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Immune Function

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PETS AND IMMUNE FUNCTION

W. Jean Dodds, DVM - The Immune System

Background

Our physical and emotional health is governed by our immune systems. The immune system is a complex network of white blood cells, immune factors, and antibodies that heal us when we are hurt, and protect our bodies from cancers, and infection by bacteria, viruses, fungi, and other foreign agents.

In the healthy person there is a delicately balanced immune system. Just the right amount of immune response is triggered to repel an infection or heal a wound, and just enough of the system is involved to stop a response. A properly balanced immune response does not "over respond" or "under respond". When properly functioning the right number and types of white blood cells and immune factors are involved to meet and resolve the challenge.

Imbalances of our white blood cells and immune factors result in immune disorders such as autoimmunity and allergies (overactivity) or susceptibility to infection and cancer (underactivity).

Immunity

As long ago as the fifth century B. C., Greek doctors knew that people who recovered from the plague would never get the disease again. This is because they had acquired immunity against the plague (NIH Publication 88-529). The white blood cells of the immune system have "memory"; they "remember" having been exposed previously to a specific organism. When becoming re-infected they are ready ("immune") to releasing the right sorts of immune products to destroy the pathogen thereby preventing re-infection of the body.

Self vs. Non-Self

The key to a well-functioning immune system is its ability to tell the difference between self- and non-self. Virtually every living organism and cell has a unique set of surface molecules called antigens ("barcodes") that identify them. The "barcodes" are recognized by our immune cells and helps them identify a cell as self, or as non-self. Normally the body will not attack its own cells ("self") , but is programmed to attack those with "non-self" or foreign "barcodes" (antigens).

When the white cells of our immune system recognize these non-self, foreign, "barcodes" they may trigger other types of white blood cells to produce large proteins (antibodies) that lock onto these antigens, to mark them for destruction. Other cells will produce small bioactive molecules (immune cofactors) that trigger other types of immune responses that will help heal or defend the body.

Proper Function of the Immune System

When balanced and stable, the immune system will destroy non-self cells such as mutated cells that multiply causing cancer, or foreign invaders (such as fungi, bacteria, and parasites) that may lead to infection if left to grow to large numbers. When it's working "right", the immune system heals the body (wound healing), fights off infections, and kills cancer cells.

Underactive Immune Responses

An underactive immune system may be caused by one's heredity, chemo- or radiation therapy, excessive exercise, aging, stress, etc. and may lead to being vulnerable to many illnesses.

An underactive immune system, often leads to opportunistic infections. These sorts of infections are caused by organisms that do not bother us when we are healthy, but when our "guard is down" (or if the immune system is not at its appropriate level) cause severe infections. Individuals with acquired immunodeficiency syndrome (AIDS) are at risk for getting opportunistic infections. Their disease is characterized by an immune disorder or a breakdown of their immune system that leaves them susceptible to parasitic, bacterial, viral, and fungal diseases. In a person with a properly functioning immune system, these organisms would be unlikely to cause disease.

People with cancers and other severe diseases may also experience lowered immune responses as a result of anticancer therapies. Also emotional stress, malnutrition, surgery, and blood transfusions may result in depressed or altered immune responses.

Overactive Immune Responses

Overactive immune systems may lead to conditions such as allergies or autoimmune conditions. Allergies are the result of an "over reaction" of the immune system to non-threatening substances such as pollen or animal dander.

Autoimmune responses are the result of overactivity of immune components and occur when the immune system confuses self with non-self and attacks its own tissues and cells. Autoimmune conditions, such as arthritis, multiple sclerosis, lupus, insulin-dependent diabetes, psoriasis fibromyalgia, inflammatory bowel diseases, etc., are typically treated with drugs that suppress one's immune response.

The Body's Defenses

The natural defenses of the immune system consist of an extremely elaborate and complex network of trillions of lymphocytes (white blood cells). Using small bioactive molecules, these cells pass information back and forth to each other like bees going out in search for pollen. Just as bees in their colonies have different jobs, the white blood cells in the body have their specific tasks and abilities. "The result is a sensitive system of checks and balances that produces an immune response that is prompt, appropriate, effective, and [in a properly functioning immune system] self-limiting" (NIH Publication 88-529).

The Organs of the Immune System

Since the immune system influences almost every physical and mental aspect of the body, it is not surprising to find "pockets" of white blood cells throughout the body. Tonsils, lymph nodes, spleen, bone marrow, and thymus are some of the concentrations of lymphocytes where cells grow and develop. It is commonly not recognized, even among scientists and clinicians, that the largest immunological organ of the body is the intestine. One accumulation of cells, embedded within the intestine wall, are the Peyer's patches.

White Blood Cells (Lyphocytes)

Lymphocytes recognize foreign invaders and coordinate the natural defenses of the body. There are many different types of lymphocytes, each group with its own function. Some of these cells are:

Regulatory T cells	Control and coordinate white blood cell traffic
B cells	Produce specific antibodies
Killer Cells	Kill cancer cells and those carrying viruses
Macrophages	Present "barcode" information (antigens) about the invader so that other white blood cells can recognize invaders. Start immune responses. Scavenge dead organisms and cells.
Phagocytes	"PAC-Men"; gobble up infected cells
Eosinophils	Kill parasites
Mast Cells	Involved in allergies; releases chemicals that trigger other cells

Many white blood cells recognize and react to specific antigens ("barcodes") which starts a specific immune response against an individual class of invaders. Other types of cells respond in a nonspecific manner killing any and all invaders.

T-Cells

T cells are involved in: 1) inflammatory reactions, 2) increasing the numbers of cells for a strong defense of the body, and 3) the destruction of cancer and infected cells.

T cells are one of the first immune cells to become aware of the presence of foreign cells. When they recognize that an infection has occurred, they release different kinds of immune cofactors, or biochemical signals, that activate B cells (to produce antibodies) and other immune cells. By using these messages, T cells recruit other cells and start an immune reaction.

Regulatory T cells defend the body by recruiting other cells. These cells "talk" to one another with immune cofactors, small bioactive signals that are produced by cells.

Regulatory T Cells

The traffic cops of the immune system, these cells direct the circulation of other immune cells that all together form the immune network. They may call in reinforcements, or "tell" cells to stop an immune response.

There are primarily two classes of regulatory T cells:

Helper cells - "turn-on" other cells like B cells, other T cells, killer cells and macrophages.
Suppressor cells that "turn off" immune responses

B-Cells (Plasma cells)

Each B cell is a self-contained factory that manufactures one specific type of antibody (immunoglobulin). These antibodies, large proteins, are "smart" bullets designed to identify invaders by the antigen or "bar-code" they carry.

Specific Antibodies

Just as one key fits one lock, each antibody produced can only "fit" (attach to) one specific "bar-code" (antigen) on bacteria, virus, parasite, or cancer cell. A specific antibody is directed against an individual antigen.

Cell Interactions

Many cells are involved in triggering the B cell to produce antibodies. Macrophages, using immune cofactors, "tell" T cells about the architecture of the invaders. Then the T cells release other factors that program the B cell to "design" the right antibody for the job. Once the B cell "knows" what sort of antibody it needs to produce, it will manufacture millions of antibody-producing plasma cells, each which manufactures millions of identical antibody proteins directed against that one specific antigen.

Immune Cofactors (Bioactive Messages)

During the process of generating antibodies, the immune cells of the body also produce different types of immune cofactors. These biochemical messages, smaller in size than antibodies, help direct the body's immune system in its natural defenses.

Delicately Balanced Immune Systems

A great deal of effort and energy goes on in the body to maintain its exquisite balance of white blood cells and immune factors. Too much activity may result in an immune response that gets "carried away" (such as an inflamed toe); a response that doesn't stop for days. If however, the immune response ends too quickly, then the infection may not be resolved completely or healing may be incomplete.

One combination of immune factors may start an immune response, and another combination of factors may "down-regulate" an immune response, either slowing or stopping it entirely. A balance of these is absolutely necessary for an "appropriate" immune response.

The Balance between Foreign Cells and Our Own Cells

The digestive system is the major entryway for bacteria and other organisms to enter the body. More than 100 trillion bacteria are in our digestive systems at any one time [Ann Rev Micro 31 1977]. The cells that make up our body are heavily outnumbered by the bacteria and other organisms in and on our bodies. (There are 10 foreign organisms for every one of our cells.)

Immunity and the Gut

Since the body needs to defend itself against many of these infectious agents, it is not surprising that about 25% of the intestine is involved in immunity. Additionally, from 70%-80% of all antibody-producing cells are located in our digestive system. These cells are so busy that at any one time they make more antibodies than any other cells in the body. [Immunobiology 184 1992].

Invasion of the Gut

Let's say we've eaten a picnic sandwich that had sat too long without refrigeration. If this meat had been contaminated from the beginning with Salmonella, a type of bacteria that causes problems in human guts, the warm temperature would have encouraged rapid growth of the numbers of the Salmonella organisms. Therefore we might be eating a sandwich contaminated with millions of bacteria. When large numbers of infectious organisms enter the gut, a number of events occur:

Specific antibodies continuously produced by the immune cells in the gut in response to previous exposure, bind to the bugs, stopping them from attaching to the gut where they might start to multiply and cause illness.
B cells, for example from the intestine's Peyer's patches, will be stimulated by white blood cell immune factors to produce new "lock and key" antibodies and mount a specific immune defense against the bacteria.
The specific antibodies lock onto the Salmonella marking them for death by other immune cells and preventing their attachment and replication in the gut.
If the infection is overcome, suppressor cells will release immune cofactors to stop other cells from being triggered and the immune process will be "down regulated".
Simultaneously with the antibody defense strategy, the Salmonella may be targeted by phagocytes or other white blood cells ,or killed with potent chemicals from white blood cells. Different types of white blood cells will be triggered by immune cofactors to try to physically destroy and gobble up the Salmonella. They in turn will release immune cofactor signals to recruit other cells.

Active vs. Passive Production of Antibodies

There are two ways that we can obtain antibodies to defend our bodies from harmful pathogens and cancer cells. These are by: 1) active production (having our own immune systems make antibody) and 2) getting "ready-made" antibodies, from foods such as eggs or milk, or as a pharmaceutical product.

Active Antibody Production

Active antibody production is the result of our B cells producing their own antibodies in response to an infectious agent or its antigens.

Depending on where they are produced, antibodies may be found in our gut or "floating around" in our blood stream. Because antibodies are large molecules, antibodies produced in the gut do not cross the digestive tract walls and those found in the blood cannot get into our digestive tracts. (Often the gut is referred to as being "outside" of our bodies since food is digested and then the remainder is excreted. That material that is excreted is always kept "outside" of our inner bodies.)

Since we always consume food that is contaminated with pathogens, and are exposed to organisms through the air we breathe, we are actively producing our own antibodies in response to foreign organisms.

Passive Immunity

Passive immunity is the transfer of "ready-made" antibodies produced in another person or animal, or obtained from food. The recipient does not "make the antibodies". The individual receives the benefit of protective antibodies without having actively produced them.

There are two ways that antibodies are passively passed onto an individual. These are by 1) injection into the blood stream or body tissues and 2) orally consuming the product. (If an antibody is able to be injected into the body, it is a drug manufactured by a pharmaceutical company.)

When a mother nurses her offspring, she is passing on, passively transferring, immunity. Her offspring will have this "ready-made" immunity to protect itself from harmful pathogens in the environment. [Since both the offspring and the mother are both exposed to the same environmental pathogens, mother's antibodies will be able to be used by the offspring to help defend itself from infection and disease.] Eventually the offspring's own immune system will mature to the point that it can actively produce its own immunity, and is no longer in need of the passively transferred antibody from its mother.

Antibodies vs. Antibiotics

When our body's immune cells recognize an invader, they may produce antibodies that are biologically programmed to defend against the harmful pathogen (bacteria, viruses, fungi, molds, etc.). Each antibody neutralizes only one specific bacteria, virus, or foreign cells. Each antibody is "custom-designed" to attach to the appropriate pathogen.

Antibiotics, on the other hand, are drugs that are prescribed to kill unfriendly bacteria. In some cases antibiotic drugs may harm the body by killing our friendly bacteria, causing harmful side effects. If the dose of antibiotic is not enough to kill all the bacterial invaders, these bacteria can then multiply, and often mutate to a more potent form of bacteria. Often they become resistant to being killed by medication and are termed antibiotic-resistant bacteria.

Antibiotic drugs kill only bacteria. Anti-virals kill viruses. Antibodies attach to, and mark for death by white blood cells, any pathogen against which they were "designed".

Inflammation

In response to an infectious agent or tissue injury, an immune response called inflammation will occur. Inflammation is accompanied by a feeling of warmth in the area, redness and swelling. Warmth and redness occur when immune cofactors dilate blood vessels to carry more blood and white blood cells. Swelling occurs with the formation of "pus" which occurs when the immune cells migrate into an area attracted by immune cofactors released by other white blood cells.

Mechanism of Disease

[based on Andrew Luster, M. D., Ph. D.; New England Journal of Medicine; 336: 436-445 1998]

Immune factors control the circulation and recruitment of different types of white blood cells throughout the body. They also control the type and length of time that an immune response such as inflammation will last. Also immune factors are involved in controlling white blood cells in their defense of the body against infectious organisms.

"Overactivity" of the immune system over a long period of time, may result in an inflammatory condition that results in autoimmune disease. Similar types of white blood cells and immune factors are involved in autoimmune, inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, psoriasis, lupus, multiple sclerosis, etc. The inflammatory reaction occurs when a particular ratio of immune cells and immune factors exist. One category of white blood cell may increase in numbers, while another type of cell may decrease.

The type of autoimmune disease one ends up with, depends on the part of the body in which inflammation is occurring. So for example, inflammation of: the joints may result in arthritis; of the digestive tract, inflammatory bowel disease; of nerve cell insulation (myelin sheath), in multiple sclerosis.

The same sort of inflammatory response associated with autoimmune diseases appears to be responsible for atherosclerosis. In such cardiovascular diseases similar categories of white blood cells and immune factors are found as are seen in other inflammatory and autoimmune conditions.

Stress, Emotional States, and the Immune System

The immune system "talks" to our nervous and hormonal systems and vice versa. All these systems are integrated as one, and together govern our emotional as well as physical feelings. Stress, dieting, joy, distress, bereavement, fatigue-- all affect our immune systems.

As most of us know, hormones are intimately involved in emotions. Certain glands in response to stress, release hormones into the blood. These hormones prepare the body for "flight or fight" and in the process increase flow of blood to the intestines, decrease antibody production, and modify the numbers and types of white blood cells.

The change in immune cell populations is controlled by immune cofactors that guide the traffic patterns and activities of other white blood cells. Stress results in the reduction of the activities and numbers of circulating surveillance white blood cells. Stress also decreases natural defenses resulting in less efficient and slower healing, and a greater susceptibility to infection. It's not surprising that constant stress depresses the immune system resulting in serious health consequences.

Individuals that feel depressed and anxious are at greater risk of developing high blood pressure as they age. Since the immune system is linked to various hormones that control blood pressure, it's not surprising that once again the immune system, by way of immune cofactors controls cardiovascular health.

Age and Immune Function

With advancing age, autoimmune conditions and cancer become more common. In some individuals white blood cells are reduced in their numbers and their activity levels, and their B cells produce antibody more slowly and at lower levels. Thus, keeping the immune system young would be ideal.

Summary

The immune network of cells defends the body from cancer cells and foreign invaders, and helps the body heal when it is hurt. Immune cells communicate with each other, and recruit other white blood cells through immune cofactors (bioactive messages). White blood cells, with the aid of large molecules called antibodies:

Attach to, and destroy or eliminate bacteria, viruses, and cancer cells before they reproduce and create harm in the body.
Indirectly stimulate certain protector cells into killing invaders.

Conclusion

The immune system is a complex network of white blood cells and immune products that regulates our physical and mental status. Balance is what it's all about! An immune network with its well-balanced components is essential to good health.

Dr. Hellen Greenblatt
Chief Science Officer
Legacy for Life