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CLS 1113 Introduction to Clinical Laboratory Practices

CLS 1113 Introduction to Clinical Laboratory Practices. Unit Four Introduction to Immunology Complement and Summary of Immune Response. Cytokines. Cytokine : Soluble molecules that mediate interactions between cells

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CLS 1113 Introduction to Clinical Laboratory Practices

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  1. CLS 1113Introduction to Clinical Laboratory Practices Unit Four Introduction to Immunology Complement and Summary of Immune Response

  2. Cytokines • Cytokine: Soluble molecules that mediate interactions between cells • Interferons (IFN): Help limit spread of certain viral infections. Several types. Induce a state of antiviral resistance to many viruses. • Interleukins: Produced mainly by T-cells, involved in directing other cells to divide and differentiate. • Lymphokines: Molecules, other than antibodies, involved in signaling between cells of the immune system and produced by lymphocytes.

  3. Interleukin 1 (IL-1) • Produced by: • Functions: • Interleukin 2 (IL-2) • Produced by: • Functions: • Interleukin 3 (IL-3) • Produced by: • Functions:

  4. Complement • Designated by the letter C and the native components are numbered 1-9 • Functions: • Opsonization • Chemotaxis • Increased capillary permeability and blood to area • Cell Lysis and Enhanced susceptibility to phagocytosis • Release of further inflammatory mediators from Mast cells

  5. Complement • Circulate in the inactive form • Most components are synthesized in the liver • Both antibodies and complement function as opsonins.

  6. Complement Activation • Two Pathways • Classical Pathway • Triggered by antigen/antibody complexes • As few as 1 IgM and 2 IgGs are necessary to activate C1 • Alternative Pathway • Does not require the presence of a specific protein. • Triggers include polysaccharides and lipopolysaccarides on surfaces of microorganisms or antibody complexes known not to activate the classical pathway.

  7. Fig.3.15 The proteins of the classical and lytic pathways are assigned numbers, C1, C2, etc. Many of the proteins are zymogens, i.e. pro-enzymes which require proteolytic cleavage to become active. The enzymatically active form is distinguished from its precursor by a bar drawn above. The cleavage products of complement proteins are distinguished from parent molecules by suffix letters, C3a, C3b, etc. The proteins of the alternative pathway are called 'factors' and are identified by single letters, e.g. factor B, which may be abbreviated to FB or just 'B'. Components are shown in green, conversion steps as white arrows and activation/cleavage steps as red arrows. The classical pathway is activated by the cleavage of C1r and C1s following association of C1qr2s2 with classical pathway activators including immune complexes. Activated C1s cleaves C4 and C2 to form the classical pathway C3 convertase C4b2a.

  8. The alternative pathway is activated by the cleavage of C3 to C3b, which associates with factor B and is cleaved by factor D to generate the alternative pathway C3 convertase C3bBb. The initial activation of C3 happens to some extent spontaneously, but this step can also be effected by classical or alternative pathway C3 convertases or a number of other serum or microbial proteases. Note that the activation pathways are functionally analogous and the diagram emphasizes these similarities. For example C3 and C4 are homologous, as are C2 and factor B. MASP-1 and MASP-2 are homologous to C1r and C1s respectively. Either the classical or alternative pathway C3 convertases may associate with C3b bound on a cell surface to form C5 convertases, C4b2a3b or C3bBb3b, which split C5. The larger fragment, C5b associates with C6 and C7, which can then bind to plasma membranes. The complex of C5b67 assembles C8 and a number of molecules of C9 to form a membrane attack complex (MAC), C5b-9.

  9. Recognition Unit • Made up of 1 C1q and 2 each of C1r and C1s • C1q recognizes the Fc region of two adjacent immunoglobulins

  10. Activation Unit • Production of enzymes C3 convertase and C5 convertase • C3 pivotal point in C’ Cascade

  11. Membrane Attack Unit • Results in damage to what ever membrane is present. • Bacterial, Red Blood Cell, etc.

  12. Summary of the T cell and B cell immune process • After a foreign substance undergoes phagocytosis in a macrophage for example, the remnants are presented outside the cell by HLA class II molecules. • A circulating CD4 (T helper) cell, specific for the antigen, attaches to the antigen with a T cell receptor site. This attachment stimulates the Antigen Presenting Cell (macrophage) to secrete Interleukin 1 (IL-1). • Secretion of IL-1 then influences the T cell to secrete IL-2.

  13. Summary of the T cell and B cell immune process • IL-2 is a growth factor that stimulates activated T cells to divide and produce large numbers of progeny (other T cells). • Once the T cells are formed, they seek out B cells with the specific antigen receptor. Once bound, other interleukins (IL-4, IL-5, and IL-6) are released to stimulate the B cells to differentiate into plasma cells or revert to resting B cells (memory cells).

  14. Summary of the T cell and B cell immune process • Our plasma cells then begin making large amounts of antibody, first IgMs and later IgGs. • Our memory cells stay in a resting state until we are exposed to the antigen again. We then do not have to repeat the whole process.

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