HIV and AIDS Tutorial

Immunology and HIV

Immune system's response to HIV

HIV is stopped by innate defenses. HIV cannot penetrate unbroken skin. HIV is transmitted through direct exchange of body fluids. Sexual intercourse is the most common mode of transmission. Blood to blood contact, such as through sharing needles for intravenous injection or blood transfusion can also transmit HIV. Infected mothers can pass HIV to their infants during pregnancy, birth and breastfeeding.

Additional information about HIV transmission

HIV transmitted through sexual activity enters the bloodstream via mucous membranes lining the vagina, rectum and mouth. Macrophages and dendritic cells on the surface of mucous membranes bind virus and shuttle it into the lymph nodes, which contain high concentrations of helper T cells (CD4+ T cells).

Once HIV has entered the body, the immune system initiates anti-HIV antibody and cytotoxic T cell production. However, it can take one to six months for an individual exposed to HIV to produce measurable quantities of antibody. The immune response is weakened as memory T cells (CD4⁺ CCR5⁺) are destroyed.

The figure shows a scanning EM picture of a dendritic cell interacting with helper T cells. This process occurs in lymph nodes and regulates immune responses.

Copyright ©1999 Massachusetts Medical Society. All rights reserved. Used and adapted with permission.
New England Journal of Medicine 340:1732

HIV mediated disease

HIV enters the body and binds to dendritic cells (orange cells with projections) which carry the virus to CD4+ T cells in lymphoid tissue establishing the infection. Virus replication accelerates producing massive viremia and wide dissemination of virus throughout the body's lymphoid tissues. An immune response against virus causes some protection but a chronic persistent infection is established. The production of cytokines and cell divisions that regulate the immune response for protection also cause HIV replication. There is a rapid turnover of CD4+ T cells that ultimately leads to their destruction and to a change in lymphoid tissues that prevent immune responses. The figure is taken from Nature Medicine 9, 839 (2003) and is reproduced with permission.

Infected cells produce massive amounts of virus


New copies of HIV bud from the surface of an infected Helper T cell	Enlarged view

Cellular immune responses to HIV

Cytotoxic lymphocyte production follows the rise of HIV in the blood.
HIV specific CD4+ T cells may be especially susceptible to attack and destruction by HIV. HIV binds to CD-SIGN, a glycoprotein expressed on dendritic cells. Migration of HIV bearing activated dendritic cells to helper T cell areas of lymph nodes may specifically infect helper T cells specific for HIV peptides.
Reductions in HIV specific helper T cell numbers may lead to decreased activation and survival of cytotoxic CD8 T cells.
Reduced CD4 T cells may also result in an incomplete activation of CD8 T cells that can remove HIV infected cells, resulting in a decreased ability to destroy virally infected cells.
The rapid loss of memory helper T cells, and the inability to replace these cells leads to increasing immunodeficiency.
High mutation rates of HIV also allow virus to escape adaptive immune responses.

Why are CD4⁺ T cells depleted by HIV?

Many models have been proposed.
The most recent ideas center around the fact that CD4 and CCR5 are co-receptors for HIV.
Expression of CD4 and CCR5 is highest in memory T cells that reside in mucosal effector lymphoid tissue.
The major site of mucosal immunity is in the intestinal immune system, and HIV rapidly infects and destroys these cells, even in patients undergoing therapy.
The progression of HIV infection to AIDS probably depends on how well our body can replace cells destroyed by virus.

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