Term
| CVID [Chronic Variable Immunodeficiency] |
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Definition
Defect in B cell development btwn "mature B cell stage" and "plasma cell" thus results in no plasma cell development --> NO secreted antibody
-group of diseases wtih similar presentations
-onset: 15-35 years
-characterized by low levels IgG, IgA and IgM [no class switching]
-low B cell production and secretion of antibodies due to decreased B cell numbers or EBV infection (latent in B cells)
-cellular immunity weakened
-pneumonia, sinusitis, GI infections common
-associated with autoimmunity and malignancy
-susceptibility region of MHC II region[?] |
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Term
| SCID [Severe Combined Immunodeficiency] |
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Definition
arrested development between HSC and mature T cell. Results in no mature T cells.
-catch all name for combined B and T cell defects, defect in any part of signalling pathway of T cells has been shown to cause this phenotype
-prone to life threatening infections
-mutant IL-2Rgamma chain
-failure to thrive
-Lack of T Cells |
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Term
| XLA [X-Linked Agammaglobulinemia] |
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Definition
-No serum Ig's present
-B cells deficiency
-Onset: 6-9 months of age
-Pneumococcus/Stapholococcus infections common
-Pneumonia, sinusitis, otitis prevalent
-do not give live vaccines
-gene defect: Xq21.3-22, mutation in Btk = "Pre-B cell" development is inhibited
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Term
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Definition
-most common type of primary immunodef [1:800]
-no serum or mucosal IgA antibody
-GI, respiratory infections
-familial, associated with celiac's disease |
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Term
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Definition
-X Linked or AR
-IgG and IgA serum levels low, IgM high -> no CSR
-T cell immunity defective
-Due to lack of IgG -> pts have problems with extracellular pathogens
-Germinal Centers malformed
-Severe respiratory infections, sinusitis
-neutropenia, autoimmunity and malignancies(lymphomas)
-three forms |
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Term
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Definition
-X linked
-CD40L absent on T Cells
-most common type |
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Term
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Definition
-Autosomal Recessive
-Activation Induced Cytidine Deaminase or Uracil-DNA Glycosylase = class switch proteins are defective |
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Term
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Definition
-autosomal recessive
-CD40 absent on B cells |
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Term
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Definition
-Onset: after birth
-Defects in Heart and Thymus
-prone to opportunistic infections (same as HIV)
-T cell numbers LOW (so also get defective CSR) [complete DiGeorge = NO T cells]
-B cells present, Serum IgM normal, no other Ig's though |
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Term
| WAS [Wiskott-Aldrich Syndrome] |
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Definition
| *ezcema/thrombocytopenia
-T cells don't respond to mitogen
-T cell activation is impaired due to lack of this similarly named protein
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Term
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Definition
T+B-NK+
-mutation in RAG1 or RAG2
-Leaky (?)
-eosinophilia, IgE elevated*
-failure to thrive
-alloreactive, clonally restricted T cells, poorly proliferative |
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Term
| AT [Ataxia Telecasdfasdjf] |
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Definition
-neurological problem - with balance and speech
-lymphopenia, thymic hypoplasia
-decreased IgA, IgG and IgE
-defect in DNA repair and cell cycle
-sensitive to radiation/sunlight |
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Term
| NBS [Nigmegen Breakage Syndrome] |
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Definition
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Term
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Definition
| without this, T cells are not properly apoptosed |
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Term
| HIM 1,3 [Hypogammaglobulinema, Infections, Mylophexis] |
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Definition
-lymphocytes don't leave Bone Marrow. (lymphocyte and neutrophil precursors can't leave BM)
-allows for disseminated infection
-No development of cells into B and T Cells |
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Term
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Definition
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Term
| XLP [X-Linked Lymphoproliferative Disease] |
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Definition
-relatively healthy, then aquire EBV, cant amount immune response to EBV and patient can no longer regulate B Cell Growth, so clonal expanison of B cells results, and lymphoma develops.
-not specific, so pt has decreased ability to fight pathogens. poor prognosis |
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Term
| defect in IL-2R or IFNgammaR |
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Definition
| inefficient activation of macrophages, problems wtih increased mycobacterial infections |
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Term
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Definition
| T and B cell defenses will be overwhlemed, pt will have chronic viral infections (hSV and chix pox) |
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Term
| CGD [Chronic Granulomatous Disease] |
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Definition
-most common phagocyte deficiency disease
-defect in phagocyte oxidative burst mechanism = no intracellular killing!
-recurrent skin, lymph node and lung infections
-X Linked mostly, or AR
-high WBC counts, normal levels of phagocytes (macrophages and neutrophils), but no intracellular killing
-diagnosed by NBT or DHR assays |
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Term
| LAD [Leukocyte Adhesion Deficiency] |
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Definition
| *not unduly susceptible to oppurtunistic infections
-phagocytes cant properly adhere to the endothelium to get out of blood and into tissue site of infection [diapedesis]
-ie defect in betaIntegrin (CD18)
-CD11 complex not expressed (CD8t + Cd11aborc form LFA-1, which binds to ICAM1)
-prone to skin infections
-very high WBC counts, because getting and respodning to signals from macrophages to produce more neutrophils, but neutrophils are stuck in cirucatlion.
-infection with no pus formation |
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Term
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Definition
| *gram neg infections
-C3 is key to all complement pathways, so its defect is most severe
-complement deficiency in general results in poor opsonization and killing |
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Term
| C1, C2, C4 Complement Deficiency |
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Definition
| -lead to autoimmune diseases, defect in C2 in classical or MBL leads to increased SLE incidence |
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Term
| C5-C9 Complement Deficiency |
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Definition
| -lead to meningococcal and gonococcal infections (Neisserial infections) |
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Term
| ALPS [Autoimmune Lymphocyte Proliferation Syndrome] |
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Definition
defect in apoptosis
high counts
B Cell accumulation (see an increased size of spleen)
Increased autoimmune syndromes |
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Term
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Definition
TLR signalling defect
recurrent pyogenic bacterial infections |
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Term
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Definition
TLR signalling defect
-EV [Epidermodysplasia verruciformis] with recurrent HPV infections
-skin cancer with muations in transmembrane channel gene family [EVER1 and EVER2] |
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Term
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Definition
TLR signalling defect
-WHIMS- warts, hypogammaglobulinemia, infections with HPV, myelokathexis
-gain of function mutation |
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Term
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Definition
-AR, TLR signalling defect
-lack of TNFalpha, IFNgamma, IL-6 in response to IL1beta
-lymphocytes negative for TNFalpha, IFNgamma, IL-6, IL1beta, IL-8 and IL-12
-fibroblasts do not activation NFkB or MAPK
-presents with poor or delayed inflammatory response
*should be considered in pts with recurrent systemic streptocoocal infections* |
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Term
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Definition
| Type 4 Hypersensitivty Disorder -organism surrounded by macrophages and T cells and contained = better! (strong immune response but fewer mycobacteria! |
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Term
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Definition
| anaphylaxis, IgE, mast cells, eosinophils, bronchoconstriction, vascular permeability, ex: allergy, etc |
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Term
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Definition
| Cytotoxic, IgG, IgM, phagocytic cells, ADCC, complement, ex: hemolytic anemia, myasthenia gravis, goodpastures, graves disease |
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Term
| Type III Hypersensitivity |
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Definition
| Immune complex, Ag-Ab immune complexes, complement, nuetorphils, fibrin, hemorrhage ex: Post-strepto Golmerulonephritis, SLE, autoimmune |
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Term
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Definition
| delayed, T cells, macrophage mediated, granulomatous ex: contact dermatitis |
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Term
| infectious trigger: type I HS |
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Definition
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Term
| infectious trigger: type II HS |
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Definition
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Term
| infectious trigger: type III HS |
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Definition
| post streptococcal glomerulonephritis |
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Term
| infectious trigger: type IV HS |
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Definition
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Term
| environmental trigger: type I HS |
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Definition
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Term
| environmental trigger: type II HS |
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Definition
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Term
| environmental trigger: type III HS |
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Definition
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Term
| environmental trigger: type IV HS |
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Definition
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Term
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Definition
| seconds if IgE pre-formed |
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Term
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Definition
| seconds if IgG pre-formed |
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Term
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Definition
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Term
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Definition
| 2-3 days (think ppd test!) |
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Term
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Definition
| Type II HS reaction disorder - ab reactive with AchR in motor end plates of skeletal muscle at NMJ -decreased ability for implus transmission -IgG mediated, down regulation of receptor type response -leads to weakness |
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Term
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Definition
| Type II HS Rxn *IgG mediated, IgG binds TSHR to alwasy be engaged = constant thyroxine secretion = overstimulation =hyperthyroidism -Exophthalmos Associated with Graves Disease: T cell infiltration of orbit of eye --> orbital ag cross reactis with thryoid ag [similar epitopes] -->results in collateral damage -thyroid follicles are increased in size - |
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Term
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Definition
| Type II HS Rxn -BV inflammation, neutrophils damage BV by being immobilized in BV wall which triggers inflammation and vasculitis [cANCA] = classic anti-neutrophil cytoplasmic antibodies are responsible -autoantibodies to proteinase3 in neutrophils because prtoeinase3 moves from cytoplasm to cell surface where it can be targeted by ab found in body. when it is bound by ab, it stimulates oxidative burst which causes inflammationa and harm to the extracellular space it was relocated to |
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Term
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Definition
| Type II HS Rxn -ab directed against alpha3 chain of Type IV Collagen - "linear staining" in basement membrane of kidney and lungs - glomerular BM *IgG mediated -cause: genetics, weedkiller/pesticides -males more affected, rare -lung kidney disease seen |
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Term
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Definition
| Type III HS Rxn -systemic immune complex disease |
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Term
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Definition
| IC disease in kidney, acute, increased blood/protein in urine, can be resolved w/ ag removal |
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Term
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Definition
| chronic, ongoing, slow, cant remove ag, SLE, hep B, IC deposited and damages basement membrane, complement and protein seen in urine, streptococcal complications* |
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Term
| poststreptococcal glomerulonephritis |
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Definition
after a streptococcal infection, IC can forma nd depost in kidney where they can damage glomeruli and cant be cleared
-associated with Type III |
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Term
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Definition
| Type III HS rxn (few hours and IgG not seconds/IgE for I) involves respiratory tract! IgG abs against proteins in mold spores of hay --> ICs trigger inflammation in alveoli -pt has precipitating IgG antibodies against mold protein, insoluble ICs form in lung tissue |
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Term
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Definition
"type III vasculitis"
localized hypersensitivity reaction 12-15 hrs after exposure -ag introduced locally, no radiation of inflammation Type III: 12 hrs, Ab mediated, forms ICs Type IV: DTH, PPD test, Tcells/macrophages - several days *associated w/ incorrectly given vaccine *self resolves |
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Term
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Definition
| mediated by Th1 T Cells and macrophages (cycle of activation of the other one) -TB, Hep B, leprosy, MS, RA, T1D, celiac, nickel -response to autoantigens and haptens |
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Term
| [RA ]Rheumatoid Arthritis |
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Definition
| Type IV HS Rxn -neutrophils activated and migrate under influence of TNFa -activated macrophages secrete metalloproteinases which break down matrix proteins and they also release TNFa which activates the osteoclasts -osteoclasts degrade bone and cause joint deformity -B cells can also be stimulated by T cells to rpoduce autoantibodies -IL-6 leave joint and initiate acute phase reaction -synovial membrane swollen, infiltratede by inflammatory cells (T/macro) -skewed cytokines (not IL4-->Type IV is a Th1 mediated thing!) |
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Term
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Definition
| Type IV HS Rxn [Th1 mediated] T cells in plaques respond to antigens such as myelin basic protein, macrophages transiently inhbit neuronal signalling -locally produced abs agains tmyelin basic protein can damage myelin = macrophages irreversibly damage the myelin sheaths - failure of self tolerance -CD4+ T Cells and macrophages into BBB secrete cks which are toxic to axons = permanent --ag wasnt available for T cell priming behind BBB so dont know its self |
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Term
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Definition
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Term
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Definition
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Term
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Definition
| Autoimmune PolyEndocrinopathy Candiadiasis, Ectodermal Dystrophy -dysfunctional AIRE gene which doesnt allow central deletion of self reactive T cells in thymus |
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Term
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Definition
| Type III HS Rxn -Th2 mediated, IgG mediated -Masking of chromatin: serum amylod P digestion of chromatin: DNase1 -issue with Ag-DNA/complement clearance: C1q, C4, C1s, C1r -lymphoctye activation: Lyn, SHP-1, CD22 -worse during pregnancy (a Th2 mediated event) so exacerabates to extreme Th2 -inheritance of HLA DR2 |
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Term
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Definition
| *gluten - gliacdin Type IV HS -transglutaminase -HLA DQ2, 75% concordance in twins -T cell mediated -villi of intestines become flattened, leads to bloating, diarrhea, cramping -exogenous antigen (gluten) triggers an autoimmune response against endogenous antigen (transglutaminase) -gliadin and tissue transglutaminase both normally present and not usually antigenic, in celiac's, tissue transglutaminase binds the gliadin and creates glutamic acid residues which cause gliadin to bind HLA-DQ2, T cells responding to gliadin provide help to B cells responding to tissue glutaminase |
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Term
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Definition
| -T cell mediated - CD 4+ Type IV HS -lack of insulin prodcution due to selective destruction of beta islet cells in pancreas. -caused by a loss of central tolerance -change in single amino acid in HLA- DQbeta at pos 57 -environmental trigger is key: enterovirus, pancreotrophic and goes to pancreas and destroys tissue beta cells whcih are normaly isolated/refractory to lymphocytes so not recognized as self and thus attacked by macrophages secreting inflammatory mediators which disrupt islets. |
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Term
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Definition
| Type II HS Rxn -have autoantibodies to AchR at NMJ, so bound but do not activate - cause it to be internalized and degraded, leads to progressive loss of AchRs which blocks NMJ impulse transmission which eventually leads to no muscle contraction --> chronic -IgG mediated disease |
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Term
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Definition
| Type II HS reaction -autoantibodies to TSHR -feedback mechanism doesnt work = hyperthyroidism |
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Term
| Autoimmune diseases that can be passively transferred [think placenta --> fetus] |
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Definition
| -Myasthenia gravis -Grave's Disease -Thrombocytopenic purpura -Neonatal lupus rash -pemphigus vulgaris *TX: plasmapheresis so baby doesnt get mom's IgG antibodies |
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Term
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Definition
| -C1inhibitor defeciency - autosomal dominant, unstopped activation of classical pathway - leads to build up of C2a, resulting in edema, edema kills by swelling of respiratory passage |
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