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Immune System (Part 1)
by June Butlin, MBANT, M.Sc., PhD

Ed: This 2-part article, written for our Site, gives a clear and thorough overview of the whole immune system and its complex, sophisticated ways of taking care of us. It also appears in the How Your Body Works section. The second part illustrates how the Immune System works with a fascinating story.

The immune system is the most complicated system in the body and very difficult to understand. In this two-part article I have given an overview of the immune system and its members and attempted to explain how the members of the immune system perform many interrelated functions to combat infection and achieve health.

The immune system and its members

The immune system is the body's defence system against invading agents. The lymphatic system is another name for all the organs of the immune system and is made up of two subdivisions, primary and secondary organs. The primary organs of immunity are the thymus and the red bone marrow and the secondary organs include the lymph nodes, spleen, tonsils, appendix, Peyer's patches and small specialised lymph nodes in the membranes of the intestines. The white blood cells or leukocytes that fight invading agents are produced in the primary organs, but do not come into contact with invading agents until they reach the secondary organs where they initiate their defensive response.

Invading Agents

Invading agents include bacteria, toxins, viruses, parasites and foreign bodies, such as food antigens. The two main invading agents are bacteria and viruses. Bacteria are unicellular organisms that can live and thrive happily in the human body. Viruses are smaller than bacteria and consist of either DNA or RNA (nucleic acids) surrounded by a protein coat. They are unable to survive on their own unless they take over the mechanisms of a cell in the body by replacing their own DNA and RNA with the cell's DNA and RNA. They can then reproduce rapidly within the cell and the resultant nucleic acid moves on to invade other cells.

Attacking Invading Agents

Internally the immune system carefully plans its attacks in two ways. Firstly, it uses a non-specific response offering immediate protection against a wide variety of pathogens and foreign substances. Secondly, it uses a specific response, which, as its name suggests, is an attack targeted at a specific, known invader. The specific response takes longer to activate, but memory is built up during this time so that a second encounter prompts a rapid response. The specialised attacking leukocytes either ingest or produce chemicals to kill the invading agents.

Non-Specific Responses

The white blood cells or leukocytes involved in the non-specific response are:

Granular Leukocytes, which include neutrophils, basophils and eosinophils. They perform the basic function of phagocytosis, the process of ingesting particulate matter such as microbes and cell debris. They also secrete histamine, which is a key chemical in the inflammation response and produce a chemical called lysozyme to destroy certain bacteria.

Agranular Leukocytes, which include monocytes and lymphocytes. Monocytes are the largest of the white blood cells found in the blood. They have the ability to become macrophages when they enter the tissues. Macrophages have a role in phagocytosis in a similar way to the granular leukocytes.

Mast cells, which produce histamine, a chemical that dilates small blood vessels as part of the body's inflammatory response to injury or infection.

Natural Killer Cells are specialised cells, which attack a wide variety of infectious microbes and tumour cells.

The key chemicals secreted in the non-specific response are:

Complement Proteins, which are series of plasma proteins that attack and destroy microbes through the process of inflammation, opsonization (enhancement of phagocytosis) and cytolysis (cell splitting).

Transferrins, which are iron-binding proteins that inhibit the growth of certain bacteria by reducing the amount of available iron.

Cytokines, which are small protein hormones produced by lymphocytes, fibroblasts, endothelial cells and antigen-presenting cells and include interleukins 1, 2, 4 and 5, tumour, necrosis factor, alpha gamma and beta interferons, lymphotoxin, perforin and macrophage migration inhibiting factor. In general these cytokines stimulate or inhibit cell growth and differentiation and regulate immune responses. Each cytokine has a specific role for example alpha and beta interferon produced by virus infected cells inhibit viral replication in uninfected cells, stimulate T cell growth, activate natural killer cells and inhibit cell growth and suppress formation of some tumours.

Specific Responses

The white blood cells or leukocytes involved with the specific response are:

The B-Lymphocytes include plasma cells and B memory cells and are specifically designed to deal with bacteria and inactivate their toxins, however they can destroy viruses before they enter the cells.

The T-lymphocytes include cytotoxic T cells or killer cells, memory T cells, T suppressor cells and T helper cells. T cells attack viruses, fungi, transplanted cells, cancer cells, and some bacteria. T cells are also responsible for transfusion reactions, allergies, and rejection of transplanted organs.

Interestingly both T-Lymphocytes and B-Lymphocytes develop from stem cells that originate in red bone marrow, but the B cells complete their development into mature cells in the bone marrow, which is a process that continues throughout one's lifetime. However the T cells develop from pre-T cells that migrate from bone marrow into the thymus. This is why they are named B and T cells, B cells for bone marrow derived and T cells for thymus derived.

The key chemicals secreted in the specific response are:

Antibodies or immunoglobulins, which are proteins, produced by the B lymphocytes in response to a specific antigen (a substance that has the ability to provoke an immune response). The antibody combines with the antigen to neutralise, inhibit or destroy it.

Complement Proteins, which are a series of plasma proteins that attack and destroy microbes through the process of inflammation, opsonization (enhancement of phagocytosis) and cytolysis (cell splitting).

Cytokines are involved with both the specific and no-specific immune system. They are small protein hormones produced by lymphocytes, fibroblasts, endothelial cells, antigen-presenting cells and include interleukins 1 2 4 and 5, tumour, necrosis factor, alpha, gamma and beta interferon, lymphotoxin, perforin and macrophage migration inhibiting factor. In general these cytokines stimulate or inhibit cell growth and differentiation and regulate immune responses.

Process of Attacking

Natural killer cells have the ability to kill a wide variety of infectious microbes and spontaneously arising tumour cells. They kill the cells in two ways either by releasing perforins which are chemicals that when inserted into the plasma membrane of a microbe make the membrane so leaky that cytolysis occurs or by binding to a target cell and inflicting damage by direct contact

Killer cells are lymphocytes, which bind virus-infected cells and attack some tumours and cells of a tissue transplant

Phagocytes are cells specialised to perform phagocytosis, the ingestion of microbes or other particulate matter. The two major types of phagocytes are neutrophils and macrophages, the latter are scavenger cells that develop from monocytes. Mobile macrophages called wandering macrophages are present in most tissues. Other macrophages are called fixed macrophages and protect specific tissues. Amongst the fixed macrophages are histiocytes in the skin and subcutaneous layer, kuppfer cells in the liver, alveolar macrophages in the lungs, microglia in the nervous sytem and tissue macrophages in the spleen, lymph nodes and red bone marrow. When phagocytosis occurs once the invading agents meets with the phagocytic cell the cell membrane of the phagocyte extends projections called pseudopods that engulf the invading agent and enclose it within a vesicle called a phagosome. The phagosome enters the cytoplasm and merges with lysosomes which release enzymes called lysosymes that break down the microbial cell walls. The phagocyte also releases superoxides, hypochlorites and hydrogen peroxides to kill the microbes. Any material that cannot be degraded further are got rid of by exocytosis and picked up by the lymph.

The Two Levels of Immunity

The first level of immunity:

Prevents toxic matter from entering the body and involves the skin and epithelial cells as well as the orifices of the body.

The epidermis or outer layer of the skin provides a physical barrier to the entrance of microbes and the regular shredding of these epidermal cells helps remove microbes at the skin surface. The sebaceous glands of the skin secrete sebum that forms a protective film over the surface of the skin and the unsaturated fatty acids in the sebum inhibit the growth of certain pathogenic bacteria and fungi. Perspiration also helps to flush microbes from the surface of the skin and contains lysosomes producing the enzyme lysosyme to break down the cell walls of certain bacteria.

The epithelial cells also act as a barrier mechanism. The epithelial cells of mucous membranes lining body cavities secrete viscous mucus, which is able to trap many microbes and foreign substances. Examples are the mucous membranes of the nose which trap and filter microbes, dust and pollutants from inhaled air. The mucous membranes of the upper respiratory tract containing cilia or hair like projections on the surface of the epithelial cells, which move inhaled dust and microbes that have become trapped in mucus towards the throat.

Other areas of prevention are:

The lacrimal apparatus of the eyes, which produce and drain away tears in response to irritants. The washing action of tears helps to dilute microbes and keep them from settling on the surface of the eye.

The saliva from the salivary glands, which washes microbes from the surfaces of the teeth and from the mucous membranes of the mouth.

The flow of urine, which retards microbial colonization of the urinary system.

Vaginal secretions and defecation, which are able to expel microbes.

Gastric juice, which is produced by the glands of the stomach and is a mixture of hydrochloric acid, enzymes and mucus and the strong acidity of gastric juice, is able to destroy many bacteria.

However, if the pathogens manage to penetrate the mechanical and chemical barriers of the skin and mucous membranes they encounter a second line of defence involving the non-specific and specific immune systems.

The second level of immunity involves the non-specific and specific immune systems.

The non-specific immune system works on recognition and instantaneous action. The members of the non-specific immune system are monocytes, macrophages, neutrophils, eosinophils, basophils, mast cells and natural killer cells and they have a two level system of recognising substances. They recognise self and non-self, meaning that if the substance is something to do with the body, they leave it alone, but if the substance is something to do with an invader, they attack.

The specific immune system works on recognition and each individual bacterium or virus is recognised and identified as being unique. Each virus/bacterium has different characteristics or antigens, which differentiate one from another. The members of the specific immune system are B-lymphocytes, plasma cells, B memory cells, and T-lymphocytes including cytotoxic T cells or killer cells, memory T cells, T suppressor cells and T helper cells.

The main function of the B-lymphocytes is to deal with bacteria and some food allergens by identifying the specific antigen and producing the correct antibodies. In a food allergy immune reaction the B lymphocytes produce plasma cells to manufacture the correct IGE antibodies in response to the food antigen. The antibodies then combine with the mast cells (white blood cells) to form a complex. The complex then combines with the food antigen to produce histamine, kinins, prostaglandins series 2, leukotriennes and complement to promote an inflammatory response and direct killing of the antigen. The inflammatory response can produces symptoms such as skin rashes, respiratory problems, congestion, runny nose and hay fever and generalised symptoms of fatigue, anxiety, mental confusion, diarrhoea and anaphylactic shock. An extreme reaction can be life threatening, e.g. a bee sting can kill a very small number of highly susceptible people, due to a massive overproduction of histamine and prostaglandins. The B-lymphocytes can destroy circulating viruses before they enter the cells.
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The T- lymphocytes are produced to deal with viruses and cancer cells. The T-lymphocytes recognise two distinguishing features on an infected cell, a foreign, specific antigen and a home antigen. Once recognised cytotoxic T cells either release perforins, chemicals that can make the infected cell's membrane so leaky that cytolysis (cell splitting) occurs or bind to the cell and inflict damage by direct contact. The T helper and T suppressor cells act as regulatory cells. If there are too many suppressor cells, the immune system doesn't function and if there are too many helper cells, the immune system attacks the body. The T- lymphocytes take time to develop but once they have recognised the invader, the memory T lymphocytes can recall them if needed at a future time. This is why childhood illnesses only attack once.

Inflammation is also involved in the second line of defence.

Cells damaged by microbes, physical agents or chemical agents initiate a defensive response called inflammation by releasing chemicals such as histamine, kinins, prostaglandins, leukotriennes and complement causing redness, pain heat swelling and sometimes loss of function in the injured area. The general effect of inflammation is to produce a fever, reduce iron levels and increase the production of leukocytes. In the process of inflammation the blood vessels vasodilate increasing the blood flow to the local area to transport more immune members to the action site and increase the permeability of blood vessel membranes to proteins and neutrophils to allow healing to take place.

Auto Immunity

Auto-immunity occurs when the body's own immune system attacks itsel,f examples of which are Pernicious and Haemolytic Anaemia, Addison's Disease, Systemic Lupus, Rheumatoid Arthritis, Myasthenia Gravis and Rheumatic fever.

It is thought that the thymus is responsible for distinguishing between self and non-self by allocating every cell in the body an identity code made from a combination of amino acids. Each code is then recorded in its memory bank. If the thymus does not recognise the code on a cell it regards it as non-self or a foreigner and the immune system will then attack it. This system works well most of the time, but the body can make errors in identifying the amino acids and the immune cells will then attack the body's own cells. This happens with transplanted organs and in these cases, patients take immune suppressing drugs so that the foreign organ does not get rejected. Occasionally foreign cells have a very similar code to self and the immune cells will recognise these foreign cells as self and leave them alone. A good example of this is the bug that causes syphilis, which has the same coding as some of the heart muscle cells called cardiolipin. The immune system either leaves it alone or it may eventually attack it, but if and when it does, it also attacks the heart muscle itself.

(continued in Part 2)

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	Immune System (Part 2)
	June Butlin (Nutrition, Sports & Therapeutic Massage, Psychotherapy)
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