BISC 307L 1st Edition Lecture 30 Current Lecture Innate Immunity Slide 3 Innate Barrier Defenses o o The stratum corneum has acidic pH is dry and sweat helps keep bacteria in o Ciliated epithelium secretes mucus o Flora protect us from pathogens compete with other bacteria that may be more pathogenic Immune System Cells o Innate cellular defenses o These are all leukocytes white cells o The ones that are clearly in the blood most of the time are basophils neutrophils eosinophils monocytes marcrophages o Tissue leukocytes mast cells dendritic cells natural killer cells and organ specific phagocytes o Most are phagocytic Neutrophils and macrophages are very active phagocytes The difference neutrophils have very short lives few hours and macrophages are longer lived Most of what they do is by means of phagocytosis main way of killing things Usually considered blood born leukocytes but they can leave the blood and enter tissues and do most of their phagocytosis in tissues Eosiophils phagocytize but their main function is attach to parasitic worms B lymphocytes are phagocytic don t kill process antigens Dentritic cells are phagocytes that don t leave the tissue Microglia also are phagocytic and don t leave the tissue Kupffer cells in the liver are also fixed phagocytes Also there are fixed phagocytes in the spleen and lymph nodes o Granulocytes Granules are vesicles Neutrophils and eosinophils Most prominent though are basophils and mast cells important in triggering inflammation o Lymphocytes B release antibodies T number of different functions one function is to be cytotoxicattack and kill other cells share a lot in common with the natural killer cells target and kill cells of their own body the difference is how they select the targets to kill T specific and natural killer cells acquired attack broad variety innate o The cells with the are generally believed to be part of the innate immunity Nonspecific o The ones without are seen as acquired immunity specific o The problem is that all of these cells cooperate need both specific and non specific immune defense o How do we recognize these threats The cells with the have receptors on their membranes that recognize molecular groups that are commonly associated with pathogens broad array that bacteria in common share These are called PAMPs and the receptors that recognize these are called tolllike receptors Innate Chemical Defenses o o Chemical defenses Lysozyme in mucus milk and saliva too that attacks bacterial cell walls GI tract protected by mucus and then there is a strong protease in the stomach that kills most bacteria Bile salts help emulsify fats and destroy bacteria membrane Cytokines are hormones of the immune system communication like neurons do with chemical signals do but not with synapses at a distance can work as autocrine paracrine or endocrine agents Chemokines are a type of cytokines that are attractant moleculesmake cells become sticky and flatten out and adhere to walls of capillaries and then crawl out and look for inflammation Interleukin 1 B is a cytokine which binds to receptors in the body temperature regulation in the hypothalamus Complements assemble into a complex that lets water in and kills the cell Can do this all by itself but the action is enhanced if the cells have antibodies bound to it Interferons 3 classes are cytokines in the defense against virusesthey slow down viral replication and in the case of tumors they slow down the mitosis and growth of tumors They also stimulate cytotoxic T cells and natural killer cells and macrophages and b cells to attack and destroy the cells infected T cells and cytotoxic are subtle and they make perforins make pores in the cell and granzymes enter and trigger apoptosis in the cell more subtle than osmotic lysis Inflamation o o Process of inflammation involves degranulation exocytosis When mast cells and basophils release their contents this mediates the response of inflammation one component is histamine causes local vasodilation and makes capillaries more leaky more fluid leaks out and proteins leak out antibodies and complement proteins leakage of protein reduces the osmotic gradient drawing back into the capillary causing edema or swelling Heparin is an anticoagulant Cytokines attract phagocytes End result is more blood goes to the area more oxygen delivered leukocytes attack the bacteria other cytokines are spreading body wide to stimulate specific and non specific immune response B cells not only destroy the bacteria but take antigens to present Acquired Immunity Overview Review of basic terminology o o Antigen evokes a specific immune response o What actually provokes an immune response is small groups on the surface of the antigen Epitopes on the antigen o Specific immune defenses Specific lymphocytes that have receptors capable of responding to a broad array of antigens Each b lymphocyte recognizes only one antigen but the other lymphocytes recognize a variety Haptens small molecules that by themselves don t evoke a specific immune response unless bound to proteins used in drug production or vaccine production Overview of Lymphocyte Function o o Everything we need to know 1 B lymphocytes Effector cells plasma cells Secrete antibodies that act in the ECF Memory cells 2 Helper T cells After clonal expansion Effector cells Active T cells o All the cytokine secrtion Memory T cells 3 Cytotoxic T Cells After clonal expansion effector cells Active CTLs Attack and kill virus infected cells or cancer cells or organ transplant cells Memory CTLs o Specific receptors on these T lymphocytes and during embryonic development these receptors become highly specific Has to bind the epitope on the antigen Only B cells can directly bind the antigen by itself Helper T cells and CTLs need to be presented with the antigen by another cell For helper T presented by phagocytic cells dendritic and macrophages and B cells For CTLs The targeted cell itself that presents the antigen o Plasma cells active B cells produce antibodies and release them into the blood Functions of Antibodies o o Mechanisms by which antibodies do their thing o Antigen presenting cells bring the antigens to them o Antibodies go out in circulation 1 Activate the complement system enhanced by the presence of antibodies on the foreign cell 2 Opsonization neutralization antibodies bound to surface of the cell will interfere with the function of the bacteria Coat bacteria with antibodies 3 Agglutination given