Acquired Immunodeficiency Syndrome(AIDS)

AIDS [Acquired Immunodeficiency Syndrome]

Think about the life of a socially isolated young boy whose mother died of AIDS recently. A number of social stigma and false beliefs are associated with the most dreadful disease –AIDS, a viral disease occurs due to reduction in number of helper T- cells which stimulate B- cells to produce antibodies. Occurrence of AIDS was first noticed amongst homosexuals in 1981 from USA and from prostitutes of Chennai , India in 1986.

AIDS virus also called Human Cell Leukaemia Virus III ( HCLV III) was first isolated by Robert Gallo (1986) but was named Human Immunodeficiency Virus (HIV) by ICVN in 1986. HIV belongs to group retrovirus characterized by the presence of RNA as genetic material and enzyme reverse transcriptase. It is believed that HIV may have passed from monkey host to human population during 1960s in Africa. Francoise Barre-Sinousi & Luc Montagnier were awarded Noble Prize in 2008 for AIDS research.

Structure & Life cycle of HIV:

Structurally HIV looks like a wheel having many radiating spokes with clubbed terminals with diameter of 90-120 nm. Each virus contains two single stranded RNA filaments associated with enzymes reverse transcriptase, protease& Integrase  and two protein coats(Core capsid P-24 and Matrix protein P-17) enveloped by lipid bilayer with projecting glycoprotein spikes   (transmembrane glycoprotein Gp-41 &surface glycoprotein Gp-120) derived from host cell membrane.

After entering into host, the virus infects macrophages where viral RNA replicates to form viral DNA with the help of enzyme Reverse Transcriptase. Now this viral DNA gets incorporated into host genome and starts producing new viral RNAs. Thus macrophages act like HIV Factory. The recognition of the specific host cell is due to the presence of glycoprotein CD-4 and co receptor in host membrane (CXCR-4 in T cells and CCR-5 in macrophages). Simultaneously HIV also enters into helper T- cells where it multiplies to produce and release new virions that lead to decrease in number of T- lymphocytes. AS a result of immune deficiency the patient fails to protect himself against any infection. Once HIV has weakened our immune system, series of multiple infections lead to AIDS.

Incubation period of HIV ranges from 6 months to 12 years. The progression of HIV includes Window period (2-12 weeks), symptomatic period (3-12 years) and AIDS period (2-3 years).

Transmission:

HIV spreads rapidly among people having multiple sex partners and injecting drugs through shared syringe. Women are biologically and socially more vulnerable to HIV infection because of periodical menstrual discharge through reproductive tract, larger vaginal surface for contact, cervical erosions and low status in society. AIDS viruses can be transmitted by various means like – Transfusion of infected blood, Sexual intercourse with infected person, Use of infected syringe /needle or razors, from mother to child through placenta and even organ transplants.

Symptoms:

It is quite difficult to identify AIDS as HIV infection leads to one or more symptoms which can be easily mistaken for many other diseases. Among those most common symptoms of AIDS include painless swollen glands in neck and armpit region, severe weight loss , persistent fatigue, night sweats, persistent diarrhea , fever lasting for several weeks, nausea and oral thrash etc.

Diagnosis:

HIV can be detected only by testing of blood samples. Diagnostic tests developed for AIDS are  ELISA ( Enzyme Linked Immuno Sorbent Assay) and Western Blotting. Western Blotting is used for the confirmation of ELISA positive cases.

Prevention & Control

It is very difficult to control AIDS because no effective drug or vaccine has been developed so far. Some anti retroviral drugs viz. Zidovudine /AZT( Azidothymidine), Didanosine ( Dideoxyionosine) are administered alone or in combination which slow down by interfering replication process of HIV. Thus prolonging the life of the HIV infected patient.

World Health Organization (WHO) , National AIDS Control Organization (NACO)and various NGOs are actively engaged in preventing the AIDS through various programmes which include many steps like educating people about AIDS, ensuring use of disposable and sterile syringe /needle, Blood testing before blood transfusion, avoiding sexual contact with multiple partners, need of safe sexual intercourse by using condoms, avoiding tatoos, ear and nose piercing from unqualified people etc. Every year December 1 is celebrated as World AIDS Day to  make aware and educate the people about AIDS so that social stigma, false beliefs  and alarming situation can be controlled in order to establish a healthy society.

Recap: AIDS-most dreadful viral disease caused by HIV –a retrovirus containing two single stranded RNA molecules associated with reverse transcriptase enzyme.Incubation period ranges from 6 months to 12 years. HIV is transmitted by Transfusion of infected blood, Sexual intercourse with infected person, Use of infected syringe /needle or razors, from mother to child through placenta. Most common symptoms include painless swollen glands in neck and armpit region, severe weight loss , persistent fatigue, night sweats, persistent diarrhea , fever lasting for several weeks & nausea. Diagnostic test for AIDS is ELISA. Some antiretroviral drugs viz. Zidovudine /AZT( Azidothymidine), Didanosine ( Dideoxyionosine) are administered to control AIDS.  NACO and WHO are actively engaged in preventing the AIDS through various programmes which include many steps like educating people about AIDS, ensuring use of disposable syringe and blood testing before transfusion.

Monoclonal Antibodies

[Hybridoma Tecchnique]

Most fantastic and wonderful use of cancer cells of lymphoid tissue called Myeloma in combination with plasma B cells of spleen came into light after the discovery of an enigmatic biomolecule – Monoclonal antibody. It not only helps to diagnose the tumour (cancer) but also to remove it without harming neighbouring normal cells.

These wonderful biomolecules are obtained from clone produced from single cell called Hybridoma and recognize only one kind of specific antigen (pathogen), hence called monoclonal antibodies.

The idea of producing monoclonal antibodies by involving human–mouse hybrid cells was first described by Jerrold Schwaber in 1973. Later three Scientists  Georges Kohler, Cesar Milstein and Niels Kaj Jerne (1975) while working on these immunoglobulin,  developed a technique for producing monoclonal antibodies for which they were awarded Noble prize in1984. The technique used for producing these unique immunoglobulin involves following steps:

1                 A mouse is inoculated with specific  desired antigen that induces the production of antibodies against antigen.

2                 Now plasma B- cells from spleen of immunized mouse are removed from suspension which have developed the ability to produce antibodies.

3                 These spleen B – cells are then mixed with cancer cells of lymphoid tissue called Myeloma cells which have an ability to proliferate indefinitely and grow continuously.

4                 The plasma B – cells and myeloma cells are fused together to form hybrid cells called HYBRIDOMA. These hybrid cells are capable of growing indefinitely in culture and producing antibodies of single type continuously.

5                Hybridoma cells are isolated through selective medium called HAT medium because it contains Hypoxanthine, Aminopterin and Thymidine. Unfused myeloma cells fail to grow on this media because they lack an enzyme hypoxanthine-guanine-phosphoribosyl transferase (HGPRT).

Since immortal Hybridoma clone  is developed from single cell, all cells of clone are genetically identical and produce one type of antibody called monoclonal antibody. As compared to ordinary antibodies, monoclonal antibodies are more uniform and pure. Therefore, they are highly specific and are used to pinpoint the antigen present on surface of parasites.

Because of great affinity and specificity to a particular antigen, these are more effective and ideal for diagnosis as well as treating many diseases. Monoclonal antibodies can be used as highly efficient diagnostic tool for identification of specific pathogen/antigen. When a monoclonal antibody conjugated with a fluorescent dye is injected in patient ,it reaches to and gets attached with specific antigen present in a particular tissue/organ which can be scanned to detect the occurrence of pathogen/antigen.  A number of diagnostic kits like GONOZYME and CHLAMYDIAZYME have been developed by using monoclonal antibodies to identify Gonorrhoea and Chlamydial urethritis respectively.

Monoclonal antibodies are very effective in treating tumours. When monoclonal antibodies against tumour antigens are injected in patient’s body, they reach to and react specifically with tumour cells and destroy them without affecting other normal cells. These antibodies may be tagged with certain drugs and will remove only cancer cells specifically without harming other tissues

Monoclonal antibodies play an important role in organ transplant as these are used to reduce the chances of organ rejection by modifying/suppressing auto immune response after organ transplant. These are also used for cleansing bone marrow before transplant in treating immune system disorder.

Recap: Discovery of the wonderful and enigmatic biomolecule called monoclonal antibody was made by George Kohler and C Milstein (1975) for which they shared Noble prize (1984). These antibodies are synthesized from a clone of Hybridoma which is formed from the fusion of Myeloma and immunized B cell. It recognizes only one kind of specific antigen. Because of great affinity and specificity to a particular antigen these are used as an effective diagnostic tool and medicine for many diseases like tumour, gonorrhea and autoimmune disorder etc.