Immune system.
A fairly complex system. We'll try to keep thing simple.
An immune response (a response to a pathogen) can be of two types:
(pathogen - disease causing organism)
1) Non specific. Anything foreign is attacked.
2) Specific. The immune system attacks only one kind of pathogen.
I. Non-specific defenses.
- skin: acts as a barrier, also secretes acids that inhibit bacteria.
- body fluids: sweat, saliva, tears, all contain anti-microbial enzymes
- stomach acid: kills many bacteria
- mucous membranes in nose and trachea trap many pathogens.
If something does get through, the first line of defense is generally an inflammatory
response:
tissue damage --> histamine is released by damaged cells --> dilates blood vessels
--> blood flow to the damaged area increases --> increasing number of
phagocytes show up.
Phagocytes engulf (“eat”) bacteria and damaged cells. They disinfect the area.
In the process, they often die and contribute to the pus found in inflamed areas.
This inflammatory response can be more widespread:
- bacteria in blood stream can cause overall increases in phagocytes.
- fever can sometimes slow bacterial growth, though if too high this is
dangerous.
- immune system can be overwhelmed and respond massively, generating
septic shock (a common cause of death in hospitals).
Other nonspecific responses include:
- release of interferon (inhibits viral replication)
- a cell infected with a virus makes interferon. This triggers
proteins in other cells that slow viral replication.
- complement proteins - interact with microbes or the immune system.
- mark surfaces of microbes so that phagocytes can get them easier.
- sometimes cut holes in microbial membranes, killing or
weakening the microbes
. Lymphatic system
- in addition to moving interstitial fluid back to the heart (& circulatory system),
the lymphatic system also helps remove pathogens.
- lymph nodes are packed with lymphocytes & phagocytes
- these can filter the fluid, attack bacteria & viruses.
- attack can be specific or non-specific.
- efficient system since much fluid in the body is filtered this way.
II. Specific defenses
Some definitions:
antigen - a molecule (usually on the surface of a bacterium or virus) that causes an
immune response.
An antigen may have several different “antigenic determinants”. These
are areas that antibodies can bind to.
antibody - a protein that attaches to a specific antigen (antigenic determinant).
Lymphocytes:
Two types (both originate in the bone marrow):
B-cells: continue ti develop in bone marrow. They provide immunity
within body fluids.
T-cells: continue to develop in the thymus (exact process is not well
understood). They provide immunity to infected cells & help B-cells.
Both B & T cells have antigen receptors on their surfaces (think of these as
antibodies attached to the cell membrane). When mature, both move to the lymph
nodes.
Humans are thought to have over 100 million different antigen receptors.
Most are never needed.
- generally each cell has only one kind of antigen receptor.
B-cell defenses:
- B-cells congregate in lymph nodes.
- as an antigen comes along, some of the B-cells may bind to the antigen
(only if they have the correct antigen receptor).
- this triggers cell growth & differentiation.
- effector cells are made that start producing large amounts of
antibody specific to the antigen. A group of effector cells made
like this are referred to as clones. They usually do not survive
long.
- some cells are converted into memory cells that can respond
much faster should the body be exposed to the same antigen in the
future.
- The first time B-cells are exposed, the immune response can be slow and
not very strong.
- But memory cells are now in place, and if the same antigen comes along
again, they can multiply very quickly and produce large amounts effector
cells quickly (a second clone).
Antibodies:
- antibodies have a variable end (specific to antigen determinants) and a
constant end.
- the variable end binds to the antigen (i.e., virus, bacteria, parasite). This
can have four possible consequences.
1) Virus or bacterium is coated with antibodies. This can prevent
the virus or bacteria from attaching to other cells.
2) Since antibodies are Y-shaped, they can bind to more than one
virus or bacterium. This causes them to clump together. This
makes it easier for phagocytes to capture them.
3) Antigen molecules can precipitate out. They’re no longer
dissolved in the body fluids, and so are easier for phagocytes to
capture.
4) Antibodies activate component proteins (from above). These
cause holes in the bacterial membrane and kill it.
- also, depending on the type of constant end, the constant end is more
easily recognized by phagocytes (so if antibodies are attached to bacteria,
these are more easily recognized).
T-cell defenses:
- fight against pathogens that have already entered cells of the body (&
help B-cells).
- Two types of T-cells:
- Cytotoxic: attack infected body cells.
- Helper T-cells: activate cytotoxic T-cells, phagocytes, & help
stimulate B-cells to make antibodies.
Suppose a phagocyte (macrophage) engulfs a microbe.
- It may become an APC (antigen presenting cell).
- exactly what it says. It presents the antigen to the helper
T-cell.
- It combines the antigen with it’s own surface proteins in
something known as the self-nonself complex (it’s a
combination of it’s own proteins (self) and the antigen
(non-self)).
- This is recognized by the helper T-cell. The helper T-
cells then does three things.
1) makes more helper T-cells of the same kind.
- including memory T-cells.
2) activates cytotoxic T-cells (for that antigen).
3) activates B-cells (for that specific antigen).
Cytotoxic T-cells
- attack cells in the body that are infected. An infected cell will
have a self-nonself complex on it’s surface.
- This is recognized by the cytotoxic T-cell.
- the cytotoxic T-cell releases perforin, which punctures the
infected cell membrane which is then destroyed.
- appear to function against many kinds of cancers as well (cancers
are abnormal body cells that keep dividing).
III. Miscellaneous topics:
The immune system recognizes self vs. non-self. Anything that isn’t “self” may be
attacked.
- this is the problem with many organ transplants.
Even so, the immune system will sometimes run haywire:
Diabetes (type I) results when the immune system destroys insulin producing cells
(the beta cells in the pancreas).
Multiple sclerosis results when the myelin sheath of the nervous system is
attacked (destroys nerve cell function).
Rheumatoid arthritis - joints are attacked by the immune system.
- the list is endless.
At the other extreme, the immune system can overreact to essentially “harmless” antigens
Allergies are caused by histamines being released in response to things like pollen
or dander.
For example, antibodies for pollen attach to mast cells (cells that make histamine).
When these cells encounter an antigen (pollen in this case), histamine is released
and can cause symptoms related to allergies (itching, sneezing, etc.).
Anaphylactic shock can result in extreme cases (causes massive dilation of blood
vessels, precipitous drop in blood pressure, and even death).
Let's look at our first human diseases:
Sleeping sickness or Trypanosoma brucei
- One reasons why some parts of Africa are still wild.
- People won't enter areas where sleeping sickness is endemic (kills people and
livestock).
- Transmitted by the bite of the tsetse fly.
- Symptoms include high fever, swelling of lymph nodes, headaches, itching (much of
this is actually caused by the immune system reaction to the parasite).
- Eventually, the nervous system becomes more involved - slurred speech,
slowing of mental processes, prolonged periods of sitting and staring, sleeping.
- Untreated, usually leads to death.
- Treatments are extreme, and involve administration of various toxic compounds (often
containing arsenic) and the hope that the parasite is killed before the patient.
Circumvents immune system as follows:
- Worm presents antigen to immune system
- Immune system reacts normally, and parasite is attacked
- After parasite levels drop, parasite presents a different antigen to the immune
system
- Levels of parasite climb again, until immune system responds to this new
antigen
- Worms have a repertoire of over 1000 different antigens that they can present to
the immune system.