IMMUNE+++SYSTEM

IMMUNE SYSTEM What is immunity? ......................... It’s the “Youuuu ca’an’t touuch me..” phenomenon

**Innate Immunity/Non-specific/Natural** =what we are born with= our first line of defence, part of our anatomy

** Adaptive Immunity/Specific/Acquired ** = what we develop as we are exposed to specific antigens = highly specialized cells/structures

**__ INNATE IMMUNITY __** __**SURFACE PHYSICAL & CHEMICAL BARRIERS**__

The skin :- strong physical barrier - keratinized cells moisturized with sebum hard to penetrate and toxic to some bacteria

+++++++++chemical barrier- pH betw. 3 - 5 inhibits bacterial growth under normal conditions vaginal secretions also highly acidic

++++++++Langerhans cells and macrophages ; human defensin ** Saliva and Tear fluid (lacrimal fluid) ** :- contain lysozome that destroys bacteria ** Gastric Mucosa ** :- HCl and protein-digesting enzymes kill microorganisms ** Sticky Mucus in digestive canal and breathing passages ** trap microorganisms & other threats. cf. the role of the breathing passages in ‘cleaning’ inhaled air.

**__INTERNAL DEFENCES__** **CELLS AND CHEMICALS** ** Phagocytes ** : - (Diagram p. 789) Macrophages (biggest eaters) = monocytes that leave bloodstream – into tissues

free macrophages; fixed macrophages = Kupffer cells in liver; microglia in brain Neutrophil become phagocytic when required

Eosinophils - weakly phagocytic

Mast cells (histaminic) actually also good at destroying bacteria through phagocytosis Phagocytosis: Adherence, opsonization (taste-disguisers = special proteins & antibodies)

respiratory burst = increased cell activity - secretions that kill foreign organisms/cells. [Fig. 21.1 (b) Events of phagocytosis]

** Natural Killer (NK) cells. ** Special lymphocytes - police of the body, external weapons (chemical warfare) perforins - on invader cells, cells that have mutated, cancer cells, cells infected with viruses etc. - enhances the body’s inflammatory response.

**__THE INFLAMMATORY RESPONSE - INFLAMMATION__** (p. 790 Fig.21.2 Flowchart of events during inflammation) Reasons for inflammatory response by the body:

Four major signs of Inflammation Redness, heat, swelling, pain - however mild
 * Prevents spread of threat further into body
 * Gets rid of debris and pathogens
 * Lays the foundation for tissue repair

**Redness & Heat** Upon injury (tissue trauma) TLR’s (Toll-like receptors) on roving cells like macrophages and other surface cells (gastro-intestinal lining & breathing passages) recognize invaders different chemicals* are released into environment : +++* histamines, complement molecules, kinins, prostaglandins etc.)

Effects of these chemicals are: Vasodilation which allows more blood to flow in area (hyperaemia) - redness & heat More blood means ↑ food, oxygen thus ↑ metabolism – ↑ heat production Increased permeability of capillaries More plasma leaks out - nourish cells - exudate contain proteins also some proteins involved in clotting – starts clot formation pressure in local tissue – swelling, pain – could immobilize area if at joint

Chemotaxis - Neutrophils, monocytes and lymphocytes to injured area

Clot and leukocytes cordon off the area.

Fibrin threads form basis for tissue repair and stabilizes clot.

Leukocytosis inducing factor is also released which further mobilize leukocytes to injured area. **= Phagocyte mobilization** Leukocytosis

**Margination** of leukocytes in blood capillary keeps leukocytes to wall and at site of injury they exit via diapedesis.

By **chemotaxis** more leukocytes attracted. These leukocytes participate in phagocytosis of pathogens and dead tissue - immediately by neutrophils and monocytes. Monocytes evolve outside of blood by developing many lysosomes and become macrophages....

macrophages linger to clean up on more long-term basis as pus may have formed and would require longer ‘mop-up’ period.

**Abscess formation:** If inflammatory response cannot control/eliminate the threat, a wall of collagenous fibres isolates the infected area from the rest o f the body. [This occurs often in an individual with a weakened immune system or simply failure to attend to a more serious wounded area = negligence]

**Infectious granulomas** are cell masses of particularly macrophages that contain pathogens resistant to phagocytic digestion (eg. Tuberculosis bacili). These infected cells are then isolated by masses of healthy macrophages to ‘neutralize’ the content. A person can live for years with such granulomas without even being aware of it. Once the immune system becomes compromised, the macrophages may not be enough to keep the granuloma secured and the bacteria find the opportunity to multiply and infect other cells. The person will then display the symptoms of the disease caused by the bacteria, eg. develop tuberculosis.

**Antimicrobial Protein**

**Interferons (IFN’s)** are a family of related proteins produced by different body cells and each type has its own physiological effect.

Lymphocytes secrete gamma γ or immune interferon

Most other leukocytes secrete alpha α interferon

Fibroblasts secrete beta β interferon which reduces inflammation

Interferons are generally antiviral - interfering with their multiplication; non-specific which means they can act against any virus.

Interferons also activate macrophages and NK cells.

**The Complement System** consist of a group of ~20 plasma proteins

C1 – C9, factors B , D, and P and a few other proteins

These molecules destroy foreign substances encountered in the body.

**The Classical Pathway of operation**: Complement fixation -- C1 binds to a complex formed when antibodies haveattached to an invader.

**The Alternative Pathway of operation** involves factors B, D, and P and MAC (Membrane Attach Complex) which breaks down the target cell by forming

and stabilizing a hole in the target membrane for excess Ca+ to enter. CRP (C-reactive protein) produced by liver checks for acute infection and ** plays a role in opsoniztion **


 * The adjacent diagram shows the process of opsonization for purposes of**
 * understanding the concept.**


 * Memorization of all the molecules involved not required.**

. **Fever (Pyrexia)** Leukocytes secrete pyrogens when exposed to foreign substances in the body. The more active leukocytes, the more pyrogens. The body thermostat is then set higher in an attempt to curb pathogenic activity,,,, it may, however, denature body enzymes and cause death.

**Advantages of feve**r - may kill pathogen, increases metabolism and speed up healing process blood flow increased - increased oxygenation and nutrients Liver and spleen less active thus reduces minerals (Zn, Fe) for bacterial reproduction.