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Basic Veterinary Immunology and Principles of Vaccination Outline 1
Lecture 1: Overview of Immunology Learning Objectives: 1. Describe the basic differences between native and acquired immunity. 2. List the major components of the native defense system and examples of each. 3. Describe the two major components of the acquired immune system. 4. Explain where antibody comes from, list the different classes of antibody and identify those that are secreted and those that are not. 5. Name the T cells important in cell mediated immunity (CMI) and describe how they contribute to a cell mediated immune response. 6. Briefly explain the important aspects of memory and tolerance as related to the acquired immune system. Two Major Components of the Immune System: 1. Native Immunity (natural immunity) • Protects a naïve animal • Protects immediately • Not antigen specific • Due primarily to recognition of PAMPS “pathogen associated molecular patterns” 2. Acquired Immunity (adaptive immunity) • Develops after exposure to an antigen • Requires several days to weeks to develop • Antigen specific and expandable • Memory (anamnestic response) and tolerance • Activate native immunity mechanisms to be more efficient and aggressive Five Major Components of Native immunity 1. Barriers to Infection • Skin, mucous membranes = epithelium • Mucus • Normal flora ‐ occupies a biological niche. • Acid in the stomach o What can happen with antacids? • Antimicrobial peptides ‐ defensins o Small molecules secreted at epithelial surfaces‐ can damage microbial membranes 2. Phagocytic Cells: phagocytose and kill bacteria, etc. • Neutrophil • Macrophage 3. Complement System ‐ series of 20‐30 proteins in blood plasma • An enzyme cascade system in plasma ‐ like coagulation • Very rapidly induced • Multiple mechanisms for controlling microbial infection • If it is induced and not regulated (turned off) the result is death 4. Native Defense Cytokines ‐ (cytokines = protein messenger molecules between cells) Basic Veterinary Immunology and Principles of Vaccination Outline •
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Pro‐inflammatory cytokines – cause fever, lethargy, loss of appetite Sentinel cells (macrophages, dendritic cells, mast cells) secrete proinflammatory cytokines in response to PAMPs Chemokines ‐ important in chemotaxis of other cells (especially leukocytes) to site of infection Interferons – interfere with replication of some viruses o Produced within 24 hours of some viral infections o Production by one cell can protect nearby cells from some viral infection 5. NK cells (Natural killer) • A type of lymphocyte • Kill virus infected cells or tumor cells • Recognize and kill cells that do not express normal proteins‐ not antigen specific Summary of Native Immunity: • Is fairly efficient and works most of the time • No memory • Extremely important as a first line of defense • Can be suppressed by crowding, stress, cold, etc. • Can work independent of acquired immunity but function can be enhanced by acquired immunity making the components of native defense even more powerful and efficient Two Major Components of the Acquired Immune System 1. Humoral • Named because it was discovered that protection from certain diseases could be accomplished by transfer of body "humors" (fluids) • Antibody and B (B = Bursa of Fabricius) lymphocytes are important in humoral immunity • Immunoglobulin = antibody = Ig = Ab = Y • Classes (Isotypes) of Antibody – IgM, IgG, IgA, and IgE can be secreted o IgM ‐ the first antibody produced in every antibody response and the largest antibody molecule o IgG ‐ high in serum, important in systemic diseases in general o IgA ‐ important on mucosal surfaces as a dimer o IgE ‐ important in allergy and parasitic infection, found on mast cells under epithelial surfaces o IgD ‐ plays a regulatory function on the B cell surface, not secreted 2. Cell Mediated Immunity (CMI) ‐ • Named because in order to transfer this type of immunity, cells needed to be transferred • T lymphocytes are important in CMI (T = Thymus) 1. CD4+ cells = TH cells (functional designation) or CD4 (surface molecule designation) • Th1, Th2, Th17, Treg • Produce cytokines that regulate native and acquired immune mechanisms • Important for directing which antibody class is produced, i.e. a B cell produces IgM and then based on cytokines from TH cells will switch and make IgG or IgA or IgE 2. CD8+ ‐ TC cell, cytotoxic T lymphocyte (CTL), CD8+ ‐ attack and kill cells that make foreign proteins, eg viral infected cell or tumor cell Basic Veterinary Immunology and Principles of Vaccination Outline 3
3. T gamma delta or Tγδ ‐ named for the type of T cell receptor it has (TH and TC have alpha beta T cell receptors) • Important at mucosal surfaces • Still much to be known about this cell type Antigen Recognition by the Acquired Immune System • Antibodies recognize a small portion of a molecule (epitope) • Example: proteins ‐ about 6‐8 amino acids • Very specific ‐ 109 different antigen specificities or epitopes recognized by B cells • T and B cells recognize antigen differently: • B cells recognize intact antigen (not processed) They recognize a wide variety of chemical types: protein, carbohydrate, etc… via membrane‐bound antibody molecules • T cells (TH and TC) – recognize only peptides (processed proteins) o Antigen must be presented on major histocompatibility complex (MHC) molecule ƒ Antigen presenting cells like macrophage, dendritic cells, and B cells present antigen on MHCII ƒ Any nucleated cell can present antigen on MHCI Gamma delta T cells recognize cell surface molecules –Most don’t require antigen presentation on MHC molecules Fundamentals of the Acquired Immune System Memory – anamnestic response ‐ re‐exposure results in a response that is: • Faster than a primary response • Antigen specific clones of B lymphocytes have expanded and matured: o Higher in titer than a primary response o The antibody can bind more tightly o Antibody class switching has already occurred (from IgM to a different class depending on the nature of the infectious agent) • T helper and CTL clones have expanded, matured, and are circulating Tolerance ‐ Acquired immune system "tolerates" self molecules (does not attack) • Antigens presented during lymphocyte maturation are recognized as self • Antigens presented after lymphocyte maturation are recognized as foreign • Tolerance can break down resulting in autoimmune diseases Immune System Dysfunction • Hypersensitivity reactions • Allergy • Autoimmune diseases • Immunodeficiency