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Transcript
Immunology: Specific Immunity • Immunity: not being susceptible to disease • Types of immunity – Innate: you have it from birth. • Species: as humans, immune to diseases of many other creatures • Genetic: presence/absence of receptors • Non-specific host defenses: Macrophages, etc. – Acquired: after exposure, your body remembers specific invader. 1 Other views of immunity 2 • 2 x 2 matrix: Immunity is either active or passive; either natural or artificial. • Active means that host is making his own antibodies; passive means the antibodies came from someone else. • Natural means the antibodies Active Active were acquired by the host thru Artificial natural natural means; artificial means Passive Passive they were injected. Artificial natural Nature of antigens • The immune system recognizes, responds to, and remembers molecules that are antigens. • An antigen: – Is foreign – Is large (> 5000 MW) – Is molecularly complex. • A molecule that is too small to be an antigen without piggy-backing onto another is a hapten • The specific part of an antigen recognized by an antibody or receptor is called an epitope. 3 4 Dual Nature of the immune system • Humoral and cell mediated – Humoral refers to body fluids, specifically that this branch of the immune system uses antibodies which are protein molecules dissolved in blood, body fluids, and secretions. • B lymphocytes are the source of antibodies – Cell mediated refers to the direct involvement of cells to attack an infection • T lymphocytes either kill cells directly or recruit macrophages to kill cells directly Basics of antibodies 5 • Protein molecules produced by activated B cells. • Belong to class of proteins called immunoglobulins (Ig), a subclass of globulins. • Y-shaped molecule with hinges – Ends include variable regions where antigen binding occurs. – Antibodies made by a single B cell are all the same, differ from those made by another in variable region. Basic Antibody structure •Molecule undergoes shape change upon binding to antigen. •Classic lock & key like an enzyme. Heavy chain Fc end: binds to host cells. 6 The Antibodies • IgG: most abundant in blood and body fluids; single Y shaped molecule, remains in circulation for long time. • IgM: 5 Y-shaped units linked together, first type of antibody made in an immune response. http://www.neuro.wustl.edu/neuromuscular/pics/igm.gif 7 The Antibodies-2 • IgA: present in large quantities in body secretions; a dimer (2 Y-shaped units, tail to tail), helps protect mucous membranes. • IgE: single Y shaped unit, in small quantities, found bound to mast cells attached by Fc end, involved in allergies (mast cells release histamine). • IgD: The receptor for antigen normally found on the surface of B cells; if it is shed into bloodstream, looks a lot like an IgG antibody. In very small amounts. 8 How DO antibodies help? • Antibodies attach to antigens. Period. But… – Because there are at least 2 binding sites, crossbridges form, linking antigens together in clumps. – Attaching covers up critical sites on the antigens. • Agglutination: Aby links cells, viruses together to make clumps that attract macrophages. • Precipitation: toxin molecules come out of solution, can be cleared out. • Neutralization: toxins, viruses no longer active. – Because critical binding site is covered. 9 How DO antibodies help?-2 10 • Opsonization: an opsonin is something that promotes phagocytosis. – By making antigens into clumps. – By providing a “handle” (Fc end of antibody tp which the phagocyte can bind). • Complement fixation – Antibody binds to antigen, antibody changes shape – Shape change activates complement • Activated complement leads to increased inflammation, opsonization, and cell lysis. The Immune response 11 • An immune response is what the immune system does when confronted by an antigen. • An immune response is an elaborate interplay between antigen, non-specific defenses, and B and T lymphocytes. • The process involves direct contact (cells, molecules bind to receptors on cell surfaces) and cytokines (messenger molecules) that also bind to receptors on cell surfaces. Immune response-2 12 • Certain cells such as macrophages encounter and process the antigen (chopping it up). – They display it on the cell surface for other cells to interact with. Macrophage = Antigen Presenting cell (APC). – Display is attached to MHC (major histocompatibility complex), your molecular UPC code. • Stimulation of cells by binding usually results in release of cytokines which tell a cell 2 things: – Get activated; multiply. Common activation 13 Macrophage which has encountered antigen processes it, display it with MHCII protein on surface. Via T cell receptor and CD4, T helper cell binds to this. APC secretes Il-1 which activates the T helper cell. http://users.rcn.com/jkimball.ma.ultranet/Bi ologyPages/A/AntigenPresentation.html#E xogenous_antigens Activation of B cells 14 Requires 2 signals: B cell binds to specific antigen. T-helper cells bind to B cells and release Il-4 which activates B cell. It becomes plasma cell and cranks out antibodies. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Th_Lymphokines.gif T-independent antigens 15 Some B cells are T-independent, e.g. those that respond vs. bacterial PS http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/ClonalSelection.html Cell mediated immunity 16 CD8 T cells (cytotoxic cells) are activated by the release of Il-2 from T helper cells. CD8 cells recognize antigens on the surface of infected cells, attach to these cells and secrete perforins Perforins punch holes into the infected cells, killing them. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/AntigenPresentation.html#endogenous 17 http://www.people.virginia.edu/~rjh9u/imresp.html Specificity and memory 18 • In all cases, the response to an antigen is carried out only by those T cells and B cells which are programmed to react to that antigen, that is, have a surface receptor with the proper fit to react with that antigen. • Both B cells and T cells, when stimulated to multiply, produce memory cells which are long lived. These are the cells that allow the quick response when the antigen is encountered at a later time. Memory and antibody titer Upon first exposure to antigen, accumulation of antibody is slow. Memory cells make for a quicker, larger response afterwards. This is the basis for booster shots. 19 Vaccines 20 • From “vaccus”, Latin for cow, from Ed Jenner using cowpox to immunize. • Live attenuated vaccine – Pathogen grown to make it weak, used alive. • Killed/inactivated vaccine – Destroyed with formalin, weaker immune response • Subunit/conjugate/engineered – A portion of pathogen used, often combined with another molecule for effectiveness; antigen may be produced through genetic engineering. Hypersensitivities-1 21 • Inappropriate immune responses • Type II are cytotoxic reactions like the Rh factor problem and bad blood transfusions. – Rh is one of many blood groups, like ABO – An Rh+ fetus in an Rh- mother means she gets immunized by baby’s blood cells, makes Aby. – Second pregnancy, fetal RBCs are attacked. – Solution: give Rho-gam during 1st pregnancy. • Type III are immune complex disorders, where too many agn-aby clumps cause inflammation. Hypersensitivities-2 Allergies 22 • Type I are immediate type, in which antigen binds to IgE on mast cells, histamine released. – Histamine: smooth muscle contraction, vasodilation. – Results in asthma, diarrhea, shock depending on where antigen enters body. Ex. Bee sting. • Type IV are delayed type, T cell produces various cytokines which affect macrophages. – The bar fight scenario: come, stay, get angry. – Angry macrophages cause much tissue damage. – Ex. Poison ivy; urushiol-coated cells killed.