Immunology Components Primary lymphoid organs: bone marrow

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Immunology
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Components

• Primary lymphoid organs bone marrow thymus
• Secondary lymphoid organs lymph nodes, spleen,
  Peyers patches, MALT

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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

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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

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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

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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

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ADCC
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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

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

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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

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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

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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

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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

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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

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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.

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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

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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.

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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.

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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

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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

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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

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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.

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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

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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.

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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.