Immune Networks

From the  Book of Allergy and Immunology
 by Stephen Gislason MD

Introduction to Immunity

Antibodies

Immune Cells

Immune Mediators

Inflammation

Hypersensitivity

Allergy Center

Food Allergy

Hypersensitivity Disease Study Guide

Immune Networks - Not System

Medical textbooks refer to the "immune system", although this is probably not the best description of immune function. Immune activity is distributed through all body systems and involves large, diverse populations of migratory cells. A more meaningful description might be immune networks (IN) which are collections of different, diverse, often unstable, components. When the term "system" is used we may get the wrong image of a well-defined, orderly device, perhaps similar to a new car or a computer with an instruction manual. We are not quite the coherent entity that we like to think we are. We are really a community of cells in prodigious array. Lymphocytes are important immune players and to get an idea of the size of immune populations, think of a young tadpole as containing about one million lymphocytes. Human immune networks contain about 10 trillion cells.

Some of our cells stay in place and do more or less predictable things. Immune cells tend to wander around and, like bees, forage in our various body parts looking for items of interest. An appropriate image of immune networks would be the foraging and swarming of ants, each moving about, with different job descriptions in the colony and a meta order achieved by the collective behavior of many individuals. The overall activity of the hive or colony decides how the society or system looks and acts. They have the property of getting excited, recruiting their peers and attacking interlopers. A second analogy is to think in terms of military organizations with many divisions and a diverse array of weapons and strategies. The main purpose of immune networks is to wage war against invading aliens. Once engaged, orderly behavior tends to become chaotic and destruction of normal tissue structures are properties of these cell networks. Fantasies about boosting your friendly, cooperative immune system have little biological basis.

A third analogy that helps us relate to the changeable patterns of immune response is the weather. We regularly observe periodic and chaotic changes in the symptom patterns of patients, especially if we observe them over years. As Alan Perelson, an immune system theorist, suggested: "The system never settles down to a steady-state, but rather, constantly changes with local flare ups and storms, and with periods of relative quiescence."

Three Network Compartments

There is a mobile blood immune network (BIN) that originates in the bone marrow and circulates in the blood stream. This division of the immune network has several distinct cell populations and receives a lot of attention in transplant programs. BIN is specially vulnerable to carcinogens - uncontrolled overgrowth of these cell populations is leukemia. The immune network in the bloodstream, BIN, is highly reactive. BIN creates anaphylaxis reactions and may display other dangerous features, such as cell destruction and/or clotting. Blood defense is designed to counter life-threats such as infection and injury. Immune cells and molecular weapons are delivered by the blood to any tissue that is threatened. Special relationships between BIN cells and the cells lining the surface of blood vessels give BIN cells access to any tissue space.

The surface of blood vessel walls interacts in dramatic ways with immune cells. If blood vessels are thought of as controlled access highways and immune cells as emergency vehicles, then immune defense procedures must involve opening vessel walls to immune cell traffic. A common IN event is the flow of fluid and cells into tissue spaces; the swelling aspect of inflammatory reactions. Blood vessel wall events may injure the blood vessel and trigger clotting. Platelets in the blood are responsible for initiating clotting and may be activated by immune mediators especially platelet activating factor, known to play an important role in asthma. Activated platelets quickly manufacture a prostaglandin, thromboxane, a potent constrictor of blood vessels which can trigger the clotting mechanism. ASA (aspirin) is effective in blocking thromboxane production even at a low dose of one tablet a day, and has been recommended in the prevention of heart attacks and stroke. The possible significance of food allergic events inside blood vessels has already been mentioned.

Another division is the lymphatic immune network (LIN) with both stationary structures like bee hives (nodes) and migratory populations of lymphocytes that move around looking for antigens as bees look for pollen. The thymus gland is the master controller of LIN. A large population of lymphocytes are said to be "thymus-dependent" and are referred to as T-cells. The organs of the immune system are called collectively the "Lymphatic System". Tonsils and lymph nodes are conspicuous members of the lymphatic defense system. They are naturally enlarged, particularly in children, who are often busy making new antibodies, and developing new immunity to infectious organisms, food, and airborne antigens. Enlarged tonsils and lymph nodes are just doing their job.

Lymph is a watery fluid that washes through all our tissues, passes through lymph node filters, and eventually returns to the blood stream. Lymphatic channels form a fluid circulation system that parallels the blood circulation system. Lymphocytes wander through the lymph spaces in the body, rest and proliferate in lymph nodes. One of the typical signs of food allergy is enlarged tonsils and swollen lymph nodes in the neck. If you have an infected finger and observe a red streak going up your arm, you are seeing a lymph channel, marked by the release of inflammatory mediators. The streak reminds us that pathogenic bacteria can also travel along lymph channels and spread rapidly. If immune defense does not stop them, then it is usually a choice between antibiotics and death.

The interior body surfaces are lined with a moist mucous-secreting surface which senses and reacts to the ambient environment. Immune sensors or lymphoid tissues live in the surface linings or mucosa of the intestine and respiratory tract. These sensors are mobile lymphocytes of both T and B varieties. Their surveillance system is technically known as the Mucosa-Associated Lymphoid Tissue or MALT. In order to make sense of the problem of food allergy we must understand MALT. An essential concept is that MALT constantly monitors the flow of molecules over the GIT surface from lips to anus. The purpose of the surveillance is to detect, and respond to foreign antigens. Lymphocytes are also contained in follicles - the solitary lymphoid nodules (SLN) - found along the length of the intestine and in much of the upper and lower respiratory tracts. The SLNs sample the soluble and particulate matter from the environment. The gut-associated lymphoid tissue is GALT and the lung or bronchus-associated lymphoid tissue is BALT. GALT and BALT are the sensing agents for the immune system, identifying and encoding antigens for antibody production and later detection. GALT, BALT, and SLNs, contain B cells which synthesize immunoglobulins (mostly IgM and IgA).

The third immune division is the tissue immune network (TIN). TIN involves mobile populations of cells that move through tissues. Within the TIN are populations of cells which lurk under every body surface exposed to the environment: skin, respiratory tract, gastrointestinal tract, and genitourinary tract. Surface defense features the Type I or immediate hypersensitivity response. This is a property of mast cells, often using IgE antibodies as sensors. These networks are prodigious. Hundreds of different chemical messengers are used in communications among IN cells and between the IN and the rest of the body. Cells move from one IN compartment to another, transforming in shape and function. The most likely movement is from blood to tissue spaces; BIN becomes TIN.

Immune networks (INs) tend to tolerate antigens which appear regularly. Tolerance is most likely to occur with antigens presented orally. The eruption of symptoms of food allergy may represent the loss of tolerance, rather than new or different sensitivities. Many patients do not understand how foods eaten routinely over many years can produce disease; how can these reliable foods now make me ill? Nothing really stays the same, especially body functions and food quality. The adaptive dysfunctional state may permit bad habits to continue for years, but sooner or later, decompensation occurs. Loss of tolerance is one interpretation of worsening trends. Increasing sensitivity is another, complementary interpretation.

Of all the organs of the body, the brain offers the least access to itself. The blood brain barrier is a property of the blood vessel linings in the brain that control the molecular and cellular input to the brain. The brain has a limited TIN. If frequent immune skirmishes occurred in the brain as they do, for example in the skin, none of us would remain mentally intact. Multiple Sclerosis results from lymphocytes and macrophages attacking myelin in the nervous system. This attack probably involves cell populations which move from LIN to BIN to TIN. Food allergy could cause Multiple Sclerosis if lymphocytes, sensitized to food antigens and activated in GIT, moved through the blood and through a defective blood brain barrier. These food-activated lymphocytes would recognize a component of myelin as their own antigen and attack. Food antigens may coincidentally resemble myelin antigen, a case of molecular mimicry. Or the food antigens may be myelin basic proteins or similar molecules that you ate. The myelin in meat resembles your own myelin. Whenever myelin is stripped from nerve circuits, information flow is interrupted; numbness, paralysis, and loss of vision are typical consequences. Lymphocytic attacks on myelin occur sporadically and major events tend to be infrequent; this is an avalanche effect - a number conditions must be aligned before the damage occurs. As soon as an acute attack begins, we suggest going on an ENF and taking a large dose of prednisone in an effort to get the immune attack to stop. If you wait too many hours the damage is done and now it will take months to repair.