Specific Defenses of the Host Adaptive or Specific Immunity

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

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

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

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

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)

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

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

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

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

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 determines antibody class: IgA, IgG, IgM, IgD, IgE

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

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

Antibody Classes  Each play different role in immune response

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

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 in agglutinating antigen (i.e. cross-linking RBCs by antibody)

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

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

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

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

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

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

B Cell: Clonal Expansion and Plasma Cell Differentiation

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

Antibody Protective Mechanisms e.g., NK cells

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

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

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

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

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

Acquired Immunity

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