Lecture Notes: Defenses / Immune Response Chapter 39

Summary Outline: Three Lines of Defense

I. Skin, Mucus Membranes

II. Non-Specific Internal Mechanisms

A. Phagocytotic, Natural Killer Cells	Eat 'em, blow 'em up
B. Antimicrobial Proteins ....Complement ....Interferons	Poke holes in 'em Harass 'em
C. Inflammatory Response	Cook 'em

III. Specific Internal Mechanisms: Immune System

Vertebrate Specific	Birds and Mammals: Full Fish: Less Complex
1. B-Cells	Humoral Response ...Target Free Antigens ...Produce Antibodies
2. T-Cells	Cell Mediated Response ...Target Cells with wrong surface proteins ...stimulate cytotoxic killer T-cells
>>>>> HIV targets
3. Macrophage	Antigen presenting cells to T-cells ...Trigger T-cell Activity

Lecture Notes, Chapter 39

I. First Line of Defense: Skin and Mucus Membranes -- Non-Specific

A. Skin Surface

1. dry, dead, thick, secretions
2. sweat and sebaceous glands: antibiotics, lactic acid, RNase


B. Mucus (moist and sometimes friendly environment... but...)

1. antibacterial enzymes (e.g. lysozyme)
2. entraps - cilia move out

a. stomach pH destroys
b. stomach and intestinal enzymes degrade

II. Second Line of Defense: Non-Specific Internal Defenses -- Non-Specific

A. Cells

1. Phagocytic Cells

a. White Blood Cells
b. Macrophages - engulfing behavior yum-yum-yum


2. Natural Killer Cells

a. recognize body cells infected with foreign bodies (i.e. viruses)
b. transfer membrane containing "hole-forming" proteins
c. secrete enzymes


B. Anitmicrobial Proteins

1. Complement System (39.16, p.870)

a. group of at least 20 proteins, circulate in blood
b. activated in a progressive (cascade) fashion;

- "clasical pathway": initiated with antibodies (specific targets).
- "alternative pathway": init. by microbial substances (non-spec.)

b. lyse invading microbes.
c. some proteins are chemoattractants for phagocytes (smell).

2. Interferons

a. produced by viral infected cells, help neighbor cells

- neighbors produce proteins which inhibit viral replication

b. three types: alpha, beta, gamma
c. pre-antibody response, early response, short-term infections
d. gamma activates phagocytes

C. Inflammatory Response

1. Damaged cells release HISTAMINE

a. histamine makes capillary walls leaky
b. relaxes smooth muscle
c. result: blood flows into wounded area: inflammation

- increased delivery of WBCs, etc.

2. Clotting response - chemically stimulated by wounded cells (platelets, etc.)
3. Attraction of Phagocytic WBCs (i.e. Macrophage) / pus
4. Fever

a. hypothalamus controls body thermostat (set point: 37^oC).
b invasion > specific WBCs release hormones: "endogenous pyrogens"
c. pyrogens travel blood > hypothalamus, inducing thermostat change
d. elevated temperature...

- inhibits bacteria metabolism
- stimulates phagocytic WBCs
- increases production of interferon in viral attacks

-- aspirin reduces fever; prolongs viral (flu) infections

III. Third Line of Defense: Immune Response -- Specific

A. Complex system of interacting cells: WBCs (2x10¹²)

1. B-Cells: Humeral Immunity

a. born and differentiate in bone marrow
b. named for bursa of Fabricius in chickens - source of discovery

2. T-cells: Cell-Mediated Immunity

a. born in bone marrow, migrate to and differentiate in thymus

3. Macrophages: trigger T-Cell response


B. Recognition

1. B-Cell Receptors: Antibodies

a. Structure

- Y-shape
- four subunits: 2 heavy chains, 2 light chains
- constant regions
- variable regions

b. Variable regions bind ligands

- each cell produces identical antibodies with identical specificities
- > 1,000,000,000,000 different specificities (more than # of lymphocytes)
- specificity in the amino acid sequence/conformation of variable ends

c. two mechanisms generate diversity (>10¹²)
- only 100,000 total genes in human; only several hundred antibody related genes

- stem line gene rearrangements - clonal lines of specific types

-- numerous variable regions, constant regions
-- for both heavy and light chains
-- early development: random joining of variable/constant regions

- somatic mutations

-- variable regions are hypersensitive to induced mutations
-- small changes produce significant differences in specificities

d. result: many cells / millions of different receptor specificities


2. Various forms of B-Cell receptors: Table 34-2

IgM, IgG, IgA, IgE, IgD: all have basic structure


3. B-cell receptors recognize foreign material: NOT SELF

a. Major Histocompatibility Complex (MHC)

- family of cell surface proteins
- unique to each individual

b. must be present from embryogenesis


4. T-cell receptors

a. different than B-Cell receptors: five peptide chains, not 4
b. similar mechanism as antibodies for generating diversity


C. Attack: B-Cell Response: extracellular invaders

1. Foreign antigen binds to antibodies of a specific B-cell
2. antigenic binding stimulates cell division of activated B-cell

a. clonal selection: antigen stimulates a line of clones

3. Activated B-Cells differentiate

a. Plasma cells: secrete antibodies
b. memory cells: persist in background, primed for future attack

4. antibodies neutralize foreign body

a. cover body
b. promote phagocytosis by covering body
c. agglutination
d. complement reaction

- blood proteins bind to certain heavy chains
- complement bound ABs recognized by certain phagocytes



CLICK FIGURE FOR LARGER IMAGE

D. Attack: T-Cell Response: intracellular invaders


1. Viral attacked cell ingested by macrophage

a. viral proteins combine with MHC proteins

- antigens recognized by specific Virgin T-cell receptors
- activates specific Virgin T-cell class

2. Activated Helper T-Cells are Core of Immune Response

a. Activated Virgin T-Cell releases Interleukin
b. Interleukin stimulated T-Cell divisions: progeny >>>>>>

- some become Memory Helper T-Cells
- others activate Cytotoxic T-Cells

3. Virgin Cytotoxic T-Cells recognize invading antigen

a. Virgins gaining experience are sensitive to Interleukin
b. Experienced Virgins divide in response to hormone
c. Cytoxic T-Cell response is amplified, along with B-Cell response

4. Suppresser T-Cells Turn off Immune Response


E. Immune Response has memory: Immunity

1. preserved in Memory B-Cells and Memory T-Cells
2. Ig-types are progressive:

--- cells producing IgMs precede cells producing IgGs


F. Note: Central Role of Helper T-Cells for BOTH B- and T-Cell Response

1. Physical and hormonal (Interleukin) interactions with...

a. Helper T-Cells - positive feed back
b. Cytotoxic T-Cells - reinforce antigenic interactions
c. B-Cells - reinforce antigenic interactions

Vocabulary