Transcript Chapter 24
Chapter 24: Innate defences and the immune system Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-1 Innate defence mechanisms • First line of defence against infection – external barriers – phagocytic cells – natural killer (NK) cells • Non-specific immunity – does not distinguish between pathogens – activated rapidly when pathogens invade or after tissue damage – stops or retards growth of pathogen population Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-2 External barriers • • Invading pathogens face defences when entering body Enzymes – e.g. lysozymes in tears and saliva • Acid – e.g. in stomach, sweat • Bacterial flora – e.g. in digestive tract, vagina Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-3 Fig. 24.1: External defences Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-4 Identifying an invader • Pathogens distinguished from own (self) cells by characteristic molecules on pathogen surface – pathogen-associated molecular patterns (PAMP) • Recognition of PAMPs results in release of cytokines (glycoproteins) – cytokines control actions of other cells Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-5 Complement system • System of c. 20 proteins in body fluid • If first protein is activated, the resulting complement cascade results in – local inflammation – increased activity of phagocytic cells – cell lysis and damage • Actions of cytokines reinforce results of complement Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-6 Inflammatory response • • Local changes in damaged area resulting in redness, swelling and warmth Changes – widening of capillaries and increased blood flow – increased vascular permeability release of plasma into damaged tissue allows host defence cells and chemicals into area – attraction of phagocytes and other defence cells to area Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-7 Specific acquired immunity • Specific immunity acts on specific pathogens (one or a few similar pathogens) – pathogens recognised by antigens on surface • Exposure to novel pathogen results in primary response • Immunological memory produces secondary response to subsequent exposure to pathogen – secondary response is more efficient Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-8 Cellular and humoral immunity • • Specific responses to invading pathogens are cellular or humoral Cellular – effective against viral infections and other intracellular parasites – mediated by T cells (T lymphocytes) • Humoral – effective against extracellular infections or phases of infections – mediated by B cells (B lymphocytes) Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-9 Lymphocytes and specificity • • • • Each lymphocyte carries a different surface receptor Variety of surface receptors generated by rearrangements during rounds of cell division When a lymphocyte encounters its specific antigen, it proliferates Cell population increases rapidly in process of clonal selection Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-10 Fig. 24.9: Immune repertoire Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-11 Fig. 24.10: Clonal selection Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-12 T lymphocytes • Stem cells mature into T cells in thymus • Possess T-cell receptor (TCR) proteins on surface for recognising antigens • T cells that recognise self cells are destroyed and remaining cells are released – helper (TH) cells produce cytokines – cytotoxic (TC) cells lyse target cells Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-13 B lymphocytes • • • • B cells mature in bone marrow Possess antibodies (immunoglobulins) on surface for binding to antigens in presence of TH cells B cells die if they do not encounter their specific antigen with a few days B cells that bind to antigens differentiate – memory cells respond to same antigen in another infection – plasma cells produce antibody molecules Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-14 Phagocytic cells • • White blood cells engulf and destroy invading pathogens, including multicellular parasites Mononuclear phagocytes (rounded nucleus) – macrophages and monocytes • Polymorphonuclear granulocytes (multilobed nucleus) – – – – neutrophils eosinophils basophils mast cells Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-15 Dendritic cells • Located in lymphatic tissue – stimulate cell differentiation – screen out self-reactive cells • Also in blood, mucosal surfaces (gut, nasal passage) and skin • Dendritic cells – break down antigen into fragments for subsequent presentation to T cells – concentrate antigen on surface to stimulate B cells Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-16 NK cells • • • Natural killer (NK) cells lyse cancerous or infected cells Lack TCR so do not recognise antigens Respond to changes in carbohydrates on surface of self cells once they become cancerous or infected Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-17 Antigens • • Surface molecule that can react with the variable region of an antibody or TCR molecule Protein antigens – sequences of ten amino acids or more – sequences (epitopes) in long proteins may be antigenic – dendritic cells break down long sequences for presentation to T cells – B cells recognise antigens as sequence of whole protein • Carbohydrate antigens – polysaccharides more likely to stimulate B cells than T cells Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-18 Antibodies (immunoglobulins) • • Antigen specificity of B cell depends on configuration of antibody on surface or secreted in solution Each antibody is made up of – variable region differs between antibodies and binds to antigen – constant region does not differ between antibodies e.g. region that binds to receptors on phagocytes Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-19 T-cell receptor (TCR) • • • TCRs are antigen-binding receptors on surface of T cells Can only recognise antigens that are bound to major histocompatibility complex (MHC) Once an antigen is recognised, the T cell proliferates and differentiates Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-20 Major histocompatibility complex • MHC presents antigen to T cells • Present on all cells, but are most abundant on professional antigen-presenting cells – dendritic cells, macrophages, B cells • T cells recognise combination of antigen and associated MHC molecule – increases specificity of T cell as T cell clones will only recognise antigen + that type of MHC molecule Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-21 Tolerance and autoimmunity • Random generation of antigen receptors means that self-reactive receptors are produced • Generally, self-reactive cells are discovered and destroyed in the thymus (T cells) and bone marrow (B cells) • When this does not happen, autoimmune diseases develop Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-22 Lymphatic network • • • Lymphocytes circulate though body in blood and lymphatic vessels Lymphatic vessels are part of lymphatic network Primary lymphoid organs – thymus and bone marrow – produce lymphocytes • Secondary lymphoid organs – lymph nodes, spleen, tonsils – act as filters and site of coordinated immune response Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-23 Humoral responses • • Foreign antigen is carried by dendritic cells from site of invasion to lymph node TH cells differentiate into daughter cells producing one of two sets of cytokines – promote cellular immunity – promote antibody production • If B cells receive a signal from TH cells to produce antibody, they differentiate into plasma cells and manufacture IgM and other antibodies Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-24 Cellular responses • Controlled by cytokines from TH cells – promote accumulation of phagocytic cells at infection sites – activate macrophages • May also involve TC cells – viral antigens from virus-infected cells appear on specialist MHC molecules and stimulate TC cells – TC cells then lyse infected cells, disrupting infection cycle Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-25 Immunity to infection • • Pathogens may possess many antigens on their surface The success of the immune response depends on which antigens elicit a response and the nature of that response – neutralising and disrupting antibodies – phagocytosis – macrophage activation • Depends on the cytokines produced in the initial stages of the infection Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-26 Defence against tumours • • Most proliferating cancer cells are self cells and so are not normally destroyed by the immune system It is possible that some cancers may be recognised as non-self – virus-induced cancers may express viral antigens on surface – fetal antigens may be expressed in adult tumours Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-27 Allergy and hypersensitivity • Reaction to non-threatening antigens can produce unnecessary immune system responses – allergic reactions • • • Production of IgE antibody in response to allergen antigen Binds to surface of mast cells, promoting inflammatory response when antigen appears Allergens in blood stream may cause severe reactions Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-28 Immunity in animals • • • Invertebrate immune systems are not as specific as those of vertebrates Phagocytic cells destroy pathogens and damaged tissue Some organisms have antisomes that mark material for destruction – can by induced (produced when needed) in some invertebrates and chordates Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-29 Immunity in plants • • • Plant cell walls provide physical barrier to invasion by pathogens Plants produce antibiotics and enzymes to destroy pathogens (humoral mechanism) Plants undergo self-destruction of damaged cell (cellular mechanism) Copyright 2005 McGraw-Hill Australia Pty Ltd PPTs t/a Biology: An Australian focus 3e by Knox, Ladiges, Evans and Saint 24-30