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BSC 260 3/28/12 Host Immunity Humans are difficult environments for newly introduced microorganism Kind of like old pioneer movie Many kinds of obstacles and barriers Physical barriers: Skin-covers most of exposed areas Skin cells die and slough off Mucus-covers majority of respiratory and GI tracts Helps prevent bacterial interaction with host cells Mechanical defenses: Ciliary escalator: Moves microorganisms out of area Most important in respiratory tract Can be damaged by smoking, disease or trauma Urine flow Makes pathogens fight against flow of liquid Coughing, sneezing and peristalsis Muscles work to move irritants out Chemical defenses: Lysozyme Enzyme in tears and mucus that degrades bacterial cell walls Very important for protection of eyes Stomach acid Low pH conditions prevent most bacteria from persisting in stomach Most GI pathogens have temporary means to survive low pH Immune responses: Broken down to two types of response Humoral response Involves B-cells, antibodies and complement Cellular immune response T-cells are main player Definitions: Cytokine-soluble molecule that helps regulate immune functions. TNF, IL-I, IL-6, IL-10 etc. Inflammation-host immune response that is includes increased localized temperature, increased permeability of the capillaries, increased blood flow. Leukocyte-any "white blood cell" Lymphocytes-T-cells and B-cells PMN's=polymorphonuclear luekocytes-includes neutrophils, eosinophils and basophils Mononuclear cells-includes lymphocytes, monocytes and macrophages Immune response and disease: Many of the symptoms associated with microbial infection are caused by host immune response Fever, inflammation, change in blood pressure We are now beginning to examine if it is best to treat symptoms or not Fever plays an important role in host defense Many NSAI drugs block fever and inflammation Many new treatments allow body to do its part Antigen-a molecule or portion of a molecule capable of eliciting an immune response Immunoglobulin-a family of molecules that bind to antigens. Includes antibodies and T-cell and B-cell receptors MHC-Major Histocompatability Complex The role of antigens in host immunity Host needs to determine what is self and what is foreign This is accomplished by sampling antigens Reacts with foreign antigens but normally will not react with self antigens. Presence of foreign antigens suggests presence of infectious agent Types of antigen presentation: Soluble antigen will occasionally bump into a soluble antibody. Simple but very rare MHC I molecules present endogenous antigens All nucleate cells produce MHC I Used for self/not self Useful for detecting viral or intracellular bacterial presence MHC II cell are present on "antigen presenting cells" Includes macrophages and "APCs" Usually begin with an infectious agent being phagocytized Organism is degraded and protein fragments are presented on MHC II molecules This signals the presence of extracellular infecting agents. Antibody structure Several kinds of antibodies but they have basic structures Y shaped with two heavy and two light chains Fab fragment binds antigen Fc fragment interacts with host cell Fab regions vary greatly and allows for a huge number of unique antigen recognition sites within a single host Each B-cell produces antibodies with only a single antigent recognition site Antibody production Facilitated by B cells B cells possess receptors on their surface that interact with antigens presented on MHC II molecules This B-cell receptor is very similar to an antibody molecule Once a B-cell receptor interacts with an antigen/MHC II complex, this causes the cell to undergo rapid reproduction During proliferation two new cell types arise: Memory cell: persist in case antigen is ever seen again Plasma cell: antibody factories. Antibodies bind to antigens and coat infecting organisms This process is called opsonization Opsonization increases the likelihood of phagocytosis Cellular Immune response Largely dependent on T cells T cells come in two main types Cytotoxic T cells (killer T cells) Possess CD8 marker Helper T cells Possess CD4 marker Cytotoxic T cells T cell receptor recognizes antigens presented by MHC I molecules CD8 molecule interacts with MHCI as well Identifies cells with intracellular infections and kills them Direct killing Perforin-punches holes in infected cell Granzymes enters through holes and kills cell Indirect killing-signals host cell to kill itself (apoptosis) While TCR and CD8 interact with MHCI/antigen complex, FasL (T cell) and Fas (infected cell) proteins interact This interaction causes host cell to self-destruct Helper T cells TCR recognizes antigens presented by MHCII molecules CD4 molecule interacts with MHCII Identifies presence of extracellular pathogens Two types of Helper T cells TH1 and TH2 TH1 triggers inflammation and cellular response TH2 triggers B cell proliferation and humoral response Also responsible for production of Memory cells Large amounts of antigen presentation will signal TH1 response After duration of cellular response, the amount of antigen presentation begins to drop and TH2 response kicks in Helper T cells direct immune response and gives orders to other cells via cytokines Other cells Natural Killer Cells (NK) bind to host cells and will kill them unless they receive the correct signal Do not rely on antigen presentation Presence of MHC I molecules is the signal Prevents intracellular pathogen from shutting off MHCI Often important in early stages of viral infections Neutrophils: important cells Recruited during inflammation Phagocytize foreign cells Granules burst inside of neutrophil Releases chemicals that kill invader Eosinophils-Important in multicellular parasite infection Parasites are too large to phagocytize Antibodies against parasite accomplish opsonization Eosinophils interact with antibodies Eosinophils contain granules like neutrophil Deliver granule contents to outside when bound to parasite