IMMUNE SYSTEM (If further material is required, check this out)
· My definition of immune system: a large, complex and diffuse network of cells and fluids that
    permeate every organ and tissue.

FUNCTION:
· surveillance ---> recognition of "self" vs "nonself"

IMMUNE SYSTEM:
1) Non-specific immunity (no exposure to antigen is required)
2) Specific immunity or acquired (happens after exposure to antigen)

Features of Nonspecific Immunity
1. General barrier
2. Phisical barrier (fever)
3. Chemical barrier (pH)
4. Biological (phagocytosis)

MONROY'S CLASSIFICATION:
1) First line of defense
    · General barriers: nutrition, sex, age, etc.
    · Physical barriers:
       * Skin: Keratin a water-proof protein, high salt concentration, desquamation, dryness, etc
       * Respiratory tract: waxy nasal hair, desquamation, mucus lining that traps and prevents
             infection; mucociliary escalator system upward motion away from the lungs.
       * GU tract: urine flushing action, urethra length
       * GI tract: peristalsis
    · Chemical: lysozyme: saliva, tears, etc; Acidity: skin due to sebaceous secretions,
         hydrochloric acid in stomach, and vaginal pH due to Lactobacillus and Streptococcus;
         Gastric juices and enzymes: stomach; Fibronectin: block attachment to host cell
          receptors;
         Iron-binding proteins: lactoferrin and transferring decrease availability of iron in serum.
    · Biological: Normal flora: antagonism (nutrient, space), bacteriocins, prevent colonization)

2) Second line of defense
    · phagocytosis
    · fever
    · inflammation
    · complement

3) Third line of defense
    · provided by B and T cells (also known as acquired immunity)
 

SECOND LINE OF DEFENSE:
a) FEVER: (abnormal increase in body temperature)
· endogenous pyrogens (IL-1 from phagocytic cells) and exogenous pyrogens (LPS and cell
    wall components) reset the hypothalamic thermostat ---> prostaglandins produced by the
    hypothalamus will alter the "hypothalamus settings".
· benefits: increases phagocytosis, decreases microbial multiplication, decreases iron
    availability

b) Phagocytosis
· A function of the mononuclear phagocytic system or reticuloendothelial system:
    * Granulocytes: eosinophils, basophils, neutrophils
    * Agranulocytes: monocytes, macrophages
· Fixed (microglial cells, alveolar and splenic macrophages, Kupffer cells, Langerhans cells)
    and wandering macrophages (monocytes, neutrophils, macrophages)
· Function:  a) surveilance
                    b) ingestion and destruction
                    c) antigen digestion and processing
· Mechanism of killing:
1) oxigen dependent (aerobic): formation of byproducts of respiration: O₂^-, H₂O₂, OH^-, O^-
2) oxygen independent (fermentation): lysosomal enzymes (proteases, phospholipases, acidic
    hydrolases)
3) Nitrogen dependent (aerobic): (O₂ + L-arginine ---> NO^-, NO₂^- (nitrite), NO₃^- (nitrate)

c) Inflammation:
· A nonspecific reaction to tissue damage.
· Steps: injury ---> cell lysis ---> chemical mediators ---> vascular reaction ---> edema & pus
    ---> tissue repair
· Effects include:
    (1) vasodilation (opening junctions between capillary cells, allowing fluid and WBCs to
          leave blood and enter surrounding tissues) --- > swelling of afflicted tissues
    (2) redness (from heightened blood flow)
    (3) pain (from prostaglandins released by tissues binding to nerve receptors)
    (4) heat (produced by pyrogens liberated at site of inflammation); may inhibit microbial
           growth
    (5) a variety of altered functions at site of inflammation; fibrin clotting, platelet aggregation,
        chemotactic signaling to attract WBCs, activation of complement factor C3.
· Function: 1) attract immune cells to site of injury, 2) destroy and block microbial invasion, 3)
    start tissue repair

d) COMPLEMENT:
· A group of 20 proteins that work in cascade to complement immune functions. In class we
    normally refer to only 9 = C1 to C9
· Present in two pathways: classical and alternative
· Classical pathway: requires antigen-antibody complex (C1q, C1r, C1s, C4, C2, C3 C5-C9)
· Alternative pathway: activated by microbial products, viruses, tumors, etc. (Properdin,
    Factors B,D, C3b---->C3, C5-C9)
· Component C3 is central in both pathways
· Function of complement:
    1) lysis (C5 - C9)
    2) opsonization (C3b)
    3) chemotaxis (C3a, C5a)
    4) Inflammation (C3a, C5a) --->mast cell degranulation: anaphylaxis
 

3) Third line of defense
Feature of Acquired Immunity
                                                Active: · Natural: Immunity after infection
                                                                          · Artifical: Deliver by vaccination

ACQUIRED IMMUNITY

TERMINOLOGY:
Antigen- Substance that generate antibody production.
    · Antigens are organic substances that induce humoral and/or cellular immunity. They are
        usually foreign.
    · Epitopes: are the smallest units of antigen that are recognized as foreign or incompatible.
       Usually several epitopes (or determinants) make up an antigen.

· Immunogens: Antigens that stimulate production of and combine with specific antigens.
· Adjuvant: Substances that enhance but do not induce Ab production nor bind to Ab
· Hapten: are well defined organic small molecule or groups that can bind to a peexisting
        antibody but can not induce production of Ab, when injected into an individual. However,
        hapten can become a full-fledged Ag or immunogen, and induce Ab, if they are made
        bigger by conversion into a hapten – protein or hapten – CHO conjugate.

     What biological molecules are most immunogenic?
    · Good Ags: Protein > CHO > Nucleic acid > Lipids

· What makes a substance immunogenic?
        * MW > 6,000
        * Chemical complexity
        * Foreigners
        * Genetic constitution of an individual
        * Made of administration of Ag into animal