Immunology
Components
• Primary lymphoid organs: bone marrow & thymus • Secondary lymphoid organs: lymph nodes, spleen, Peyer’s patches, & MALT
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; eg…IgA, IgG, IgM, IgD, IgE – Early B cell development is antigen independent – Bone marrow (differentiation) Spleen or LN
Antibodies
• IgM – first Ab formed during immune response • IgG & IgM – complement activation • Ab bind Ag…opsonization/phagocytosis by NK cells or macrophages
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
T Lymphocytes cont
• CD4+ T cells – helper T cells TH1 & TH2 to produce cytokines
– TH1: IL-2 & IFN-γ, 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
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
ADCC
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
• Membrane attack complex (C5-9) disrupts membrane integrity lysis
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 (APC’s)..B lymphocytes, macrophages
Antigen Presenting Cells (APC’s)
• Initiate immune response by taking up, processing, presenting Ag to T lymphocytes
– ex. dendritic cells > B lymphocytes > macrophages
• Co-stimulatory signal required
– otherwise T cell anergy (inability to respond on subsequent exposure to Ag)
Importance of MHC
• Severity of rejection based on MHC disparity • Class II mismatches trigger rejection b/c disparities MHC II drive CD4+ TH cells --> amplify immune response • Tissue typing is used to optimize HLA-A, HLA-B, HLA-DR(HLA-DQ) match
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
Rejection
• Hyperacute: minutes p revascularization; ABO or HLA
– pre-formed Ab’s, complement activation injures graft endothelium --> fibrin / plt deposition --> hemorrhagic graft necrosis – Pretransplant cross matching of receipient serum v donor lymphocytes – kidney most commonly affected
Rejection
• Acute: most frequent; occurs w/in several weeks of transplant
– foreign MHC --> clonal expansion of alloreactive T cells --> CD4 activates CD8 cytotoxic T cells (via cytokines) – Cytotoxic IgG
Rejection
• Chronic: months-years
– humoral & cell mediated – incl. non-immune mechanisms: ischemiareperfusion & infections – Liver is less susceptible
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 Ab’s. D. T lymphocytes develop in the fetal liver & subsequently bone marrow
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 Ab’s D. Cytotoxic T cells may destroy target cells by recognizing foreign Ag’s on the target cell surface. E. Various types of T cells may be identified by binding of specific monoclonal Ab’s to Ag’s on the T cell surface.
3. With regard to MHC, which is/are correct?
A. 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 Ag’s are coded for by the D region of the MHC Class II Ag’s are important for presenting Ag to the immune system. Class I Ag’s are present on nucleated cells only
B. C. D. E.
4. With regard to Ab’s, which is/are correct?
A. Ab’s 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.
B.
C. D. E.
5. With regard to immunogens, which of the following statements is/are correct?
A. 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.
B. C. D. E.
6. With regard to phagocytosis, which is/are true?
A. B. 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
C. D.
E.
7. With regard to nonspecific immune reactivity, which is/are correct?
A. NK cells are large granular lymphocytes that don’t 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-γ 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
B. C. D. E.
8. With regard to T cell activation, which is/are correct?
A. B. C. D. E. Some Ag’s 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
9. With regard to IL-1, which is/are true?
A. B. C. D. E. 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.
10. With regard to IL-2, which of the following is/are true?
A. B. C. D. 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
11. With regard to the complement cascade, which is/are true?
A. 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.
B. C. D. E.
12. With regard to TNF, which is/are correct?
A. B. C. D. It’s 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.