Diseases Flashcards
X-linked agammaglobulinemia
B-cell disorder
Defect in BTK -> no B cell maturation…stops maturing at the Pre-B cell stage because BTK functions to help make the BCR
X-linked recessive
presentation: recurrent bacterial and enteroviral infections after 6 months
findings: absent B cells in peripheral blood; decrease Ig of all classes; absent/small lymph nodes and tonsils
treatment: IVIG, antibiotics
Selective IgA deficiency
B-cell disorder
most common primary immunodeficiency
presentation: majority Asymptomatic. can see Airway and GI infections, Autoimmune disease, Atopy, Anaphylaxis to IgA containing products
findings: low IgA levels with normal IgG and IgM
treatment: IVIG, antibiotic, do not give blood products
Common variable immunodeficiency
B-cell disorder
many causes but lead to a defect in B cell differentiation
Presentation: age ~20-30s, increase risk of autoimmune disease, bronchiectasis, lymphoma, sinopulmonary infections
findings: decreased plasma cells and Igs
treatment: IVIG
DiGeorge syndrome
T-cell disorder
Deletion: 22q11.2; failure to develop 3rd and 4th pharyngeal pouches leads to absent thymus and parathyroids
presentation: tetany (hypocalcemia), recurrent viral/fungal infections (T cell-deficiency), conotruncal abnormalities
findings: low T cells, low PTH, low Ca+2, absent thymic shadow on CXR
treatment: thymus transplant in leg, HSCT
IL-12 receptor deficiency
T cell disorder
low TH1 response; autosomal recessive
presentation: disseminated mycobacterial and fungal infections; may present after administration of BCG vaccine
findings: decreased IFN-gamma
Hyper IgE syndrome
T cell disorder
also called Job syndrome
mutation in STAT3 leads to deficiency of TH17 cells which leads to impaired recruitment of neutrophils to sites of infection; autosomal dominant
presentation: FATED: coarse Facies, cold (noninflamed) staphylococcal Abscesses, retained primary Teeth, increased IgE, Dermatologic problems (eczema)
findings: increased IgE and decreased IFN-gamma
Chronic mucocutaneous candidasis
T-cell disorder
many causes
presentation: noninvasive candida albicans infections of skin and mucous membranes
findings: absent in vitro T cell proliferation in response to Candida antigens; absent cutaneous reaction to Candida antigens
Severe combined immunodeficiency (SCID)
T and B cell disorder
X-linked: mutation in IL-2R gamma chain (T-B+NK-)
somatic: mutation in ADA (toxic accumulation of adenosines in lymphocytes; T-B-NK-), PNP (toxic accumulation of inosines in lymphocytes; T-B-NK-), JAK3 (signaling pathway on gamma chain for lymphocytes; T-B+NK-), RAG1/2 (no TCR/BCR receptors; T-B-NK+)
presentation: failure to thrive, chronic diarrhea, thrush, recurrent viral, bacterial, funagal and protozoal infections
treatment: bone marrow transplant asap
findings: low T cell-receptor excision circles (TRECs), absence of thymic shadow, germinal centers and T cells
Ataxia-telangiectasia
B and T cell disorder
defects in ATM gene -> failure to repair DNA DSB -> cell cycle arrest
presentation: triad: cerebellar defects (Ataxia), spider Angiomas (telangiectasia), IgA deficiency
findings: increased AFP, decreased IgA, IgG and IgE, lymphopenia, cerebellar atrophy
treatment: IVIG
Hyper IgM syndrome
B and T cell disorder
most commonly due to defective CD40L on Th cells -> class switching defect; X-linked recessive
can also be autosomal: mutation in activation-induced deaminase (AID), which is important in germical center antibody class switching; no somatic hypermutation
presentation: severe pyogenic infections early in life; opportunisic infection with Pneumocystis Cryptosporidium, CMV
findings: normal or increased IgM, very low levels of IgG, IgA, and IgE
treatment: IVIG
Wiskott-Aldrich syndrome
B and T cell disorder
mutation in WAS gene: T cells unable to reorganize actin cytoskeleton; x-linked recessive
presentation: WATER: Wiskott-Aldrich = Thrombocytopenia, Eczema, Recurrent infections; increased risk of autoimmune disease and malignancy
findings: low to normal IgG, IgM; increased IgE and IgA; fewer and smaller platelets
treatment: IVIG, antibiotics
Leukocyte adhesion deficiency (type I)
phagocyte dysfunction
defect in CD18 (LFA-1 integrin, CR3 or CR4) protein on phagocytes -> impaired migration and chemotaxis of neutrophils and poor opsonophagocytosis; autosomal recessive
presentation: recurrent bacterial skin and mucosal infections, absent pus formation, impaired wound healing, delayed separation of umbilical cord
findings: increased num. neutrophils, absence of neutrophils at infection sites
treatment: HSCT
Chediak-Higashi syndrome
phagocyte dysfunction
defect in LYST (lysosomal trafficking regualtor gene) -> microtubule dysfunction in phagosome-lysosome fusion; autosomal recessive
presentation: recurrent pyogenic infections by staphylococci and streptococci, partial albinism, peripheral neuropathy, progressive neurodegeneration, infiltrative lymphohistiocytosis
findings: giant granules in granulocytes and paltelets, pancytopenia, mild coagulation defects
treatment: HSCT
Chronic granulomatous disease
phagocyte dysfunction
defect of NADPH oxidase -> decreased ROS and decreased respiratory burst in neutrophils; X-linked recessive is most common
presentation: increased susceptibility to catalase positive organisms: Nocardia, Pseudomonas, Listeria, Aspergillus, Candida, E coli, Staphylococci, Serratia, B cepacia, H pylori
findings: abnormal dihydrohodamine test (decreased green fluorescence); nicroblue tetrazolium dye reduction test obsolete (not blue)
treatment: antibiotics, neutrophil transfusions, recombinant IFN-gamma to activate macrophages, HSCT
C1 esterase inhibitor deficiency
causes hereditary angioedema due to unregulated activation of kallikrein -> increases bradykinin. ACE inhibitors are contraindicated
autosomal dominant
C1 inhibitor is a protease inhibitor whose target enzymes are C1r and C1s of complement cascade, factor XII of the coagulation pathway and the kallikrein system…unregulated activity can give rise to vasoactive peptides such as bradykinin
treatment: protease inhibitor (kallikrein/bradykinin or plasminogen/plasmin) and danazolol (increases liver production of C1 inhibitor)
C3 deficiency
increases risk of severe, recurrent pyogenic sinus and respiratory tract infections; increases susceptibility to T3 hypersensitivity rxns
C5-C9 deficiencies
terminal complement deficiency increasees susceptibility to recurrent Neisseria bacteremia
DAF deficiency
causes complement-mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria
Serum sickness
T3 hypersensitivity
an immune complex disease in which antibodies to foreign proteins are produced (takes 5 days). immune complexes form and are deposited in membranes where they fix complement -> leads to tissue damage
mostly caused by drugs acting as haptens - symptoms include fever, urticaria, arthralgia, proteinuria, lymphadenopathy occur 5-10 days after antigen exposure
arthus reaction
a local subacute antibody-mediated hypersensitiviy reaction. intradermal injection of antigen into a presensitized (has circulating IgG) individual leads to immune complex formation in the skin.
characterized by edema, necrosis and activation of complement
test: immunofluorescent staining
graft vs. host disease
type IV hypersensitivity
treatment: corticosterids, methotrexate/cyclophosphamide, cyclosporine, mycophenylate, anti-CD25 (Daclizumab)
multiple sclerosis
type IV hypersensitivity
protein antigens in CNS myeling (myelin basic protein, proteolipid protein)
clinical manifestations: demyelination in CNS with perivascular inflammation; paralysis, ocular lesion
treatment: glucocorticosteroids (immunosuppress), IFN-beta (decrease antigen presentation, increase apoptosis of T cells, increase production of Treg cells and increase production of IL-10 and TGF-beta)
contact dermatitis
type IV hypersensitivity - CTL (CD8+) is the majority
skin inflammation with blisters
ex: poison ivy, nickel allergy
systemic lupus erythematosus (SLE…lupus)
type III hypersensitivity
antibody: anticardiolipin, lupus anticoagulant…antibodies to nucleic acids (ANA, anti-dsDNA)
predominately affects skin and joints - most common presentation is a butterfly rash on the face, low-grade fever, nephritis and nondeforming arthritis
treatment: cyclosporine, methotrexate, azathipurine, hydroxychloroquine, cyclophosphamide, steroids
poststreptococcal glomerulonephritis
type III hypersensitivity
streptococcal cell wall antigens; may be “planted” in glomerular basement membrane
clinical manifestation: nephritis
Goodpasture syndrome
Type II hypersensitivity
anti-basement membrane antibody (and in 60% of patients they may have antibodies to pulmonary alveolar basement membranes) - binds to type IV collagen
clinically characterized by rapidly progressive glomerulonephritis, circulating antibodies and pulmonary hemorrhage
treatment: plasmphoresis, anti-inflammatory and immunosuppressive drugs (like corticosteroids like predisone)
