Immunology: Specific Immunity

1. 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.

2. 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.

3. Nature of antigens • The immune system recognizes, responds to, and remembers molecules that are antigens. • An antigen: • Is foreign • Is large • 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.

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

5. Basics of antibodies • Protein molecules produced by activated B cells. • Belong to class of proteins called immunoglobulins (Ig), 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.

6. Basic Antibody structure • Molecule undergoes shape change upon binding to antigen. • Classic lock & key like an enzyme. Fc end: binds to host cells.

7. 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

8. The Antibodies • 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.

9. 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.

10. 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.

11. Take Immunology to learn the details of how an immune response happens Now for more on antibodies, vaccines, and hypersensitivities.

12. 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.

13. 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). • Complement fixation • Antibody binds to antigen, antibody changes shape • Shape change activates complement • Activated complement leads to increased inflammation, opsonization, and cell lysis.

14. 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.

15. 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.

16. 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.