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Here is what Step 1 covers- did we get them all?

Here is what Step 1 covers- did we get them all?. Production/function granulocyte, NK cells and macrophages/DC Production/function of T cells, TCR, cytokines/chemokines Production/function of B cells and PC, Ig structure, classes, molecular basis for specificity, receptors

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Here is what Step 1 covers- did we get them all?

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  1. Here is what Step 1 covers- did we get them all? • Production/function granulocyte, NK cells and macrophages/DC • Production/function of T cells, TCR, cytokines/chemokines • Production/function of B cells and PC, Ig structure, classes, molecular basis for specificity, receptors • Antigenicity/immunogenicity, host defenses(read Innate I), primary/secondary responses, passive transfer of immunity(all ways) • In vitro complement, other diagnostic tests and antigen antibody reactions • Mediators, complement, aa, histamine, NO and cytokines • MHC structure and function, RBC antigens. Transplantation • Vaccines, protective immunity, tumor immunity • Disease states like ID, HIV and pharmacological immunosuppression

  2. INNATE IMMUNITY • NOT ANTIGEN SPECIFIC • HAS NO MEMORY • MEDIATED BY • NEUTROPHILS • MACROPHAGES/MONOCYTES • NATURAL KILLER CELLS • EOSINOPHILS • BASOPHILS/MAST CELLS • MANNOSE BINDING PROTEIN AND COMPLEMENT • PROSTAGLANDIN & KININ SYSTEMS INDISCRIMINATE DESTRUCTION

  3. PRO-INFLAMMATORY CYTOKINES

  4. ADAPTIVE IMMUNITY • ANTIGEN SPECIFIC • CLONAL EXPANSION • AMPLIFIES AN IMMUNE RESPONSE AFTER A SPECIFIC RECEPTOR INTERACTION • INTEGRATES THE INNATE RESPONSE INTO THE REACTION • MEMORY OF THE ENCOUNTER

  5. KNOW THESE DIFFERENCES

  6. ANATOMY OF THE IMMUNE SYSTEM

  7. B-CELL DEVELOPMENT

  8. ANTIBODY STRUCTURE

  9. ANTIBODY FUNCTIONS

  10. ANTIBODY FUNCTIONS

  11. COMPLEMENT • FLUID PHASE AMPLIFIER OF INNATE AND ANTIBODY MEDIATED RESPONSES • THREE ARMS • ALTERNATE-BACTERIAL CELL WALLS • MANNOSE BINDING-BACTERIAL CELL WALLS and MBP • DIRECT(CLASSIC)-SPECIFIC Ag/Ab REACTIONS

  12. COMPLEMENT

  13. COMPLEMENT • ENZYME ACTIVATED CASCADE WITH GENERATION OF INFLAMMATORY AND REGULATORY FRAGMENTS • ACTIVATES INFLAMMATORY CELLS BY SPECIFIC RECEPTOR INTERACTIONS • HAS IMPORTANT IMMUNOREGULATORY AND IMMUNE COMPLEX DISPOSAL ROLES • Measured by serum C3 and C4, total hemolysis and individual components

  14. COMPLEMENT-RELATED DISEASES • Rare • C1esterase deficiency with angioneurotic edema- • Deficiencies in the direct sequence associated with IC diseases like SLE • Homozygous C3 is lethal • Deficiencies in the alternate path very rare • Individual component deficiency after C5 associated with Neisserial bacteremia

  15. ANTIGEN PRESENTING CELLS

  16. MHC

  17. T-CELL DEVELOPMENT

  18. T-CELL FUNCTIONS

  19. QUESTIONS • From stem cell to T cell • why the thymus • CD4 versus CD8 • gamma delts versus alpha bets • peripheral blood • CDs to remember………. • 3,4,8,25,19,16,20,

  20. MORE CYTOKINES TO REMEMBER Il-12, INF- and IL-2 =TH1 response IL-4 =TH2 response & antibody formation IL-10, IL- 4 = suppression of Th1 INF- = suppression of TH2 IL-8 = neutrophils IL-5= eosinophils TGF- = healing IL-6 = fever and cachexia TNF- =inflammation (RA),sepsis and SIRS, monoclonals available to inhibit some syndromes

  21. MHC • Co-dominant alleles • Present on Chromosome 6 in humans • A,B,C loci are Class I • D loci are class II and control immune responses and rejection

  22. MLC

  23. TRANSPLANT TYPES • Autograft • Isograft • Allograft (also known as Homograft) • Xenograft

  24. IMMUNOSUPPRESSION • Corticosteroids-inhibit NFB • Cyclosporine-inhibit T-cell activation • Tacrolimus- inhibit T-cell activation • Rapamycin- block IL-2 receptor activation • Anti-cytokine/ligand monoclonals

  25. PREDICT THE TYPE OF INFECTION • Pure B cell…encapsulated bacteria and systemic spread of GI viruses..frequent after 6 mos of age • “pure” T cell….TB, fungi, pneumocystis since helper function is lost…occurs at birth. B cell infections will not occur until maternal antibody gone-approx 6 mos • B & T cell..at birth, severe and fatal if not transplanted • CGD –neutrophil inability to kill bacterial that produce catalase..esp staph • cytokine..IL-12, Interferon gamma, IL-4

  26. DISEASES ASSOCIATED WITH T-CELL DEFICIENCY • HIV/AIDS • THYMIC APLASIA • SENESCENCE • BIRTH • WISKOTT-ALDRICH • ATAXIA-TELANGIECTASIA • TREATMENT

  27. DISEASES ASSOCIATED WITH B-CELL DEFICIENCY • X-LINKED AGAMMAGLOBULINEMIA • COMMON VARIABLE IMMUNODEFICIENCY • SELECTIVE IgA DEFICIENCY • CLL • HYPER IgM SYNDROME • TREATMENT

  28. DISEASES ASSOCIATED WITH T & B CELL DEFICIENCY • SCID • THERAPY: • STEM CELL TRANSPLANTS • BMT • GENE REPLACEMENT- recent problems with the retroviral vector insertion has led to leukemia

  29. TESTING IMMUNE FUNCTION • B-CELLS • SERUM IG LEVELS • ELECTROPHORECTIC DETECTION OF CLONALITY • ENUMERATION OF B-CELLS • DETECTION OF SPECIFIC ANTIBODIES • IMMUNOHISTOPATHOLOGIC

  30. Know your Flow!

  31. TESTING IMMUNE FUNCTION • T-CELLS • IN VIVO SKIN TESTING- will not be valid in patients with malnutrition, on steroids etc • ENUMERATION OF T-CELLS-can be misleading because doesn’t reflect tissue distribution • IMMUNOHISTOPATHOLOGIC • IN VITRO FUNCTIONS- rarely needed

  32. HYPERSENSITIVITY REACTIONS • TYPE I- Atopy, asthma & anaphylaxis • TYPE II-Antibody to cell structures-immune thrombocytopenia, AIHA • TYPE III- Immune complex diseases-SLE is prototype • TYPE IV- Delayed hypersensitivity-sarcoidosis

  33. ALLERGY MEDIATORS

  34. ASTHMA

  35. Asthma • Limited early exposure to infections-so-called hygiene hypothesis • Obesity • Genes • Maternal 11 for IgE increase • T-bet gene abnormalitiesfor deficient INF- • IL-13

  36. AUTOIMMUNE DISEASES

  37. AUTOIMMUNE DISEASES

  38. IMMUNE COMPLEX DISEASE-AKA SERUM SICKNESS

  39. AUTOANTOBODIES • SLE- • ANA is a SCREENING TEST ONLY(HIGH SENSITIVITY, LOW SPECIFICITY) • double stranded(ds/native) DNA correlates loosely with renal disease, very specific • Sm very specific for SLE-low sensitivity • Histone- present in drug induced lupus but also SLE and other diseases • Ribonucleoprotein (RNP)- associated with mixed connective tissue disease

  40. AUTOANTOBODIES • ANCA • cANCA high specificity for Wegeners Granulomatosus • pANCA found in some glomerulonephritis, microscopic vasculitis and other vasculitis Polymyositis/Dermatomyositis……anti-JO-1 SS-A(Ro)/SS-B(La)- Sjogren syndrome, congenital heart block

  41. MORE AUTOANTIBODIES • Scleroderma • SCL-70( aka anti-topoisomerase) specific but very low sensitivity • Centromere-high sensitivity for CREST(limited scleroderma) and codes for presence of pulmonary hypertension

  42. Other Autoantibodies to remember • AntiAcR- myasthenia • Anti-endomysial- Sprue (anti gliadin) • Rheumatoid factor- not specific for RA

  43. Acute Phase reactants • C-reactive Protein- • Most accurate indicator of an inflammatory reaction • Proxy for IL-6 • May correlate independently of Lipids for CA • High likelihood something about CRP will be on Boards!..especially as independent indicator of coronary artery disease Transferrin, ceruloplasmin, C3, haptoglobin increase with infection, albumin and hemoglobin decrease

  44. HLA ASSOCIATIONS WITH SPECIFIC DISEASES • Ankylosing spondylitis-B27……………….90RR* • Reactive Arthropathy-B27.………………...40 • Rheumatoid Arthritis-DR4.………………...4 • Behcet’s-B51.………………………………4 • SLE-DR3.…………………………………..6 • IDDM-DR3,4……………………………….6 • Dermatitis Herpetiformis-DR3.…………….16 • MS-DR2…………………………………….4 • Goodpastures-DR2…………………………16 • Birdshot Retinochoroidopathy-A29.……….109** • *…remember the caveats, ** …..for that extra point

  45. TERMS TO REMEMBER • ANTIGEN • IMMUNOGEN • EPITOPE • HAPTEN • ADJUVANT • STEM CELLS • PRIMARY AND SECONDARY IMMUNE RESPONSE

  46. TERMS TO REMEMBER • INNATE(AKA NATURAL) • ADAPTIVE(SPECIFIC OR ACTIVE) • CELL-MEDIATED IMMUNITY • HUMORAL/ANTIBODY IMMUNITY • PASSIVE IMMUNIZATION • ACTIVE IMMUNIZATION • ARTHUS REACTION

  47. TERMS TO REMEMBER • ISOTYPE • IDIOTYPE • MONOCLONAL • SYNGENEIC • ALLOGRAFT • AUTOGRAFT • ELISA & RIA

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