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The internal environment of animals provides attractive conditions for the growth of bacteria,
viruses, and other organisms. Although some of these organisms can live symbiotically within
animals, many either cause destruction of cells or produce toxic chemicals. To protect against
these foreign invaders, humans possess three levels of defense.
The skin and mucus membranes provide a nonspecific first line of defense against invaders
entering through the skin or through openings into the body. A nonspecific defense is not specialized
for a particular invader. Rather, it is a general defense against all kinds of pathogens.
The first line of defense features the following characteristics:
1. Skin is a physical and hostile barrier covered with oily and acidic (pH from 3 to 5) secretions
from sweat glands.
2. Antimicrobial proteins (such as lysozyme, which breaks down the cell walls of bacteria)
are contained in saliva, tears, and other secretions found on mucus membranes.
3. Cilia that line the lungs serve to sweep invaders out of the lungs.
4. Gastric juice of the stomach kills most microbes.
5. Symbiotic bacteria found in the digestive tract and the vagina outcompete many other organisms
that could cause damage.
The second line of defense involves several nonspecific mechanisms, as follows:
1. Phagocytes are white blood cells (leukocytes) that engulf pathogens by phagocytosis.
They include neutrophils and monocytes. Monocytes enlarge into large phagocytic cells
called macrophages. Other white blood cells called natural killer cells (NK cells) attack
abnormal body cells (such as tumors) or pathogen-infected body cells.
2. Complement is a group of about twenty proteins that “complement” defense reactions.
These proteins help attract phagocytes to foreign cells and help destroy foreign cells by
promoting cell lysis (breaking open the cell).
3. Interferons are substances secreted by cells invaded by viruses that stimulate neighboring
cells to produce proteins that help them defend against the viruses.
4. The inflammatory response is a series of nonspecific events that occur in response to
pathogens. When skin is damaged, for example, and bacteria or other organisms enter the
body, the following events occur:
• Histamine is secreted by basophils, white blood cells found in connective tissue.
• Vasodilation (dilation of blood vessels), stimulated by histamine, increases blood
supply to the damaged area and allows for easier movement of white blood cells (and
other body fluids) through blood vessel walls. This also causes redness, an increase
in temperature, and swelling. The increase in temperature, like a fever, may stimulate
white blood cells, and they may make the environment inhospitable to pathogens.
• Phagocytes, attracted to the injury by chemical gradients of complement, arrive and
engulf pathogens and damaged cells.
• Complement helps phagocytes engulf foreign cells, stimulate basophils to release
histamine, and help lyse foreign cells.
The immune response is the third line of defense. It differs from the inflammatory response in
that it targets specific antigens. An antigen is any molecule, usually a protein or polysaccharide,
that can be identified as foreign. It may be a toxin (injected into the blood by the sting of
an insect, for example), a part of the protein coat of a virus, or a molecule unique to the plasma
membranes of bacteria, protozoa, pollen, or other foreign cells.
The major histocompatibility complex, or MHC, is the mechanism by which the immune
system is able to differentiate between self and nonself cells. The MHC is a collection of glycoproteins
(proteins with a carbohydrate) that exists on the membranes of all body cells. The proteins
of a single individual are unique, originating from twenty genes, each with more than fifty
alleles each. Thus, it is extremely unlikely that two people, except for identical twins, will possess
cells with the same set of MHC molecules.
The primary agents of the immune response are lymphocytes, white blood cells (leukocytes)
that originate in the bone marrow (like all blood cells) but concentrate in lymphatic tissues such
as the lymph nodes, the thymus gland, and the spleen. The various kinds of lymphocytes are
grouped as follows:
1. B cells. These are lymphocytes that originate and mature in the bone marrow (remember
B cell for bone). B cells respond to antigens. The plasma membrane surface of B cells is
characterized by specialized antigen receptors called antibodies. Antibodies have the
following properties:
• Antibodies are proteins.
• Each antibody is specific to a particular antigen.
• There are five classes of antibodies (or immunoglobulins): IgA, IgD, IgE, IgG, IgM.
Each class is associated with a particular activity.
• Each class of antibodies is a variation of a basic Y-shaped protein that consists of
constant regions and variable regions. The variable regions are sequences of amino
acids that differ among antibodies and give them specificity to antigens.
• Antibodies inactivate antigens by binding to them. Inactivation is followed by
macrophage phagocytosis. In addition, by binding to surface antigens of nonself
cells, antibodies stimulate complement proteins to bring about the lysis of pathogens.
When B cells encounter antigens that specifically bind to their antibodies, the B cells proliferate,
producing two kinds of daughter B cells, as follows:
• Plasma cells are B cells that release their specific antibodies which then circulate
through the body, binding to antigens.
• Memory cells are long-lived B cells that do not release their antibodies in response
to the immediate antigen invasion. Instead, the memory cells circulate in the body
and respond quickly to eliminate any subsequent invasion by the same antigen. This
mechanism provides immunity to many diseases after the first occurrence of the
disease.
2. T cells. T cells are lymphocytes that originate in the bone marrow, but mature in the thymus
gland (T cell for thymus). Like B cells, the plasma membranes of T cells have antigen
receptors. However, these receptors are not antibodies, but recognition sites for
molecules displayed by nonself cells. Self and nonself cells are distinguished as follows:
• The MHC markers on the plasma membrane of cells distinguish between self and
nonself cells.
• When a body cell is invaded by a virus, by a foreign cell, or by any antigen, the body
cell displays a combination of self and nonself markers. T cells interpret this aberrant
display of markers as nonself.
• Cancer cells or tissue transplant cells, or other cells that display aberrant markers, are
recognized as nonself cells by T cells.
When T cells encounter nonself cells, they divide and produce two kinds of cells, as
follows:
• Cytotoxic T cells (or killer T cells) recognize and destroy nonself cells by puncturing
them, thus causing them to lyse.
• Helper T cells stimulate the proliferation of B cells and cytotoxic T cells.
When an antigen binds to a B cell or when a nonself cell binds to a T cell, the B cell or T cell
begins to divide, producing numerous daughter cells, all identical copies of the parent cell. This
process is called clonal selection, since only the B or T cell that bears the effective antigen receptor
is “selected” and reproduces to make clones, or identical copies of itself. Clonal selection
results in a proliferation of B cells and T cells that will engage a specific, invading antigen.
The responses of the immune system are categorized into two kinds of reactions, as follows:
1. The cell-mediated response uses mostly T cells and responds to any nonself cell, including
cells invaded by pathogens. When a nonself cell binds to a T cell, the T cell undergoes
clonal selection, initiating the following chain of events.
• T cells produce cytotoxic T cells. These cells destroy nonself cells.
• T cells produce helper T cells.
• Helper T cells bind to macrophages. Macrophages that have engulfed pathogens
display aberrant plasma membrane markers. Helper T cells identify these marker
combinations as nonself and bind to these macrophages.
• Helper T cells produce interleukins to stimulate a proliferation of T cells and B
cells. When helper T cells bind with macrophages, they release interleukins, or communication
chemicals “between leukocytes.” The interleukins initiate a sequence of
positive-feedback events that result in the proliferation of interleukins, macrophages,
helper T cells, B cells, and cytotoxic T cells.
2. The humoral response (or antibody-mediated response) involves most cells and responds
to antigens or pathogens that are circulating in the lymph or blood (“humor” is a
medieval term for body fluid). It includes the following events:
• B cells produce plasma cells. The plasma cells, in turn, release antibodies that bind
with antigens or antigen-bearing pathogens.
• B cells produce memory cells. Memory cells provide future immunity.
• Macrophage and helper T cells stimulate B cell production. In many cases, the
antigen will not directly stimulate the proliferation of B cells. Instead, the antigen or
antigen-bearing pathogen must first be engulfed by a macrophage. T cells then bind
to the macrophage in a cell-mediated response. Interleukins secreted by the helper T
cells stimulate the production of B cells.
Humans have learned to supplement natural body defenses. Three important approaches
follow:
1. Antibiotics are chemicals derived from bacteria or fungi that are harmful to other
microorganisms.
2. Vaccines are substances that stimulate the production of memory cells. Inactivated viruses
or fragments of viruses, bacteria, or other microorganisms are used as vaccines. Once
memory cells are formed, the introduction of the live microorganism will stimulate a swift
response by the immune system before any disease can become established.
3. Passive immunity is obtained by transferring antibodies from an individual who previously
had a disease to a newly infected individual. Newborn infants are protected by passive
immunity through the transfer of antibodies across the placenta and by antibodies in
breast milk. | 
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