Innate ImmunitySlide 3- Innate Barrier DefensesThe stratum corneum has acidic pH is dry and sweat helps keep bacteria inCiliated epithelium secretes mucusFlora protect us from pathogens-compete with other bacteria that may be more pathogenicImmune System CellsInnate cellular defensesThese are all leukocytes (white cells)The ones that are clearly in the blood most of the time: are basophils, neutrophils, eosinophils, monocytes (marcrophages)Tissue leukocytes: mast cells, dendritic cells, natural killer cells, and organ specific phagocytesMost are phagocyticNeutrophils and macrophages are very active phagocytesThe difference: neutrophils have very short lives (few hours) and macrophages are longer livedMost 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 tissuesEosiophils phagocytize but their main function is attach to parasitic wormsB lymphocytes are phagocytic (don’t kill, process antigens)Dentritic cells are phagocytes that don’t leave the tissueMicroglia also are phagocytic and don’t leave the tissueKupffer cells in the liver are also fixed phagocytesAlso there are fixed phagocytes in the spleen and lymph nodesGranulocytesGranules are vesiclesNeutrophils and eosinophilsMost prominent though are basophils and mast cells (important in triggering inflammation)LymphocytesB: release antibodiesT: number of different functions (one function is to be cytotoxic- attack 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))The cells with the * are generally believed to be part of the innate immunity. NonspecificThe ones without * are seen as acquired immunity (specific)The problem is that all of these cells cooperate – need both specific and non specific immune defenseHow 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 toll-like receptorsInnate Chemical Defenses’Chemical defenses:Lysozyme- in mucus (milk and saliva too) that attacks bacterial cell wallsGI tract protected by mucus and then there is a strong protease in the stomach that kills most bacteriaBile salts help emulsify fats and destroy bacteria membraneCytokines 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 molecules- make cells become sticky and flatten out and adhere to walls of capillaries and then crawl out and look for inflammationInterleukin 1 B is a cytokine which binds to receptors in the body temperature regulation in the hypothalamusComplements 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 itInterferons (3 classes) are cytokines in the defense against viruses- they 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)InflamationProcess 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 anticoagulantCytokines attract phagocytesEnd 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 responseB cells not only destroy the bacteria but take antigens to presentAcquired Immunity OverviewReview of basic terminologyAntigen: evokes a specific immune responseWhat actually provokes an immune response is small groups on the surface of the antigen (Epitopes on the antigen)Specific immune defensesSpecific lymphocytes that have receptors capable of responding to a broad array of antigensEach b lymphocyte recognizes only one antigen but the other lymphocytes recognize a varietyHaptens: small molecules that by themselves don’t evoke a specific immune response unless bound to proteins (used in drug production or vaccine productionOverview of Lymphocyte FunctionEverything we need to know1. B lymphocytesEffector cells: plasma cellsSecrete antibodies that act in the ECFMemory cells2. Helper T cellsAfter clonal expansion:Effector cells: Active T cellsAll the cytokine secrtionMemory T cells3. Cytotoxic T CellsAfter clonal expansion: effector cells: Active CTLsAttack and kill virus infected cells or cancer cells or organ transplant cellsMemory CTLsSpecific receptors on these T lymphocytes and during embryonic development these receptors become highly specificHas to bind the epitope on the antigenOnly B cells can directly bind the antigen by itselfHelper T cells and CTLs need to be presented with the antigen by another cellFor helper T: presented by phagocytic cells (dendritic and macrophages and B cells)For CTLs: The targeted cell itself that presents the antigenPlasma cells (active B cells) produce antibodies and release them into the bloodFunctions of AntibodiesMechanisms by which antibodies do their thingAntigen presenting cells bring the antigens to themAntibodies go out in circulation1. Activate the complement system- enhanced by the presence of antibodies on the foreign cell2. Opsonization- neutralization- antibodies bound to surface of the cell will interfere with the function of the bacteria . Coat bacteria with antibodies3. Agglutination: given that all antibodies are polyvalent results in a clumping of