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HOW
THE IMMUNE SYSTEM WORKS
A very basic primer
A healthy body has a very sophisticated system--the immune system--to constantly guard
against infection. This system developed over millions of years as an adaptation for our species
to survive in a world that is teeming with microorganisms (bacteria, viruses, fungi, and parasites).
Some microorganisms, called human pathogens, are particularly adept at evading
the human immune system and causing disease.
This is especially true when we have not previously encountered the pathogen. The role of vaccination is to stimulate the immune
system into action, without causing the health effects--such as illness, disability, or
death--that the pathogen causes. So, to understand immunization, it helps to understand the immune
response. Doctors must take lengthy courses to understand this process, so keep in mind that the
description below represents just the basics. We are presenting it as a very orderly process when
in fact, immune response may not always occur in a neat, orderly progression. Also, some cells
play many roles in the immune system in addition to the roles described here.
Before a microorganism can enter the body, it must first get past
some natural barriers that work against it. In the respiratory tract, for example, cilia (fine,
hair-like projections) are in constant motion, moving mucus and contaminants upward and out of the
respiratory tract, preventing them from lodging in the lungs and causing problems. Some viruses,
such as the common cold, don't even bother to run this obstacle course: They simply pause at the
lining cells of the nose and sinuses and cause misery there.(3)
Some components of saliva and acid in the stomach provide an unwelcoming environment for
disease-causing agents;(4) however, polio can survive even this,
travelling through the gastrointestinal tract and then settling in the spinal cord to reproduce.(5)
Once a virus or bacterium manages to get beyond the initial barriers,
it is confronted by macrophages, specialized cells that are produced in the bone marrow.
Macrophages circulate constantly in the bloodstream to guard against harmful substances.(6) When these nosy little cells encounter foreign substances, they
ask, with the biochemical equivalent of a sentry, "Who are you? Why are you here?" This
confrontation may occur at the site of entry (for example, an open wound), or the substance may be
carried to the nearest lymph nodes,(7) which serve as filters,
clearinghouses, and powerhouses in the immune system.
If the substance is recognized as one that does not pose a threat,
the macrophage goes on its way. But sometimes the macrophage can be tricked. Some infectious
agents have developed the ability to get past macrophage inspections by disguising themselves or
by hiding: for example, inside red blood cells. Others have material on their cell surfaces that
resembles human tissue closely enough to fool the macrophage "sentry" into thinking that
the substance is "self." Sometimes the success or failure of an infectious agent depends
on being able to hide from macrophages long enough to dig in and begin reproducing.(8)
If a never-before-encountered bacteria gets into the body, a highly
specialized white blood cell, the polymorphonuclear leukocyte (PMN), is called in by biochemical
messengers to kill the invader. The big name of this cell refers to its segmented nucleus, which
makes it possible for the PMN to squeeze between the cells that cover and protect each organ.
Because they can do this, PMNs can reach the location of infection, even if the bacteria are deep
within the kidneys, pancreas, or other organs.(9) PMNs are hard
workers and they are very tidy. They completely engulf offending bacteria to digest them, and in
the same manner, scoop up and destroy any debris they encounter.(10)
Ironically, the substances produced by PMNs can make us feel sick, and the powerful biochemicals
that are produced to activate PMNs and other agents of the disease-fighting process ultimately
destroy PMNs, which do not have a very long life.(11)
If a macrophage encounters a virus, a similar process occurs. A
biochemical alarm is sent out, and the process of cell-mediated immunity--resistance to disease,
with various types of cells acting as traffic directors in the process--is initiated. The virus is
passed to a helper T cell (T cells are made in the thymus), where it is checked out once again. B
cells (which originate in bone marrow) are also called to the scene. T and B cells have a kind of
checklist of substances that they have encountered in the past. This checklist appears as
receptors on the surface of the cells. A virus or other substance that cannot fit exactly right
with these receptors, like a key in a lock, are considered unwelcome and dangerous invaders. The T
or B cell commits the genetic identification of the invader to the immune system's memory, so that
this particular invader will be banned for a very long time, in many cases, throughout life.(12)
If the immune response is no longer functioning well (for example,
because of AIDS, other disease, or treatment with certain powerful drugs), viruses, bacteria, some
fungi, and parasites have a greater opportunity to invade and multiply, causing illness.
Once the T cell perceives that an invader is foreign, a biochemical
signal spurs B cells to manufacture a protein(13)--an antibody--that
is tailored specifically for that substance. B cells with the formula for this protein remain in
circulation, or are stored in the bone marrow, in some cases throughout life. If the threatening
agent, called an antigen, shows up again, the B cells with the formula are called into action.
They divide into new B cells(14) that can produce the unique
antibodies needed to fit with the antigen and destroy it.(15)
Another segment of the immune system, the complement system (essentially, a collection of
proteins) is called in to amplify the work of the antibodies, so that destruction of the antigen
is complete. Capillaries (the smallest blood vessels) help by becoming more permeable and speeding
the flow of leukocytes (white blood cells) and other helper substances into the vicinity of the
attack.(16)
As Richard Hong, M.D., Professor of Pediatrics at the University of
Wisconsin reports, our bodies are capable of reacting against more than a million antigens, and
therefore, "...the immune response is inordinately complex and an appropriate response
requires an extremely well-coordinated cellular apparatus. It is impossible to survive if a
significant deficiency of T- and B-cells exists."(17) This is
why the disease AIDS is so deadly. HIV, the virus that causes AIDS, disrupts immunity. Among its
effects, it reduces the level of CD4 T cells from more than 1,000 (normal level) to 200 or less.
In fact, a level of 200 CD4 T cells is one of the defining features of AIDS. During the course of
the disease, levels dip much lower.
An important feature of the immune system is that it can weaken with
age, resulting in a greater risk of certain diseases.(18) This is
one reason why pneumococcal pneumonia is more likely in an older person than a young person.(19) Some diseases, such as influenza and pneumococcal disease, can
be more dangerous in older people because of existing heart or circulatory problems, diabetes, or
other conditions that are worsened by the disease or make it more difficult to overcome.
If the same organism has the audacity to show up again, however, the
antibodies promptly attach to the organism, and as one would expect from a good bodyguard,
"pins it to the wall," allowing macrophages or PMNs to inactivate and destroy it.
Immunization is a method of working with nature to preserve health.
It is a procedure in which weakened or killed forms of the disease-causing agent are administered.
Immunization activates the immune response, including production of antibodies, just as if you had
the disease but without having the degree of discomforts and risks associated with the disease. If
you have had measles, mumps, or rubella, a blood test would undoubtedly reveal that you have
antibodies to these diseases in your bloodstream, even many years later. If you have a measles,
mumps, or chicken pox vaccination, you develop the same antibodies, but you avoid the risks that
accompany the disease.
For a more complete explanation of how the immune system works, in plain language and with
helpful illustrations, an excellent booklet titled Understanding Vaccines is available from the
National Institutes of Health, National Institute of Allergy and Infectious Diseases.
You can obtain a copy by letter, by e-mail, or online.
- Write to NIAID at:
Office of Communications and Public Liaison Building 31, Room 7A-50 31 Center Drive MSC 2520
Bethesda, MD 20892-2520
- E-mail NIAID directly from its web site.
- View the booklet
online.
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Footnotes |
3. Kauffman RS, Fields BN. Chapter 10:
Pathogenesis of viral infections. In: Fields BN, Knipe DM, editors. Fundamental Virology.
NY: Raven Press, 1986:153-167.
4. Ganguly R, Waldman RH. Immunity to
infectious diseases. In: Waldman RH, Kluge RM, editors. Infectious Diseases. New Hyde Park,
NY: Medical Examination Publishing Co., 1984:28-44.
5. Kauffman RS, Fields BN. Chapter 10:
Pathogenesis of viral infections. In: Fields BN, Knipe DM, editors. Fundamental Virology.
NY: Raven Press, 1986:153-167.
6. Ganguly R, Waldman RH. Immunity to
infectious diseases. In: Waldman RH, Kluge RM, editors. Infectious Diseases. New Hyde Park,
NY: Medical Examination Publishing Co., 1984:28-44.
7. Ganguly R, Waldman RH. Immunity to
infectious diseases. In: Waldman RH, Kluge RM, editors. Infectious Diseases. New Hyde Park,
NY: Medical Examination Publishing Co., 1984:28-44.
8. Kauffman RS, Fields BN. Chapter 10:
Pathogenesis of viral infections. In: Fields BN, Knipe DM, editors. Fundamental Virology.
NY: Raven Press, 1986:153-167.
9. Kauffman RS, Fields BN. Chapter 10:
Pathogenesis of viral infections. In: Fields BN, Knipe DM, editors. Fundamental Virology.
NY: Raven Press, 1986:153-167.
10. Mandell GL, Bennett JE, Dolin R. Principles
and Practice of Infectious Diseases. 4th edition. Volume 1. New York: Churchill Livingston,
1995:34.
11. Graziano FM, Lemanske RF Jr. Clinical
Immunology. Baltimore: Williams & Wilkins, 1989:16-17.
12.Hong, R. Chapter 1: B and T lymphocytes. In: Graziano FM, Lemanske RF Jr. Clinical
Immunology. Baltimore: Williams & Wilkins, 1989:4-15.
13. Locksley RM, Wilson CB.
Cell-mediated immunity and its role in host defense. In Mandell GL, Bennet JE, Dolin R.
Principles and Practice of Infectious Diseases. 4th edition. Volume 1. New York: Churchill
Livingstone, 1995:102-149.
14.Atkinson W, Furphy L, Gantt J,
Mayfield M, Rhyne G. Epidemiology and prevention of vaccine-preventable diseases. 3rd edition.
Atlanta: Department of Health and Human Services and the Centers for Disease Control and
Prevention, January 1996:14.
15. Hong R. Chapter 1: B and T
lymphocytes. In: Graziano FM, Lemanske RF Jr., editors. Clinical Immunology. Baltimore:
Williams & Wilkins, 1989:4-15.
16. Hong R. Chapter 1: B and T
lymphocytes. In Graziano FM, Lemanske RF Jr., editors. Clinical Immunology. Baltimore:
Williams & Wilkins, 1989:11.
17. Hong R. Chapter 1: B and T
lymphocytes. In Graziano FM, Lemanske RF Jr., editors. Clinical Immunology. Baltimore:
Williams & Wilkins, 1989:4.
18.Ershler WB. Immune senescence. In
Graziano FM, Lemanske RF Jr., editors. Clinical Immunology. Baltimore: Williams &
Wilkins, 1989:106-110.
19. Ershler WB. Immune senescence. In
Graziano FM, Lemanske RF Jr., editors. Clinical Immunology. Baltimore: Williams &
Wilkins, 1989:106-110.
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