Chapter 15 Topics - Adaptive Immunity - Second line of Defense - B cells - T cells System has Specificity and Memory Immune means free from burden. Antigens are large molecules, The immune system consists of a generally proteins, although number of organs, tissues, cells, antigens may be carbohydrates, cellular products and mechanisms nucleic acids, etc. that are coordinated to protect us from foreign insults. Immunogens are antigens that Vulnerable is the opposite of immune can stimulate an immune and means susceptible to foreign response and are immunogenic. insults. Receptors Cytokines in Inflammation and Disease • Present on B and T cells Low molecular weight proteins secreted by –BCR on B cells - is an ANTIBODY - white blood cells and other cells in response to stimuli, including invading pathogens recognizes native antigen –TCR on T cells – a heterodimer that Inflammation and Disease recognizes processed antigen that •Th1 - type response – Cell Mediated Immunity is presented on MHC IL-2, IFN-γ, IL-12 •Th2 - type response – Humoral Mediated Immunity • B cell receptors are secreted as IL-4, IL-10, IL-13 antibodies 1 Two arms of the adaptive immune system Properties of antigens Humoral immunity - B cells mature into mature plasma cells when they encounter foreign antigen. Cellular immunity - certain types of T cells An antigen is a foreign Two classes of T cells - TH (T helper cells) and T C substance that has the capability (cytotoxic T cells) to elicit an immune response B cells and T cells can be distinguished by phenotypic markers on their surfaces called cellular differentiation or CD markers. The sites on the antigen that are B cells - CD19, CD20, CD21 - SURFACE ANTIBODY immunogenic are the epitopes TH cells - CD4 TC cells - CD8 NK cells - CD16, CD56 Characteristics of antigens Superantigens • Bacterial toxins • T cell activation much greater than normal antigens • Large release of cytokines • Results in toxic shock syndrome and some autoimmune diseases • S. aureus releases TSST Humoral immunity Immune response distinguishes foreign from self Clonal selection - An antigen is presented by an APC to a specific B cell that is specific for the antigen. The B cell proliferates into a plasma cell that secretes antibody specific for the epitope presented by the APC. Memory cells also!! 2 Antibody B cells • Product of B cell (plasma cell) • Antibody activation • Antibody-antigen interaction –Immunoglobulin (Ig) or antibody • Response • Structure • Classes - there are 5 Isotypes of Antibodies • Based on the Fc (constant) fragment –IgG - peripheral –IgA - gut/mucosal –IgM - surface & secreted –IgD - surface –IgE - allergies - worms Characteristics of the immunoglobulins Antibody-antigen interactions • Opsonization • Neutralization • Complement fixation 3 Neutralization Opsonization • Antibody binds to • Microbes or particles coated with –The microbe or virus receptor antibodies - similar to C3b –Antigenic site of a molecule • Enables macrophages to (Eg. Exotoxin) recognize and phagocytize • Prevents further binding of microbe microbe (no cell entrance for virus) or toxin Complement fixation Summary of antibody functions (activation) • Antibodies interact with complement proteins - activate complement cascade (Eg. Classical pathway ) • Lysis of microbial cell Elimination of Foreign Antigens Primary Response • First exposure – Latent period - initial response to Ag – Synthesis of antibodies • Slower response - less antibody generated • IgM first • Followed by IgG 4 Secondary Response Primary and secondary responses to antigens • Re-exposure to the same immunogen • Antibody synthesis, titer, and length of antibody persistence is rapid and amplified –Due to presence of memory cells Antigen presenting cells Macrophages (APC) – 3 total Most antigens are processed by antigen-presenting cells including • Macrophages and dendritic cells macrophages such that the antigen –Process and present antigen in fragments are in a state that association with MHC I/II lymphocytes can be stimulated. –T cell receptor recognize Antigen presentation is in the context antigen/MHC I/II of the major histocompatibility B - cells are the 3rd major APC complex (MHC). Classes of MHC Cell-mediated immunity (CMI) • Each individual has a unique MHC genetic profile CMI is the type of immunity where T cells protect against many viral infections, and • Class I – all nucleated cells reject tumors and transplants - • Class II – macrophages, dendritic T cells do not make antibody cells, B cells - oR – APCs • CLASS I = CD8 T cell Good at killing intracellular pathogens • CLASS II = CD4 T cell 5 TH - THE GENERAL TC - THE KILLER • Regulate immune reactions to antigens • Bind and lyse cells (apoptosis) – microbe, viral infected cells, foreign cells, by releasing cytokines cancer cells • CD4 receptor • CD8 receptor • Type of cytokine will determine subset • Perforins – punch holes in the of T H membrane – TH1 (CMI) • Granzymes – degrade proteins – TH2 (Humoral) • Natural killer (NK) cells – related to T C • Cytokines activate macrophages & other cells – attack virus infected cells and cancer cells • Most prevalent T cell in the blood Activated TH cells produce cytokines that regulate T cells, B cells and other cells of the immune system. HIV destroys T H cells and abrogates both humoral and cell-mediated immunity. TC kill virus-infected cells and tumor cells by releasing cytotoxins such as perforin (perforates the cells) and granzyme. NK cells are large lymphocytes that kill tumor cells, virus-infected cells and foreign cells (transplants). Effect of Immune System on Viruses Reactions in Cell Mediated Immunity 6 Specific Immunities Active • Active • Natural or artificial • Passive • Antigen activates B and T • Natural cells • Artificial • Memory cells • Long-term protection Natural Passive • Natural or artificial • Immunity produced by normal biological • Receive antibodies from another exposure, no medical intervention individual or animal – Natural active • Eg. Infection • No memory cells – Natural passive • No antibody production • Eg. Mother to child • Short-term protection Artificial There are many, many, many, many, very, very, very important terminologies that are very, very, very important in understanding • Immune protection through medical immunology. procedures or intervention Fortunately, there are only a few cells that – Artificial active are important to us in our collective defense • Eg. vaccination against foreign invaders. – Artificial passive All in all, understanding how the immune • Eg. immunotherapy - anti-toxins system interacts with microorganisms is the or anti-venoms (antibodies) other half of the infectious disease story 7.