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333 Cards in this Set

  • Front
  • Back
disorders arising form excessive or inappropriate activity of immune system

disorders due to absence or hypofunction of some elements of immune system or tissues.
two basic mechanisms for immunologically related diseases to occur
-anaphalactic or "atopic reactions" (type I)
-cytotoxic, anti-tissue Ab reactions (type II)
-immune complex deposition reactions (type III)
type of reactions mediated by antibodies
-delayed type hypersensitivity (DTH)
-granulomatous diseases
lymphocyte mediated immune responses (type IV)
type I, mediated by antibodies
anaphalactic or "atopic" reactions
type II, mediated by antibodies
cytotoxic, anti-tissue antibody reactions
type III, mediated by antibodies
immune complex desposition reactions
type IV
lymphocyte mediated immune responses
mediated by antibodies
lymphocyte mediated immune responses
mixed Ab and lymphocyte disorders
disorders arising form excessive or inappropriate activity of immune system
acquired--iatrogenic, infectious
disorders due to absense or hypofuncion of some element of immune system or tissues.
type I hypersensitivity reaction
mediated by IgE and products of mast cells, eosinophils, and/or basophils
type II hypersensitivity reaction
mediated by direct antibody binding to cells or tissue components
type III hypersensitivity reaction
mediated by deposition of antigen-antibody complexes and activation of complement and neutrophils
type IV hypersensitivity reaction
mediated by T-lymphocytes and macrophages.
type I immune reactions
mast cells stimulated (typically via IgE bound to surface receptors) to release vasoactive and spasmogenic substances that act on endothelial cells and smooth muscle cells locally or systemically.

reactions can easily prove lethal
localized anaphalactic/atopic reactions
asthma, hay fever, insect bites (mosquito, flea, etc.)
systemic anaphalactic/atopic reaction
insect stings (esp. Hymenoptera species)
drug allergies
some food allergies
anaphalaxsis (the syndrome)
IgE and Mast Cells
Type I reactions mediated by these
dendritic cell processing
dendritic cell
Th2 cell stimulated
T cell "help"
B-cell plus antigen
B cell
plasma cell making IgE
FcRe on Mast cells
IgE armed mast cell + antigen
C3a and C5a
events occurring on respiratory mucosa after inhaled antigen encounter

hay fever, asthma
Pollen-->antigen/allergen-->dendritic cell-->T cell receptor on TH2 cell-->IL-4-->IgE B cell-->IgE antibody-->IgE Fc receptor on Mast cell-->Antigen crosslinking-->release of primary and secondary mediators-->smooth muscle spasm, edema, leukocyte infiltration, mucus secretion, epithelial damage.

Mast Cell or TH2 cell-->Il-3, IL-5, GM-CSF-->eosinophil recruitment/activation-->release of granules and mediators.
mast cells
can be triggered to degranule by many mechanisms, but IgE-mediated mechanism most common
two stages of Type I (anaphylactic) reactions
immediate stage of Type I anaphylactic reactions, within one hour after allergen exposure
IgE on mast cell surface binds its specific antigen, mast cell degranulates releasing preformed mediators into area
delayed stage of type I anaphylactic reactions, 4-20 hours after allergen exposure
once triggered, mast cell begins synthesis of other soluble mediators
tissue events in type I reactions
mast cell degranulation
vascular congestion
mediators of both primary and secondary response are initiated at ___ time(s), but released in ___phase(s)
events in mast cell degranulation
Ag, IgE, IgE Fc receptor, signals for activation of PLA2/cytokine gene activation/degranulation, secreted cytokines/membrane phospholipids/granule contents
initial response in type I hypersensitivity reaction
5 min to 1 hr
vasodilation, vascular leakage, smooth muscle contraction, glandular secretion
secondary response in type I hypersensitivity reaction
2 hours to days
tissue infiltration by eosinophils, basophils, neutrophils and some T cells; tissue injury, mucosal damage and remodeling
primary mediators, type I hypersensitivity reactions
biogenic amines
chemotactic mediators
secondary mediators, type I hypersensitivity reactions
prostaglandins (D2)
platelet activating factor (PAF)
major basic protein from eosinophil
causes mast cell degranulation
epithelial desquamation
major basic protein
severe urticaria
puffiness, matter of minutes
cold/heat induced, not IgE, have for rest of adult life, not in kids.
localized type I reaction
localized type I reaction
atopic keratoconjunctivitis
abnormal repair response to epithelial injury
smooth muscles around bronchiole hypertrophy so can contract more, airway reduced
structural changes of airways in chronic asthma
epithelial shedding
gland hyperplasia
matrix remodeling
basement membrane pseudothickening
inflammatory infiltrate
muscle hyperplasia
systemic anaphylaxis
bee stings, drug-reactions, etc
type II immune reactions
cytotoxic, lytic or anti-tissue antibody attacks
type II immune reactions
by binding antigen, antibody causes cell or tissue damage
type II immune reactions
humoral antibodies participate directly in injuring cells, rendering them susceptible to lysis or phagocytosis, making tissue elements susceptible to complement damage, or by altering the function of specific cell surface molecules/receptors
cytotoxic or anti-tissue antibody reactions (type II)
antibodies that fix complement
cytotoxic or anti-tissue antibody reactions (type II)
circulating antibodies that localize to its antigen on cell surface or on some other tissue constituent
cytotoxic or anti-tissue antibody reactions (type II)
site of damage defined by location at which antibody binds
cytotoxic or anti-tissue antibody reactions (type II)
often causes severe disease and tissue injury
antibodies coat erythrocytes making them susceptible to phagocytosis in spleen or liver or fixing complement to generate MACs
erythrocyte-->Ab binding-->opsonization and phagocytosis OR lysis
acute hemolysis
preexistent Ab high titer-->rapid intravascular hemolysis
delayed hemolysis
1-2 weeks
low/rising titer Ab-->slow extravascular hemolysis
cell activation
IC processing
cell lysis after antibody binding and complement activation
Anti-B antibody (IgM) binds to B antigen on type B RBC
ABO incompatibility-->immune complex formation-->activation of complement-->C5-9 MAC-->membrane lesion/cell lysis
erythroblastosis fetalis
Rh disease
erythroblastosis fetalis
RBC precursors seen in liver, spleen, muscle, wherever can put RBC
Goodpasture's disease
anti-collagen type IV
anti-GBM antibody (glomerular basement membrane)
Goodpasture's disease
hemorrhage into lungs, kidney. renal failure due to hemorrhage.
type II hypersensitivity reactions
induction of anti-self antibodies
binding of Ab to self-constituents
complement fixation/activation
tissue lysis/opsonization/phagocytosis/cell-mediated cytotoxicity
type II hypersensitivity reactions
direct attack on cells/tissues by antibodies
type I hypersensitivity reaction
mast cell/basophil mediated
type III hypersensitivity reaction
damage secondary to deposition of immune complexes (IgG-Ag)
type IV hypersensitivity reaction
T-cell/macrophage mediated-DTH (delayed-type hypersensitivity)
classical type II hypersensitivity disease
rheumatic fever
rheumatic fever
cross-reacting antibodies in streptococcal infections
rheumatic fever
vegetations on mitral valve leaflets
rheumatic fever
thickening, shortening and fusion of chordae tendineae
rheumatic fever
"fish-mouth" deformity of aortic valve
type II mechanism
antibodies can cause "autoimmune" overstimulation or receptor blockade
Graves' disease, type II
antibody has natural ligand activity
TSH can't bind b/c there's Ab to TSH receptor
Ab binding stimulates excess production of thyroid hormone
Myasthenia gravis, type II
antibody blocks natural ligand activity
tissue binding Ab, not destructive
ACh from nerve ending can't bind to receptor on motor end plate of muscle b/c of Ab
type I hypersensitivity reactions
asthma, hives, allergic rhinitis (hayfever)
type I hypersensitivity reactions
type I hypersensitivity reactions
allergic rhinitis (hayfever)
type I hypersensitivity reactions
inudction of IgE response--antigen exposure--TH2 cells
"arming" mast cell
mast cell degranulation
parimary, secondary
recruitment of cells-eosinophils
eosinophil mediators
type II hypersensitivity reactions
hemolytic anemia
type II hypersensitivity reactions
erythroblastosis fetalis
type II hypersensitivity reactions
Goodpasture syndrome
type II hypersensitivity reactions
myasthenia gravis
type II hypersensitivity reactions
rheumatic fever
type II hypersensitivity reactions
Graves' disease
type II hypersensitivity reactions
induction of anti-self antibodies
binding of antibodies to self-constituents
complement fixation/activation
tissue lysis/opsonization/phagocytosis/cell-mediated cytotoxicity
type III hypersensitivity reactions
type III hypersensitivity reactions, systemic
serum sickness
type III hypersensitivity reactions
polyarteritis nodosa
type III hypersensitivity reactions, localized
Arthus reaction
type III hypersensitivity reactions
induction of Ab
formation of Ab-Ag complexes
complex deposition in tissue or on cells
complement activation--production of complement factors
complement damage to tissue
neutrophil attraction and degranulation
tissue destruction
type IV hypersensitivity reactions
tuberculin reaction
type IV hypersensitivity reactions
granuloma formation
type IV hypersensitivity reactions
contact dermatitis (nickel allergy)
type IV hypersensitivity reactions
sensitization of T cells
Ag processing and presentation
rechallenge or chronic Ag challenge
cytokine/chemokine production
attraction of other cells, esp activated macrophages
giant cell formation
cytotoxic T cells (CD8+)
structure of granuloma
graft or transplant rejection
importance of HLA/MHC matching
renal allograft rejection as prototype for teaching
hypersensitivity types II-IV but not type I
rejection from combination of these hypersensitivity types
antibody mediated
hyperacute rejection; thrombosis, vessel attack
acute rejection
host become sensitized to donor tissue
cellular and Ab mediated
attack on vessels (vasulitis), parenchymal attack and damage
chronic rejection
mixed mcehanism, many macrophages, T- and plasma cells
extensive and longstanding damage and fibrosis to graft
graft vs. Host disease (GvHD)
acute and chronic
transplanted tissue (i.e. T-cells) attack host
skin, liver, GI track most affected
rheumatic fever
excrescences fuse into fishmouth valve
aschoff bodies
type III immune reactions
disease due to deposition of Ag-Ab complexes, can be localized or systemic
type III immune reactions
sensitization of immune system-->Ab produced
continuous or repeated Ag exposure
Ag-Ab complexes formed and deposited in tissue
complement cascade activated (C3a, C3b, C5 frags, MAC)
attraction and activation of neutrophils and macrophages
focal acute inflammation causes tissue destruction
type III immune reactions
type and location of tissue damage determined by where and how complexes deposited
type III hypersensitivity reactions, systemic
type III hypersensitivity reactions, systemic
drug reactions
type III hypersensitivity reactions, localized
type III hypersensitivity reactions, localized
type III hypersensitivity reactions, localized
type III hypersensitivity reactions, localized
sequence of events in tissue damage caused by deposition of immune complexes
Ag-Ab complexes-->vessels, glomeruli, etc.-->C42-->
C3b phagocytosis
C3a+C5a increased vascular permeability
C3,C5 fragments, C567 chemotaxis
C5-C9 Lysis
-->vasculitis, glomerulonephritis, arthritis, endocarditis
pathogenesis of type III hypersensitivity reaction
Ag/Ab immune complexes-->
Fc receptor engagement, complement activation, platelet aggregation, activation of Hageman factor
-->neutrophil/monocyte recruitment, vasodilation/edema
type III hypersensitivity reactions
involve neutrophils that do most of actual damage to tissue
constituents of granules of neutrophils
microbicial enzymes
neutral serine proteases
acid hydrolases
cationic microbicidal peptides
membrane receptors
localized type III reaction
post-streptococcal glomerulonephritis
post-streptococcal glomerulonephritis, type III
neutrophils in glomerulus, Ag/Ab complexes
immune complex formation, deposition, inflammation
Ag in circulation, B cell-->plasma cell-->Ab
Ag/Ab copmlex deposition, inflammatory cell-->cytokines
complement onto Ab, neutrophils, platelet aggregation
-->fibrinoid necrosis, neutrophil lysosomal enzymes
small vessel vasculitis (type III reaction) often induced by this
systemic type III hypersensitivity reaction
serum sickness (true classic example)
one-shot serum sickness
day 12: heart, joint, kidney lesions; low complement level, Low Ag level, Low Ag/Ab complex level, free Ab rises right after
type IV immune reactions, DTH
diseases of this type result form cell or tissue injury caused by attack of Ag-specific, sensitized T-cells accompanied by macrophages
cell-mediated hypersensitivity
DTH, T cell mediated cytotoxicity, rejection of transplanted organ
delayed-type hypersensitivity (DTH)
CD4+ cell and macrophage mediated, e.g. Tuberculin Reaction
delayed-type hypersensitivity (DTH)
Granulomatous reactions, distince type of this reaction
T-cell mediated cytotoxicity
largely CD8+ cell mediated
e.g. response to tumors, viruses and allogenic cells
rejection of transplanted organ
both CD4+ and CD8+ cells participate
B-cells/Ab may also be involved
detrimental macrophage-monocyte-microglial cell products
nitric oxide
hydroxyl radicals
neuron toxins
beneficial (possibly) macrophage-monocyte-microglial cell products
Growth & Trophic factors
chromosome 6
human MHC gene locus
type IV, DTH
T-lymphocytes, Ag presenting cells and macrophages absolutely essential for this type of immune reaction
type IV hypersensitivity reaction (DTH)
APC presenting tissue antigen to CD4+ T cell which releases cytokines causing inflammation
Normal tissue presenting antigen to CD8+ T cell which releases cytokines causing inflammation or tissue injury
type IV hypersensitivity reaction (DTH)
1 hr: injection of Ag
5 hr: rxn of sensitized lymphocytes with Ag
12 hr: release of lymphocyte mediators
24-48 hr: attraction and retention of unsensitized cells
72+ hr: destruction of Ag by activated cells and resolution
endothelial cell changes with inflammation
leaky junctions,
activated like HEV's!!
VCAM-1, MECA-352, CD49, MadCAM, E-Selectin, P-Selectin, transferrin Receptor
granuloma formation
type IV hypersensitivity reaction that persists and causes tissue damage and scarring
granuloma formation
APC presents Ag to CD4+ TH1 cell, which releases TNF, IL-2, IFN-y, monocytes.
fibroblasts, giant cells, lymphocytes, macrophage, epithelioid cell make up ___
allograft rejection
aka Transplant Rejection
allograft rejection
both CD4+ and CD8+ cell participate; B-cells/Antibodies may also be involved
ransplantation rejection reactions
based on timing, mechnism and morphology
hyperacute, acute, chronic
hyperacute rejection
moments to 48 hours
involves preformed Ab
Ag-Ab reaction at endothelium
results in rapid thrombosis of vessels
acute rejection
weeks to months
acute cellular rejection
involves sensitized CD4 and CD8 cells, lymphocyte/macrophage infiltrates
acute humoral rejection
involves anti-graft Ab
vasculitis, thrombosis, endothelial prolif.
chronic rejection
months to years
vasculitis, intimal fibrosis, obliteration of lumen, organ ischemia, interstitial mononuclear cell infiltrates, organ atrophy
chronic rejection
graft arteriosclerosis, tubular atrophy, interstitial fibrosis
graft vs. host disease
when you are the tissue being rejected
post bone marrow transplantation
acute graft versus host disease
onset: up to day 100
organs: limited-skin, liver, GIT
primary pathology: destruction of epithelium
inflammatory responses: mild
chronic graft versus host disease
onset after day 100
organs: widspread
primary pathology: mixed epithelial and mesenchymal lesions
inflammatory response: often marked
acute cellular rejection
lymphocytes in renal parenchyma
acute rejection
T cells in this kind of rejection
direct pathway of T cell rejection
donor class I and class II antigens on APC in graft (along with B7 molecules, not shown) are recognized by CD8+ cytotoxic T cells an CD4+ helper T cells, respectively, of the host. CD4+ cells proliferate and produce cytokines that induce tissue damage by a local delayed hypersensitivity reaction and stimulate B cells and CD8+ T cells. CD8+ T cells responding to graft antigens differentiate into cytotoxic T lymphocytes that kill graft cells
indirect pathway of T cell attack
graft antigens are displayed by host APC’s and activate CD4+ T cels, which damage the graft y a local delayed hypersensitivty reactions.
results from multiple factors, including susceptibility genes that may interfere with self-tolerance and environmental triggers (inflammation, other inflammatory stimuli, particularly infections) that promote lymphocyte entry into tissues, activation of lymphocytes and tissue injury. Self-reactive lymphocytes.
HLA genes are best defined genes known to be associated with it
organ-specific autoimmunity
thyroid: Hashimoto's thyroiditis, primary myxedema, thyrotoxicosis
stomach: prenicious anemia
adrenal: Addison's disease
pancreas: insulin-dependent diabetes mellitus
non-organ-specific autoimmunity
ermatomyositis: skin, muscle (7 vasculitis)
systemic lupus erythematous: skin, kidney, joints
predominantly type II or III
predominantly type IV
mixed T cell and B cell
type II hypersensitivity reaction in autoimmune disease
autoimmune hemolytic anemias, neutropenias, lymphopenias, throbocytopenias
Good pasture disease
antireceptor Ab diseases
myasthenia gravis
Graves disease
anti-insulin Ab
bullous skin diseases
type III hypersensitivity reaction involved in autoimmune disease
systemic lupus erhthematosus
rheumatoid arthritis
Sjogren syndrome
hematologic, arthritis, skin, fever, fatigue, weight loss, renal, CNS, pleurisy, myalgia, pericarditis, GI, raynaud phenomenon, ocular, peripheral neuropathy
acute malar rash is a sign of this disease
Libman-Sack's vegetations in this disease
membranous lupus nephritis
membranoproliferative glomerulonephritis type I in this disease
diffuse proliferative glomerulonephritis in this disease
arterial occlusion in patient with this disease who has retinal vasculitis
systemic rheumatoid arthritis
constitutional signs and symptoms of this disease:
fatigue, weight loss, myalgias, excessive sweating, low-grade fevers, morning stiffness, lymphadenopathy
process of synovial inflammation in rheumatoid arthritis
antigen processing
antigen presentation by RF-specific B cells to T cells
collagenase activation, lysosomal enzymes, metalloproteinases, serine proteases, cathepsins, tissue destruction
early rheumatoid arthritis
symmetric synovitis, atlantoaxial subluxation with basilar invagination, and deformities in this disease
invasive synovial pannus in this disease
reactive lymphadenopathies, amyloidosis, muscle wasting, peripheral NS, neuropathy, mononeuritis, multiplex, scleritis, keratoconjunctivitis, pleural effusions, lung fibrosis/nodules/effusions, pericardial effusions, splenomegaly, amyloidosis of gut, anemia, thrombocytosis, skin thinning/ulceration
bursitis and nodulosis
intersitital pneumonitis in this disease
primary amyloidosis, RA
hypertrophic, shoulder pad sign in this disease
amoyloid, RA
nodule occlusion of auditory canal in this disease
amyloidosis, RA
not all of these are created equal
not all pink and waxy materials are this
parimary amyloidosis
classifcation of amyloidosis with multiple myeloma, K or lambda light chains
secondary amyloidosis
classification of amyloidosis with protein A
familial amyloidosis
classification of amyloidosis with transthyretin mutant, protein A
serile systemic amyloidosis
serile cardiac classification of amyloidosis with transthyretin normal
dialysis amyloidosis
systemic amyloidosis from B2-microglobulin deposition
forms of amyloidosis
acute phase reaction
fibrobalsts and epithelial cells to macrophage to liver, acute-phase reaction proteins then serum amyloid protein for opsonization of pathogens and modulation of inflammation
amyloid precursor protein (APP) coded for by gene on this chromosome. APP protein clipped to produce AB amyloid that's deposited in brains of individuals with Alzheimer's disease
diabetes mellitus
1-3% of American population
autoimmune disease
caused by immunological destruction of B-cells of islet
diabetes mellitus
exceptionally strong genetic influence/predisosition
probably T cell mediated
not currently preventable
antigen unknown but must be B-cell speciic
loci associated with type I diabetes
MHC locus - chromosome 6
insulin/IFG-2 - chromosome 11possible association of 18 other loci
systemic sclerosis and scleroderma
disease pathogenesis involves T and B cells, endothelial cells, fibroblasts and myofibroblasts
systemic sclerosis and scleroderma
disease involves autoimmunity, vasculo pathy (raynaud's, nailfold capillaries), ECM abnormalities and fibrosis, skin disease, pulmonary fibrosis, pulmonary HT, renal crisis
systemic sclerosis and scleroderma
in this disease, risk of internal organ involvement strongly linked to extent and progression of skin theckening
Sjogren's syndrome
parotid enlargement in this disease
graft rejection
multiple mechanisms acting simultaneously in this disease
antigen in SLE
immunological tolerance
how immune system learns to distinguish self form foreign
central tolerance
mechanism of tolerance that involves clonal deletion, negative selection
peripheral tolerance
mechanism of tolerance that involves activation-induced apoptosis, anergy induction, suppression
failure of immunological tolerance leading to autoimmunity
breakdown of T cell anergy, failure of activation induced cell death, failure of suppression, molecular mimicry, polyclonal lymphocyte activation, release of sequestered antigens, exposure of cryptic angens, epitope spreading
multisystem disease-many organs affected
more women than men
in this disease, there are antibodies against DNA, histones, proteins bound to RNA, nucleolar antigens, "anti-nuclear antigens" (ANAs)
in this disease, there are 4 basic staining patterns of patient's serum antibodies on nuclei in tissue
in this disease, gneetic factors are important; however it is multigenic, no one bad gene
possible pathogenesis:
genetic susceptibility->environmental trigger->T cell and subsequent B cell stimulation->antibody production->various forms of antibody induced tissue damage
end-organ damage in this disease: many tissues damaged but kidneys most frequently and severely damaged organ. renal failure is common endpoint, but skin, heart, blood vessels, brain and CT are also involved in various combinations in a variety of ways
disease of synovial joints, but multiple tissues are damaged
chronic, systemic inflammatory disease
rheumatoid factor
found in most RA patients. predominantly IgM directed against Fc component of IgG Ab
in joints, this disease induces reactive, non-supperative (non-pus forming) inflammation fo synovium with T cell, plasma cells and macrophage infiltration. synovium proliferates and destroys articular cartilage of joint.
"pannus" forms in this disease
possible pathogenesis:
genetic susceptibility->environmental trigger (?virus/bacterium?)->T cell and subsequent B cell stimulation->antibody (rheumatoid factor) production->various forms T cell and possibly antibody induced tissue damage
not all forms of this disease are the same chemically. this is not of itself an inflammatory disease.
deposition is byproduct of chronic inflammatory activity against a spectrum of stimuli occurring in diverse tissues
this term refers to a pale-pink, amorphous material seen deposited in a wide range of tissues, materials that constitute it are highly heterogeneous
recognized by its birefringent (acting like a lens) properties when congo red stained tissue is viewed thru microscope under polarized light. glows bright apple-green
congo red
this dye binds to unique molecular conformation assumed by all forms of amyloid, beta-pleated sheet configuration
causes damaging effects in most organs by filling up interstitium of tissue until it blocks, crowds-out, or causes atrophy of adjacent normal structures
AB amyloid
this type of amyloid in Alzheimer's may actually act like irritating stimulus inducing chronic activation of macrophage-like cells (microglia) in the vicinity
AL amyloid form
disease association of this amyloid form is myeloma/B cell tumors
source protein: Ig light chains
AA amyloid form
disease association of this amyloid form is reactive/chronic inflammatory conditions
source protein: SAA
Ab2M amyloid form
disease association of this amyloid form is chronic renal failure
source protein: B2-microglobulin
disease association of this amyloid form is Alzheimer's Disease
source protein: amy. precursor prot. encoded on Chr 21
primary immunodeficiencies
global, selective, cytokine or cytokin receptor mutations, adhesion molecule mutations, complement component abnormalities, mutations of regulators of complement
secondary immunodeficiencies
naturally occurring, infectious, iatrogenic
primary: global immunodeficiencies
all components affected in this type of immunodeficiency
primary: selective immunodeficiency
only B or T cells affected in this type of immunodeficiency
primary: selective: restrictive immunodeficiencies
subsets of T cells or isolated antibody types abnormal/missing
secondary: naturally occurring immunodeficiencies
type of immunodeficiency
tumors: lymphoma, myeloma, leukemia, etc.
primary immunodeficiencies
X-linked agammaglobulinemia, common variable immunodeficiency, hyper IgM syndrome, DiGeorge Syndrome, severe combined immunodeficiency diseases (SCID), complement or complement regulatory problems
secondary immunodeficiencies
type of immunodeficiency due to certain neoplasms that displace immune system
secondary immunodeficiencies
type of immunodeficiency due to iatrogenic (physician caused) from anti-neoplastic Rx
HIV-1 infection resulting in AIDS
single most important acquired immunodeficiency of our era
X-linked agammaglobulinemia
failure of B cells to develop in this disease
X-linked agammaglobulinemia
btk (b-cell tyrosine kinase) mutations in this disease
X-linked agammaglobulinemia
X-linked disease, thus almost exclusively in males
X-linked agammaglobulinemia
in this disease: problems in early childhood: viral infections, Girardia, arthritis
Common Variable Immunodeficiency
heterogeneous group of disorders - various causes
Common Variable Immunodeficiency
all antibody classes usually involved in these types of disorders
Common Variable Immunodeficiency
B cell developmental defects in this group of disorders
Common Variable Immunodeficiency
URIs, pulmonary, herpetic, and Giardia infections in this group of disorders
Common Variable Immunodeficiency
this group of disorders afflicts both sexes, onset in later childhood, adolescence
Common Variable Immunodeficiency
in this group of disorders, high frequency (20%) of autoimmune disease development
hyper IgM syndrome
T-cell disorder
hyper IgM syndrome
isotype switching from IgM to IgG or IgA is impaired in this disease
hyper IgM syndrome
CD40/CD154 interactions abnormal in this disorder
hyper IgM syndrome
has both X-linked an dautosomal forms
hyper IgM syndrome
in this disorder, recurrent pyogenic infections and Pneumocystis pneumonitis
DiGeorge Syndrome
ambryonic malformation of pharyngeal pouches 3 & 4
DiGeorge Syndrome
thums and parathyroids fail to develop in this disease
DiGeorge Syndrome
severe T cell deficiencies in this disease
DiGeorge Syndrome
Tetany due to Ca++ dysregulation in this disease
DiGeorge Syndrome
disease due to unidentified gene on chromosome 22
DiGeorge Syndrome
partial form of this disease exists, is self-correcting
Severe Combined Immunodeficiency Diseases (SCID)
both B and T cell limbs of the immune system absent in this disease
Severe Combined Immunodeficiency Diseases (SCID)
immunological problems from birth (Candida infections, GvHD) in this disease
Severe Combined Immunodeficiency Diseases (SCID)
most common (50-60%) form is X-linked, thus more in males
Severe Combined Immunodeficiency Diseases (SCID)
mutation causing disease is in a common chain shared by numerous cytokine receptors
Severe Combined Immunodeficiency Diseases (SCID)
autosomal mutations in this disease
adenosine deaminase (ADA) deficiency
Complement or Complement Regulator Problems
hereditary angioedema in this disorder
hereditoary angioedema
C1 inhibitor deficiency
double-stranded RNA virus
pathogenesis of AIDS
how cells get infected (CD4, CXCR4, CCR5)
replication steps
cell-cell spread
macrophage transport
transformation from asymptomatic infection to AIDS
AIDS syndromes
opportunistic infections
Kaposi's sarcoma
CNS lymphoma
CNS is the second target organ beyond the immune system
disease affecting stem cell to lymph
disease affecting lymph to B cell
Common Variable
disease affecting B cell to plasma cell
disease affecting T cells
disease affecting Th cells
Chediak-Higachi, Kostmann's
disease affecting myeloid cells
Reticular dysgenesis
disease affecting bone marrow to stem cell
disease affecting neutrophils, monocytes, eosinophils
X chromosome associated diseases
Chronic granulomatous disease (21)
Wiskott-Aldrich syndrome (11)
severe combinded immunodeficiency (13)
agammaglobulinaemia (XLA) (22-23)
X-linked lymphoproliferative syndrome (XLPS) (24-27)
B cell deficiencies
selective IgA deficiency
X-linked agammaglobulinemia of Bruton, common variable immunodeficiency
what type of immunodeficiency?
T cell deficiencies
DiGeorge Syndrome, what type of immunodeficiency?
combined B & T cell deficiencies
SCID, what type of immunodeficiency?
acquired or naturally occurring "secondary" immunodeficiency illnesses
lymphoma, Hodgkin's disease, iatrogenic (chemo)
selective IgA deficiency
maturation defect in IgA producing cells
common: 1 in 700 people
most asymptomatic
some with recurrent infections
HIGH incidence of autoimmune diseases
X-linked agammaglobulinemia of Bruton
disease with block in production of Ab light chains--heavy chains made
X-linked agammaglobulinemia of Bruton
disease in which low or absent IgG in serum
X-linked agammaglobulinemia of Bruton
frequent and severe bacterial infections
X-linked agammaglobulinemia of Bruton
increased risk of autoimmune disease
X-linked agammaglobulinemia of Bruton
high risk of developing poliomyelitis from vaccination
X-linked agammaglobulinemia of Bruton
get chronic encephalitis in this disease
type I
typ eof Common Variable immunodeficiency with predominant B-cell defect
type 2
typ eof Common Variable immunodeficiency with predominant immunoregulatory T-cell defect (inbalance)
decreased Th
increase T suppressor
type 3
typ eof Common Variable immunodeficiency with autoantibodies to T- or B-cells
common variable immunodeficiency
low or high numbers of B-cells
bacterial infections
high incidence of autoimmune diseases
common variable immunodeficiency
everything turns white
auto-immune attack on melanocytes in hair follicle and base of skin
not immunodeficiency problem, getting into auto-immune rxn
common variable immunodeficiency
verruca vulgaris in this disease
common variable immunodeficiency
aphthous ulcers in this disease
common variable immunodeficiency
lung disease, lymphoid interstitial penumonitis (not infection)
DiGeorge syndrome
congenital malformation causes this disease
DiGeorge syndrome
T cells absent or very low and T cell responses markedly abnormal in this disease
B cells normal
DiGeorge syndrome
with this disease, high susceptibility to viruses and fungi
DiGeorge syndrome
cardiac malformations very common in this disease--principal cause of death
Candida infection, DiGeorge
causes oral thrush
DiGeorge syndrome
in this disease, subcortical thymus dependent region shows marked depletion of lymphocytes
lymphopenia, hypogammaglobulinemia, high risk of viral, bacterial and fungal infections
lymphopenia, SCID
low or absent T cells
frequently low/absent B cells
mostly due to defect in cytokyne receptors (IL-7 receptor) leading to poor lymphoid tissue formation
in this disease, get herpes simplex virus infection
in this disease, get varicella superinfected with bacteria
in this disease, get pneumocystis carinii pneumonia
C2 deficiency
most common complement deficiency
more common in Europeans, Caucasians
C2 deficiency
50% homozygotes develop SLE-like disease
C1-C4 deficiency
this type of primary complement deficiency disorder has
clinical features: infectious and autoimmune disorders
lab findings: decreased complement activity, absent specific component
pathogens: encapsulated bacteria, strep pneumoniae, H. influenze
C5-C9 deficiency
this type of primary complement deficiency disorder has
clinical features: severe Neisseria infections
lab findings: absent specific components; decreased complement activity
pathogens: N meningitidis, disseminated gonococcal infection
this type of primary complement deficiency disorder has:
clinical features: meningococcal meningitis
lab findings: abnormal alternative pathway
pathogen: N. meningitidis
C1 inhibitor deficiency, hereditary angioedema
in this complement deficiency, complement cascade proceeds unchecked
C1 inhibitor deficiency, hereditary angioedema
in this complement deficiency, mast cells degranulate-vessels leak=edema
C1 inhibitor
this blocks enzymes responsible for activating various systems
blocks Hagemann Factor (F-XII), a coagulation factor
blocks Kallikrein, acute response, inflammation factor
blocks plasmin that's used to make fibrinogen

one factor: multiple different functions
Hereditary angioedema, C1 Inhibitor Deficiency
Minor trauma, maybe even just cold weather or minor scratch, something trivial, coagulation pathway and other pathways get activated, activate Hageman factor, start coagulation and complement pathways, get C3a and C5a causing mast cells to degranulate

minor trauma, infection, tissue damage--> activated Hageman factor--> plasminogen to plasmin--> activated C1--> complement cascade (anaphylotoxins)
hereditary angioneurotic edema, C1 inhibitor deficiency
little scratch causes hand to puff up
hereditary angioneurotic edema, C1 inhibitor deficiency
swollen face, eyes swollen shut. if trauma back of throat, around larynx, in trachea, will swell right up, people die of asphyxiation
most of the time will subside, not quickly, over hours and day or 2, not permanent
chronic inflammatory diseases that induce specific T-cell defect
TB, leprosy, sarcoidosis, measles
naturally occurring secondary immunodeficiencies: humoral immunity affected
type of immunodeficiency that involves B cell neoplasms, B cell lymphomas and plasmacytoma, Waldenstrom's macroglobulinemia
naturally occurring secondary immunodeficiencies: cellular immunity affected
type of immunodeficiency that involves Hodgkin's disease, thymoma and other T cell tumors, TB, sarcoidosis, leprosy, measles
naturally occurring secondary immunodeficiency: combined cellular and humoral immunity affected
type of immunodeficiency associated with AIDS aging
naturally occuring secondary immunodeficiency
type of immunodeficiency associated with AIDS
replaces normal lymphoid elements
lot of myeloid elements, dark cells, lot of progenitor cells
can't see any hematopoietic elements, even at higher power. few residual red cell elements hanging around. no immune system for weeks/months
virus that has highest mutation rate normally of any element
Long terminal repeat makes virus so insidious
When turn it on? When start making virus?
If T-cell sees antigen in right context, signal tells virus to start replication.
When need elements of immune system and call them up, that’s what turns virus on and causes it to replicate
NFKB, etc. bind to LTR, start making virus.
Long Terminal Repeat (LTR)
contains control regions that bind host transcription factors (NF-KB, NFAT, Sp1, TBP)
Long Terminal Repeat (LTR)
required for initiation of transcription
Long Terminal Repeat (LTR)
contains RNA trans-acting response element (TAR) that binds Tat
HIV insidiousness
protein that promotes virus assembly at cell surface, RNA binding protein, virion binding, overcomes inhibitory effect of unidentified host factor promoting cell-free viral transmission, promotes CD4 degradation and influences virion release, chemokine receptor binding, fusion, downregulation of surface CD4 and MHC I expression, blocks apoptosis, virion infectivity enhanced, enhances RNA Pol II-mediated elongation of integrated viral DNA, promotes nuclear export of incompletely spliced viral RNAs, G2 cycle arrest, HIV infection of macrophages, viral enzymes encoded
viremia in HIV
causes headache, swollen lymph nodes, people think it's just bad cold
primary infection in blood, mucosa
infects CD4+ T cell and dendritic cell
drainage to lymph nodes, spleen
infection established in lymphoid tissue, eg lymph node
acute HIV syndrome, spread of infection thruout body, viremia
immune response, anti-HIV Ab, HIV-specific CTLs
partial control of viral replication
clinical latency, latent infection/provirus, low-level infection
other microbial infections: cytokines (TNF)
extensive viral replication and CD4+ cell lysis
destruction of lymphoid tissue: depletion of CD4+ T cells
gp120 on virus binding to CD4 on cell, conformational change, gp120/CD4 bind CCR-5(chemokine receptor), gp41 on virus penetrates cell membrane, membrane fusion, HIV RNA genome into cell, RT-mediated synthesis of proviral DNA, integration of provirus into host cell genome, HIV RNA transcript, synthesis of HIV proteins, assembly of virion core structure, budding and release of mature virion

cytokine activation of cell/transcription of HIV genome/transport of viral RNAs to cytoplasm
cytopathic effect of HIV
chronic T cell activation-->viral replication in infected CD4+ T cells--> death of infected cells
apoptosis by HIV
chronic T cell activation-->activation of uninfected CD4+ T cells-->activation-induced cell death
killing of infected cells by virus-specific CTLs by HIV
chronic T cell activation-->Expression of HIV peptides on infected CD3+ T cells-->CTL
HIV infection to AIDS
possible acute HIV syndrome, wide dissemination fo virus, seeding of lymphoid organs-->clinical latency-->constitutional symptoms-->opportunistic diseases-->death
HIV infection to AIDS
viral particles in plasma, then CTLs specific for HIV peptides, then anti-envelope Ab then anti-p24 Ab
activation of cell-mediated immunity after Mycobacterium tuberculosis infection GONE IN THIS DISEASE
diseases secondary to AIDS
mycobacterium avium intracellulare (MIA), carinii, toxoplasmosis, Karposi's sarcoma
not everyone with HHV8 has this, but everyone with this disease has HHV8
synergy HHV8 and HIV, spindle cells (HIV infected), synergize and cause massive lesions