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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

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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
  • 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
innate immunity
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

adaptive immunity
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
complement
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
complement14
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
complement related diseases
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
questions
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,
more cytokines to remember
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

slide22
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
transplant types
TRANSPLANT TYPES
  • Autograft
  • Isograft
  • Allograft (also known as Homograft)
  • Xenograft
immunosuppression
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
predict the type of infection
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
diseases associated with t cell deficiency
DISEASES ASSOCIATED WITH T-CELL DEFICIENCY
  • HIV/AIDS
  • THYMIC APLASIA
  • SENESCENCE
  • BIRTH
  • WISKOTT-ALDRICH
  • ATAXIA-TELANGIECTASIA
  • TREATMENT
diseases associated with b cell deficiency
DISEASES ASSOCIATED WITH B-CELL DEFICIENCY
  • X-LINKED AGAMMAGLOBULINEMIA
  • COMMON VARIABLE IMMUNODEFICIENCY
  • SELECTIVE IgA DEFICIENCY
  • CLL
  • HYPER IgM SYNDROME
  • TREATMENT
diseases associated with t b cell deficiency
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
testing immune function
TESTING IMMUNE FUNCTION
  • B-CELLS
    • SERUM IG LEVELS
    • ELECTROPHORECTIC DETECTION OF CLONALITY
    • ENUMERATION OF B-CELLS
    • DETECTION OF SPECIFIC ANTIBODIES
    • IMMUNOHISTOPATHOLOGIC
testing immune function33
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
hypersensitivity reactions
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
asthma38
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
autoantobodies
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
autoantobodies43
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

more autoantibodies
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
other autoantibodies to remember
Other Autoantibodies to remember
  • AntiAcR- myasthenia
  • Anti-endomysial- Sprue (anti gliadin)
  • Rheumatoid factor- not specific for RA
acute phase reactants
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

hla associations with specific diseases
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
terms to remember
TERMS TO REMEMBER
  • ANTIGEN
  • IMMUNOGEN
  • EPITOPE
  • HAPTEN
  • ADJUVANT
  • STEM CELLS
  • PRIMARY AND SECONDARY IMMUNE RESPONSE
terms to remember49
TERMS TO REMEMBER
  • INNATE(AKA NATURAL)
  • ADAPTIVE(SPECIFIC OR ACTIVE)
  • CELL-MEDIATED IMMUNITY
  • HUMORAL/ANTIBODY IMMUNITY
  • PASSIVE IMMUNIZATION
  • ACTIVE IMMUNIZATION
  • ARTHUS REACTION
terms to remember50
TERMS TO REMEMBER
  • ISOTYPE
  • IDIOTYPE
  • MONOCLONAL
  • SYNGENEIC
  • ALLOGRAFT
  • AUTOGRAFT
  • ELISA & RIA
here is what step 1 covers did we get them all51
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