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The Basics of Immunology The Immune System Simplified (?) Immune System • protects an organism against potential pathogens (viral, bacterial, fungal, protists) • consists of innate immunity and acquired (adaptive) immunity Innate Immunity • nonspecific • present all of the time or may be activated • immediate • all animals Innate Immunity Barriers: skin - pH 3-5 acidic that prevents the growth of pathogens secretions - saliva and tears have lysozyme mucus membranes (produce defensins): nasal, reproductive, digestive, respiratory, urinary Cellular : Leukocytes - phagocytic white blood cells Neutrophils - most abundant, attracted to infected cells which are then engulfed Macrophages - migrate throughout the body, others reside in tissues (lymph nodes, spleen) Eosinophils - defend against multicellular parasites such as worms Dendritic cells - populate tissues in contact with the environment Natural Killer Cells (NK) - recognize cancer cells, those infected by viruses Innate Immunity Peptides and Proteins: Interferons - produced by virus infected cells, limit cell-to-cell spread of viruses Complement - 30 proteins in blood, circulate in inactive form but are activated by substances on surface of pathogens, leads to lysis Inflammation: Mast cells release histamine, triggers permeability of blood vessels Macrophages send out signals promoting blood flow to injured site, clotting Antimicrobial peptides enter the tissue Neutrophils and macrophages - phagocytosis of microbes Pus accumulates (WBC, debris, dead microbes) Acquired (Adaptive) Immunity • only in vertebrates • specific • diverse • distinguishes self from nonself • immunological memory • slow Acquired Immunity Bone Marrow (stem cells) Lymphocytes (WBC) Thymus T cells Thymus all T cells produced as a child thymus shrinks as an adult B cells Both B and T cells recognize and inactivate foreign cells and molecules Antigens/Antibodies Antigens 1. any foreign substance(protein or polysaccharide) that is recognized by lymphocytes and elicits a response from them 2. some are released from microbes as toxins others protrude from surface of pathogens 3. epitope is the region of an antigen that an antibody recognizes T cell receptors are antigen receptors Antibodies 1. produced by B cells that have become plasma cells 2. secreted soluble form of antigen receptor (antibody or immunoglobulin) 3. antigen receptors on B cells Antibodies (Immunoglobulins Ig) • tetramer - 4 polypeptide chains- 2 identical light chains, 2 identical heavy chains • held together by a disulfide bond • each chain has a constant region and each has a variable region • constant region determines general structure and function, may insert into membrane • variable region different for each specific Ig, 3-D antigen binding site due to secondary structure, responsible for antibody specificity 5 Classes of Ig • IgG - secreted by B cells (80% of circulating antibodies) • IgD - cell surface receptor on B cells, clonal selection • IgM - first to be produced after antigen exposure, promotes neutralization of antigens • IgA - present in secretions, saliva, tears, mucus, breast milk(provides immunity to baby) • IgE - present in blood, triggers release of histamine from mast cells, activates allergic response Major Histocompatibility Complex (MHC) genes that produce host cell protein receptors (HLA) capable of presenting antigen fragments to a T cell Human Leukocyte Antigens (HLA) vary from individual to individual, important in transplantation • Class I MHC molecules - all cells except RBC, cells infected can display antigens on the MHC molecules to be recognized by immune system cells (cytotoxic T cells) • Class II MHC molecules - made only by antigen-presenting cells such as macrophages, B cells, dendritic cells, display antigens after cells have digested the foreign material, recognition by helper T cells and cytotoxic T cells B Cells and T Cells • lymphocytes • recognize and inactivate foreign cells and molecules • contribute to immunological memory • macrophages/dendritic cells ingest microbes then secrete cytokines that activate lymphocytes B Cell and T Cell Receptors • B cell receptor similar to antibodies but are membrane bound, bind several antigens • T cell receptors membrane bound but only bind to one antigen • B cell receptors bind to an intact antigen that is free or on the surface of a pathogen • T cell receptors bind only to antigen fragments that are displayed on the surface of host cells Lymphocyte Diversity • Humans respond to 10 million different antigens • Each person has > 1 million different B cells and ~10 million different T cells • Recognition of an antigen precludes an immune system response where lymphocytes with the right specificity to the antigen are activated • After T and B cells form, DNA rearrangements (mutations) occur generating many diverse T cell receptors and antibodies Cell Mediated Immune Response T Helper Cells 1. respond to nearly all antigens 2. proliferates (mitosis) after encountering antigens or antigen-presenting cells 3. clone of cells are now activated T helper cells and memory helper T cells 4. secrete cytokines that activate B cells Killer T cells also cytotoxic T cells Humoral Immune Response Clonal Selection Amplification of B Cells Primary Immune Response 1. peaks 10-17 days after initial exposure 2. B cells generate antibody secreting cells (plasma cells) 3. T cells are activated to T helper cells and cytotoxic T cells Secondary Immune Response 1. peaks 2-7 days after second exposure 2. reaction is stronger and prolonged 3. relies on T and B memory cells 4. rapid formation of effector cells (short lived, attack antigen and any pathogen producing the antigen)