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Immunology Components Primary lymphoid organs: bone marrow

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Immunology Components Primary lymphoid organs: bone marrow & thymus Secondary lymphoid organs: lymph nodes, spleen, Peyer s patches, & MALT Cells of the Immune ... – PowerPoint PPT presentation

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Title: Immunology Components Primary lymphoid organs: bone marrow


1
Immunology
2
Components
  • Primary lymphoid organs bone marrow thymus
  • Secondary lymphoid organs lymph nodes, spleen,
    Peyers patches, MALT

3
Cells of the Immune System
  • B lymphocytes HUMORAL immune response
  • Exposure to antigens ? memory or plasma cells ?
    antibodies
  • Antibodies four protein chains (2heavy/2light)
    w/ S-S bond link egIgA, IgG, IgM, IgD, IgE
  • Early B cell development is antigen independent
  • Bone marrow (differentiation)? Spleen or LN

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Antibodies
  • IgM first Ab formed during immune response
  • IgG IgM complement activation
  • Ab bind Agopsonization/phagocytosis by NK cells
    or macrophages

7
T Lymphocytes
  • Cellular mediated immune response
  • Exit bone marrow as pluripotent stem cells ?
    thymus (differentation)
  • Positive selection of T cells specific for
    peptides bound to self MHC
  • Negative selection to delete autoreactive T cells
  • 2 classes of T cells based on accessory
    molecules
  • CD4 binds MHC II CD8 binds MHC I

8
T Lymphocytes cont
  • CD4 T cells helper T cells ? TH1 TH2 to
    produce cytokines
  • TH1 IL-2 IFN-?, induce phagocytosis, Type IV
    delayed hypersenstivity rxn
  • TH2 IL-4,5,10,13 which trigger IgM (humoral
    response) mast cells eosinophils
  • CD8 T cells cytotoxic T cells

9
NK Cells
  • Derived from bone marrow pluripotent lymphoid
    stem cells
  • Lack receptors for specific Ag on surface (unlike
    T cells)..do NOT require prior sensitization nor
    memory
  • Considered part of innate immune reposnse
  • Antibody dependent cell-mediated cytotoxicity
    (ADCC) viral eradication

10
ADCC
11
Complement
  • Primitive system of innate immunity
  • Classical pathway IgM / IgG bind Ag C1 binds Fc
    of Ab
  • Alternative pathway triggered thru bacteremia or
    endotoxin converges w/ classical at C3 level

12
  • Membrane attack complex (C5-9) disrupts membrane
    integrity ? lysis

13
Histocompatibility
  • MHC Ag surface glycoproteins human leukocyte
    antigen (HLA)
  • Located on chromosome 6
  • Class I (A,B,C)-present on all nucleated cells
    are primary target for cytotoxic T lymphocytes
  • NK cells eliminate cells lacking MHC I expression
    (tumor cells)
  • Class II (DR,DQ,DP)-seen on bone marrow Ag
    presenting cells (APCs)..B lymphocytes,
    macrophages

14
Antigen Presenting Cells (APCs)
  • Initiate immune response by taking up,
    processing, presenting Ag to T lymphocytes
  • ex. dendritic cells gt B lymphocytes gt macrophages
  • Co-stimulatory signal required
  • otherwise T cell anergy (inability to respond on
    subsequent exposure to Ag)

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Importance of MHC
  • Severity of rejection based on MHC disparity
  • Class II mismatches trigger rejection b/c
    disparities MHC II drive CD4 TH cells --gt
    amplify immune response
  • Tissue typing is used to optimize HLA-A, HLA-B,
    HLA-DR(HLA-DQ) match

17
Cytokines
  • Soluble factors secreted by lymphocytes,
    dendritic cells, endothelial cells, macrophages
  • Autocrine paracrine effects
  • Il-2 is critical for T lymphocyte
    proliferation.cyclosporine tacrolimus used in
    immunosuppression inibit IL-2

18
Rejection
  • Hyperacute minutes p revascularization ABO or
    HLA
  • pre-formed Abs, complement activation injures
    graft endothelium --gt fibrin / plt deposition --gt
    hemorrhagic graft necrosis
  • Pretransplant cross matching of receipient serum
    v donor lymphocytes
  • kidney most commonly affected

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Rejection
  • Acute most frequent occurs w/in several weeks
    of transplant
  • foreign MHC --gt clonal expansion of alloreactive
    T cells --gt CD4 activates CD8 cytotoxic T cells
    (via cytokines)
  • Cytotoxic IgG

21
Rejection
  • Chronic months-years
  • humoral cell mediated
  • incl. non-immune mechanisms ischemia-reperfusion
    infections
  • Liver is less susceptible

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1. Which of the following statements is / are
true?
  • A. Primary immune response is more intense
    rapid than secondary response
  • B. Cell mediated immune response primarily by T
    lymphocytes.
  • C. B lymphocytes are precursors for plasma cells
    which produce Abs.
  • D. T lymphocytes develop in the fetal liver
    subsequently bone marrow

24
2. With regard to T cells, which of the following
are true?
  • A. T cells develop primarily in the thymus bone
    marrow, which are referred to as the primary
    lymphoid organs
  • B. T cells subsequently migrate to the spleen, a
    secondary lymphoid organ, and to the lymph nodes
    which are considered tertiary lymphoid organs
  • C. Helper/inducer T cells may be activated to
    produce Abs
  • D. Cytotoxic T cells may destroy target cells by
    recognizing foreign Ags on the target cell
    surface.
  • E. Various types of T cells may be identified by
    binding of specific monoclonal Abs to Ags on
    the T cell surface.

25
3. With regard to MHC, which is/are correct?
  • MHC refers to gene cluster on chromosome 6 that
    codes for proteins.
  • Part of the MHC codes for some components of the
    complement cascade.
  • Class I Ags are coded for by the D region of the
    MHC
  • Class II Ags are important for presenting Ag to
    the immune system.
  • Class I Ags are present on nucleated cells only

26
4. With regard to Abs, which is/are correct?
  • Abs composed of variable region, which interacts
    w/ host, and a constant region, which interacts
    w/ Ag
  • Ab molecules are composed of 4 polypeptide chains
    consisting of 2 heavy chains 2 light chains
    stabilized by inter- intra-chain disulfide
    bonds.
  • IgA is able to bind complement as an opsin
  • IgG is the largest Ab, w/ pentameric structure
  • IgM is the major Ab produced during the primary
    response.

27
5. With regard to immunogens, which of the
following statements is/are correct?
  • Immunogens have mult. Ag epitopes, each of which
    may react w/ an Ab or T cell Ag receptor specific
    for it.
  • An Ag may be defined as any molecule recognized
    as foreign by the immune system.
  • Immunogenecity is greater w/ a xenogeneic Ag than
    w/ a syngeneic Ag.
  • 4000 dalton molecule would be highly immunogenic
  • Proteins are more complex and more immunogeneic
    thannucleic acids.

28
6. With regard to phagocytosis, which is/are true?
  • Monocytes are the major tissue phagocytic cells
  • Phagolysosome is composed of membrane encased
    foreign particle and collections of enzymes.
  • Lysosomal granules require oxygen to destroy
    foreign particles
  • Chronic granulomatous dz. results from a flaw in
    production of superoxide anions and hydrogen
    peroxide in neutrophils.
  • Once a monocyte migrates to tissue to become a
    macrophage, it loses all fx, except for
    phagocytosis

29
7. With regard to nonspecific immune reactivity,
which is/are correct?
  • NK cells are large granular lymphocytes that
    dont express T cell or B cell phenotype and
    require previous exposure to Ag to express
    cytotoxicity
  • NK activity is NOT restricted by MHC.
  • Interferons augment macrophage, T cell, NK cell
    activity.
  • INF-? is produced by fibroblasts in response to
    trauma
  • B/C NK cells DO NOT express cell surface markers,
    they can be identified only by their cytotoxicity
    against a large of tumor agents

30
8. With regard to T cell activation, which is/are
correct?
  • Some Ags are processed expressed on AP
    macrophages.
  • Ag recognition is NOT specific, which allows
    clonal expansion differentiation
  • Ag recognition requires T cell to be MHC
    compatible w/ APC.
  • T cells produce IL-1 in response to Ag
    presentation
  • Plasma cells are responsible for synthesis of IL-2

31
9. With regard to IL-1, which is/are true?
  • The major cells producing IL-1 are monocytes
    macrophages.
  • IL-1 leads to vasoconstriction HTN by
    stimulating the hypothalamus
  • IL-1 may induce fever.
  • T lymphocyte production of IL-2 is inhibited by
    IL-1
  • IL-1 may augment wound healing by increasing
    fibroblast proliferation collagen synthesis.

32
10. With regard to IL-2, which of the following
is/are true?
  • Proliferation of T lymphocytes is inhibited by
    IL-2
  • IL-2 is produced by activated T lymphocytes.
  • NK cell cytotoxicity is augmented by IL-2.
  • Cytokine release by macrophages is inhibited by
    IL-2

33
11. With regard to the complement cascade, which
is/are true?
  • Complement is a system of related serum proteins
    important to regulation of coagulation
  • Complement may be activated by immune complexes.
  • Components C3a C5a are useful for inhibiting
    mast cell release of granules.
  • Components C5b6,7,8,9 form a complex that causes
    cell lysis
  • C3a C5a are chemotactic for macrophages and
    neutrophils.

34
12. With regard to TNF, which is/are correct?
  • Its produced predominantly by monocytes
    macrophages
  • TNF release is stimulated by endotoxin
  • TNF exerts its effect as an anabolic stimulant of
    the host, leading to increased deposition of
    muscle protein fat.
  • By inducing necrosis in GN bacteria, TNF may be
    useful in the treatment of GN sepsis.
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