Immunology PDF

Immunology Antigen  Immunogen: A substance that induces a specific immune response (humoral or cell mediated immune response). Antigen (Ag): A substance that reacts with the products of a specific immune response (antibody molecule or T cell receptor). Not all antigens are immunogens....

Immunology Antigen  Immunogen: A substance that induces a specific immune response (humoral or cell mediated immune response). Antigen (Ag): A substance that reacts with the products of a specific immune response (antibody molecule or T cell receptor). Not all antigens are immunogens. For example, haptens. Hapten: Low molecular weight substance can not stimulate the immune response alone (not immunogenic) If it is bounded to a larger molecule, it becomes antigenic.  Epitope or Antigenic determinant: Epitopes are the immunologically active portion of an antigen that can react with antibodies and TCR Antibody (Ab): Glycoproteins present in serum and tissue fluids, mainly found in gamma globulin fraction of serum. Produced by plasma cells in response to an antigen. They react specifically with that antigen Paratope: The part of the antibody molecule that reacts with the epitope is called the paratope.  Types of antigens A. T dependent antigens: T dependent antigens are those that do not directly stimulate the production of antibody without the help of T cells. B. T independent antigens: T independent antigens are antigens which can directly stimulate the B cells to produce antibody without the requirement for T cell help.  Antigen receptors and recognition molecules A. Pattern recognition receptors: Pattern recognition receptors recognize a molecular pattern, called a pathogen-associated molecular pattern (PAMP), that is present on the surface of many microbes. Examples of pattern recognition receptors of phagocytes: Toll like receptors (TLRs) mannose receptors scavenger receptors B.B and T Cells receptors: They recognize different substances as antigens and in a different form C. Major histocompatibility complex (MHC) molecules: Three of these genes (HLA-A, HLA-B, and HLA-C) code for the class I MHC proteins. Several HLA-D loci determine the class II MHC proteins (i.e., DP, DQ, and DR) 1- Class I MHC antigens: Location: They are glycoproteins found on the surface of virtually all nucleated cells. Composition: The complete class I protein is composed of heavy chain noncovalently bound to a β2-microglobulin 2- Class II MHC antigens: Location: They are glycoproteins found only on the surface of professional antigen- presenting cells (APCs). Composition: They are highly polymorphic glycoproteins composed of two chains called alpha and beta that are noncovalently bound Innate (Non-Specific, native, natural) Immunity  Innate Immunity The innate immune system is composed of physical barriers, cells, and circulating factors that are always active and ready to repel microbes. Innate immune cells are also important for cleaning up debris from dying cells and repairing damaged tissues. The innate immune system is our First Line of defense against invading organisms. Although the innate and adaptive immune systems both function to protect against invading organisms, they differ in a number of ways  Phagocytosis It is a process of ingestion of particles larger than 0.5 μm in diameter by phagocytic cells (PMNs, macrophages and monocytes).  The process of phagocytosis involves the following steps: A. Recruitment of Phagocytes to Sites of Infection (Chemotaxis): B.Membrane binding C.Internalization (endocytosis) D.Intracellular digestion and killing: This is achieved by 2 mechanisms: 1) Oxygen-dependent (oxidative mechanism): These mechanisms lead to generation of toxic compounds like superoxide anion O2-, hydrogen peroxide H2O2, singlet oxygen O2, hydroxyl radical OH. 2) Oxygen-independent (non-oxidative) mechanism: It is less powerful than the oxidative mechanism. The organism is killed and digested by hydrolytic enzymes, low E. Extracellular killing: Neutrophils can release microbicidal granule contents into the extracellular environment. Adaptive immunity  Adaptive immunity Acquired or adaptive immunity refers to all of the antigen specific defense mechanisms that take several days to weeks to become protective and are designed to react with and remove specific antigens. Acquired immunity develops throughout one’s life and is completely dependent on T and B lymphocytes.  Adaptive immunity Cell-Mediated Immunity Humoral Immunity Mediated by T lymphocytes Mediated by proteins called Destruction of infected cells antibodies by cytotoxic T cells Ab produced by activated B Destruction of ingested pathogens lymphocytes by macrophages. Defense against extracellular microbes. Phases of T cell mediated response:  A. Antigen Recognition: The T cell receptor (TCR) recognizes MHC- associated peptide antigens 1. Exogenous antigen processing: Extracellular proteins are ingested by APCs such as dendritic cells, macrophages and B lymphocytes into vesicles where they are degraded into peptides fragments 2. Endogenous antigen processing: Antigenic proteins may be produced in the cytoplasm from: 1-Viruses that are living inside infected cell. 2-Some phagocytosed microbes that may leak from or be transported out of phagosomes into the cytoplasm. Exogenous pathway of antigen processing Endogenous pathway of antigen processing.  B. Activation of Th cells: Two signals are required for full activation of Th cells: 1. The first (initial) signal: The interaction of an the peptide-MHC complex with the TCR complex. 2. The second signal: The full activation of T cells depends on the recognition of costimulators on APCs in addition to antigen. This interaction occurs between: The binding of CD28 on T cells to B7 on the APCs CD40 on APCs binds to CD40 ligand (CD40L) on T cells. Activation of Th cells:  C. Clonal Expansion of T cells: lymphocytes activated by antigen and costimulation begin to proliferate within 1 or 2 days, resulting in expansion of antigen specific clones  D. T cell differentiation & effector function: 1. CD4+ T helper cells (Th cells): Naive T cells can differentiate into at least four major lineages: Th1 subset: Produces IFN gamma which activate macrophage to kill microbes Promotes more T-helper one development Inhibits the development of T-helper 2 and T-helper 17.  D. T cell differentiation & effector function: Th2 subset: Stimulate phagocyte-independent eosinophil mediated immunity which is especially effective against helminthic parasites Mediate allergic reactions through secrections of IL4, IL5,IL13 Th17 subset: Induces inflammation which functions to destroy extracellular bacteria and fungi Production of antimicrobial peptide (defensins) by secretion of IL-17, IL-21 and IL-22 Treg cells: They function to downregulate the immune response T cell differentiation & effector function:  D. T cell differentiation & effector function: 2. CD8+ T cytotoxic cells (Tc cells): Activated Tc cells kill by release of cytotoxic proteins (perforins and granzymes) that induce apoptosis of target cells.