Monocytes/Macrophages
Monocytes are only a small percentage of the many kinds of blood cells when found localized outside the blood circulation, in tissues they undergo physical and morphological changes and are called macrophages. Macrophages are important in the regulation of immune responses. They are often referred to as scavengers or antigen-presenting cells (APC) because they pick up and ingest foreign materials and present these antigens to other cells of the immune system such as T cells and B cells.
Lymphocytes
There are two kinds of lymphocytes: B lymphocytes and the T lymphocytes. Lymphocytes start out in the bone marrow and either stays there and mature into B cells, or they leave for the thymus gland, where they mature into T cells. The major function of B lymphocytes is the production of antibodies in response to foreign proteins of bacteria, viruses, and tumor cells. Antibodies are specialized proteins that specifically recognize and bind to one particular protein. Antibody production and binding to a foreign substance or antigen, often is critical as a means of signaling other cells to engulf, kill or remove that substance from the body. So the B lymphocytes are like the SAS intelligence system seeking out their targets and sending defenses to lock on to them.
The T helper subset is a pertinent coordinator of immune regulation. The main function of the T helper cell is to augment or boost immune responses by the secretion of specialized factors that activate other white blood cells to fight off infection. Both B lymphocytes and T lymphocytes have the ability, biochemically, to remember previous exposure to a specific antigen, so upon repeated exposure a more effective destruction of the antigen can take place.
Proteins
The three kinds of proteins in the immune system, found in the plasma are immunoglobulins, cytokines and complement proteins.
Immunoglobulin
There are literally thousands of different kinds of immunoglobulins which are also known as antibodies. An antibody or immunoglobulin is a y shaped protein molecule that is made by a B lymphocyte in response to a particular antigen. Each antibody combines exactly with one specific kind of antigen and neutralizes it. This immense diversity characterizes the immune system as a whole
Cytokines
Cytokines are small secreted proteins which mediate and regulate immunity, inflammation, and hematopoiesis. They must be produced in response to an immune stimulus. They generally (although not always) act over short distances and short time spans and at very low concentration. Cytokine is a general name; other names include lymphokine (cytokines made by lymphocytes), monokine (cytokines made by monocytes), chemokine (cytokines with chemotactic activities), and interleukin (cytokines made by one leukocyte and acting on other leukocytes). Some cytokines amplify or increase an ongoing immune response, others instruct cells to proliferate, and still others may suppress an ongoing response. The immune system like many other body systems must be regulated in this way so that it is active when appropriate but not pathologically overactive.
The Complement Proteins
The complement system consists of a series of about 25 proteins that work to complement the work of antibodies in destroying bacteria. Complement also helps rid the body of antigen-antibody complexes. When an antibody binds to it’s antigen the compliment proteins may then bind to the complex thus formed facilitating phagocytosis by immune system cells.
The Immune Response
The six immune system components described above act in correlation to develop an effective immune response. Microbes attempting to get into the body must first get past the skin and mucous membranes. This not only poses a physical barrier but are rich in granulocytes and monocytes which with antibodies and complement proteins they will neutralize or partly neutralize the antigen. Next, they must elude a series of nonspecific defenses - cells and substances that attack all invaders regardless of the epitopes they carry. These include patrolling scavenger cells, complement, and various other enzymes and chemicals.
Infectious agents that get past the nonspecific barriers must confront specific weapons tailored just for them. These include both antibodies and cells. Lymphocytes and macrophages then interact at the invasion site, amplifying the immune response more specific and effective antibodies are developed to the biochemical memory of the invading bacterium. As these lymphocytes accumulate in the affected area, the tissue often becomes enlarged. Similar amplification of the immune response may take place in the nearest lymph nodes, as well as in more distant sites of lymphocytes formation such as the spleen and bone marrow. If the immune response is successful it would overtake the antigen so that the disease is under control. Suppressive self regulatory mechanisms then work to shut down the immune response, the cytokines are especially important in this suppressive process. Once the antigen is destroyed by this combination of actions the immune system is primed to respond more effectively if the same kind of microorganism should invade again.
Innate Immunity
Innate immunity is immunity that you are born with. Innate immunity involves barriers that keep harmful materials from entering your body. These barriers form the first line of defense in the immune response. Examples include:
- Cough reflex
- Enzymes in tears and skin oils
- Mucus, which traps bacteria and small particles
- Skin
- Stomach acid
If an antigen gets past the external barriers, it is attacked and destroyed by other parts of the immune system.
Acquired Immunity
Acquired immunity is immunity that develops with exposure to various antigens. Your immune system builds a defense that is specific to that antigen.
Passive Immunity
Passive immunity involves antibodies that are produced in a body other than your own. Infants have passive immunity because they are born with antibodies that are transferred through the placenta from the mother. These antibodies disappear between 6 and 12 months of age.
Passive immunization involves transfusion of antiserum, which contains antibodies that are formed by another person or animal. It provides immediate protection against an antigen, but does not provide long-lasting protection. Gamma globulin and equine (horse) tetanus antitoxin are examples of passive immunization.
Vaccinations
Several infectious diseases overwhelm the normal primary immune response and so can be fatal on first exposure. Thankfully there is way to speed up the specific immune response by giving vaccines against the pathogens that cause them. The basic idea behind a vaccine is that it contains some form of the pathogen so that it stimulates memory cells to develop, ready to destroy the real pathogen should it be encountered. Obviously the vaccine can’t simply be the pathogen itself, or the toxins it makes. Somehow the vaccine must be made less virulent, less able to produce disease.
Inflammation
The inflammatory response (inflammation) occurs when tissues are injured by bacteria, trauma, toxins, heat, or any other cause. The damaged tissue releases chemicals including histamine, bradykinin, and serotonin. These chemicals cause blood vessels to leak fluid into the tissues, causing swelling. This helps isolate the foreign substance from further contact with body tissues.
The chemicals also attract white blood cells called phagocytes that "eat" microorganisms and dead or damaged cells. This process is called phagocytosis. Phagocytes eventually die. Pus is formed from a collection of dead tissue, dead bacteria, and live and dead phagocytes.
Blood Clotting
Whenever blood vessels break, blood leaks out and clots. We can see this happening when we cut ourselves but blood can also clot deep inside the body. Clotting enables the body to avoid blood loss and at the surface to prevent infection. It is important that blood clots only when it should, because when a blood clot, a thrombus blocks a vital blood vessel it can cause a fatal heart attack or stroke.
Immune Diseases And Deficiencies
Certain clinically important diseases are related primarily to deficiencies of the immune system and others are related to an abnormally functioning (but other wise deficient) immune system. An immune deficiency disease occurs when one or more cells within the immune system do not operate properly, or the system is absent altogether. Some immune deficiency diseases are relatively common, while others are extremely rare.
Failure or deficiency of the immune system can be a primary phenomenon that is congenital, acquired or it can occur secondarily as a consequence of other diseases, such as cancer. Immunosuppression may also occur subsequent to treatment for other diseases, including cancer.
Primary Immunodeficiencies
Primary immunodeficiencies are usually congenital and range from mild abnormalities to severe deficiencies incompatible with life.
A primary immune deficiency occurs when the abnormalities of the immune system develop from an inborn defect in the cells. Affected cells include T-cells, B-cells, phagocytic cells or the complement system.
Most primary immune deficiencies are inherited diseases; examples include X-linked agammaglobulinemia (XLA) and severe combined immunodeficiency (SCID), and this appears to run in families. Other primary immune deficiencies, such as common variable immunodeficiency (CVID), appear less obviously inherited, but the causes of the defects are unknown and genetic factors cannot be ruled out.
Failure of B lymphocytes and absence of antibodies are relatively common problems, affecting perhaps one in 500 people, and are usually associated with recurrent infections (primary with bacteria). This type of failure frequently can be treated with monthly injections of gamma globulin, which contains many productive antibodies. Failures of T lymphocyte function and cellular immunity are much less common than antibody related deficiencies; they are primary associated with viral and fungal infections and are less amenable to treatment. The most sever primary immunodeficiency’s involve a combined deficiency of both B cells and T cells virtually all of these are fatal without radical treatment such as a bone marrow transplant. In recent years the acquired immunodeficiency that has drawn the greatest public attention is acquired immune deficiency syndrome.
Secondary Immunodeficiencies
Secondary immunodeficiencies occur when damage is caused by an environmental factor. Radiation, chemotherapy, burns and infections contribute to the many causes of secondary immune deficiencies. Acquired Immune Deficiency Syndrome (AIDS) is a secondary immune deficiency caused by the Human Immunodeficiency Virus (HIV). In leukemia and multiple myeloma, cancerous immune cells crowd out the normal stem cells of the bone marrow. These abnormal cells reduce the number of B cells and lead to hypogammaglobulinemia, another type of secondary immune deficiency.
Allergies
Allergy is caused by an oversensitive immune system, which leads to a misdirected immune response. The immune system normally protects the body against harmful substances, such as bacteria and viruses. It reacts to substances (allergens) that are generally harmless and in most people do not cause a problem. But in a person with allergies, the immune response is oversensitive. When it recognizes an allergen, it releases chemicals, such as histamines. This causes itching, swelling, mucus production, muscle spasms, hives, rashes, and other symptoms, which vary from person to person.
Autoimmune disorders
Normally the immune system's army of white blood cells helps protect the body from harmful substances, called antigens. Examples of antigens include bacteria, viruses, toxins, cancer cells, and foreign blood or tissues from another person or species. The immune system produces antibodies that destroy these harmful substances. But in patients with an autoimmune disorder, the immune system can not tell the difference between healthy body tissue and antigens. The result is an immune response that destroys normal body tissues. The response is a hypersensitivity reaction similar to allergies, where the immune system reacts to a substance that it normally would ignore. In allergies, the immune system reacts to an external substance that would normally be harmless. With autoimmune disorders, the immune system reacts to normal body tissues
Immunodeficiency disorders
When the immune system detects an antigen, it responds by producing antibodies that destroy the harmful substances. The immune system response also involves a process called phagocytosis. During this process, certain white blood cells swallow and destroy bacteria and other foreign substances. Immune system disorders occur when the immune system does not fight tumors or harmful substances as it should. The immune response may be over active or under active. Immunodeficiency disorders may affect any part of the immune system. Most commonly, such a condition occurs when specialized white blood cells called T or B lymphocytes (or both) do not work as well as they should, or when your body does not produce enough antibodies.
Immune Response To Transplants
Although the immune system is essential for human survival it presents an obstacle in clinical organ transplantation. The biggest problem facing most transplant recipients is that of rejection. The cells of transplanted tissue are covered in antigens that stimulate the specific immune response of the recipient notably the cell-mediated response brought about by T cells. Once the immune system recognizes these cells as foreign it will attempt to destroy them; without immunosuppressive medication such as cyclosporine transplanted kidneys, livers, and bone marrow will be rejected. As might be predicted however the immunosuppressive therapy can itself lead to problems with infections. Thus the patient under treatment is constantly in danger of either infection or rejection.
Relationship To Cancer
For many years a great deal of interest has focused on the relationship between the immune system and cancer. Cancer patients have an increased rate of infection, and immunological abnormalities can be seen in laboratory studies of cells and serum from some of these patients. On the other hand, the occurrence of cancer is much higher than would otherwise be expected both in patients with primary immunodeficiencies and in patients on immunosuppressive therapy. Also increasing the response of the immune system by therapeutic intervention in patients with cancer has led to some limited positive effects. Manipulation of the immune response and the development of immunologically based treatment will undoubtedly have a positive impact on attempts to treat cancer.
Research
The immune system continues to be a fertile area of research. One major area of interest is the study of how the immense diversity of the immune system evolves. Another is the analysis of the relationship between specific clinical diseases and faulty immunoregulation. Research efforts are being devoted to finding ways of manipulating the immune response not only to treat immunodeficiency diseases but also to improve results in clinical transplantation and cancer. The identification of the receptor molecule by witch T cell recognize antigens and cloning of the interleukin-2 receptor gene in the early 1980s were significant developments in this ongoing research.
References