NON SPECIFIC DEFENSES: Skin and Mucous membranes, antimicrobial chemicals, natural killer cells, phagocytosis, inflammation and fever

I Surface Membrane Barriers- skin and mucous membrane

A. Skin (epidermis)
1. Keratin resists physical stress, resistant to weak acids and base
2. "Acid Mantle" pH 3-5
B. Membranes secrete protective chemicals 1. Vaginal Secretions
2. Hydrochloric acid in stomach
3. Saliva and lacrimal fluid have Lysozyme, bacteria destroying enzyme
4. Mucous is a sticky trap for micro-organisms
II. Cellular and Chemical A. Phagocytes - engulf particles but sometimes thatís not enough. Sometimes they also secrete chemicals to destroy the cells they are about to phagocytize. 2 major types 1. Macrophages
2. Neutrophils
B. Natural Killer Cells- a type of lymphocyte (WBC) 1. found in blood and lymph
2. kill cancer cells and virus infected cells
3. non-specific
4. non-phagocytic
C. Inflammation- prevents spread of damaging agents. Disposes of cell debris and pathogens. Makes ready for repair. Four cardinal signs: Redness, Heat, Swelling, Pain 1. Vasodilation and increased vascular permeability a. Inflammatory chemicals from the damaged cells promote vasodilation.  this leads to redness and heat
b. These chemicals also cause local capillaries to leak fluids (inc. vasc. perm) 1.) Fluids contain clotting factors and antibodies
2.) This "exudate" causes edema (swelling) a.) Dilutes harmful substances
b.) Brings in O2 and nutrients
c.) Clotting proteins enclose site
2. Phagocyte Mobilization- soon after inflammation starts. Inflammatory chemicals attract the various phogcytic cells to the area.
D. Antimicrobial Proteins- complement and interferon 1. Complement system. 20 plasma proteins. Its a Major mechanism for destroying foreign cells
2. Interferon. a bunch of non-specific anti-viral proteins.
E. Fever- a systemic response (meaning it happens all over your body) 1. Benefits: a. increase metabolic rates of cells speeding repair
b. liver and spleen sequester iron and zinc needed by bacteria
2. Drawback: high temps denature proteins (enzymes)  
IMMUNITY-  two types: Humoral immunity, or antibody-mediated immunity, and Cell-Mediated immunity

I. Antigens- substances that provoke an immune response

II. Humoral Immune Response

A. Clonal selection and differentiation of B-cells 1. B-cell is activated when antigen binds to its surface
2. B-cell grows and multiplies rapidly (all identical=clone) a.) Most of the cells become plasma cells cranking out antibodies which bind to that antigen, marking it for destruction
b.) some clone cells become memory cells ready to act fast if exposed again.
B. Immunological Memory 1. "Primary Response"- has 3-6 day lag time, plasma antibody levels peak in about 10 days
2. Re-exposure leads to "secondary response" 2-3 days antibody blood levels even higher than in Primary. Stay high for weeks to months
3. This is similar to what happens to T-cells too.
C. Active and Passive humoral immunity 1. Active- antibodies produced after exposure to antigen a. naturally
b. artificially
2. Passive- antibodies come from serum of an immune individual (not always human) a. immediate protection
b. short lived protection
c. mother/ fetus
D. Antibodies- also known as "Ig"s (for immunoglobulins). Secreted by plasma cells or by activated B-cells 1. Basic structure - a. "variable" region - antigen binding site
b. "constant" region (the stem) - determins the cells and chemicals an antibody can bind to, and how that class of antibody will function.
2. Antibody targets and functions. The antigen-antibody complex is the first part of 4 different defense mechanisms. a. neutralization - the antibody blocks sites on viruses or exotoxins (bacterial toxins), then they canít bind to tissue cells and do them harm.
b. complement fixation and activation - the main defense against cellular antigens. After the antibody binds to the antigen, the C region changes, exposing complement binding sites. This promotes complement fixation and subsequent lysis of the cell.
c. antibodies can bind to more than one antigenic determinant. This can have the effect of clumping together many foreign cells. This agglutination is similar to
d. precipitation, only precipitation is when molecules (as opposed to cells) are clumped together. In both agglutination and precipitation, the clumps are more easily phagocytized.
IV Cell Mediated Immune Response.

Some pathogens reproduce inside your cells, in that case, antibodies arenít effective (not like the four steps above). A cell-mediated immune response begins with activation of a small number of T-cells by a particular antigen. Once activated the T-cells can undergo proliferation and differentiation into a clone of effector cells that recognize the same antigen and carry out some aspect of the immune attack.

3 major populations of T-Cells

cytotoxic T-Cells (effector cells for killing)

Helper T-cells (regulatory cells)

Suppressor T-cells (regulatory cells)

T-cells donít recognize free antigens. They only recognize and respond to processed protein fragments on the bodies own cells. Thus they attack corrupted cells. Consequently, one of the first things will we look at is antigen recognition. A. Clonal Selection and Differentiation of T-Cells 1. Antigen recognition. T-Cells look for two thingson the outside of the cell: "self" and "non-self" before they act.  These are found in "MHC" that proteins signal the immune system cells that infectious organisms are hiding within the cells. a) MHC proteins hold bits of antigen
b) they also have some "self", which is necessary to activate T-cells
2. T-Cell activation.  T-Cell Antigen Receptors (similar to the B-cell receptors) bind to antigen-MHC protein complex. Most times a "costimulator" is required before the T-cells can form clones. T-cells enlarge and proliferate. Many of the clone become memory cells.
B. Specific T-Cell Roles 1. Helper T-cells: stimulate proliferation of other T-cells a. no immune system without them
b. most antigens canít trigger B-cells without helper T-cells
c. they release chemicals which amplify the non-specific defenses
2. Cytotoxic T-cells: Directly attack and kill other cells a. binds to target cell, inserts cytotoxic chemicals
b. releases and moves on, in search of more antigen-MHC complexes
3. Suppressor T-cells: inhibit the activity of T-cells and B-cells. Useful when antigen has been wiped out.