The War Within: A Look at the Immune System
I. The First Line of Defense
- "the moat around the castle"
A. General characteristics
This provides a barrier to the entry of an invader, just like a
moat around a castle protected the occupant from the barbarians. There are two major features: (1) it is non-specific. In other words,
it doesnt respond to a specific pathogen, rather, it is a generalized response; and
(2) it is an external defense mechanism, that is, one that deters the entry of the invader
into body. Characteristic of all animals; in some, it is their only line
of defense against pathogens.
B. Examples. There are a variety of mechanism that prevent pathogen
entry into the body. These include:
- Intact skin and mucous membranes
- Lysozyme - enzyme in secretions like tears and saliva; digests microbial cell walls.
This is somewhat analogous to filling the moat with acid.
- Ciliated cells - sweep away invaders, block entry
- Gastric juices - harsh, acidic environment - more acid in the moat
- Normal microflora out-competes invader - putting microbes to work for us.
- Lactic acid - sebaceous glands in skin
- Desquamation of skin cells - in other words, skin cells slough off,
"washing off" pathogens
- Hairs - block entry
- Saliva, tears, sneezing - wash out invaders
- Anaerobic bacteria - reduce oxygen levels, produce lactic acid
C. Back-up system
Pathogens that make it past the "first line" are confronted
by additional lines of defense (some are general and others specific to the type of the
II. Innate Immunity - a second line of defense - responds to internal threats; more specific
A. Cellular defenses - occur in blood and lymph. These are derived from stem cells in
Make up 60-70% of white blood cells, amoeboid, follow
- Macrophages & Dendritic cells
Amoeboid with distinct pseudopodia; phagocytic cells.
many "loiter" in organs where invaders come to them. These are antigen presenting cells
- which essentially "advertises the kill" to other components of
the immune to get ready for possible attack.
- Neutrophils and macrophages together comprise the
Approx. 1.5% of white cells; limited phagocytic activity; these cells are
granulated contain grains with digestive enzymes which are released on contact with an
invader. Especially involved in fighting large parasites.
- Natural Killer Cells
Destroy the bodies own infected cells
B. Antimicrobial Proteins
Secreted from virus-infected cells; there are three types alpha, beta and
gamma; interferons ultimately interfere with the further spread of virus. Interferon
stimulates other cells to produce proteins to inhibit viral replication. Interferon also
activates natural killer cells that destroy viral-containing cells.
Regulates various cells of the immus system.
Secreted by macrophages and leucocytes.
- Tumor Necrosis Factor (TNF)
Kills tumor cells, stimulates inflammatory response.
- Complement system
Group of about 20 blood proteins; inactive initially, become
activated when bind to antibody bound to antigen. Once activated, this system is
responsible for: (a) releasing chemicals to attract phagocytes; (b) bind to surface of
invader to target for removal by phagocytosis (macrophages); and (c) induce lysis of
C. Inflammatory Response
Triggered by tissue damage. Injured cells (basophils) release histamine
which: (1) dilates blood vessels → increases blood flow → heat,
redness, increased numbers of phagocytic cells; and (2) increases capillary permeability
→ release of fluid and white blood cells into interstitial fluid →
swelling (edema), phagocytosis, clotting
Interleukin-1 released by macrophages and other cells.
Rests temperature in hypothalamus.
III. Acquired Immunity - another line of
defense - Cells of the Immune System
A. Immunology is the study of disease resistance.
The job of the immune system is to: (1) recognize self vs. non-self (an
invader); and then (2) inactivate, remove or destroy the invaders. This is an example of a
very specific defense.
B. Immunity is acquired by:
- previous exposure (by accident or
vaccination) to a particular antigen (active immunity); or
- mother to child transfer
through milk or placenta (passive immunity); or
- receiving antibodies from others
(i.e., rabies; passive).
C. MHC (major histocompatibility
Marker proteins occur on the
surface of cells. These are unique for each individual. The Class I MHC are located on all
nucleated cells, important in self vs. non-self recognition; class II MHC are on immune system
cells; class III MCH - involved in complement system. The immune system ignores cells
with these markers.
D. Two main components to the immune system:
- Humoral response - circulation of free antibodies; destroys free (not inside a cell)
pathogens; extracellular. Named because it is associated with the "humors"
- Cell-mediated immunity - destroys cells containing intracellular pathogens (and
transplanted tissues, cancer cells).
These are large molecules that initiate an immune response. Most are
proteins (or large polysaccharides). They are called antigens because they are
Antibodies are proteins (actually glycoproteins). Specifically, they are
examples of immunoglobulins (Ig). All are basically Y-shaped molecules made
of four polypeptide chains, 2 light and 2 heavy, that are held together by
disulfide bonds. There are variable (V region) and constant (C region)
regions in both chains. The constant regions are the same for all antibodies
in a particular class. The variable region differs for every different
antibody, of which there are countless numbers. The ends of the arms of the
"Y" are sites for binding antigen. The base of the Y binds to B cells.
There are 5 different classes based on their general molecular structure:
IgG, IgM, IgA, IgD, IgE. They differ in the C region and have slightly different functions (i.e., IgA - is involved in allergic
responses and IgE with histamine-secreting cells).
Antibodies recognize specific antigens. They can: (1) neutralize the antigen
directly (i.e., when bind to a toxin or flu virus); or (2) target an antigen for
elimination by complement system or phagocytes.
- Antibodies are produced by B cells.
- B cells make about 1015 different antibodies. These are coded by a limited number
of genes which randomly make different polypeptide chains resulting in many
kinds of antibodies.
Main cell of the immune system; develop in bone marrow. They are
concentrated in lymph nodes and other organs. They have cell surface receptors to detect
antigens. There are two types of lymphocytes:
- B lymphocytes
Mature in the BONE marrow, involved in humoral immunity (antibody-mediated), antibody
producing. Antibodies stick out from cell surface. Types:
virgin B cells - not yet
activated to produce antibodies;
plasma cells - B cells activated to produce antibody;
memory B cells (continue to produce antibody long after exposure).
These are antigen presenting cells (APC)
- T lymphocytes
Mature in the THYMUS, involved in cell-mediated immunity. Functioning in
recognizing between self and no-self. They have a R cell antigen receptor (TCR).
- helper T's - master switch, the
"commanders" of the immune system; CD4 receptor; they stimulate division of B cells and
cytotoxic T cells;
- cytotoxic T's - destroy infected cells, cancer cells; CD8 receptors; and
- suppressor T's - controls/slows immune response.
IV. The immune system in action
Scenario - let's imagine that the hepatitis A virus has
breached our first wall of defense and is intent on attacking our liver.
- Macrophages engulf virus. However, some virus makes it to the liver and infects the
- Macrophages that have phagocytized the virus, transport pieces of the virus (antigens)
to the cell surface where they bind to MHC II markers. This results in an
complex which advertises the kill to other immune system cells. This
macrophage is now considered to be an "antigen presenting cell".
- Antibodies sticking out from the surface of virgin B cells (those not previously exposed
to antigen) bind to some of the virus. Binding of the virus antigens to the surface of the
B cell "activates" the B cell. The B cell responds by transporting virus antigen
that it has engulfed to the cell surface where it combines with the MHC II complex. Thus,
the B cell is now an "antigen presenting cell" and it will respond to stimuli
from helper T cells.
- The "antigen-presenting" macrophages activate helper T cells by: (a) secreting
interleukin-1 (cytokines); and (b) binding with helper T cells. The helper T cells bind to
the antigen-MHC II complex on the macrophage cell surface. The interaction between the MHC
II - antigen complex and the T helper cells is facilitated by another surface marker
- In response to activation, the helper T cell begins to: (a) proliferate;
and (b) secrete its
own cytokines (interleukin-2).
- Interleukin-2 secreted by activated helper T cells causes "previously
activated" B cells to start dividing to yield a populations of B cells that (a)
produces more antibodies (plasma cell; antibody factories) and (b) remember the invader
for subsequent action (B memory cells).
- Interleukin-2 secreted by activated helper T cells stimulates other helper T cells to
grow and divide more rapidly (positive feedback).
- The activated helper T cells: (a) divide to produce other T cells (including
memory T cells and cytotoxic T cells; and (b) activate cytotoxic T cells (using interleukin and other
cytokines). The cytotoxic T cells then bind with an antigen-MHC I complex. Thus, this
targets the bodies own cells which are infected with antigen for disposal (like infected
liver cells, which move the virus antigen to the cell surface). Cytotoxic T cells release
perforins (proteins that punch holes in cells causing them to lyse). Another cell surface
molecule, CD8, helps the T cell in its interaction with the MHC I-antigen complex on the
V. Secondary response - much quicker because of memory cells
- Introduce killed or weakened (attenuated) pathogen (i.e., anthrax)
- Introduce closely related pathogen with same antigens (i.e., cowpox/small pox)
- Move the antigen-encoding genes into an innocuous virus and introduce that
- Purify antibody from other source and inject them; doesn't last. Tetanus and rabies are
good examples, hence regular boosters. Another source of antibody is mother to offspring
transfer thru milk or placenta.
VII Immune system problems
- Allergies - recognize antigens on pollen, etc., stimulates production of histamines,
- Autoimmune disorders - attack your own cells (i.e., rheumatoid arthritis, SCID)
- Immunodeficiency - cell mediated response is weakened (i.e., HIV/AIDS)
Last updated: May 04, 2007
� Copyright by SG Saupe