Mechanism of Actions of Antibodies
The antibodies protect the body from the invaded organisms in two ways (Fig. 9).
1. By direct actions and
2. Through complement system.
FIGURE 9. Mechanism of immunoglobulins action
1. Direct Actions of Antibodies
The antibodies directly inactivate the invading organ? By any one of the following methods:
1. Agglutination: In this, the foreign bodies of blood cells or bacteria with antigens on their surfaces are bound together into a clump by antibodies.
2. Precipitation: In this, the soluble antigens like tetanus toxin are converted into insoluble forms and then precipitated.
3. Neutralization: During this, the antibodies cover the toxic sites of antigenic products.
4. Lysis: It is done by the most potent antibodies. These antibodies rupture the cell membrane of the organisms and then destroy them.
2. Actions of Antibodies through Complement System
The indirect actions of antibodies are stronger than the direct actions and play more important role in defense mechanism of the body than the direct actions.
The complement system is the one that enhances or accelerates various activities during the fight against the invading organisms. It is a system of plasma enzymes, which are identified by numbers from C1 to C9. Including the three subunits of C1 (C1qC1rC1s) there are 11 enzymes in total. Normally, these enzymes are in inactive form and aге activated in two ways, namely:
A. Classical pathway.
B. Alternate pathway.
A. Classical pathway
In this the C, binds with the antibodies and triggers a series of events in which other enzymes are activated in sequence. These enzymes or the by-products formed during these events produce the following activities:
1. Opsonization: Activation of neutrophils and macrophages to engulf the bacteria, which are bound with a protein in plasma called opsonin
2. Lysis: Destruction of bacteria by rupturing the cell membrane
3. Chemotaxis: Attraction of leukocytes to the site of antigen antibody reaction
4. Agglutination: By causing clumping of foreign bodies like red blood cells or bacteria
5. Neutralization: Covering the toxic sites of antigenic products
6. Activation of mast cells and basophils, which liberate histamine. Histamine dilates the blood vessels and increases capillary permeability. So, plasma proteins from blood enter the tissues and the antigenic products are inactivated.
B. Alternate pathway
The complementary system can also be activated in another way, which is called alternate pathway. This is due to a protein in circulation called factor I. It binds with polysaccharides present in the cell membrane of the invading organisms. This binding activates C3 and C5, which ultimately attack the antigenic products of invading organism.
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Specificity of В Lymphocytes
Each В lymphocyte is designed to be activated only by one type of antigen. It is also capable of producing antibodies against that antigen only. This property of В lymphocyte is called specificity. In lymphoid tissues, the lymphocytes, which can produce specific antibody, are together called the clone of lymphocytes.
NATURAL KILLER CELL
Natural killer (NK) cell is a large granular cell with indented nucleus. It is considered as the third type of lymphocyte and it is often called the non-T, non-B cell. NK cell kills the invading organisms or the cells of the body without prior sensitization. It is not phagocytic cell but its granules contain hydrolytic enzymes. The hydrolytic enzymes play an important role in the lysis of cells.
NK cell destroys the viruses and the viral infected or damaged cells, which might form tumors. It also destroys the malignant cells and prevents development of cancerous tumors. NK cell is said to be the first line of defense in specific immunity particularly against viruses.
NK cell secretes two cytokines, interferons and tumor necrosis factors.
IMMUNE DEFICIENCY DISEASES
Immune deficiency diseases occur due to lack of some components or some defective components of immune system. Normally, the defense mechanism protects the body from invading pathogenic organism. When the defense mechanism fails or defective, the organisms of even low virulence produce severe disease. The organisms, which take advantage of defective defense mechanism, are called opportunists. The immune deficiency diseases caused by such organisms are of two types namely:
1. Congenital immune deficiency diseases
2. Acquired immune deficiency diseases
HLA SYSTEM
In human chromosome 6, there is a series of molecules called human leukocyte antigen (HLA). The HLA system monitors the immune system in the body. The HLA molecules are recognized by the T and В lymphocytes and hence these molecules are called antigens. HLA is distributed in almost all the tissues of the body. The antibodies are directed against the tissues possessing the HLA leading to autoimmune diseases. Most of the autoimmune diseases are HLA linked.
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IMMUNIZATION
Immunization is defined as the method of preparing the body to fight against a specific disease. It is a technique used to induce the immune resistance of the body to a specific disease. It is done by subjecting the individual to an antigen in order to produce antibodies against that antigen
PASSIVE IMMUNITY
Passive immunity or immunization is produced without challenging the immune system of the body. This is done bу administration of serum or gamma globulins form a person who is already immunized (affected by the disease) to a non-immune person. Passive immunity can bе acquired either naturally (immunoglobulins G can pass through placenta) or artificially (sera).
ACTIVE IMMUNITY
Active immunity or immunization is acquired by activating immune system of the body. The body develops resistance against disease by producing antibodies following the exposure to antigens. Active immunity can be acquired either naturally or artificially.
Active Natural Immunity
Naturally, acquired active immunity involves activation of immune system in the body to produce antibodies. It is achieved in both clinical and subclinical infections.
Clinical infection: During the disease, the plasma cells produce immunoglobulins to destroy the invading antigens. Later, due to the activity of memory cells, body retains the ability to produce the antibodies against the specific antigens invaded previously.
Subclinical infection: Some times the disease may not be severe to develop any manifestations. However, it causes the activation of В lymphocytes resulting in production of antibodies.
Active Artificial Immunity
This type of immunization is achieved by administration of vaccines or toxoids. Vaccines consist of dead pathogens or live but attenuated (artificially weakened) organisms. The toxoids consist of microbial components or toxins secreted by the pathogens.
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CYTOKINES
Cytokines are the hormone like small proteins acting as intercellular messengers by binding to specific receptors of target cells. These non-antibody proteins are secreted by white blood cells and some other types of cells. Their major function is the activation and regulation of general immune system of the body.
Depending upon the source of secretion and effects, the cytokines are classified into five types.
1. Interleukins
2. Interferons
3. Colony stimulating factors
4. Tumor necrosis factors and
5. Chemokines
Interleukins
The polypeptide cytokines produced mostly by the leukocytes and exerting the effects on other leukocytes are known as interleukins (IL). These cytokines are secreted by helper T cells, other T cells, В cells, monocytes and macrophages. The actions of interleukins are:
· Activation of T cells, macrophages and NK cells
· Promotion of growth of hemopoietic cells and В cells
· Acceleration of inflammatory response by activating eosinophils and
· Chemotaxis of neutrophils, basophils and T cells
So far, about 16 types of interleukins are identified. IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, and IL-8 play important role in the process of immunity. Recently IL-12 (otherwise called natural killer cell stimulatory factor) and IL-II also considered as an important cytokines.
Interferons
The interferons (IFN) are the glycoprotein molecules set produced by white blood cells, natural killer cells and it blasts. Considered as antiviral agents, these cytokines have the following effects:
1. Fighting against the viral infection by suppress the virus multiplication in the target cells
2. Inhibition of multiplication of parasites and cells
3. Promotion of phagocytosis by monocytes and macrophages
4. Activation of NK cells. Interferons are of three types namely, INF-б, INF-Я and INF-г.
IMMUNODEFICIENCY is a failure of some part of the immune system to function properly. It can be congenial (present at birth) or acquired. Congenital immunodeficiencies usually involve failure of the fetus to form adequate numbers of B cells, T cells or both. Severe combined immunodeficiency (SCID), in which both T cells and B cells fail to form, is probably the best known. Unless the person suffering from SCID is kept a sterile environment or is provided with a compatible bone marrow transplant, death from infection results.
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Acquired immunodeficiency can result from many different cases. For example, inadequate protein in the diet inhibits protein synthesis and, therefore, antibody level decrease. Immunity can be depressed as a result of stress, illness, or drugs such as those used to prevent graft infection. Diseases such as leukemia cause an overproduction of lymphocytes that do not function properly.
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