IMMUNODEFICIENCIES HIV 324 PHT Dr. Sarah I. Bukhari PhD in Clinical Microbiology Department of Pharmaceutics Office: rd floor

Objective:  Describe immunodeficiency  Types of immunodeficiency diseases  HIV  Origin and history  Structure  Pathogeneicity  Stages of HIV infection

Immunodeficiency  The absence of a sufficient immune response, which can be either: CongenitalAcquired

Congenital Immunodeficiencies  Defect or absence in a number of inherited genes  DiGeorge’s syndrome  An animal equivalent; is the Nude hairless mouse

Acquired Immunodeficiencies  A Varity of drugs, cancers or infectious agents  Hodgkin's disease: (a type of cancer) lowers the cell-mediated response.  Removal of spleen : decreases humoral immunity.  Many viruses including HIV

HIV

Origin & history  1981: In US, cluster of Pneumocystis pneumonia and Kaposi's sarcoma in young homosexual men discovered. The men showed loss of immune function.  1983: Discovery of virus causing loss of immune function and was called the human immunodeficiency virus or HIV.  1986: A second strain of HIV was identified and was called HIV-2 and the first strain was renamed HIV-1  HIV-1 and HIV-2 differ in their virulence and geographical location

Origin & history  Genetic studies indicated that the HIV-2 is a mutation of a simian immunodeficiency virus (SIV) where mangabey monkeys in West Africa are naturally and harmlessly infected with this SIV  More recently, studies show that HIV- l (the primary HIV found worldwide in humans) is genetically related to another SIV that is carried by chimpanzees in Central Africa  HIV is thought to have crossed the species barrier into humans in central Africa in the 1930 

Origin & history  Patient who died in 1959 in Congo is the oldest known case.  Virus spread in Africa as result of urbanization. World-wide spread through modern transportation and unsafe sex.  Norwegian sailor who died in 1976 is the first known case in Western world.

The human immunodeficiency virus (HIV)  HIV is not synonymous with AIDS  The structure of HIV  HIV, of the genus lentivirus, is a retrovirus  Clades (Subtypes) of HIV

Infectiveness & Pathogenicity of HIV 1. Attachment2. Fusion3. Entry ** T-cells, Macrophages and monocytes HIV is often spread by dendritic cells, which pick up the virus and carry it to the lymphoid organs. There it contacts cells of the immune system, most notably activated T cells, and stimulates an initial strong immune response. Figure 19.13

Latent vs. Active HIV Infection in CD4+ T Cells LatentActive

Latent vs. Active HIV Infection in Macrophages Latently infected macrophages Activated macrophages

Evasion of immune system  Subset of HIV infected cells, become long lived memory cells  Cell-cell fusion  Rapid antigenic changes  Retroviruses have high mutation rate compared with DNA viruses  lack the corrective “proofreading” capacity of DNA viruses.  These dramatic numbers illustrate the potential problems of drug resistance and obstacles to the development of vaccines and diagnostic tests.

The stages of HIV infection  Phase 1: Asymptomatic or chronic lymphadenopathy  Phase 2: Symptomatic; early indications of immune failure such as infections by Candida albicans, which can appear in the mouth, throat, or vagina. Other conditions may include fever and persistent diarrhea.  Phase 3 is AIDS: Characterized by indicator conditions, such as: CMV, TB, Pneumocystis, toxoplasmosis, and Kaposi's sarcoma

The Progression of HIV Infection

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