsorbent assay( 7$@, human
immunodeiciency *irus,
pa+e AA
pa+e A6
Table 3-3. 4rgan Systems *ffecte, by *IDS
4rgan System Con,ition Comments
Central ner*ous system
(C.1)
-$D1&dementia complex Caused by 7$@
0ultinucleated micro+lial cells reser*oir o
*irus
Primary C.1 lymphoma Caused by <B@
0ost common extranodal site or lymphoma
Cryptococcosis Cause o C.1 un+al inection
Toxoplasmosis Cause o space&occupyin+ lesions
C0@ retinitis Cause o blindness
4astrointestinal <sopha+itis
Colitis
Caused by Candida, herpes*irus, C0@
Caused by Cryptosporidium, C0@
7epatobiliary Biliary tract inection Caused by C0@
8enal ?ocal se+mental
+lomerulosclerosis
Causes hypertension and nephrotic
syndrome
8espiratory Pneumonia Caused by Pneumocystis jiroveci and
Streptococcus pneumoniae
1#in /aposi sarcoma
Bacillary an+iomatosis
Caused by 77@&8
Caused by Bartonella henselae
-$D1, ac3uired immunodeiciency syndrome( C0@, cytome+alo*irus( <B@, <pstein&Barr *irus( 77@&8, human
herpes *irus type 8( 7$@, human immunodeiciency *irus,
Complement system disorders
Table 3-5. Complement Disor,ers
Disor,er Comments
7ereditary an+ioedema -utosomal dominant disorder with deiciency o C2 esterase inhibitor
Continued C2 acti*ation decreases C' and C4 and increases their
clea*a+e products, which ha*e anaphylatoxic acti*ity
.ormal C5
1wellin+ o ace and oropharynx
C' deiciency 0ost common complement deiciency
-ssociation with septicemia (usually Streptococcus pneumoniae) and
lupus&li#e syndrome in children
C6&CD deiciency $ncreased susceptibility to disseminated Neisseria gonorrhoeae or N.
meningitidis inections
Paroxysmal nocturnal
hemo+lobinuria
-c3uired stem cell disease
Deect in molecule anchorin+ decay acceleratin+ actor (D-?), which
normally de+rades C5 and CA con*ertase on hematopoietic cell
membranes
Complement&mediated intra*ascular lysis o red blood cells
(hemo+lobinuria), platelets, and neutrophils
pa+e A;
pa+e A8
2, Complement pathways
a, Classic and alternati*e pathways
b, C2 esterase inhibitor inacti*ates the protease acti*ity o C2 in the
classic pathway,
c, 0embrane attac# complex (CA&CD) is the inal common pathway or
both the classic and alternati*e pathways,
', Testin+ o the complement system
a, - decrease in C4 or C' indicates acti*ation o the classic pathway,
b, - decrease in actor B indicates acti*ation o the alternati*e pathway,
c, - decrease in C5 indicates acti*ation o either system,
*myloi,osis
-myloid
2, ?ibrillar protein that orms deposits in interstitial tissue, resultin+ in or+an
dysunction
', Characteristics
a, %inear, nonbranchin+ ilaments in a N&pleated sheet
b, -pple +reen&colored birerin+ence in polari9ed li+ht with Con+o red
stain o tissue
c, <osinophilic stainin+ with 7Kamp L< (hematoxylin and eosin) stain
d, Deri*ed rom *arious proteins
5, 0a>or types o amyloid proteins
a, -myloid li+ht chain (-%)
Deri*ed rom li+ht chains (e,+,, Bence Cones protein)
b, -myloid&associated (--)
Deri*ed rom serum associated amyloid (1--), an acute
phase reactant (see
c, N&-myloid (-N)
Deri*ed rom amyloid precursor protein (protein product o
chromosome '2)
-myloid
2, ?ibrillar protein that orms deposits in interstitial tissue, resultin+ in or+an
dysunction
', Characteristics
a, %inear, nonbranchin+ ilaments in a N&pleated sheet
b, -pple +reen&colored birerin+ence in polari9ed li+ht with Con+o red
stain o tissue
c, <osinophilic stainin+ with 7Kamp L< (hematoxylin and eosin) stain
d, Deri*ed rom *arious proteins
5, 0a>or types o amyloid proteins
a, -myloid li+ht chain (-%)
Deri*ed rom li+ht chains (e,+,, Bence Cones protein)
b, -myloid&associated (--)
Deri*ed rom serum associated amyloid (1--), an acute
phase reactant (see
c, N&-myloid (-N)
Deri*ed rom amyloid precursor protein (protein product o
chromosome '2)
Types o amyloidosis
Table 3-6. Common Types of *myloi,osis an, *ssociate, Clinical
Fin,ings
Type of *myloi,osis Clinical Fin,ings
Primary and secondary .ephrotic syndrome, renal ailure (common cause o death)
-rrhythmia, heart ailure
0acro+lossia, malabsorption
7epatosplenome+aly
Carpal tunnel syndrome
1enile cerebral Dementia (-l9heimer!s type) caused by toxic -N deposits in neurons
-myloid precursor protein coded by chromosome '2
-ssociated with Down syndrome
pa+e A8
pa+e AD
2, 1ystemic
a, 1imilar tissue in*ol*ement in both primary and secondary types
b, Primary amyloidosis
i, -% amyloid disposition
ii, -ssociated with multiple myeloma (5EI o cases)
c, 1econdary (reacti*e)
i, -- amyloid
ii, -ssociated with chronic inlammation (e,+,, rheumatoid
arthritis, tuberculosis)
', %ocali9ed
a, Conined to a sin+le or+an (e,+,, brain)
b, -l9heimer!s disease
i, -N
ii, 0ost common cause o dementia
5, 7ereditary
o -utosomal recessi*e disorder in*ol*in+ -- amyloid (e,+,, amilial
0editerranean e*er)
Patho+enesis
-bnormal oldin+ o normal or mutant proteins

Techni3ues
used to
dia+nose
amyloidosis
2, $mmunoelectrophoresis (to detect li+ht chains) in primary amyloidosis
', Tissue biopsy (e,+,, adipose, rectum)