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MDtruth.com Note: the following material is for personal use only (see below for full disclaimer). Cardio Heme/Onc Endo ID Neuro Renal Pulmonary GI Liver Rheum Bone / Joint / Muscle Male / Female Allergy Immunology Derm Surgery / Ortho Acid-Base / Metabolic / Electrolytes Ophtho Environment/Nutrition/Vitamins Pediatrics Emergency Pharm Micro Ddx Procedure vids! ICU Guide One [pic] – cardiac / pulmonary equations ICU Guide Two [pic]– intubation / respiratory physiology / creatinine clearance / drug levels Immunology
20% of plasma proteins / 2 light chains (kappa or lambda) and 4 heavy chains (gamma, alpha, mu, delta, epsilon) IgA (15%) – secretions / 2 IgA molecules linked by J-segment (secreted by epithelial cells) IgG (75%) – crosses placenta / major antibody IgM (10%) – most efficient activator of compliment IgE (trace) – hypersensitivity reactions / bound to Fc receptors on mast cells and basophils IgD (1%) – surface of B-cells 4 major types of immune-response Type I: hypersensitivity Type II: cell-mediated Type III: immune-complex Type IV: delayed-type hypersensitivity Type I hypersensitivity (derm) IgE, mast cells (his, 5HT, TNF-a, TGF-B, IL-4), Th2, (y-IFN is inhibitory) urticaria, atopic dermatitis, anaphylactic shock
Long term: avoidance, drugs, allergen immunotherapy (how does that work?) Insect stings: reaction in < 15 mins / venom immunotherapy may help / note: honeybee stings different from other stinging insects
IgM > IgG / complement / ADCC / organ-specific (Goodpasture’s, pemphigus) / receptor-specific (Grave’s, Myasthenia gravis) / hemolytic anemia / Derm: pemphigus, bullous pemphigus, herpes gestationis, epidermolysis bullosa Treatment: immunosuppression, plasmapheresis Type III immune-complex (derm) leukoclastic vasculitis (PAN) / fibrinoid necrosis / polyarthritis, skin, serum sickness, arthus reaction Treatment: anti-inflammatory agents, immunosuppression Type IV delayed-type hypersensitivity Th-1 - contact dermatitis, Tb, sarcoidosis, Wegener’s, IBD Treatment: corticosteroids, cytotoxic agents, antimicrobials GVHD Affects: skin, liver, GI tract, eye, kidney (reports) Occurs following transplantation (e.g. BMT) / patients at high-risk for fungal infections for several weeks/months after engraftment (current debate over when and what to use for prophylaxis 1/07) / immunosuppressive agents used to prevent GVHD can look like EM [pic] [dermis]
no thymus (no T-cells), no parathyroids / failure of 3rd (upper parathyroids), 4th pharyngeal (lower parathyroids) pouches / presents with tetany owing to hypocalcemia Chronic Mucocutaneous Candidiasis (CMC) T-cells do not respond to Candida albicans Defects of mainly B Cells IgA deficiency 1 in 500 (most common immunodeficiency) / B-cells have it, but can’t secrete it / risk factor for celiac sprue Presentation: recurrent sinusitis, GI infection (giardia), otitis media Note: do NOT give IVIG due to presence of anti-IgA antibodies (44%) Common variable immunodeficiency (CVID) Most common primary immune deficiency requiring medical attention / 1 in 50,000 sporadic / 10% familial / 15-35 yrs Mechanism: hypo-IgG from various defects (CD27+ memory B-cells cannot differentiate into plasma cells) / suspected genes involved (BAFF, APRIL, TACI, ICOS)
XLR / no functional B-cells (cannot get EBV infection) / low Ig / recurrent bacterial infections beginning at age 6 months / low IG predisposes to chronic aseptic meningitis (with secondary dermatomyositis) Duncan’s Syndrome (X-linked Lymphoproliferative Disease) XLR / impaired response to EBV nuclear antigen (2/3 mortality ) / survivors develop hypogammaglobulinemia and/or B-cell lymphomas / decreased NK function and ADCC against EBV-infected cells Defects of B and T Cells Wiskott-Aldrich XLR / mutation of WASP gene / B and T-cells regress / cannot mount IgM response to capsular polysaccharides elevated IgA, normal IgE, low IgM / recurrent pyogenic infections, eczema, thrombocytopenia / increased incidence of lymphoreticular neoplasm Ataxia-Telangiectasia B and T-cell deficiency, with associated IgA deficiency / presents with ataxia, spider angiomas / recurrent infections / can get lymphomas / secondary diabetes mellitus? Severe Combined Immunodeficiency Syndrome (SCIDS) no functional B and T cells / defective IL-2 receptors, MHC II, or ADA (½ of autosomal forms)
excess ATP and dATP provides negative feedback on ribonucleotide reductase, prevents DNA synthesis, lowers lymphocyte count / can produce SCID Defects of Phagocytes [NEJM] Guideline: these are rare but important diseases, and can be diagnosed by examination of peripheral phagocytes and a few special stains / must catch these early and consider IFN-gamma, g-CSF, broad antibiotics Cyclic Neutropenia Autosomal dominant / ?mutation in neutrophil elastase (ELA2) recurrent neutropenia ( < 200 cells/mL) lasts 3-6 days / cycle usually ~21 days, but in 30% of patients, ranges from 14-42 in 30% During neutropenia: fever, apthous stomatitis, gingivitis, stomatitis, cellulitis, cervical LAD Severe congenital neutropenia Autosomal recessive in 90% (unknown mutation) / heterozygous in 10% / Presents during first year of life / cellulitis, perirectal abscess, peritonitis, stomatitis, meningitis (Staph, Burkholderia) / increased risk for myelodysplasia, AML Labs: < 500 neutrophils, but increased circulating monocytes, eosinophils Treatments: nearly all improve with exogenous g-CSF
Autosomal recessive (rare) / Presents within first yr of life / average life expectancy 35 yrs Exocrine pancreatic insufficiency, skeletal abnormalities, bone marrow dysfunction, recurrent infection / all have neutropenia (cyclic or intermittent), and 10-25% also have pancytopenia / increased risk of marrow aplasia, myelodysplasia, AML Treatments: exogenous g-CSF (not considered a risk factor for malignant transformation) CD18 (leukocyte adhesion deficiency type 1) Autosomal recessive loss of B2 integrin adhesion molecules (from lack of CD18 or B-chain) / neutrophils cannot aggregate or bind endothelial cells / life expectancy is < 10 up to 40 yrs (depends on amount of CD18) Delayed separation of umbilical cord, severe periodontitis (early tooth decay), recurrent infections of all mucosal surfaces, AND delayed wound healing (enlarging borders, dysplastic scars)
Growth retardation, dysmorphic features, neurological deficits / lack of sialyl-Lewisx (ligand for selectins) / Treatment with oral fructose has proven helpful Job’s syndrome neutrophils fail to respond to chemotactic stimuli (C3a, 5a, LT-B4) / recurrent cold staph abscesses / dental problems / elevated IgE levels / ?Rac2 (predominant GTPase in neutrophils) Defective INF-gamma/IL-12 Axis Autosomal recessive and autosomal dominant forms / complete loss of ligand-binding chain causes disseminated NTM in infancy or fatal BCG vaccination / partial loss is less severe (NTM develops in early childhood) / defect of IFN-gamma receptor signaling chain resembles complete loss of ligand-binding chain / defect in IL-12 receptor (B1 chain) and IL-12 increases susceptibility to NTM and Salmonella infections Treatment: all respond to exogenous INF-gamma except (complete loss of ligand and receptor signaling)
XLR (gp91phox) make up 70% / presents within first 2 yrs / neutrophils lack hydrogen peroxide burst (myeloperoxidase system) / Autosomal recessive (P47phox) make up 30% / onset may be later Organisms: S. aureus, Burkholderia cepacia, aspergillus, nocardia, serratia, proteus, E. coli Obstructive granulomas of GI/GU tracts, pneumonia, skin infections, osteomyelitis, liver abscesses, draining adenopathy (at BCG injection site, but mycobacterial disease still rare) Diagnosis: can be delayed by blunted fever, inflammatory symptoms / severe resistant facial acne and painful inflammation of nares, gingivitis, apthous ulcers, NOT periodontal disease Nitroblue tetrazolium test or flow cytometry with dihydrorhodamine dye Treatment: bactrim (one/day) may reduce serious infections from 1/yr to 1 every 4 yrs / IFN gamma reduces bacterial and fungal infections by 70% / stem-cell transplantation and gene therapy protocols under investigation Download 3.95 Mb. Share with your friends:
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