Acquired ImmunoDeficiency Syndrome اعداد الطالبين : عمار بشار - عمر رزوقي

Acquired immunodeficiency syndrome: is an infectious secondary form of immunodeficiency caused by the retrovirus HIV-1, resulting in a defect in cell-mediated immune response (therefore, leads to immune suppression) that is manifested by increased opportunistic infections and to certain rare cancers HIV: A retrovirus that causes AIDS by infecting helper T cells of the immune system. The most common type, HIV-1, is distributed worldwide, while HIV-2 is primarily confined to West Africa.

HIV virus can be classified into 2 groups on the basis of their ability to infect macrophages an T- helper cells into:HIV virus can be classified into 2 groups on the basis of their ability to infect macrophages an T- helper cells into: 1. M-tropic which can infect both macrophages and freshly isolated peripheral T-cell.1. M-tropic which can infect both macrophages and freshly isolated peripheral T-cell. 2. T-tropic which can infect only activated T-cell.2. T-tropic which can infect only activated T-cell.

Structure of the Human Immunodeficiency Virus

Receptors and co-receptors on the cell surface of the target cell infected by HIV

Routes of transmission: HIV is transmitted primarily via sexual intercourse, contaminated blood transfusions and hypodermic needles, and from mother to child during pregnancy (vertical transmission), delivery, or breastfeedingHIV is transmitted primarily via sexual intercourse, contaminated blood transfusions and hypodermic needles, and from mother to child during pregnancy (vertical transmission), delivery, or breastfeeding

Pathogenesis:Pathogenesis: The main targets for HIV virus : The main targets for HIV virus : 1.immune system “immunopathogenesis”1.immune system “immunopathogenesis” 2.C.N.S2.C.N.S

1. immunopathogenesis : the HIV infect mainly cells which have CD4 receptor on their surface, which are: 1. T-helper cells 2. Macrophages 3. Dendritic cells 4. Microglial cells 5. other cells

Immunopathogenesis of HIV disease (continued) the main event that occur during the infection is the destruction of CD4+ cells by HIV.the main event that occur during the infection is the destruction of CD4+ cells by HIV. since the CD4+ cells are very crucial to the immune system,it ’ s destruction leads to immune suppressionsince the CD4+ cells are very crucial to the immune system,it ’ s destruction leads to immune suppression Due to immune suppression, opportunistic infections occur and neoplasms develop Due to immune suppression, opportunistic infections occur and neoplasms develop

The mechanism of CD+4 destruction or loss:The mechanism of CD+4 destruction or loss: A. Death of infected cell (cytopathic effect of the virus)A. Death of infected cell (cytopathic effect of the virus) B. Activation-induced cell death (apoptosis)B. Activation-induced cell death (apoptosis) C. Killing of the infected cells by virus specific cytotoxic T-cellC. Killing of the infected cells by virus specific cytotoxic T-cell

Pathogenesis of C.N.S. involvement:Pathogenesis of C.N.S. involvement: Nervous system is a major target of HIV infection either directly or indirectly.Nervous system is a major target of HIV infection either directly or indirectly. Macrophages and microglial cells are the predominant cell type infected with HIVMacrophages and microglial cells are the predominant cell type infected with HIV Infected macrophages can act as HIV reservoirs and as vehicles for viral transport especially to C.N.S.Infected macrophages can act as HIV reservoirs and as vehicles for viral transport especially to C.N.S.

C.N.S. injury can occur directly by the infection of the virus itself (the mechanism is obscure because the virus doesn ’ t attack the neurons) or indirectly by the viral products & factors produced by macrohages /microglial cells e.g. IL1,TNF, &IL6C.N.S. injury can occur directly by the infection of the virus itself (the mechanism is obscure because the virus doesn ’ t attack the neurons) or indirectly by the viral products & factors produced by macrohages /microglial cells e.g. IL1,TNF, &IL6

Life cycle of HIV

Initially, HIV-1 infects T cells and macrophages directly or is carried to these cells by Langerhans cells. Viral replication in the regionalInitially, HIV-1 infects T cells and macrophages directly or is carried to these cells by Langerhans cells. Viral replication in the regional lymph nodes leads to viremia and widespread seeding of lymphoid tissue. The viremia is controlled by the host immune response and the patient then enters a phase of clinical latency.lymph nodes leads to viremia and widespread seeding of lymphoid tissue. The viremia is controlled by the host immune response and the patient then enters a phase of clinical latency.

During this phase, viral replication in both T cells and macrophages continues unabatedDuring this phase, viral replication in both T cells and macrophages continues unabated There continues a gradual destruction of CD4+ cells by productive infection Ultimately, CD4+ cell numbers decline, and the patient develops clinical symptoms of full-blown AIDS.There continues a gradual destruction of CD4+ cells by productive infection Ultimately, CD4+ cell numbers decline, and the patient develops clinical symptoms of full-blown AIDS.

Syndromes associated with AIDSSyndromes associated with AIDS A. Opportunistic infection B. Neoplasms B. Neoplasms A. Opportunistic infection: CandidiasisCandidiasis ToxoplasmosisToxoplasmosis Herpes simplex virusHerpes simplex virus Pneumocystis jiruvechii (formerly P.carinii)Pneumocystis jiruvechii (formerly P.carinii) CytomegalovirusCytomegalovirus MycobacteriaMycobacteria and othersand others

B.Neoplasms Kaposi sarcomaKaposi sarcoma B-cell non-Hodgkin lymphomasB-cell non-Hodgkin lymphomas Invasive cancer of uterine cervixInvasive cancer of uterine cervix Primary lymphoma of the brainPrimary lymphoma of the brain othersothers

Oral thrush )candidiasis)

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