ANATOMY AND PHYSIOLOGY OF THE IMMUNE SYSTEM

 

LEUKOCYTES

IMMUNOGLOBULINS

INFLAMMATION

The immune system can be referred to as the body’s defense mechanism. This system includes components of blood and body fluids and the products of these components which are necessary to help defend against antigens, or foreign agents. Examples of these components are lymphocytes and antibodies which are associated to organs in the lymphatic system, such as the tonsils, thymus, spleen, appendix, and bone marrow. The immune system is a means of fighting off any harmful or foreign agents which may enter the body. An antigen is any foreign substance not normally found in the body. Examples of antigens are bacteria, viruses, even organs used in transfusions. All antigens induce antibody production. Once an antigen enters the organism, a series of steps take place to defend against this invader.

Leukocytes

One example of these transient substances in the blood and body fluids are leukocytes. Leukocytes are white blood cells which contribute to 1% of the total blood volume. They function as a blockade or destruction mechanism for any antigens which enter the body. There are five types of leukocytes: neutrophils, eosinophils, basophils, monocytes, and lymphocytes. All types of leukocytes circulate in the blood stream. (URL 10)

Upon exposure to antigens such as viruses or cancer cells, leukocytes release interferons, which are a family of proteins that interfere with the antigen’s normal destruction and reproduction processes. Interferon action may inhibit the ability of a virus to replicate thereby preventing the host cells from dividing and spreading the virus. Interferons stimulate phagocytosis (the ingestion of an antigen), and the activity of lymphocytes.

Neutrophils are the most common cell and constitute 55-70% of all leukocytes. When an infected or injured area is identified, neutrophils immediately migrate to the sight and adhere to the vessel walls. They then migrate into surrounding tissue and consume the bacteria.

Eosinophils constitute 2-5% of all leukocytes. These cells contain protein which regulate inflammatory reactions.

Basophils account for less than 1% of white blood cells and are associated with immediate immune response to external antigens. They contain chemical substances such as histamine and heparin which produce reactions such as hay fever and asthma in the system. (URL 1)

Monocytes are the largest of the leukocytes and account for 5-8%. Monocytes are an immature cell which travels in the blood. When maturation occurs, monocytes leave the blood vessels and develop into macrophages in the tissue spaces. The macrophage is a scavenger that will digest any foreign material and is responsible for defense against certain antigens like fungi. This defense is accomplished by consuming the virus, breaking it down, and then displaying pieces of the virus on its surface to B and T lymphocytes, which are activated by the macrophages. Helper T cells (a type of lymphocyte) identify the antigen on the surface of the macrophage and then bind to it. Interleukin is a substance secreted by the macrophage which stimulates additional cell division of B and T cells in bone marrow. It transmits information about the type of antigen present to B cells (another type of lymphocyte). The B cells then bind to the virus itself. This process makes the virus more "appetizing" to macrophages who will essentially consume more of the virus.(Book, 5)

Lymphocytes are leukocytes which have antigens covering their surface. All lymphocytes are formed in red bone marrow. Once these cells are formed, they follow one of two pathways to differentiate into T lymphocytes or B lymphocytes. These two pathways are not completely distinct from one another, there is interaction between them. What is the difference between T and B lymphocytes?

T lymphocytes

Lymphocytes which are to become T cells mature in the thymus and are then added to the blood stream and lymph. These cells also inhabit lymphoid organs. There are different classes or families of T-cells. Two examples are CD4+ and CD8+. The CD refers to Cluster Designation and describes the antigens which are on the surface of the cell, while the number refers to proteins on the membrane of the plasma.(Book, 1) The function of CD4+ is to help plasma cells produce immunoglobulins, therefore it is referred to as a helper T cell. CD8+ participates in the cell mediated immune response and is termed a killer T cell.

Natural kill cells (NKC) are thought to be a separate line of T cells and distinct from killer T cells, although they have similar actions. NKC are capable of killing certain cells spontaneously without other lymphocytes or antibodies present. NKC are considered a first line of defense since they line tissues of the body.(Book, 5)

B lymphocytes

These cells bypass the thymus and go straight to the blood stream. B lymphocytes mature in bone marrow and they too inhabit blood, lymph and lymphoid organs. When a B lymphocyte encounters an antigen, it differentiates into plasma cells which releases antibodies. This process is aided by CD4+. There are five types of antibodies or immunoglobulins released (these two terms are interchangeable), and these cells participate in antibody mediated immune response. The job of an antibody is to bind to and then inactivate an antigen. On an antibody, the base remains constant, while the top is variable. So if each antigen is like a puzzle piece, its match is the top half of an antibody. Each antigen is different, so antibodies must be specific to be effective. Certain substances may be foreign to some people but not to others. These antigens are referred to as allergens and include pollen, dust, certain foods, medications, insects, etc.

Immunoglobulins

There are five classes of immunoglobulins (Ig) or antibodies. Each group is based on an amino acid sequence and has a specific function within the system.

IgG accounts for approximately 75% of all antibodies. IgG are able to cross barriers within the body, such as the placenta. They are found in blood, lymph and the intestines and work against most bacteria and viruses.

IgA accounts for 15% of immunoglobulins. They are found in tears, saliva, mucus, milk, intestines, blood, and lymph. IgA is known as a "local" antibody and can be found in orifices where antigens may enter the body. As foreign agents enter the body, they are killed instantly. The purpose if immunoglobulin A is to eliminate foreign particles before they reach a more critical point. Levels of IgA decrease as stress levels increase.

IgM accounts for 5-10% of all antibodies. It is the first immunoglobulin to be secreted by plasma cells after exposure to an antigen. It can be found in blood, lymph, and on the surfaces of B lymphocytes. These antibodies are responsible for the ABO agglutinogens on the red blood cells. In other words, they are responsible for blood typing.

IgD accounts for less than 1% of all immunoglobulins. IgD is found in blood, lymph and on B cells. It is involved in the activation of B lymphocytes and works in an effort to attack certain antigens. For example, penicillin, milk proteins, or possibly insulin. This antibody does not play any major role in the attack of bacteria or viruses.

IgE accounts for less than 0.1% of all immunoglobulins. IgE is involved with allergic reactions and possibly certain parasitic infections. It is located on mast cells which are outside the blood, and basophils which are in the blood. Even though, approximately 0.004% of total antibodies are involved with allergic reactions or hypersensitivity’s, their effects on the body are so great, they call about the most attention. IgE has a significantly different role than any of the other immunoglobulins. Examples of allergens include; dust, pollen, animal fur, certain foods, or drugs, just to name a couple. In response to environmental antigens, called allergens, the helper T-cells discriminate against certain substances and they are phagocytosized by macrophages. However, in an allergic individual, the following reaction occurs: (Book, 1)

1. Upon the first encounter to an allergen, often times, no unusual reaction occurs. A macrophage will breakdown the allergen and present the fragments to T and B cells. CD4+ cells then release interleukin which stimulates B cells to mature into plasma cells. The plasma cells then release IgE. IgE antibodies attach to receptors on mast cells and basophils. This process is called sensitization.

2. In the second step, activation of the mast cells occurs. Upon a following encounter, the allergen molecules binds to the IgE antibody, which causes the mast cell to release chemicals into the blood and tissue spaces. These chemicals cause the superficial signs of allergies. Symptoms include reddening of the skin, swelling, increased flow of mucous which causes a runny nose, coughing, and difficulty breathing. Some of the compounds released which cause these symptoms are histamine, cytokines, prostoglandins, leukotrienes, and serotonin. In extreme cases, constriction of the smooth muscle of the alveoli occurs. (Alveoli are air sacs in the lungs and are the site of gas exchange between the lungs and the blood stream.) This reaction will decrease gas exchange in the lungs. A severe allergic reaction is referred to as anaphylactic shock. In this case, excess amounts of chemicals are released from the mast cells which may cause circulatory and respiratory failure. A bee sting kit contains epinephrine (adrenaline) which counteracts the constriction of muscle.(Book, 7)

 

When an antigen invades the body, the immune system responds using the cell mediated immune response or the antibody mediated immune response, or a combination of the two. In the cell mediated immune response (CMI), T-lymphocytes (CD+8) proliferate into killer T-cells. Killer T-cells are shuttled from the lymphatic tissue directly to the antigen via the blood stream. They recognize the antigen, attach to it, and use a variety of chemicals (cytokines) to kill the antigen causing cytolysis or the death of the cell. CMI is used to attack fungi, parasites, certain viruses, foreign tissues, and cancer cells. In the antibody mediated immune response (AMI) , when B-lymphocytes are confronted by an antigen, they differentiate into plasma cells. There are different antigen receptors on each B cell. Once an antigen has been effectively conquered, the body retains the antibody or "puzzle piece," enabling the body to easily fight the antigen upon any future encounter. (URL, 10)

Inflammation

There are certain generalized events which take place outside of CMI and AMI whenever an antigen is present. Inflammation occurs, and the events associated with inflammation usually precede T and B cell activation. General reactions occurring with inflammation include:

1. An increased flow of blood to the injured area bringing platelets and leukocytes. Specifically the neutrophils and macrophages are recruited.

2. Platelets release histamine and leukotrienes causing dilation of blood vessels and an increase in capillary permeability.

3. Temperature is increased and reddening of the area occurs. This is a result of a pooling of tissue fluid. Also swelling occurs, also known as edema.

4. Platelets initiate clotting; in an bacterial infection, the neutrophils and macrophages destroy and consume the antigen. Ingestion is also referred to as phagocytosis.

5. Pain endings are stimulated in the area.

All of the above steps are usually not adequate to prevent the entry of at least some antigens into the blood which stimulates the B and T cell response.(Book, 7)

Relation to the Lymphatic System

The immune and lymphatic systems are closely related in that both include many of the same structures. The lymphatic system consists of vessels scattered throughout the body, which drain excess interstitial fluid to prevent swelling. Essentially, the lymphatic system cleans up after the immune system. Fluid, called lymph, passes through lymph nodes which are organs in the body that clean, filter, and contribute leukocytes to the lymph. This filtering system is a form of protection for the body. Following this process, the lymph is returned to the blood stream via lymph vessels. Lymphatic organs are essential in the maturation and differentiation processes of lymphocytes, in the synthesis of immunoglobulins, and the recognition and destruction of antigens in the body. It is essential that these two systems work in conjunction to accomplish the goal of total body health.(Book, 7)

Auto Immune Diseases

In an auto immune disease, the body fails to recognize healthy cells within the organism. As a result, it begins to systematically attack the system by and producing antibodies against healthy cells and normal protein. Aids was discovered in 1981 and is now the leading cause of death from age 25-44. The virus binds to CD4+ and destroys the helper cells. This makes it impossible for the body to fight off other diseases.(URL 1)