Immunology

Host defense systems

The pathogenicity of an organism varies from mild attack to severe fatal attacks. The host has many mechanisms to resist or to avoid the pathogens apart from immune systems. One or few of these will be activated when the pathogen enters into the body. Following are some of the listed natural host defense mechanisms.

1. Natural host resistance: The host has the natural ability to resist the pathogen. For example, the anthrax may cause mild pustules to man whereas cause fatal blood poisoning to cattle.
2. Age, stress and diet: Very young and very old are susceptible whereas the adults are generally resistant against pathogens. Similarly the physical stress induces the susceptibility of the host against pathogens. Malnutrition is also allowed the pathogens to act very rapidly.
3. Anatomical defenses: The body of host (man) has so many defense mechanisms to avoid the pathogens. lysozyme of tears; rapid passage of air in nose; highly acidic pH of stomach (pH 2); rapid change in pH of intestinal track; native microflora of large intestines; skin layers; mucous membranes of lungs; coughing; sneezing are some anatomical defenses our body pocess to resist the pathogens.
4. Fever and inflammation: Redness, swelling, pain, heat and fever are some non-specific reactions carried out by host against pathogens.
5. Immune system: The specific and non-specific immunity is the well-advanced resistance mechanism, which will be discussed in this chapter.

Immunology

Immunology is the study deals with the mechanism by which an organism able to resist the infection by pathogens. Immunity is defined as the ability of an organism to resist the pathogens` infection. The immunity can be classified in to two groups.

1. Non-specific immunity – refers the general ability of certain cells of the body to resist the most of the pathogenic organisms like bacteria, fungi, virus etc.
2. Specific immunity – refers highly sophisticated mechanism found in the vertebrates for developing resistance to individual pathogens.

These two immune systems were triggered when the foreign molecule (pathogenic microorganisms or their toxins) enters to the cell. These foreign molecules, macromolecule components of pathogens, such as surface proteins and excreted proteins (toxins) are collectively referred as immunogens or antigens. In response to antigen, the host immune system will produce soluble proteins to detoxify the antigen’s effect is referred as antibody.

Once antibody is produced by an immune system for particular antigen, the second time infection by same microorganism or same antigen will be resisted by rapid antibody production. This capacity of immune system for responding the challenge of additional exposure to pathogen or antigen is referred as immune memory.

Blood and Lymph:

Blood and lymph are the two major body fluids responsible for all these immune systems. Blood consists of both cellular and acellular components.

Cellular components:

• Erythrocytes (red blood cells) – Non nucleated cells; major function is the O₂ carrier to cells
• Leucocytes (white blood cells) – involves in the immunity; two kinds are present
• Phagocytes / monocytes : They are the phagocytic cells (eating cells) which will engulf the pathogens
• Lymphocytes: responsible for antibody production against antigens

Acellular components

Plasma – When the cellular components removed from blood, is referred as plasma. It has an important protein called fibrinogen, which is responsible for blood clotting. In plasma, if the blood clotting protein is removed, that fluid is referred as Serum.

Lymph: is a fluid similar to blood but lack of red blood cells and travels through separate circulatory system (the lymphatic system). This system has capillary like arrangement called lymph node to filter the pathogenic cells.

Non-specific immunity refers the general ability of certain cells of the body to resist the most of the pathogenic organisms like bacteria, fungi, virus etc. The non-specific immunity is a common resistance for all pathogens whereas the specific immunity is specific to every pathogens. The common non-specific immunity is phagocytosis (Engulfing the pathogens).

Phagocytes and Phagocytosis:

Some leucocytes (white blood cells) found in the cell are phagocytes. They are motile, amoeboid action, which contain lysosomes. By chemical attraction, the phagocytes move towards pathogens and engulf them. By the action of lytic enzymes, they kill the pathogens. This phenomenon is referred as phagocytosis.

There are two groups of phagocytes in blood.

• Neutrophiles – short lived (2-3 days), small sized, large numbered phagocytes. They can move very quickly (40 mm/min).
• Monocytes & macrophages – Large sized phagocytes which live for long time. Macrophages are fixed in tissues and monocytes are circulating in blood.

During phagocytosis,

• Phagocytes changed their metabolism from aerobic to anaerobic form
• Formation of lactic acid drastically reduced the pH to 2
• Hydrolytic lysozymes excreted

Due to all these causes, the lysis of pathogenic organism will be killed. Sometimes bacterial pathogens show resistance against phagocytes because of the presence of capsules.

Specific Immunity

Specific immunity refers the ability of immune system to interact with specific antigens, which is referred as specific immunity. The white blood cells (Lymphocytes type of leucocytes) are responsible for such specific immunity. These lymphocytes produce soluble proteins against antigens, which can interact with antigen and neutralize the effect, referred as antibodies. The lymphocytes are of two types based on their action and origin. They are B Lymphocytes (shortly as B cells) and T Lymphocytes (T cells). B lymphocytes developed from bone marrow cells (designated as B cells) and T lymphocytes developed from thymus (designated as T cells).

B Lymphocytes

• They are really responsible to produce antibody against antigens and also for immune memory.
• The antibody produced by B cells are referred as immunoglobulins (Ig).

T lymphocytes

• They have Antigen Specific T Cell Receptor (ATC), similar to antibody of B cells, which can interact with antigens.

They have multiple functions such as

• A They recognise antigen and facilitate B cell to act on the antigen
• A They recognise antigen and release ATC which can suppress the antigens

Antibodies

Immunoglobulins, ATCs and cytokines are the proteins produced by B cells and T cells respectively against antigens, which can be referred as antibodies.

A. Immunoglobulins (IG)

• They are the soluble proteins produced by T cells against antigens
• They are found in the serum, and the serum rich of antibodies is referred as antiserum.
• The immunoglobulins are the circulating antibodies
• Molecular weight ranges from 150,000 to 970,000 daltons
• Five classes of imunoglobulins are recognized (Ig G, Ig M, Ig D, Ig E and Ig A).
• All the immunoglobulins (Ig G,M,D,E) present both in blood and serum whereas Ig A is present in saliva.

When antigen is introduced to the body, the immunoglobulin production slowly increased to a level and again slowly decline in the body. This response is referred as primary antibody response. When second time introduced same antigen, the immunoglobulin production suddenly increased (10 – 100 time more than first time). This large raise of antibody production due to second introduction is referred as secondary antibody response. A typical immune system response is production of broad spectrum of immunoglobulin molecules against antigens. Normally a single clone of B cell will produce single type of immunoglobulin. So, when antigen is introduced, heterogeneous population of immunoglobulins will be accumulated in the serum, which is referred as polyclonal antiserum.

However, It is possible to produce a single antibody population (identical in structure and action) against antigens. This antibody is referred as Monoclonal antibodies.

• The monoclonal antibodies are used for research and clinical purpose
• Used for therapeutic applications
• Highly useful to cure cancers
• Identification of microorganisms is also possible by monoclonal antibodies.

B. Antigen specific T cell receptors (ATCs): They are the surface proteins produced by T cells. They are present on the surface of the T cells, whereas the immunoglobulins are present in serum. These proteins have short chained peptides, which can bind with antigens. These proteins are referred as ATC. The T cells can interact with antigens through ATC. After a complex formed, these T cells with antigen can move to B cell or phagocytes or memory cells to deactivate the antigens.

C. Cytokines: A soluble immune response modulators produced by leucocytes. They are the regulatory soluble proteins produced by lymphocytes during immune response. They are responsible for signal transduction and send information inside the cell for rate of metabolism, cell division, protein synthesis etc. Various leucocytes against antigens produce these three proteins as specific immune response.

Antigen - Antibody reaction

The study of antigen – antibody relation in vitro is called as serology. There are so many reactions will occur when antigen is reacted with antibody produced. The common reactions are as follows:

Neutralization – The toxin portion of antigen may be blocked by antibody so that it cannot act to cause the disease, referred as neutralization. The antibodies are here referred as antitoxins.

Precipitation – Generally antibodies have two binding sites. If two different antigens combined with antibody leads to precipitation of the complex occur which reduce the toxicity of the antigens.

Agglutination – If antigen is not soluble, the antibody forms a clumping ( mass like insoluble aggregates) when react with that antigen. The agglutinated clumps can be seen under microscopes.

IMMUNIZATION

So for the discussion is mainly about the immunity naturally developed against the pathogen or antigen. This immunity is inherent character, meaning the individual acquired the infection and that was controlled by natural immune system. This immune system is referred as natural active immunity. On the other hand, it is possible to induce the immune system of an individual by introducing antigens to the body. This process is known as vaccination or immunization. It is an artificial active immunity. The introducing material, antigen to the body is known as vaccine. The material used to induce the artificial immunity of the body, antigen or mixture of antigens, are referred as vaccines.

Following are some antigens used as vaccines:

1. Toxoids – Many pathogens produce exotoxins and endotoxins. These toxins were modified and used to induce the immune system, as vaccines are referred as toxoids. Ex. Diphtheria, Tetanus toxoids used as vaccines.

2. Attenuated cells – It is possible to isolate a mutant strain of pathogen which is avirulent but still has antigen are referred as attenuated strains. These cells when introduced, can induce the immunity without causing disease. Ex. Yellow fever, measles, mumps, polio causing viruses can be attenuated and used as vaccines.

3. Inactivated cell – Ex. Rabis virus inactivated cells used as vaccines.

4. Killed cells – Ex. Typhoids, Plague causing organisms – killed and used as vaccines

5. Polysaccharide of cell – Ex. Pneumonia causing bacterial polysaccharide used as vaccine

6. DNA – Ex. Hepatitis A and B viruses DNA were used after genetic recombination as vaccines.

DNA vaccines: The specific antigen producing gene can be introduced to host cell. The gene produces antigenic protein and stimulates the immune system. This type of vaccines is DNA vaccines.

Artificial Passive Immunity: The above discussed immunity development is artificially induces the native immune system. On the other hand, introduction of antibody directly to the body is also possible. The antibodies may be produced using some other mammals like cattle, horse etc. by introducing antigen to their body. Then, the antiserum (serum containing antibodies) obtained from cattle may be introduced to the individual. Such developed immunity is referred as passive immunity. In passive immunity,

• The individual will not expose to antigens;
• The individual’s immune system will not be induced;
• No immune memory will be there;
• Immunity development is rapid.

(Note: All these characters are just opposite to artificial active immunity).

Natural passive immunity: Passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta or through breastfeeding of milk to the born babies.