Acquired Immunodeficiency Syndrome (AIDS)
Introduction of Acquired Immunodeficiency Syndrome (AIDS)
Acquired Immunodeficiency Syndrome (AIDS) is caused by a lentivirus i.e., humans immunodeficiency virus (HIV). It has the following characteristics,
- Opportunistic infections lead to suppression of the immune system.
- Secondary tumors and neurological manifestations are seen.
Etiology of Acquired Immunodeficiency Syndrome (AIDS)
Causative agent is a retrovirus called Human immunodeficiency virus (HIV) which belongs to the family Retroviridae. HIV-1 and HIV-2 cause the disease with same properties and antigens, but differ only in genetic terms. HIV-1 is common in Europe, United States and Central Africa whereas HIV-2 E is found in West Africa and India.
The features of both forms include,
- Incubation period which is followed by slow fatal outcome.
- Tropism for haematopoietic and nervous system.
- Suppression of Immunity.
Routes of Transmission of Acquired Immunodeficiency Syndrome (AIDS)
- By sexual contact.
- Parenteral transmission (use of contaminated needles during blood transfusion).
- Transplacental transmission from infected mother to foetus (during pregnancy or during parturition through amniotic fluid)
Structure of HIV
Retrovirus (HIV) is spherical in shape with size ranging in between of 100 – 140 nm. It contains an electron dense core surrounded by a lipid membrane. The core is made up of two RNA strands, reverse transcriptase enzyme and core proteins (p24 and p18). The core is surrounded by a lipid bilayer which is studded with two viral glycoproteins (gp120 and gp41). These glycoproteins are important for HIV infection. HIV-1 genome contains genes namely gag, pol, env and fat.
- Gag for the production of core proteins (p24 and p18).
- Pol for reverse transcriptase enzyme.
- Env for envelope or lipid proteins (gp120 and gp41).
The above genes act as markers for diagnosis in laboratory.
- Tat gene (transactivator) is responsible for carrying out the functions of viral amplification, budding and replication.
Pathophysiology of Acquired Immunodeficiency Syndrome (AIDS)
The two major systems affected by HIV are immune system (T cells and B cells) and central nervous system.
1. Pathogenesis of Immune System
Immune system is made up of T cells (cell-mediated immunity) and B cells (antigen-antibody mediated immunity).
(a) T Cells
HIV mainly affects the cell-mediated immunity. The normal function of T cells is recognition and binding to specific of T cells receptors. T cells express a variety of molecular protein complexes like CD3, CD4, CD8, CD11 and CD2. Of all these protein complexes CD4+ T cells (60% T celles) and CD8+ T cells (30% T cells) are epxressed as mutually exclusive subsets. CD4+ T cells have the following functions.
1. They are the master regulator of the immune system.
2. Secrete some soluble factors like cytokines which influence other T cells of the immune system. Hence, if CD4+ T cells count are less, then it indicates that the regulations of immune system is not proper. Intensity of the disease is measured by counts of CD4 and CD8 cells.
Pathogenesis of destruction of Immunity of HIV
HIV enters the human body and exhibits selective tropism for CD4 cells (acts as a receptor). It also enters monocytes and macrophages. The initial step is binding of HIV to CD4 through gp120. This binding is followed by fusion of HIV with T cell. This is known as internalization. The virus lacks DNA (which is necessary for cell multipliaction), hence reverse transcriptase produce c-DNA (complementary DNA – a proviral DNA which helps in multiplication) through reverse transcription process. The state of T cell also plays an important role during viral replicaton. If the T cell remains in a crescent state, then the virus remains in the T cell for many years without dividing. But, if the T cells are active, then the virus divides. During division of T cell, the c-DNA enters the T cell and integrates into the post genome of T cell by budding. Such type of infection is known as productive infection. Initiation of pro-viral DNA transcription occurs which the infected cell is activated by exposure to antigen.
Macrophages and monocytes are also infected by HIV. Majority of macrophages infected by HIV are express CD4+ T cells (but in low quantities) which aids in the binding of HIV to macrophages. Budding and multiplication of infected macrophages occur in a slow manner when compared to infected T cells. The infected macrophages act as, reservoir for the viral particles, safe vehicle for the transportation of virus from one part of the body to another.
(b) B cells
B cells are destroyed by glycoprotein (gp120) of HIV. The cell-mediated immunity (by T cells) is relatively affected than anti-gen antibody mediated immunity (by B cells).
Phases of HIV infection
- Early/Acute Phase
It represents the initial response of the body to virus. Non-specific symptoms like sore throat, rashes occur which subside after 2-3 weeks.
- Middle/Chronic Phase
It is a period of clinical latency as no signs and symptoms are observed. The immune system is intact and HIV replication occurs slowly (confined only to lymphatic system). Latent phase last for 7 to 10 days.
- Final/Crisis Phase
During this phase the patient is diagnosied, whien the immune system is at total risk. The symptoms include, long-lasting fever, severe weight loss, persistent diarrhea, fatigue, reduced CD4+ T cell count, high risk of developing infections or oral candidiasis.
Signs and Symptoms of Acquired Immunodeficiency Syndrome (AIDS)
Individuals may not show any symptoms initially but in severe cases, there may be weight loss, diarrhea, fever, night sweats, oral candidiasis (fungal infection), skin rashes, flaky skin, short term memory loss, severe pain or numbness in hands and feet.`
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