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Unit - IV B Immune System

        Immunity is the ability to resist or eliminate harmful foreign microbes and their products. The network of organs, cells and proteins that protect the body from harmful foreign microbes (e.g.: Bacteria, viruses, parasites, fungi etc.,) and their products is known as Immune System. Study of Immune system is known as   Immunology. Edward Jenner was considered as Father of Immunology.
 

I. Basic concepts of Immunology


1. Lines of immunity or lines of defence in the body:
i. Whenever harmful microbes try to enter the body, the skin, mucous membranes and the enzyme lysozyme in saliva and tears prevent their entry. It is the first line of defence.
ii. If the harmful microbes cross the first line of defence, the phagocytes, natural killer cells, antimicrobial substances, fever etc., destroy them. It is the  second line of defence.
iii. If the harmful microbes cross the above two barriers, lymphocytes and  antibodies fight against them. It is the third line of defence.

* The first two types of defences are fast reacting and non specific.
* The third type is highly specific and takes long time.
* If the above three lines of defence are failed, the result is disease.

2. Cells of Immune System:
A. Lymphoid Cells:
These are the chief cells of immune system. They are classified into three types.
i. B - Lymphocytes (B - cells): These lymphocytes are capable of producing antibodies and capture the circulating antigens. They are produced from stem cells in the bone marrow in adults and in foetus, from liver (From bursa fabrici in birds). Mature B - cells produce antibodies. As these antibodies take antigens, they are called immuno competent B - Cells. The mature B - cells enter the secondary lymphoid organs and then become two types of functional cells, namely memory cells (Long lived and store information about specific antigen for quick response) and plasma cells (produce specific antibodies).
ii. T - Lymphocytes (T - cells): These lymphocytes are not capable of producing antigens. They are produced in bone morrow, reach the thymus gland and mature. Now they are called immuno competent T - cells. In secondary lymphoid organs, they become functional cytotoxic T - cells and memory T-cells.

        On the surface of T - lysmphocytes, cluster of differentiation molecules (CD markers) [Glycoproteins] are present. Based on them, T - lymphocytes are divided into two types, viz, CD4 + cells or T4 cells and CD8 + cells or T8 cells functionally, T - lymphocytes are divided into T - helper cells and T - cytotoxic cells.
      T - helper cells (TH cells) - These are CD4 + type cells. They recognise the antigens presented by the antigen presenting cells (APCs). They help the B - cells in producing antibodies; help the mononuclear phagocytes in phagocytosis and activate cytotoxic T cells (Tc Cells) to initiate cell mediated immunity.
→ TH cells are involved in humoral immunity and cell mediated immunity.
→ TH cells involved in rejection reactions of transplants.
→ TH cells secrete gamma interferon which stimulates the cells like macrophages (which secrete cytokinins).
T - Cytotoxic cells (Tc - Cells) or Killers T - Cells: These are CD8 + cells.These cells recognise the antigens presented by the antigen secreting cells. Whenever they receive an antigen, they become cytotoxic T - cells or effector T - cells and kill , analyse the infected host cells and tumour cells. Hence Tc cells are involved in cell mediated immunity only.

iii. Large granular lymphocytes (Natural killer cells - NK Cells)
           These cells form the most important cells of defence and they destroy the infected cells or altered self cells such as cancer cells in an antibody independent manner (non specific). The action of NK is very fast.
B. Phagocytes: (2 Types)
a. Mononuclear Phagocytes (MNP):
These are uninucleate cells of blood, known as monocytes. They reach the extra cellular fluid through capillaries and become histiocytes (in connective tissue); Kupffer cells (in liver); microglia (in brain); Osteoclasts (in bone) and synovial cells (in joints).
b. Polymorphonuclear Phagocytes: These are granulocytes in blood (neutrophils, basophils and oesinophils) 
 These cells are capable of ingesting and digesting microorganisms, dead cells, cellular debris etc.

C. Auxillary cells:
          Cells that help the lymphocytes in immune responses are called auxillary cells. These cells include basophils, mast cells, platelets etc., These cells produce inflammatory mediators which cause inflammation in the surrounding tissues.

3. Organs of Immune system: (2 Types)
A. Primary lymphoid organs:
The organs in which lymphoid stem cells become mature lymphocytes are considered as primary lymphoid organs.
e.g.: Thymus gland and bone marrow of mammals. Bursa fabrici in birds.
B. Secondary lymphoid organs: The organs in which mature lymphocytes are transformed into functional lymphocytes are considered as lymphoid organs. These organs provide sites for interaction of lymphocytes with antigen.
e.g.: Lymph nodes, tonsils, appendix, payers patches of intestine, spleen etc.
 Spleen lies below the diaphragm in the left side of abdomen. It contains lymphocytes and phogocytes. It filter the blood and trap the microorganisms in it. It is the reservoir of RBC and grave yard of worn out RBC.
 Lymph nodes are located at different places along the lymphatic system.They trap microorganisms and antigens.

4. Soluble mediators of Immunity: (3 types)
A. Complement proteins:
These are a group of inactive plasma proteins and cell surface proteins. On activation, they form membrane attack complex that forms a pore in plasma membrane allowing ECF to enter the cell to make it swell and burst. Some of the complement proteins form a cover on antigens and attract neutrophil and macrophases to destroy them.
B. Cytokines: These are low molecular weight substances secreted by the TH - cells or infected cells. They bind to cell surface receptors to initiate cells of immune system to act on infected cells. Cytokinins are of two types, namely, interleukins and interferons.
i. Interleukins: These are the cytokines secreted by leucocytes. They are involved in differentiation of the cells of immune system.
ii. Interferons: These are produced by virus infected cells and are involved in protecting the neighbouring cells from the virus infected cells. Interferons are of three types, namely, α, β and γ interferons.
C. Immunoglobulins or antibodies:
           Whenever antigens enter the body, B - lymphocytes produce antibodies, that   bind to the antigens and destroy them. Antibodies are highly specific.

i. An antibody consists of four polypeptide chains, viz, two light chains (L) and two heavy chains (H). The H chain and L chain are linked by disulphide bonds to form Y - shaped molecule.

ii. The ends of two arms of Y are called variable regions.
iii. The distal end of each arm of Y is known as Fab region, which binds to antigen.
iv. The lower parts of arms are called constant regions (C).
v. The stem of Y is known as Fc region. It binds to the complement proteins or Fc receptors of cells (like phagocytes, mast cells etc.,). 

 The part of antibody that recognises and attached to antigen is known as paratope.
    The portion of antigen that binds to paratope is called  epitope.

vi. Based on the type of heavy chains, antibodies are classified to five types, namely, IgM, IgG, IgD, IgA and IgE.
vii. Antibodies are of two types-
 Membrane bound antibodies - Present on cell membrane of immuno competent B - cells.
 Secreted antibodies - Circulate in the body fluids.

5. Antigens or Immunogens: 
     A substance that binds specifically to the B - lymphocyte receptor, or to the T - lymphocyte receptor when complexed with major histocompatibility complex (MHC) is known as an antigen or immunogen. Antigen is a substance capable of eliciting an immune response.
 i. Immune system does not recognise the entire infectious organism but recognises particular   macromolecues of it, generally either proteins or polysaccharides.
ii. Antigens may be freely circulating in body fluids or present inside the infected cells or on the cell surface (like antigens of blood groups).
iii. The epitope of antigen binds to the paratope of the antibody. An antigen can have repeats of the same or different types of epitopes.
iv. Whenever antigen enters the cell, it was broken by the enzymes of lysosomes. The broken pieces are the antigenic determinants (epitopes). [This is called processing of antigens].
v. These antigenic determinants are presented by special groups of molecules called MHC, which are of two types.
 Class - I MHC molecules - Found on the surface of all nucleated cells of the body. They present antigens to Tc cells for cell mediated immunity.

Class - II MHC molecules - Found on the surface of antigen presenting cells and lymphocytes. They present antigens to TH cells for cell mediated or humoral immunity

II. Types of Immunity:
     Based on the immune response, immunity is mainly divided into two types, viz., innate and acquired.
1. Innate immunity: It is the inborn resistance to diseases. It consists of four types of barriers
    a. Physical barries - Skin, mucus membranes etc.
    b. Physiological barries - HCl in stomach, saliva in mouth, tears in eye etc.
    c. Cellular barriers - Polymorpho neuclear leucocytes, monocytes, NK cells etc.
    d. Cytokine barriers - Secreted by the immune cells protect non infected cells from infected cells.
2. Acquired (Adaptive) immunity: The immunity developed during the life of an individual is known as acquired immunity. It is characterised by specificity, diversity and memory. It is of two types, viz., active acquired immunity and passive acquired immunity.
A. Active acquired immunity: Immunological resistance developed by the production of antibodies due to antigenic stimuli. It is long lasting immunity. This immunity is of two types:
a. Natural acquired active immunity: It is the resistance developed by an individual in response to a natural infection.
e.g.: Aperson can acquire life time immunity after recovering infection of small pox, chicken pox etc.

b. Artificial acquired active immunity: It is the immunity developed by an individual due to inoculation of weakened antigens.
e.g.: Vaccination for Polio
B. Passive acquired immunity: It is the immunological resistance developed due to transfer of readymade antibodies. It is divided into two types:
    a. Natural passive immunity: It is the transfer of preformed antibodies from mother to child.
   e.g.: Transfer of antibodies from mother to foetus through placenta. 
           Transfer of antibodies from mother to child through colostrum.
     b. Artificial passive immunity: It is the immunity developed due to transfer of antibodies from an immunised donor to non immunised recipient.
    e.g.: Injection of Anti Tetanus Serum (ATS),
            Injection of antivenin against poison of snake.
            Based on types of responses, immunity can be divided into two types,namely, humoral immunity and cell mediated immunity.

A. Humoral Immunity: Immunity mediated by antibodies that are released into body fluids (e.g.: Plasma, lymph) is called humoral immunity. It involves the interaction of B - cells with free antigens
Mechanism:
i. In secondary lymphoid organs, the free antigens bind to Fab end of the antibodies that are present on the surface of mature B - cells.
ii. B - cells engulf and process the antigens.
iii. Then they display the antigenic fragments on their membrane with the help of class II - MHC molecules.
iv. Then appropriate TH cells recognise them and interact with the antigen MHC - II complex and release a type of interleukin, which stimulates the B - Cells to proliferate and differentiate into memory cells and plasma cells.
v. The plasma cells release specific antibodies into the plasma or ECF.
vi. These antibodies help in opsonising and cross linking of antigens leading to agglutination of insoluble antigens and precipitation of soluble antigens.
vii. They also activate the phagocytes and complement system.

The products of antigen and antibody reactions are known as antigen - antibody complexes or immuno - complexes, which are removed by oesinophils and monocytes.

B. Cell Mediated Immunity: Immunity mediated by the activated T - cells, NK cells etc., is known as cell mediated immunity. It does not involve antibodies.
Mechanism: Antigen presenting cell engulf the antigens. It processes the antigen and displays antigenic fragment on their membrane, bout to clean II MHC molecule. TH cell recognises and interacts with antigen class II MHC molecule complex. Activated TH cells secrete interleukin - 2. Tc cells bind to antigen class I MHC molecule complex an altered self cells. Interleukin - 2 causes proliferation and differentiation of antigen activated Tc cell into a clone of effector CTLs. CTLs attach to appropriate target cells and release perforins and grazymes. Perforins form pores on the target cell membrane. Granzymes enter the target cells and initiate reactions that destroy the infected cell DNA. Some Tc cells remain as long lived memory T cells.

III. Immunisation/Vaccination:
1. The process of immunisation involves the inoculation/introduction of attenuated or weakened pathogens or antigenic proteins of pathogen into the body of host.
2. They induce the production of antibodies in the host and also generate memory B - cells and memory T - cells.
3. On subsequent exposures, the memory cells recognise that pathogen quickly and over come the invader with a rapid and massive production of antibodies.
 
Large scale production of vaccines is now possible with r DNA technology.
e.g.: Hepatitis - B vaccine is produced by using genetically modified yeast.

IV. Immunological disorders:
1. Immunodeficiency disorders:
A. Acquired Immuno Deficiency Syndrome (AIDS):

           AIDS is a collection of symptoms and infections in the final stage of the disease caused by Human Immuno deficiency Virus (HIV). It is a non congenital, transmissible, lethal, sexually transmitted disease. It was first recognised in 1981 in USA. HIV is a retrovirus (RNA Virus that uses reverse transcriptase).

Mode of infection:
i. Homosexual and heterosexual contact
ii. Syringe needles
iii. Blood transfusion
iv. Organ transplantation
v. Artificial insemination
vi. Mother to foetus through placenta
vii. Mother to child through breast feeding
 HIV is not transmitted by insects or casual contact such as shaking hands or sharing household items.

Structure of HIV:
     HIV is a retrovirus containing two single strand RNA (ss RNA) molecules (genetic material) and two molecules of reverse transcriptase. They are surrounded by a protein coat, then a layer of proteins and then outer lipid layer. Lipid layer contains a number of glycoproteins such as gp41 and gp120. During infection there glycoproteins bind to host cell surface proteins.


Replication of HIV:
i. After infection to a person the HIV enters the TH cells macrophages or dendric cells.
ii. In these cells, the ss RNA synthesises a DNA strand complementary to viral RNA in presence of reverse transcriptase.

iii. Reverse transcriptase catalyses the synthesis of another strand of DNA and thus a double strand DNA is formed.
iv. This viral DNA gets incorporated into the DNA of the host cell with the help of viral enzyme - integrase.
v. Transcripted RNA from this DNA will act as the genome for the new or it can be transmitted into viral proteins.
vi. Now the infected host cells act as HIV generating factories. New viruses are bud off from the host cell.
vii. As a result, progressive decrease in the number of TH cells of the infected person leading to immuno deficiency.
viii. Attack on certain types of cells or tissues only by viruses such as HIV is referred to as tissue tropism.

 

Symptoms
      The progression from HIV infection to AIDS takes about 10 years in adults. Progress of HIV Infection in adults can be divide into three phases.

i. Asymptomatic or chronic lymphadenopathy (swollen lymph nodes).
ii. Symptomatic stage is characterised by persistent infections by Yeast, shingles (a viral infection) and certain cancerous conditions of cervix.
iii. In clinical AIDS stage, several opportunistic infections characteristic of AIDS such as Yeast, Tuberculosis, Pneumonia, Taxoplasmosis of brain and Kaposi's sarcoma (rare cancer caused by a virus) appear.
Diagnosis:
       The diagnosing test for HIV infection is ELISA [Enzyme Linked Immuno  Sorbent Asasy]. It is a screening test. The reliable test for HIV infection is Western  blot test.
Treatment:
        Reverse transcriptase inhibitors and protease inhibitors are used in the treatment (anti retroviral drugs). Nucleoside analogs such as Zidovidine or Azidothymine are used to inhibit reverse transcription. These drugs only delay the progress of infection but are not a cure.
Prophylaxis:
I. Discouraging casual and indiscriminate sexual relations.
II. Use of condoms.

III. Proper Sterilisation of Syringes and needles.
IV. Screening of blood donors. 
 In our country, National AIDS Control Organisation (NACO) and other non Governmental Organisations are doing a lot to educate the people about AIDS

B. Hypersensitivity (Allergy):
      The undesirable reactions produced by the normal immune system including allergies and autoimmunity. These reactions may be damaging, uncomfortable or occasionally fatal.
      Hypersensitivity reactions are of various types in which Type I - hypersensitivity is called allergy. Allergy is due to secretion of histamine and/or serotonin from the mast cells. IgE type antibodies are responsible for the allergies. The allergy inducing substances are know as allergens (e.g.: dustmites, pollen, animal dander etc.,). The common symptoms of allergy are watering of eyes, rhinitis (running nose), difficulty in breathing etc.

2. Auto immune disorders:
i. Our immune system can recognise our proteins and does not attack on own tissues.
ii.Rarely, in some cases, our immune system fails to recognise some of the own proteins and treat them as foreign antigens and attack on own tissues. It leadsto fatal conditions, known as auto immune disorders.
iii.  Rheumatoid arthritis, grave's disease etc., are examples for auto immune disorders.
iv. Auto immune disorders can be controlled to some extent by administering immuno suppressants.

3. Graft Rejection:
i. A surgical procedure to transplant a tissue (e.g.: Cornea, heart, liver, kidney etc.,) from a donor to a recipient (when such tissue fails) is known as grafting.
ii.The recipient body identifies the graft and initiates graft rejection. Hence tissue matching and blood group matching are essential before transplant surgery.
iii. After the surgery, the recipient will be given immuno suppressant drugs to avoid graft rejections.

Posted Date : 29-10-2020

గమనిక : ప్రతిభ.ఈనాడు.నెట్‌లో కనిపించే వ్యాపార ప్రకటనలు వివిధ దేశాల్లోని వ్యాపారులు, సంస్థల నుంచి వస్తాయి. మరి కొన్ని ప్రకటనలు పాఠకుల అభిరుచి మేరకు కృత్రిమ మేధస్సు సాంకేతికత సాయంతో ప్రదర్శితమవుతుంటాయి. ఆ ప్రకటనల్లోని ఉత్పత్తులను లేదా సేవలను పాఠకులు స్వయంగా విచారించుకొని, జాగ్రత్తగా పరిశీలించి కొనుక్కోవాలి లేదా వినియోగించుకోవాలి. వాటి నాణ్యత లేదా లోపాలతో ఈనాడు యాజమాన్యానికి ఎలాంటి సంబంధం లేదు. ఈ విషయంలో ఉత్తర ప్రత్యుత్తరాలకు, ఈ-మెయిల్స్ కి, ఇంకా ఇతర రూపాల్లో సమాచార మార్పిడికి తావు లేదు. ఫిర్యాదులు స్వీకరించడం కుదరదు. పాఠకులు గమనించి, సహకరించాలని మనవి.

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