There are several host factors that determine our susceptibility to disease:
i) premunition - this is our innate resistance to infection that is acquired over time due to repeated contact with infectious agents.
ii) age - very young (immature immune systems) and very old (deteriorating immune systems) are more susceptible to disease.
iii) nutrition (body abuse)
iv) occupation - health care workers (HIV, hepatitis etc), ranchers and abbatoir workers (brucella, leptospirosis), prostitutes etc.
v) other diseases - diabetes, cancer etc. However, basically once a pathogen gets into the body, its a race between your defense systems and the bug.

NON-SPECIFIC RESISTANCE
First line of defense: Chemical/physical barriers (see Figure 18:1) Bascially a pathogen has to get into the body. Therefore the first line of defense is at the portals of entry. These include:
a) skin surface - this is the integument, contains fatty acids, high slat concentrations, low pH (pH5) and also contains a natural flora that competes with the pathogen. Rupture the skin (i.e. cut or abrasion) allows access for the bug.
b) mucous membranes - all orifices of your body are lined with mucous, which is a viscous liquid that contains neuraminic acid (see Figure 18:2).
c) specifc organ components - ear wax, nose hair, tears etc. in addition, many of these specific organs contain enzymes that digest invading bacteria (e.g. lysozyme that digests peptidoglycan; lytic enzymes (proteases, lipases, nucleases); low pH of the stomach, urine flushing out the bacteria etc).

Two important lines of defense are:
1) Many regions in the body have what is known as a normal flora. These are organisms that live with us. Act by covering up sites and also by producing antimicrobial agents.
2) Mechanical flow - the flow of tears, saliva, urine and blood is all out. Consequently, this washes the organisms away.

Second line of defense: elements within the blood
These include lymph, the RES system (reticuloendothetial system) and inflammatory components.

Blood is very important stuff against disease - contains 50% cells, the rest is fluid. The fluid portion is called plasma, and if the clooting factors have been removed is refered to as serum. Plasma exists the blood to bathe tissues in O2 and nutrients. If too much leaves then you get swelling (edema). The fluid is returned to the blood via the lymphatic system. Plasma has lots of good stuff in it (e.g. toxic peptides, complement, antibody, interferon etc).

There are various cell types within the blood (see Figure 18:3):
erythrocytes - these are red blood cells and they transport O2.
white blood cells - granulocytes (i.e. they have specific granules within their cytoplasms) and agranulocytes (no granules).

Granulocytes
There are three types based on their staining with eosin.
a) eosinophiles - these cells are involved in down-regulating the inflammatory response, are involved in allergic reaction, and in controlling parasitic diseases.
b) basophils - the granules in basophils contain primarily histamine which is the stuff that causes inflammation. Some of these histamine producing cells become stuck in the endothelium and are called mast cells.
c) neutrophils (sometimes called polymorphonuclear cells or PMNs, or sometimes macrophages). These are the most abundant cells in plasma, and their granules contain many toxic components (e.g. lytic enzymes, alkaline phosphatase). These are phagocytic cells (i.e. they ingest and degrade foreign material. They quickly exit the blood in pursuit of bad stuff.

Agranulocytes
There are four main cell types:
a) monocytes - these are large phagocytic cells (the main blood stream type are called macrophages). They can enter and leave the bloodstream. They are very important in initiating the immune response and are critical elements in the destruction of foreign material.
b) lymphocytes - these are cells that mediate the specific immune response (i.e antibody production, cell-mediated immunity etc).
c) platelets - these are very small cells that are involved in blood clotting.
d) natural killer cells - these are a subset of lymphocytes that can directly kill foriegn cells.

Pathogens encounter the above cell types in:
lymphatic system - this is a passive circulatory system that returns the lymph back to the blood
RES - this is a system of fixed and circulating phagocytes (e.g. macrophage and PMNs). They are found in the lymph nodes, spleen and liver. So what happens to an invading bacterium when they encounter these cells (see Figure 18:4). Answer - they are phagocytosed (see Figure 18:5).

The actual mechanism of intracellular killing is not totally understood. However, it involves non-oxidative events (e.g. the activation of hydrolytic enzymes, production of highly basic proteins) as well as oxidative killing.

Oxidative killing basically is as follows:
O2 yields superoxide (O2-) which react with myeloperoxidase = H2O2 (hydrogen peroxide)

In the presence of halides (bromide ions, chloride ions etc), acidic pH and myeloperoxidase this oxidises the the bug to death. The leftover superoxide ion is then removed by superoxide dismutase. Overall this is just nasty stuff.

INFLAMMATORY RESPONSE
This occurs due to tissue damage. In the short term this is good, long term bad.

When tissues are damaged, mast cells release histamine.
Histamine is:
1) chemotactic for PMNs and macrophages.
2) increases vascular permeability (i.e. vessels leak) which allows access for the plasma components.
3) increases vascular dilation (i.e. blood vessels get wider) which brings in ÒcoreÓ blood to the site.
4) constricts smooth muscles - compresses the area and prevent the bad guys from leaving.
5) causes pain due to promoting the influx of bradykinin

The four cardinal signs of inflammation are:
heat -increases blood flow
pain - caused by the pressure of plasma and cells, histamine also causes pain
swelling - volume of plasma, swollen vessels and cells
redness - increased flow

FEVER
The bodyÕs thermometer resides in the brain (hypothalmous). However, the brain responds to chemical stimuli that are released following certain infections. The obvious candidate is endotoxin (LPS from gram-negative bacteria) however certain lymphocytes release chemokines (sometimes called cytokines; e.g. interleukin-1) following phagocytosis. There are a few benefits of inducing a fever:
1) antibody production and T cell proliferation are better at high temperatures
2) all metabolic processes probably occur at a higher rate than at normal temperatures.

For summary see Figure 18:6).

Return to Bios 213 Home page
Return to Dr. Hill's Home Page
Return to the Biology Home page.