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
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-2Allergies • 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.