Worm diet encourages immune system
Use of New Vaccines to Fight Common Diseases; Flu Vaccine Improvements; Malaria Vaccine
Use of Umbilical Cord Blood to Repair Immunity; Stem Cells to Grow Organs
Designer Babies: Eliminating Bad Genes
Eating pizza helps the immune system 4/99
The UNDERLYING UNIVERSAL PRINCIPLE of the immune system deals with recognizing SELF FROM NONSELF (FOREIGN) based on the principle of ligand/receptor binding described in the figure above. In a competitive and deadly world, self is usually GOOD and nonself is usually BAD. This LAW defines both the strengths and the weaknesses of the immune system and foreshadows its inherent problems. It is like the predicament one often sees portrayed in the movie plots where the hero/heroine find themselves in a dangerous situation with a weapon in hand and surrounded by people of unknown character, each claiming to be their friend ("trust me") while warning the hero/heroine that the others are their enemies. The dilemma is "how do you know who to trust and who is telling the truth?"; There is a scene in "Indiana Jones and the Last Crusade" where Jones has to chose between a beautiful woman and his father that illustrates the complexities of this problem. The immune system can thus be viewed from two perspectives:
How is SELF recognized?
How is NONSELF (foreign) recognized?
Clearly these are two sides of the same coin and the answer to one inevitably leads to understanding the other. Consider the DEVELOPING EMBRYO in a multicellular organism like a mammal; in a real sense to the mother the embryo is NONSELF!! With immunity a multicellular organism must take into account the fact that its cellular constituents, except for identical twins, belong to a very unique gene pool of ONE. However, although a fetus is not SELF, it can not be attacked as nonself if the species is to survive. Once self recognition is achieved the multicellular organism must now differentiate between self and ALL the other NONSELF material on the planet, including its own progeny; clearly a formidable task.
As has been described previously, the problem of COMMUNICATION between biological molecules such as enzymes, their substrates, and their regulatory molecules, as well as in phage/virus binding etc. has been solved through the principle of SPECIFIC LIGAND/RECEPTOR INTERACTION. Thus the problem of differentiating between self and nonself is not one of developing a "specific recognition system", since that already exists, but how does a multicellular organism design a system for discriminating self from the millions of NONSELF substances in the environment throughout its life time? It turns out that the immune response depends upon the process of genetic recombination to solve this problem.
One final point: We CAN NOT SURVIVE without a functioning immune system. Without it, no amount of antibiotics or medical treatment can keep us alive for more than a brief time. This is painfully illustrated by the death of AIDS victims.
To recognize the various types and levels of immunity
To learn the basic components of the immune system
To understand how the immune system works at a fundamental level
To gain an understanding of the future of immune research and its potential impact on OUR LIVES.
Women in a number of undeveloped countries put breast milk in the infected eyes of their infants. Why might they do that? If you were a health worker would you advise them to continue this "treatment" or would you warn them that milk is a great medium from the growth of microbes and advise them to stop doing this?
THE SPECIFIC IMMUNE SYSTEM = Previously we have discussed the nonspecific defense system that protects us, more or less, from all pathogens. The specific immune system (often called the IMMUNE SYSTEM) protects us against SPECIFIC NONSELF ORGANISMS and substances. It is an INDUCED response; that is it must be TAUGHT which things to attack.
ANTIGEN = An antigen is anything that ELICITS the formation of a specific immune response. Older definitions limits the definition of an antigen to ".....formation of an antibody.", however, as you will learn there are two levels (duality) to the immune system.
EPITOPES = These are the PARTICULAR UNIQUE CHEMICAL GROUPS on a molecule that are antigenic; i.e., that elicit a specific immune response.
ANTIBODY = A SPECIAL GROUP OF SOLUBLE PROTEINS that are produced in response to foreign antigens. To view the structure of an antigen, antibody and epitope see the RasMol:Gallery and view the section on Antibody and antigen binding. Also take a look at the following:
What the heck is an antibody? | More pictures of antibodies | Index of antibody movies. You'll have to have the right "Helper Applications" and a lot of memory to see these so take care.
This site contains the best tutorial on antibody structure I've seen (Go to INDEX>ARCHITECTURE OF PROTEINS>LECTURE 5>STRUCTURE OF HUMAN IMMUNOGLOBULIN G). It requires the helper application Chime, Netscape 3.0 or better and a fast computer. It is fantastic, although it is advanced for Micro 101/102 students, if however you go through this & learn it, I guarantee that you'll understand what antibodies are and how they work.
FAQ: "Exactly what are ANTIGENS and how can they cause problems like allergies?"
Antigens are usually MACROMOLECULES like proteins and polysaccharides; small molecules usually make POOR antigens, but they can be antigenic under certain circumstances. For example, antibodies against hormones are how pregnancy tests work.
Antibodies are a group of soluble, PROTEINS that have UNIQUE BINDING SITES on them which recognize and bind to the EPITOPES of antigens. As previously described with enzymes, allosteric sites and other binding site-situations, the antibody binding sites are HIGHLY SPECIFIC. There are SEVERAL TYPES of antibodies with a variety of different functions in the specific immune response which will be discussed as appropriate. Figure 1 illustrates the relationship between an antigenic molecule, its epitopes and the soluble antibodies produced against it.
Figure 1. Epitopes. On the left is illustrated a folded, functional protein. It might be an enzyme, or a cell wall receptor site protein or a ribosomal protein etc. On this protein there are certain GROUPS OF ATOMS that comprise EPITOPES. These groups are defined as epitopes BECAUSE THEY ELICIT AN IMMUNE RESPONSE and for no other reason. Since each of the epitopes is a DIFFERENT and unique chemical cluster, each one of them induces a UNIQUE ANTIBODY. Each antibody will bind tightly to its particular epitope and NOT TO ANY OF THE OTHERS. Within this cartoon lies the core information one needs to understand how the immune system works. That is, if you know how one car works, you have the core information on how all cars work, only some details differ.
INNATE IMMUNITY = This can best be described as GENETIC IMMUNITY or immunity an organism is BORN WITH. Part of this immunity is the NATURAL DEFENSE SYSTEM described in the previous chapter. This type of immunity can be an immunity that applies to the vast majority of the members of a species (SPECIES IMMUNITY), or it can be an immunity that applies to only a certain subgroup within a species down to a few individuals within that species. Some examples are:
Cattle suffer from the cowpox virus, but appear to have a SPECIES
IMMUNITY to the closely related smallpox viruses, whereas;
Smallpox is a deadly disease to humans, but cowpox is, in
humans, a mild localized skin infection (usually on the hands).
| Humans are susceptible to the HIV virus, but most of our
related primates are immune to HIV, but they suffer from HIV-like viruses to
which we appear to be immune. | |
Within a species there may exist SUBGROUPS that are STATISTICALLY immune or resistant to particular pathogens. For example:
Northern Europeans appear to be more resistant to
tuberculosis than are most Africans, whereas Africans are innately resistant
to a variety of African diseases to which "whites" are highly
susceptible.
Because of the genetic variation within every species
INDIVIDUALS are statistically more resistant to some diseases, and more
susceptible to other diseases. Most of you know those within your own
families that "rarely" get colds or the flu, while other family
members repeatedly catch respiratory infections. While there are many
factors (diet, stress etc.) that could explain these individual differences,
one of them is that certain COMBINATIONS OF GENES render some more resistant
to the common cold viruses, whereas others are very susceptible. | |
INNATE immunity is different from the SPECIFIC immunity discussed in this section. However, both system interact so as to provide better protection to the host.
PASSIVE acquired immunity is short lived as the antibodies eventually die off or are themselves removed from the body as foreign protein. Since the person receiving the passive dose DOES NOT PRODUCE their own antibodies, the immunity is TRANSIENT.
The ACTIVE forms of immunity are generally long lived, particularly in the case of recovery from a CLINICAL INFECTION. Sometimes this immunity is lifelong, but in other cases it is not. Vaccinations may induce long-lived immunity, but recent data indicate that vaccinations may not last as long as once was hoped. For example, there is a very effective vaccine against tetanus, but it lasts only a few years and every year hundreds of people who have been vaccinated against this bacterium die because they have not gotten their BOOSTER SHOTS (vaccinations given periodically to booster the immunity of previous vaccinations) every three to five years.
Currently vaccines come in three forms
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FAQ: "Are vaccines safe to use?"
It is never possible to prove that any medical treatment is
totally safe for all people under every set of conditions. The safety of
medical procedures and agents always carry a degree of risk, just as driving
your car to work always carries a degree of risk.
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Should we bother to immunize ourselves and our children? Isn't the US so safe that vaccinations are not needed anymore?
This is a decision that each individual must make for
themselves and their children, but it should be an informed decision and not
one made from scary tales told over the back fence or from the tabloids.
Modern vaccines are about as safe as anything in this dangerous world.
Everyone who drives or is driven on the highways is in far more danger of
harm than they are being vaccinated.
The US is one of the safest countries in the world when it
comes to communicable diseases, but we probably are not the safest. Diseases
are always present and they do not recognize borders. We are so intimately
connected with the rest of the world today that diseases can appear from
anywhere. The strawberries or lettuce you just purchased at the supermarket
yesterday may have come from a country with far less sanitation than we
practice, or the person you sit by on the bus/subway may be a recent
immigrant or traveler coming from another country that is rife with a
disease the US is "free" of. In these cases your only real
protection is vaccination. Think about it!
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The future of vaccination looks very promising due to three emerging technologies. These are, the use of DNA to vaccinate animals, including humans, new injection devices and novel drying techniques that convert vaccines into dry forms that can be stored for long periods without refrigeration:
DNA VACCINES
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DNA carrying genes that make a substance that elicits a
strong immunological response in a host against a pathogen are
identified, cloned and isolated.
This DNA is coated onto tiny beads that are
fired at high velocity into the host's body (e.g. into the arm, or
butt).
| The DNA-coated beads penetrate the cytoplasm of
cells without killing them.
| The DNA comes off the beads and is transcribed and
translated, but not replicated.
| The translated product is recognized by the body as
being FOREIGN and a vigorous immune response is initiated. | |
NEW DRYING TECHNOLOGIES
Most vaccines require constant refrigeration to remain functional. This makes vaccination in remote areas of the world difficult and expensive, and is called the "refrigeration element". Maintaining a "cold chain" to remote areas like central Africa costs over $200 million per year. Recently it has been found that a number of living organisms can protect themselves from damage by drying if they contain a high concentration of the simple disaccharide sugar trehalose. Such organisms (cryptobionts) that have been completely dried can be returned to life, without apparent harm, by the addition of water.
| This trehalose-based drying and stabilization technology is being applied to vaccine antigens. Measles vaccine dried with trehalose suffered no loss of activity after two months at room temperature compared with commercially dried material that lost >90% of its activity in the same period. Trehalose-dried DT&P vaccine could be stored at 60oC for 12 weeks without loss of activity. |
INJECTION DEVICES
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The specific immune system exists throughout the body, but a major portion of it circulates in the blood and lymphatic systems, as they flow throughout the body. The human specific immune system is a two level or DUAL SYSTEM consisting of soluble antibodies and special immune cells. The two systems work intimately as a coordinated unit. Foreign material is dealt with by both components of this dual system. The cellular components of the specific immune system includes a host of specialized cells; new ones are being discovered all the time. The entire process of specific immunity is initiated by non-specific immune cells, the phagocytic cells of the nonspecific defense system, which act as general scavengers and a kind of "attack dogs". These cells engulf or ingest any material they perceive as foreign/nonself. Once inside these phagocytic cells the engulfed material is digested and its chemical components are processed for use by the specific immune system. The two components of the specific immune system are described in greater detail below.
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Shown in Figures 2 & 3 are some of the various white blood cells involved in the immune system. Some are part of the nonspecific defense system and some are components of the specific immune system. Telling the difference between these cells is difficult, but because their individual form (morphology) and relative numbers of the different types are important tools in disease DIAGNOSIS, they are carefully studied. A variety of different stains are used to help the medical technologist and pathologist distinguish between the different cell types. However, many are indistinguishable morphologically and can only be differentiated by antigenic differences. Click here to view immune cells.
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One of the professions open to Microbiologists is that of Medical Technology. Medical Technologists are responsible for analyzing patient's fluids, including determining the types and numbers of the various different cells present in a patient's blood. Thus a Medical Technologist would be expected to identify each of the blood cells shown in Fig. 2 & 3. However, as computer imagery gets better slides will be scanned by computers and diagnoses only verified by medical personnel.
One part of the dual level specific immune system is called the HUMORAL system. The humoral system involves the soluble ANTIBODIES described above. These antibodies circulate through the blood and lymph system. When blood is spun in centrifuge (or allowed to sit quietly in the refrigerator), the red blood (RBC) & white cells (WBC) settle or PELLET to the bottom of the tube, leaving behind a straw-colored liquid called the SERUM. The antibodies, and other soluble components of the blood, are located in the blood serum. Antibodies are made by SPECIAL B-CELLS, called PLASMA CELLS that make and excrete huge quantities of antibody molecules.(Fig.3).
The second component of the specific immune system involves a special class of cells called T-cells. There are many different types of T-cells and new ones are being discovered frequently. Each population T-cells has a unique role in the immune process. Although T-cells do not produce antibody, they contain antibody-like receptors on their cell surfaces that specifically bind to foreign ligands in exactly the same way that antibodies do. Further, they also have other receptors on their surfaces that identify other cells within the body with which they are designed to interact. They have many roles. One important role is to act as the HIT-MEN of the immune system. When a foreign cell is pointed out to these "killer cells" they gang up on it, beat the dickens out of it until there is nothing left but a few bit 'n pieces of garbage floating around. Once in while they go crazy and decide to attack their own host cells and then there is a serious problem (e.g. arthritis).
Cells of the #nonspecific defense system, known as macrophages, neutrophils and polymorphonuclear neutrophils, are involved in a complex relationship in which they recognize and then ATTACK NON-SELF MATERIAL, destroy it and process it for use by the specific immune system. All the components of the immune system are intimately tied together much like the members of a smooth running sports team or an army. They use chemical signals to each other to coordinate their defense of the host. This entire process is only partly understood and is so exceedingly complicated that it should keep a lot of biological scientists off the streets for a long time into the future (just ask their mates). But these scientists seem to need to eat (every time we train one not to eat they die on us) so they will be coming to you citizens FOR MONEY to pursue this research.
Another important component of the specific immune system is a group of proteins called the COMPLEMENT SYSTEM. Complement is a GROUP OF PROTEINS that, like the antibodies, are soluble and reside in the serum. Complement is a COMPLEX OF ENZYMES that mainly act on foreign cells by punching holes in their membranes to cause their LYSIS AND DEATH. Complement works in concert with the SPECIFIC ANTIBODIES that "point out" the cells to be attacked by the complement; i.e., the antibodies act to "FINGER" (identify) a target cell and the complement acts as the "HIT MAN" that kills the targeted cell. In addition complement, plus antibody, designate which cells are to be engulfed by the phagocytic cells. Complement can also result in immunological damage to ones own cells in the case of diseases caused by faulty immune systems. One such reaction is the serious allergic response known as ANAPHYLACTIC SHOCK.
Now we come to the issue brought up in the introduction, namely: How does the body distinguish the good-guys from the bad-guys?
The steps in the immune system development are:
Stem cells, which are the PARENT CELLS of all immune cells, enter the liver of the fetus and develop to a point there.
From the liver some stem cells move into the bone marrow (at the center of the bones) where they differentiate into B CELLS and NATURAL KILLER CELLS.
Other stem cells move from the liver into the thymus gland located in the middle of your chest.
The thymic stem cells differentiate into a variety of T cells.
Other stem cells go on to differentiate into other blood cell lines such as macrophages.
Immunologists are making rapid headway in unraveling the complexities of these various differentiation's, but the differentiation process is extremely complex and subtle. From my perspective of >40 years in microbiology I have observed tremendous progress in the area of immunology. However, my guess would be that we are not even half way to a full understanding of the entire system. I am optimistic that the immune system will be completely understood in your lifetimes.
The immune system is spread throughout the entire body and includes the following (a partial listing):
Adenoids & tonsils
The lymph nodes & lymphatic system
| The Spleen, appendix and small intestine
| The bone marrow
| The thymus gland | |
Figure 4. This figure shows the location in the body of various
components of the nonspecific and specific immune systems. The B cells
and a variety of other lymphatic cells are made in the bone marrow. The lymph
nodes contain the macrophages, B cells and T cells, which is why your lymph
glands swell up and become tender to the touch when you have an infection. The
thymus gland is the gland where the differentiation of the T cells occurs. Other
macrophages, monocytes and phagocytes reside in the liver, spleen and lungs.
Special immune cells have been found in the brain, in the skin and in the cells
lining the intestine. Breast milk contains a variety of the mother's white blood
cells that kill microbes in the infant's gut and stimulate the development of
the infant's immune system as well as antibodies and 10 other microbial
inhibitors (Sci. Am. Dec. 1995)
Consider the problem an immune system faces. It must defend its host against thousands of unknown POTENTIAL PATHOGENS, each a MOSAIC of different antigens (epitopes). Further, it must distinguish between millions of self antigens and other millions of foreign antigens; the penalty for failure is DEATH by a pitiless nature. What makes this goal even more difficult is that many of the self-antigens are chemically very similar to the nonself-antigens. As the early immunologists defined this incredible diversity they were awestruck and puzzled as to how this could possibly be. It was one of these situations that was demonstrability true, but seemed impossible to achieve; but then life itself fits in that category doesn't it? As usual in science the answer came from the brilliant reasoning of a few people. The thought process that broke the "case" went something like this.
Instead of thinking that the immune system had to be INSTRUCTED AHEAD OF TIME as to which antibodies would be required throughout a life time, clearly an impossible task, N.K. JERNE suggested that the immune system was SELECTIVE rather than instructive. Jerne reasoned that the immune system must RANDOMLY make billions of different SPECIFIC-EPITOPE-BINDING ANTIBODIES and then let the antigens that accidentally stumbled into the host choose or select which antibodies would be produced in quantities large enough to be protective. In a sense this is just another twist on the "survival of the fittest" process in #EVOLUTION. Burnet in Australia and Talmage in CO hypothesized:
That antibodies SIT
ON THE SURFACE
of lymphocytes and
That each lymphocyte manufactures only a SINGLE
ANTIBODY (which recognizes and binds to only a SINGLE
EPITOPE). | |
This theory, which has come to be called the CLONAL SELECTION THEORY, has been shown to be correct.
If you take the time to understand the following information and the Figs. 5-8, understanding the immune system is relatively easy & you'll be able to figure out most of the answers to exam questions on this material.
1. During fetal development the body randomly produces millions of B & T CELLS, each of which produces only a SINGLE EPITOPE BINDING ANTIBODY.
2. The B cells that produce self antibodies (antibodies against self antigens) are DESTROYED, leaving only lines or CLONES of B cells that produce random antibodies to foreign epitopes.
3.When a particular foreign epitope (e.g. antigen No. 2,025) is introduced into the host's body it is PROCESSED by lymphocytic cells of the nonspecific defense system. This sets off a sequential series (cascade) of events that eventually acts on a small population of randomly-produced B/T cells that happen (by chance) to have on their surface, antibody (No. 2,025) which binds to ANTIGEN No. 2,025.
4. These events trigger a RAPID PROLIFERATION of that PARTICULAR B (and T-cell) cell population (No. 2,025), producing a large number of clones. These No. 2,025 B cell-clones differentiate into PLASMA CELLS (Fig. 3) which are ANTIBODY-PRODUCING-FACTORIES that spew out prodigious quantities of ONE ANTIBODY-#2,025, that binds to the specific antigen-epitope No. 2,025 that stimulated it.
5. The specific antibody floods through the host and wherever it binds to its epitope it MARKS IT FOR ATTACK and destruction by the appropriate cells and associated components of the immune system (complement and PMNs etc.).
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So at this point we know that there are millions of B-cell-antibody-producing types, just waiting to be "triggered" by contact with their respective antigen, but we still don't know how we get these millions of different B-cells in the first place. To understand how this occurs you have to know something about antibody structure.
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There are five different types of antibodies, however in this course we will discuss only the most common one, IgG, in detail.
However, note that the other 4 types physically resemble the basic structure of IgG (requires Chime). IgG does most of the humoral immune work. Figure 7 shows the physical structure of the IgG molecule. This site shows mobile models of IgG (requires Chime)
The Y-shaped structure is real as electron microscopic pictures show. However, even before they viewed IgG in an electron microscope immunologist had discerned its basic shape. They knew that each antibody had to have two equivalent binding sites for its specific epitope. It turns out that those two binding sites are located at the end of the short arms of the Y (Fig. 10).
The IgG molecule is further divided into CONSTANT and VARIABLE REGIONS OR DOMAINS. The constant regions have mostly the SAME amino acid sequence in all IgG molecules (we won't discuss the differences here), whereas the amino acid sequences in the variable regions are DIFFERENT for each unique antibody produced by a clone of plasma cells. The amino acid sequence in the variable domains are such that they tightly bind to particular epitopes. Thus they show the same LOCK-KEY relationship as do enzymes/substrates and enzymes/allosteric molecules and viruses/target cell receptors.
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Figure 8B. Random Ab formation. Each of the colored squares in the light chain (L.C.) and heavy chain (H.C.) regions represent a GENE FRAGMENT. If three of these fragments are required to make one gene for the VARIABLE REGION a large number of combinations are possible, some of which are shown below each cluster of fragments. Then on the far left are several examples of combinations between the variable light and heavy chain genes that form the variable arms of IgG. As you can see from the limited numbers of color bars used in the illustration many different combinations could be formed. |
It may help you to understand Fig. 11 if you think of each of the L.C. and H.C. colored rectangles as different cards and then each of the light and heavy chain combinations of 3 cards each as "HANDS" of cards dealt to the players.
Click here to see a series of views of antibody molecules.
Antibody variability comes about through an unusual SHUFFLING of the genes that code for the variable portions of the IgG molecule (Fig. 11). The antibody genes are inherited as GENE FRAGMENTS. During lymphocyte development these gene fragments are joined together in RANDOM ARRANGEMENTS that form the COMPLETE GENES in the individual B & T cells. The fact that the IgG molecules are composed of two proteins, each with its independently produced variable regions adds increased variability to the whole process. It is estimated that >100 million distinct antibodies can be made by this process. In addition the genes for receptors of B lymphocytes MUTATE extremely rapidly when the B cell is activated by binding to a foreign substance or antigen. Once a B lymphocyte binds antigen to its receptor, it differentiates and secretes specific antibody molecules that have been specified by the genes that created the receptor on the parent B cell.
The basic reaction of all Ab's with their epitopes is the same (a binding of ligand and receptor), but the physical MANIFESTATIONS of that reaction differs depending on the PHYSICAL NATURE of the antigen. The point to remember is that the Ab has TWO binding sites so a single Ab molecule can bind to two independent antigen molecules or particles.
NEUTRALIZATION
= When the antigen is a soluble toxin, the addition of an Ab against it
will usually render the toxin INEFFECTIVE (nontoxic), that is it NEUTRALIZES
it. Such neutralized toxins are called TOXOIDS
and can be used as vaccines. For example, if you were suspected of
suffering from either tetanus or botulism poisoning the treatment would
involve giving you a shot of the appropriate antitoxin,
which is a common name for the Ab against a toxin. The antitoxin
circulates through your body and binds and neutralizes any toxin it
contacts.
PRECIPITATION
= Under the proper conditions a soluble antigen can be precipitated in the
presence of its Ab because of the antigen-antibody net-work that forms
gets large enough to form masses that SETTLE
OUT (precipitate) on their own.
| AGGLUTINATION
= When the antigen is a large PARTICLE,
like a whole bacterium or a RBC, the addition of its Ab will form an Ab-antigen
net work that causes the particles to CLUMP IN LARGE MASSES like milk
coagulating when it spoils. This agglutination is easy to see and is
useful for diagnostic purposes. For example, if you want to see if a
person is making Ab against a particular bacterium, mix the person's serum
with the suspected bacterium; if the bacteria clump into large globs it
means that Ab are present. Both precipitation and agglutination are
illustrated below | |
The second component of the adaptive immunity system involves a set of special immune cells called T cells. We will only deal with three of the T cell types. The T cells develop in the thymus gland (Fig. 7), but the process is not completely understood. Briefly, the stem cells in the thymus undergo differentiation's that form two major groups of T cells, the KILLER T CELLS (Tc or Tk) and the HELPER T CELLS (Th). The process of immunological diversification through DNA fragment shuffling is the same as that which was described for the B cell development so that EACH Tk and Th cell responds only to a unique epitope (Fig. 3). T cells that react with self antigens DIE OFF during the early stages of differentiation. The T cell clones migrate throughout the lymphatic system. When a T cell encounters its antigen (epitope) it goes through a series of changes that convert it into its final immunological defense posture.
The special role of the T-helper (Th-cell) in developing immunology is described below:
Therefore, the Th helper cell acts as a MASTER CONTROL CELL of the immune system. It is REQUIRED for both the humoral and cellular immune systems to function. When Th cells are not present the host's fate is sealed because the correct B-cells will not proliferate and the correct antibody will not be produced (like a football team without a quarterback) with the result that death ensues. (See discussion on AIDS)
The T killer cells (Tc) have a different function. The Tc cells are designed to recognize foreign antigens on the SURFACE OF HOST CELLS. Foreign cell epitopes appear on host cells mainly in two types of situations, in viral infection and in cancer cells. In both these case there are changes in the composition of the host's cells that cause foreign antigens to be PRESENTED ON THE SURFACE of the modified cell. The Tc cells recognize these foreign epitopes and are stimulated to attack and destroy the infected or modified (e.g. cancer) cell.
Figure 10. Activation of & killing by Tc killer cells of cells
displaying a unique surface antigen. Note the virus particles in the
cell on the right and the presence of unique viral proteins on its surface to
which the Tc cells bind.
Other T cell types exist and probably more types will be found. The above is an incomplete and simplified explanation of what is currently known about the immune system. Some of it will undoubtedly be modified as new facts come to light and we will surely find that it is even more complex and subtle than previously imagined. It's like human relationships which usually start out simple, but they become more complex as time goes on.
The adaptive immune system can, on occasion, make antibodies against the body's own cells. These antibodies activate complement which damages or destroys the targeted self-cells. When this happens you have an AUTOIMMUNE disease. Examples of autoimmune diseases include multiple sclerosis, juvenile diabetes, myasthenia gravis, Graves disease and rheumatoid arthritis. Autoimmune diseases are as insidious and terrible as cancer as they represent the BETRAYAL OF THE BODY by something that is intended to be of benefit to the body. Five percent of adults in Europe and North America, 2/3 of them women, suffer from autoimmune disease and this is likely to be a low estimate.
Since you've been paying attention, you should suspect by now that autoimmune disease is complex. In many autoimmune illnesses, genetic factors play a crucial role. For example, identical twins have a high chance of suffering from the same autoimmune disease. The causes of autoimmune diseases are virtually unknown, but the human genome is sequenced we will begin to learn about the genetics of these diseases. A significant amount of data indicates that infections can trigger them (e.g. Strep-throat/rheumatoid arthritis), or they can be provoked simply by an injury or stress. There are some hopeful signs of treatment for some of these autoimmune disease, but much more needs to be learned about them.
Allergies and their more dangerous relative, hypersensitivity's, are very common. Basically they can be seen as OVER REACTIONS to foreign antigens by a HYPERACTIVE or misdirected specific immune system. These conditions include allergic rhinitis (hay fever), asthma, sneezing or fighting for air after inhaling certain chemicals. Asthma is a serious disease and a frequent cause of death of young adults; I have lost three friends, all under 40, in my life time to asthma and I have several relatives who suffer from this dreadful condition. The antigens that trigger allergy attacks are called ALLERGENS. We don't understand why allergies are so common, but one theory is that they are the results of our immune system evolving a way of dealing with parasites (worms, etc.).When the body is invaded by a parasite it responds by producing IgE, a form of antibody different from IgG. IgE is the antibody that is responsible for allergy reactions. The stages of an allergic reaction are:
An initial exposure of the immune system to an ALLERGEN. At this time there are NO SYMPTOMS as the immune system must first synthesize the IgE in response to the unique allergen.
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On subsequent exposures to the allergen, it binds to IgE molecules that are located on the surface of MAST CELLS.
This induces a CASCADE (series) of events that cause the mast cells to release chemicals present in granules in the mast cells.
These chemicals include histamines, leukotrienes and prostaglandins, which in turn INDUCE THE VARIOUS SYMPTOMS typical of an allergic response.
This entire process can take JUST SECONDS, thus explaining the suddenness with which allergic and hypersensitive reactions can occur. Allergies include a WIDE VARIETY of diseases. For example chronic allergic rhinitis (runny nose, stuffed up sinuses) is commonly caused by the feces of the COMMON HOUSE LOUSE, to CAT & DOG allergens & to the COMMON COCKROACH all of which live in most of our homes. Seasonal allergies are often caused by pollens or mold spores in the air. Asthma effects approximately 5 to 10% of children, but another 5 to 10% acquire asthma in adulthood and others become afflicted in their 80s. There are numerous forms of asthma, only some of which may involve IgE-mediated activity. For recent (8/99) information on asthma and allergies visit this site.
Mast cells have recently been shown to have an important role in the bodies early defense against many pathogens. Mast cells serve as an early warning system at the body's borders that's equipped to kill some of the invading bacteria. Its main role is to alert the heavy artillery of the immune system that the body is under attack. An understanding of this role may allow mast cells to be manipulated so as to produce a more effective immune system.
BOTTOM WAR: After the end of the second world war some American service men in Japan suffered from painful and itchy blisters developing on their elbows and in a ring around their buns. Was this a subtle form of chemical warfare developed by the Japanese as retaliation for losing? No, it turned out that a common Japanese wood used to make toilet seats and bar tables contains a chemical that was very similar to poison ivy allergen and the Americans were reacting to it because of their exposure to poison ivy in the US. I suspect that few service men gave up the activities that brought them into contact with this allergen! |
One of the more dangerous allergic reactions is ANAPHYLAXIS. This frightening response to an allergen can KILL AN INDIVIDUAL in a few minutes. Typically, it occurs following an INSECT STING or the ingestion of a tiny bit of food (e.g. peanut butter). It is characterized by the allergen inducing an EXPLOSIVE RELEASE of chemicals from the MAST CELLS. The rush of these chemicals can induce shock which quickly leads to death. In some cases rapid swelling can close off the trachea causing the victim to suffocate. Less dangerous responses, often to foods, result in symptoms like hives or a transient swelling in the face or area effected. The danger with food anaphylaxis is that small quantities added in with the major food can induce this response. If you've even had even a mild response to a food or an insect bite, you are always in DANGER as the next one could kill you. Sensitive people should see an allergist and be tested. People who are in danger from anaphylactic reactions should carry kits with them containing drugs that they can inject quickly into themselves to stop the reaction.
There are many myths and much misunderstanding about allergies. Profuse sums of money are spent on testing for allergies and for allergy treatments, but RIGOROUS PROOF is often lacking both for the cause of specific allergies or for the efficacy of the, usually expensive, treatments. The role of industrial pollutants in producing allergies is not clear, but considerable data suggests a relationship between air quality, asthma and other respiratory difficulties. Substantial work remains to be done before this relationship is resolved. There are treatments for eliminating the sensitivity to specific allergens, but they generally required a lifetime commitment to the treatment. Before embarking on a long series of expensive, sometimes painful injections to treat your allergies, it is a good idea to get a second opinion and to explore alternative treatments. For example, three of the most common causes of household allergies are the feces of a louse that lives in all our homes, cat and/or dog proteins (flakes of skin and the hair; even from the neighbors' pets) & cockroach proteins (feces). The following simple treatments may help an allergy problem:
Vacuum your home frequently using special (costly) bags
that TRAP the LOUSE FECES,
THE HAIR AND SKIN FLAKES OF PETS
and COCKROACH BITS;
but cleaning them up completely may be a problem.
Wash the bedding frequently, as bedding is often infested
with the house louse.
| Remove things like rugs, bookcases and pictures that
collect dust.
| Installing an air purification and filtration system.
| Wearing protective particle masks when engaging in
activities that are likely to expose you to allergens (e.g. cleaning the
house, cutting the grass, cleaning out the garage).
| Change clothes/bath immediately after such activities, to
prevent allergy attacks. This is another case of MOMMIE being right when she
told you to "clean yourself
and your room".
| Stay inside when the pollen and mold count it high. | |
The immune response is being used as a possible treatment against cancer. As described above, the Tc cells destroy cells that present nonself epitopes on their cell surface. This includes cancer cells. Some data suggests that many cancers arise throughout our lives but that they are routinely destroyed by the immune system. However, for unknown reasons it doesn't get all of them. There is evidence suggesting that if we could "turn on" the immune system properly it would destroy many cancers that escape destruction initially. Such experiments against the skin cancer melanoma are currently underway and we can only hope they will succeed.
The Rh factor is a concern to all pregnant women as it can result in the death or damage to a newly born infant. What happens is as follows:
There is a protein in red blood cells called the Rh-factor.
Most of us have this factor, and we are said to be Rh+.
Those that lack this protein are Rh-.
| The problem comes about when a woman who is Rh- bears an Rh+
baby. Generally there is no problem with the FIRST BABY, because the mother
is not exposed to the Rh+ blood UNTIL BIRTH. However, at that time she may
produce antibodies against the Rh protein as it is a foreign antigen to her
immune system.
| The problem comes when the woman bears other Rh+ children.
| Under these conditions Rh antibodies many enter the babies
blood, usually near birth, and attack the baby's RBC causing them to lyse.
The lack of oxygen-carrying RBC can damage the baby's brain or even result
in death. If such a condition is expected the baby's blood can be replaced
immediately after birth (or even in utero) and before damage is
done.
| Today the mother can be desensitized to the Rh antigen and
prevented from producing Rh antibodies. | |
Some children are born lacking the ability to make a functioning immune system. Without treatment these children are doomed to an EARLY DEATH. Some of the genes responsible for this deficiency have been identified and their defect known. Currently GENE THERAPY is underway to replace the missing genes with a functioning healthy gene. Although the experiment is far from being finished, the early results, although mixed are encouraging and several children are living normal lives today who would have surely died without this treatment. Of concern, however is the HIGH cost entailed to treat these children. These costs are generally borne by the TAXPAYER. The hope is that the experiments on these children (and on others with genetic diseases) will result in a treatment for this, and other, inherited diseases that can be applied at an acceptable cost.
Immunological testing is important in criminal and other legal circumstances, such as proving parenthood. Sensitive immunological tests along with techniques like DNA fingerprinting and related techniques provide added sensitivity and specificity to both disease and forensic diagnosis. Techniques are being developed to combine the two which will improve sensitivity even more.
If you are having trouble understanding my explanations give these sources at try:
This site contains a fantastic tutorial using Chime on antibody structure and Ab/Ag interaction. The best presentation I've seen so far of antigen/antibody reactions. Must load the following: RasMol, Chime and Shockwave. When on the INDEX page scroll click on the "Protein Domains". It may take a while to load (I've had trouble here). View the series of slides illustrating the structure of antibodies. Use the right mouse button to see different views of the molecules and the left button to rotate the molecules. If you study this material you will know than I do about antibodies.
Collection of antibody images.
Still another course on the immune system. Very good images and cartoons. Start with Chap. 6.
Even another course on the immune system.
Copyright © Dr. R. E. Hurlbert, 1999.
This material may be used for educational purposes only and may not be
duplicated for commercial purposes.