Specific Defenses to Microbes

Specific Defenses to Microbes B Cells and Humoral Immunity Review: Nonspecific Defenses • Macrophages --> cytokines --> fever, inflammation, acute phase proteins • Neutrophils and macrophages --> phagocytosis, pathogen killing • Complement --> opsonin, inflammation, lysis • Interferons --> block virus replication • NK Cells --> lyse virus-infected cells Acquired/Adaptive Immunity • Specific resistance to certain pathogens (antigens) • Discriminates foreignness (danger) • Slow starting – needs nonspecific defenses to be engaged • Immune memory – faster response on repeat exposure Acquired Immunity B and T Lymphocytes B and T Cells have receptors that recognize (bind) antigens specific to individual pathogens • Antigens are foreign to host – Proteins and large polysaccharides • Antibodies are host proteins that bind specifically to antigens • Each antigen has many epitopes = antibody-binding sites Antigens Antigen binding --> activation/proliferation -> effector cells + memory cells Antibody = B Cell Antigen Receptor • Each B cell has a uniquely specific receptor • B cells with certain receptors are produced randomly in the bone marrow Ig Gene Loci Antibody Binding Specificity Generation of B Cell Antigen Specificity (Diversity) • As a B cell differentiates in the bone marrow, gene segments are randomly selected and combined to encode a unique V region • Immature B cells that bind “self” die by apoptosis • Mature B cells go to the lymph nodes and spleen to await clonal selection by antigen. Antigen Presenting Cells • Professional APC are – Dendritic cells – Macrophages – B cells • T cells must bind antigen presented on MHC B Cell Activation Antibody Structure • Antibody V regions bind specific antigen • Antibody C regions determine antibody functions Antibody Functions Antibody Functions • Agglutination: clumps pathogens, makes them easier to phagocytose • Neutralization: block cell binding of pathogens and toxins • Opsonization: coat pathogen; Fc regions bind to Fc receptors on phagocytes • ADCC: signals killer cells to kill pathogen ADCC AntibodyDependent Cellmediated Cytotoxicity Immune Memory Natural Immune Responses are Polyclonal Monoclonal Antibodies • Diagnosis • Therapy • Research Measuring Humoral Immunity • When someone has antibodies to a pathogen, they are seropositive • The amount of antibodies is the titer • Antibodies are detected by their functions: agglutination, neutralization, complement lysis Measuring Immunity • Antibodies (IgM) agglutinate pathogens and cells Some Viruses Agglutinate RBC by Binding Membrane Sugars • Neutralizing antibodies block virus hemagglutination Humoral Immunity • Humoral immunity is due to antibodies made by B cells –Eliminates extracellular pathogens –Works with phagocytes and complement –Can be passively transferred Cellular Immunity • Cellular immunity is due to T cells –Eliminates intracellular pathogens, transplanted tissue, cancer –Kills infected host cells –Helps macrophages kill phagocytosed pathogens –Difficult to passively transfer