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

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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

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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

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PRO-INFLAMMATORY CYTOKINES
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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

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KNOW THESE DIFFERENCES
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ANATOMY OF THE IMMUNE SYSTEM
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B-CELL DEVELOPMENT
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ANTIBODY STRUCTURE
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ANTIBODY FUNCTIONS
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ANTIBODY FUNCTIONS
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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

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COMPLEMENT
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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

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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

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ANTIGEN PRESENTING CELLS
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MHC
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T-CELL DEVELOPMENT
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T-CELL FUNCTIONS
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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,

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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

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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

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MLC
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TRANSPLANT TYPES

• Autograft
• Isograft
• Allograft (also known as Homograft)
• Xenograft

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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

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PREDICT THE TYPE OF INFECTION

• Pure B cellencapsulated bacteria and systemic
  spread of GI viruses..frequent after 6 mos of age
• pure T cell.TB, fungi, pneumocystis since
  helper function is lostoccurs 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

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DISEASES ASSOCIATED WITH T-CELL DEFICIENCY

• HIV/AIDS
• THYMIC APLASIA
• SENESCENCE
• BIRTH
• WISKOTT-ALDRICH
• ATAXIA-TELANGIECTASIA
• TREATMENT

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DISEASES ASSOCIATED WITH B-CELL DEFICIENCY

• X-LINKED AGAMMAGLOBULINEMIA
• COMMON VARIABLE IMMUNODEFICIENCY
• SELECTIVE IgA DEFICIENCY
• CLL
• HYPER IgM SYNDROME
• TREATMENT

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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

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TESTING IMMUNE FUNCTION

• B-CELLS
• SERUM IG LEVELS
• ELECTROPHORECTIC DETECTION OF CLONALITY
• ENUMERATION OF B-CELLS
• DETECTION OF SPECIFIC ANTIBODIES
• IMMUNOHISTOPATHOLOGIC

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Know your Flow!
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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
  doesnt reflect tissue distribution
• IMMUNOHISTOPATHOLOGIC
• IN VITRO FUNCTIONS- rarely needed

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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

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ALLERGY MEDIATORS
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ASTHMA
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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

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AUTOIMMUNE DISEASES
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AUTOIMMUNE DISEASES
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IMMUNE COMPLEX DISEASE-AKA SERUM SICKNESS
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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

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AUTOANTOBODIES

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

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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

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Other Autoantibodies to remember

• AntiAcR- myasthenia
• Anti-endomysial- Sprue (anti gliadin)
• Rheumatoid factor- not specific for RA

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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

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HLA ASSOCIATIONS WITH SPECIFIC DISEASES

• Ankylosing spondylitis-B27.90RR
• Reactive Arthropathy-B27....40
• Rheumatoid Arthritis-DR4....4
• Behcets-B51.4
• SLE-DR3...6
• IDDM-DR3,4.6
• Dermatitis Herpetiformis-DR3..16
• MS-DR2.4
• Goodpastures-DR216
• Birdshot Retinochoroidopathy-A29..109
• remember the caveats, ..for that extra point

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TERMS TO REMEMBER

• ANTIGEN
• IMMUNOGEN
• EPITOPE
• HAPTEN
• ADJUVANT
• STEM CELLS
• PRIMARY AND SECONDARY IMMUNE RESPONSE

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TERMS TO REMEMBER

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

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TERMS TO REMEMBER

• ISOTYPE
• IDIOTYPE
• MONOCLONAL
• SYNGENEIC
• ALLOGRAFT
• AUTOGRAFT
• ELISA RIA

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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

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T-CELL FUNCTIONS
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Isotype switching