Specific Defenses of the Host

1. Specific Defenses of the Host Adaptive or Specific Immunity

2. Adaptive Immunity • Developed during one’s lifetime • Immunity involves specific defensive response against foreign MOs or substances that invade body • Two components: • Humoral Immune Response – “liquid”; antibody, complement found in plasma of blood • Cell-Mediated Immune Response – “cells” in blood; T lymphocyte, macrophage, NK cell

3. Antigen: Stimulate Immune Response • Also termed immunogen • Produce highly specific immune response • Body distinguish between “self” and “nonself” (foreign) antigen • Immune response generated against “nonself” antigen

4. Antigen: Macromolecule • Most are protein, nucleoprotein, lipoprotein, glycoprotein, nucleic acid, large polysaccharide • Notice these are structural components of invading MOs • Invader does not have to be MO; may be transplanted tissue or blood cell

5. Antigen: Epitope • Usually molecular weight >10,000 kd • Antibody formed against small region of antigen - antigenic determinant or epitope • Antigenic determinant typically molecular weight of 200-1,000 kd

6. What Is Antigen? • Valence: number of antigenic determinant sites on surface of antigen • Most antigens are multivalent • Antigenic determinant does not stimulate immune response by itself, but as part of an antigen (macromolecule) • If immune response generated, antigen combine with antibody made against it (“lock & key” recognition)

7. Hapten • Foreign substance with low molecular weight • Not antigenic unless bound to carrier molecule such as serum protein • Combination of hapten and carrier molecule stimulate immune response • Classic example is penicillin

8. The Humoral Immune Response • Involves antibody (immunoglobulin) in blood and lymph • Produced by B lymphocyte upon exposure antigen ( foreign, stimulates specific immune response)

9. Serum Antibody (Antiserum) • Electrophoresis of serum proteins separate into: , ,  globulins, albumin • Antibody found in gamma fraction (gammaglobulin)

10. Antibody: Specificity • Protein secreted by plasma cell (activated B lymphocyte) in response to antigen • Combine specifically with antigen that stimulated its secretion • Valence – two antigen combining sites; bivalent antibody molecule termed monomer • Monomer may combine via a J chain to form multimer

11. Antibody: Polypeptide Chains • Composed of four polypeptide chains held together by disulfide bonds: • Two short polypeptide - light chains • Two long polypeptide - heavy chains • Type of heavy chain determinesantibody class:IgA, IgG, IgM, IgD, IgE

12. Antibody: Binding Site • Variable region (V) - two sections at end, antigen binding site (two per monomer) • Specificity -variation in amino acid sequence determines binding for specific antigenic determinant • Constant region (C) - amino acid sequence invariant

13. Antibody: Fc Fragment • Stem of the C heavy chain called Fc • Participates in opsonization and complement fixation • Hinge region gives flexibility

14. Antibody Classes • Each play different role in immune response

15. IgG Antibody • Account for ~70-75% of serum antibody • Monomer • Cross placenta to protect (may also attack) developing fetus • Move out of blood vessel into tissue fluid • Participate in complement fixation and opsonization • Important in protecting from circulating bacteria, virus and toxin • Relatively long half life ~3-4 weeks

16. IgM Antibody • Make up ~10-15% of serum antibody • Pentamer joined by a J chain (what is valence?) • Can’t cross placenta or move out of blood vessel tissue, in part because of large size • First antibody to appear • Have short half life of ~5 days • Participate in complement fixation and opsonization • Very effective inagglutinating antigen (i.e. cross-linking RBCs by antibody)

17. IgA Antibody • Make up ~15-20% of serum antibody • Found in body secretions and breast milk • Dimer held by J chain • sIgA - complexed with secretory component that protects from enzymatic degradation • Do not participate in complement fixation or opsonization • Function locally to protect mucosal surface • Prevent attachment of pathogenic bacteria and virus

18. IgD Antibody • Makes up <1% of serum antibody • Found as monomer • No known function in serum • Cannot participate in complement fixation or opsonization • Present on B cell surface serve as receptor for specific antigen

19. IgE Antibody • Makes up <1% of serum antibody • Monomer • Attach by Fc region receptor on mast cell and basophil • Participate in allergic reaction - antigen attach to IgE molecule on mast cell or basophil, cells release granules containing histamine and chemical mediators cause inflammatory response • Protective when antibody binds to parasitic worms; attract IgG, complement, and phagocytic cells

20. B Lymphocyte Differentiation • Stem cells of bone marrow produce immature B cells • Localize in specialized lymphoid tissue • Mature to immunocompetent B cells; have antibody receptors on surface capable of interacting with antigen

21. B Cell: Antigen Recognition • Antibody on cell surface is receptor for specific antigen • All antibodies on surface of a single B cell recognize same epitope

22. B Cell: Antigen Dependent Maturation • Binding of antigenic determinant to antibody on B cell surface, stimulated to become plasma cell • Produce and secrete antibody of specificity on B cell surface • Therefore, B cell produces antibody that specifically react with antigen that stimulated its production

23. B Cell: Clonal Expansion and Plasma Cell Differentiation

24. Humoral Antibody Response • Primary Response - produced first time antigen encountered • IgM first, declines • IgG increases • Secondary Response - produced on subsequent antigen exposure • IgM response same • IgG response quicker and higher • Memory or anamnestic response due to memory cells produced during primary response

25. Antibody Protective Mechanisms e.g., NK cells

26. The Cell-Mediated Immune (CMI) Response • T lymphocyte in blood and lymphoid tissue • T cell receptor - on cell surface, recognize and bind antigen • T cell receptor similar in structure to an antibody

27. T Lymphocyte Differentiation • Stem cells produce immature T cells • Migrate to thymus where mature to immunocompetent T cells • Have CD4 (for T4 cell) or CD8 (for T8 cell), and T cell receptors on surface capable of interacting with antigen

28. T Cell Receptor • Receptors on surface of a T cell recognize one antigenic determinant • Recognize antigenic determinants that are linear pieces of proteins (peptides) • After binding of T cell receptor with specific antigenic determinant, cell differentiates into activated effector cell • Different types of effector cells: helper, supressor, cytotoxic

29. Effector T Cells • T helper cell (CD4+) - produce cytokines, activate own proliferation, also B cell, cytotoxic T cell • Cytotoxic T cell (CD8+) - lyse target cell, may be infected cell, tumor cell • T suppressor cell (CD8+) - inactivates immune response

30. Mechanism of Immune Response • B cell, T cell, macrophage often work together • Antigen Presenting Cell - B cell, macrophage process antigen and present pieces of it (antigenic determinant) to B or T cell for activation • T dependent antigens - require T helper cell to stimulate differentiation of B cell

31. Acquired Immunity

32. MICR 301 Midterm Exam • Tue., Oct. 25, 2011; 8:30-9:40am • Specimen Collection & Processing through Host Defense • Lecture, Reading, Key Terms, Learning Assessment Questions, Viral Case Study 1 & 2, Bacterial Case Study1 • Exam Format: Objective Questions (M.C., T/F, ID) and Short Essay