Associated with the skin are several accessory
structures which aid in this external protection. Hair, especially
that guarding the entrance to the nostrils and external ear canals, prevents
entry of foreign particles. Sebaceous (oil) glands
along the skin and associated with hairs secrete sebum, which is
composed of water, triglyceride fatty acids, salts, proteins, and cholesterol,
and is bacteriostatic. Ceruminous (wax) glands associated
with the external ear canal excrete secretions which mix with sebum to
form cerumin or ear wax, which traps bacteria and also inhibits their growth.
Sweat glands secrete a combination of water, sodium chloride, and
metabolic waste products which inhibit the growth of non-normal microflora
(some normal flora thrive on certain sweat secretions such as those produced
by the apocrine sweat glands associated with hairs of the armpits and groin
of adults and pubescent teens, and their metabolism of these compounds
intensifies body odor associated with such bodily areas).
The molecules responsible for humoral immunity to disease are called immunoglobulins, also known as antibodies. Antibodies are proteinaceous cell markers which differ from other receptor site proteins, in that they have the ability to detach themselves from the cells which produce them and circulate independently throughout the fluid compartments of the body. Some have the ability to be secreted across membranes, which allows them to confer protection to external body surfaces, or to pass through the placental barrier to provide protection to a developing fetus, while others are relatively large and incapable of migrating out of the bloodstream.
The basic immunoglobulin structure consists of four protein chains, two light chains and two heavy chains, bound to one another by sulfide bonds. At the distal end of the light/heavy chain pairs are areas called variable regions, which have an affinity for specific antigenic determinants. Antibodies which are unbound to antigens have a Y-shape, due to the conformation of light and heavy protein chains, but these can assume a T-shape when attached to two separate antigens expressed by two separate cells or particles by bending at the hinge region of the molecule. At the base of the heavy chains is an area called the constant (Fc) region which can bind to other antibodies, or serve as a binding site for the receptor proteins on a wandering macrophage, mast cell, basophil, or lymphocyte. During the phenomenon called opsonization, an antibody which has attached itself to an antigenic determinant can "lead" a macrophage to the cell or molecule expressing the antigen and facilitate phagocytosis. Some antibodies also have complement binding sites, which enhances their ability to inactivate and kill foreign cells.
There are five major classes of immunoglobulins:
Immunoglobulin G (IgG) is found in the greatest concentration in the blood and other fluids of the body, accounting for over 80% of all of the circulating immunoglobulins. IgG has two variable regions, complement-binding sites, and can promote opsonization. It functions as an agent of agglutination (clumping of cells or particles bound by antibodies), precipitation (causing clumped antigens to condense and fall out of serum), complement fixation and cell lysis, and as an antitoxin, by binding to exotoxin epitopes to neutralize them. It can cross the placental barrier and is present in colostrum and breast milk, so it provides the developing fetus and newborn infant with a measure of immune protection.
Immunoglobulin A (IgA) composes about 15% of the circulating antibodies in the system. IgA is a dimer, composed of two Y-shaped molecules joined by a secretory protein which allows it to be secreted on the surface of the epithelium. It can be found in saliva, tears, colostrum, breastmilk, and mucus, and functions in agglutination and precipitation.
Immunoglobulin E (IgE) has a structure similar to that of IgG, but is produced in extremely small quantities (0.002%). This immunoglobulin is often called reagin, because its primary function is in the elliciting the degranulation of mast cells and basophils in immediate-type hypersensitive reactions. This form of hypersensitive reaction occurs when small antigen molecules called allergens bind to the variable region of IgE when the antibody is concurrently bound by its Fc region to to a receptor site on a mast cell or basophil. The formation of this allergen-antibody-cell complex triggers degranulation and the release of histamines and leukotrienes which mediate the inflammatory response, which in this case generally exhibits itself as sneezing, watery eyes, running nose, or uticaria (hives).
Immunoglobulin D (IgD) is also a single molecule, and is found in very small (0.2%) concentrations. The real functions of IgD are not well understood, but since these molecules are generally observed to be bound to cells, it has been hypothesized that their function involves the regulation of the differentiation of immune cell types.
Immunoglobulin M (IgM) is the largest of the immunoglobulins, composing about 5% of the total quantity of circulating antibodies, and is the first circulating antibody to appear in the bloodstream following an initial infection, though its titer (concentration) soon drops as more IgG appears. It is a pentamer, composed of five subunits having the same basic structure as IgG. Because of its large size, IgM cannot cross membrane barriers, so it remains in the bloodstream. IgM functions in precipitation, agglutination, complement fixation and lysis,and opsonization. Since it has ten variable sites, IgM has very strong agglutination properties and is used in such in- vitro serological tests such as blood typing.
Immunoglobulins are produced by lymphocytes called B cells (the name comes from a structure called the Bursa of Fabricus located just superior to the cloaca of birds such as chickens). B cells, like all other formed elements (cells) of the blood, are derived from stem cells called hemocytoblasts in red bone marrow. These migrate to the lymphatic system to lymph nodes where they mature. On the surface of each pre-B lymphocyte are receptor sites composed of four polypeptide chains with two variable regions for the binding of antigenic determinants on the surface of antigens. While it is possible for some B cells to bind directly to antigens, most antigenic determinants must be first processed in the cytoplasm, then expressed on the outer surface of special antigen-presenting cells (APCs), such as wandering macrophages, fixed dendritic cells, and other B cells. APCs express processed antigens bound to their MHC proteins, where they deliver them to B cell receptors. There are two classes of MHC protein; MHC class I proteins bind antigens produced in cells, such as the early proteins of viral replication, and MHC class II proteins bind antigens made outside of cells, such as proteins produced by bacteria. APCs also produce chemical agents called interleukins, which stimulate division of activated lymphocytes.
When the cell comes in contact with a new antigen, it responds by differentiating into two types; B plasma cells which produce antibodies specific to the particular antigen and release these into the system, and B memory cells which do not produce antibodies, but retain the genetic memory of how to make the same specific type of antibody. B memory cells can circulate in the bloodstream or reside in the lymphoid tissue for long periods of time, until they are presented with the same antigen.
When this occurs, they differentiate and clone
new plasma and memory cells, increasing the titer of circulating antibodies
much more rapidly than when the original pre-B cell was first introduced
to the antigen. If the concentration of antibodies is graphed over
time for both differentation events, patterns emerge. These patterns
are called the Primary and Secondary Responses to infection
by the same antigen. Upon the first contact with a new antigen, the
primary response occurs. The bulk of circulating antibodies produced
are IgM, with fewer IgG. This response peaks fairly rapidly, then
subsides. On the second exposure to the same antigen, the secondary
response begins as memory cells differentiate, with the titer of circulating
antibodies increasing markedly over that of the primary response.
The bulk of produced antibodies in the secondary response, however, are
IgG, with fewer IgM. Any additional contact with the same antigen,
called shocking doses, triggers even greater antibody titers, insuring
that the antigen is quickly neutralized. The reason all reactions
to the same antigen following initial exposure are so rapid is called the
anamnestic response, meaning the ability of the B memory cell to retain
Several cell types are responsible for the
cell-mediated immune response.These can be separated from one another on
the basis of a group of peripheral proteins on the cell membrane called
cluster of differentiation (CD) markers.
Natural killer cells (N-K cells) are not Tor B lymphocytes and have
no CD markers. They target and destroy host cells which have been invaded
by viruses, so they are generally considered to be part of the nonspecific
defense against infection. N-K cells can locate these specific cells, since
they usually express viral antigens on their cell membranes once infection
has occurred. CytotoxicT cells have CD8 markers and kill any
cell expressing foreign antigens, such as cells which have been invaded
by viruses, cellular parasites, and cancer cells. They also produce
lymphokines such as perforin, which lyse target cells, and interferon
to block transcription of viral mRNA. T memory cells retain
genetic information about specific antigens. They, like B memory
cells, can differentiate into other T cell types upon exposure to an antigen
delivered by an APC. Delayed-type hypersensitivity cells (DHC)
have CD4 antigens and produce chemotactic compounds and lymphokines such
as macrophage arming factor (MAF) and specific macrophage
activating factor (SMAF) which lead macrophages to the site of an
antigen and elicit inflammation. The activity of DHC cells is responsible
for delayed hypersensitive reactions such as contact dermatitis
caused by exposure to chemicals such as urushiol found in the leaves of
plants such as poison ivy (Toxicodendron radicans), soaps, detergents,
and makeup. T helper and T suppressor cells
regulate the activities of other specific immune cell types. T helper
cells have CD4 antigens, and they activate B and T lymphocytes, while T
suppressors have CD8 antigens and suppress or slow lymphocyte activity,
thus reducing the risk of potential autoimmune disease.
1. Attenuated vaccines, produced by removing the virulence factors of an microorganism, then injecting the active agent into the body. Examples include the vaccinations for small pox, polio (Sabin oral form), measles, mumps, and yellow fever.
2. Killed or inactivated vaccines such as polio (Salk injection), influenza A virus, rabies, cholera (Vibrio cholera), bubonic plague (Yersinia pestis), typhoid fever (Salmonella typhi), and MMR (measles, mumps and rubella viruses).
3. Recombinant vaccines produced by genetic engineering, such as the Hepatitis B vaccine.
4. Toxoid (antitoxin) vaccines composed of denatured toxins, including those diptheria (Coynebacterium diptheriae), pertussis (Bordetella pertussis), and tetanus (Clostridium tetani; combined they are called DPT), spiders, snakes, scorpions, and centipedes.
5. Component vaccines composed of parts or fragments of
cells containing specific antigens, such as pneumovax
(23 capsular antigens of different strains of Streptococcus pneumoniae),
meningiococcal meningitis vaccine (Neisseria meningitidis) and Hib
1. Skin, mucus membranes, and chemical defenses all make up ______________
2. __________ defenses are based in the body fluids, and are due to the activity of antibodies.
3. Whole, infected cells are destroyed by the ___________ __________ immune response.
4. The living layer of cells which gives rise to the epidermis is called the _____________.
5. Two external chemical agents which limit bacterial growth are __________ and __________.
6. __________ cell produce mucus which lines the external surface of the upper respiratory tract.
7. The combination of mucus-producing cells and cilialted
epithelium of the upper respiratory tract
is called the __________ __________.
8. __________ are enzymes found in lacrimal fluid, saliva, nasal mucus, and sweat.
9. __________ are synthesized from plasma proteins and serve to stimulate pain receptors.
10. Eosinophils and monocytes release __________ __________ which
raise body temperature.
The major formed elements of blood, including red blood cells and leukocytes are derived from undifferentiated
_______________ found in red bone marrow. The two major categories of leukocytes are __________ and __________.
Granulocytes such as __________ release chemical mediators of inflammation, such as kinins, prostaglandins, and
__________ which trigger vasodilation and smooth muscle contraction, while __________, the most common type of white
blood cell, are actively phagocytic and can undergo diapedesis to reach a site of injury from the bloodstream. Agranulocytes
include __________ cells which actively secrete antibodies, and __________ cells, which function in the cell-mediated
II. Critical Thinking
1. An individual picks up a splinter in her foot. Describe
the process of inflammation which occurs
after this injury.
2. Compare and contrast the terms antigen and allergen.
3. What is immunological tolerance, and why is it important to
the body's defense against infection?
4. In the primary immune response, more IgM is produced than IgG,
but in the secondary response,
the opposite is true. Why is this so?
5. How does the HIV virus suppress the activity of the entire
6. Why do hypersensitivity reactions occur?