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.

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. Not all of a large foreign molecule is recognized. The specific part of an antigen recognized by an antibody or receptor is called an epitope. A molecule that is too small to be an antigen without piggy-backing onto another is a hapten

Nature of epitopes Big enough to be noticed. Specific parts recognized to distinguish one from another. http://www.automedia.com/NewCarBuyersGuide/photos/2005/Pontiac/Vibe/Wagon/2005_Pontiac_Vibe_ext_1.jpg

Dual Nature of the immune system Humoral and cell mediated Humoral refers to body fluids Specifically antibodies: 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 T helper cells help B & T cells thru direct contact

Basics of antibodies 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.

Nature of antibodies Ends attach to antigens. Two ends means can attach to 2 different antigens at the same time. Fc end: attaches to molecules on host cell surface; a handle for host.

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

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. Useful site: http://www.webmd.com/a-to-z-guides/Immunoglobulins

How DO antibodies help? Antibodies attach to antigens. Period. But… Because there are at least 2 binding sites, cross-bridges 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.

Crosslinking by antibodies Antibodies have at least 2 combining sites; can react with different antigens at the same time to form a clump. Soluble antigens: clump is too big, becomes insoluble: precipitation. Insoluble antigens: clump settles out; agglutination.

Neutralization Toxin (or virus) cannot bind to receptor on cell surface because antibody physically blocks access.

How DO antibodies help?-2 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.

Opsonization Antibodies provide a handle (Fc end) for phagocytes to grab onto to improve phagocytosis. Clumped cells are bigger, easier to grab than single cells http://content.luxology.com/modo/201/img/modo201_Macrophage_C.jpg

Lysis function of complement Antibody binding to antigen on bacterial cell surface activates first component of complement. Complement cascade: one protein activates another. Complement components assemble to create “hole punch”; cell lysis. http://people.eku.edu/ritchisong/complement2.gif

The Immune response 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 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 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/BiologyPages/A/AntigenPresentation.html#Exogenous_antigens

Activation of B cells 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 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 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

Summary

Specificity and memory 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.

Vaccines 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 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 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.

Other views of immunity 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 were acquired by the host thru natural means; artificial means they were injected. Active Artificial natural Passive Passivenatural