Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Immune system wikipedia , lookup
Polyclonal B cell response wikipedia , lookup
Hygiene hypothesis wikipedia , lookup
DNA vaccination wikipedia , lookup
Molecular mimicry wikipedia , lookup
Cancer immunotherapy wikipedia , lookup
Adaptive immune system wikipedia , lookup
Psychoneuroimmunology wikipedia , lookup
Adoptive cell transfer wikipedia , lookup
Anergy is called a generalized deficiency in DTH responses after lymphoma (Hodgkin's disease) Viruses other than HIV are known to impair immune responses; include the measles virus and human T cell lymphotropic virus 1 (HTLV-l) Aquered Immunodeficiency syndrome (AIDS) Associated opportunistic infections and malignant tumors, wasting, and central nervous system (CNS) degeneration HIV infects a variety of cells of the immune system, including CD4+ helper T cells, macrophages, and dendritic cells HIV epidemic was first identified only in the 1980s HIV has infected 50 to 60 million people and has caused the death of over 22 million adults and children Approximately, 70% are in Africa and 20% in Asia, and almost 3 million die of the disease every year Approximately, 14,000 new infections every day, and by the year 2010, 50 to 75 million infected people will be added Approximately, 5 million new cases every year occur in young adults (15-24 years old) Molecular and Biologic Features of HIV HIV, retroviruses, is a member of the lentivirus family of animal and long-term latent infection of cells and short-term cytopathic effects Two closely related types of HIV (HIV-1 and HIV-2), have been identified HIV-1 is by far the most common cause of AIDS, but HIV-2, which differs in genomic structure and antigenicity, causes a similar clinical syndrome HIV Structure and Genes Consists of two identical strands of RNA packaged and surrounded by a phospholipid bilayer envelope derived from the host cell membrane Long terminal repeats (LTRs) at each end of the genome regulate viral gene expression, viral integration into the host genome, and viral replication gag sequences encode core structural proteins env sequences encode the envelope glycoproteins gp120 and gp41, which are required for infection of cells pol sequences encode reverse transcriptase, integrase, and viral protease enzymes required for viral replication Also, HIV-1 includes six other regulatory genes, namely, the tat, rev, vif, nef, vpr, and vpu genes, whose products regulate viral reproduction in various ways Viral Life Cycle Most important chemokine receptors that act as coreceptors for HIV are CXCR4 and CCR5 More than seven different chemokine receptors are coreceptors for HIV entry into cells as the leukotriene B4 receptor Macrophage-tropic (M-tropic), T-tropic and both T cell lines and macrophages (dual-tropic virus)HIV virus Macrophage-tropic virus isolates express a gp120 that binds to CCR5, which is expressed on macrophages (and some memory T cells) Whereas, T cell-tropic viruses bind to CXCR4,which is expressed on T cell lines T-tropic strains tend to be more virulent, presumably because they infect and deplete T cells more than do M-tropic strains Naive T cells are resistant to HIV infection because these cells contain an active form of an enzyme that introduces mutations in the HIV genome This enzyme has been called APOBEC3G (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like editing complex 3) Pathogenesis of HIV Infection and AIDS HIV disease begins with acute infection, which is only partly controlled by the adaptive immune response, and advances to chronic progressive infection of peripheral lymphoid tissues Acute (early) infection is characterized by infection of memory CD4+ T cells (which express CCR5) in mucosal lymphoid tissues, and death of many infected cells Transition from acute phase to a chronic of infection is characterized by dissemination of the virus, viremia, and development of host immune responses Dendritic cells in epithelia capture the virus and pass HIV on to CD4+ T cells through direct cell-cell contact In the next, chronic phase of the disease, lymph nodes and the spleen are sites of continuous HIV replication and cell destruction Clinical latency period It is estimated that HIV destroys up to 1 to 2* 109 CD4+ T cells every day Progression of HIV infection Clinical course of HIV disease Mechanisms of Immunodeficiency Caused by HIV An important cause is the direct cytopathic effect Chronic activation of the T cells may predispose the cells to apoptosis HIV-specific CTL can kill infected CD4+T cells HIV-infected CD4+T cells and target the cells for antibody-dependent cellmediated cytotoxicity (ADCC) Defective maturation of CD4+ T cells in the thymus Functional defects in the immune system include a decrease in T cell responses to antigens and weak humoral immune responses Proportion of IL-2 and IFN-γ-secreting (Th1) T cells decreases and the proportion of IL-4 and IL-10 secreting (TH2-like) T cells increases Increased numbers of CD4+ CD25+ regulatory T cells Macrophages, dendritic cells, and follicular dendritic cells also play important roles in HIV infection and the progression of immunodeficiency Transmission of HIV Sexual contact is the most frequent Mother- to-child Inoculation of a recipient with infected blood or blood products Major groups at risk for the development of AIDS in the United States include homosexual or bisexual males, intravenous drug abusers, heterosexual partners of members of other risk groups, and babies born of infected mothers Clinical Features of HIV Disease Immune Responses to HIV HIV-specific humoral and cell-mediated immune responses, but imited protection Initial adaptive immune response CD8+ T cells specific for HIV peptides Antibody responses to a variety of HIV antigens are detectable within 6 to 9 weeks after infection (Neutralizing antibodies against gp120) Mechanisms of Immune Evasion by HIV Extremely high mutation rate because of error-prone reverse transcription Evade CTLs through down-regulation of class I MHC Inhibit cell-mediated immunity Treatment and Prevention of AIDS and Vaccine Development Three classes of antiviral drugs, used in combination First type of drug to be widely used consists of nucleoside analogues that inhibit reverse-transcriptase activity, as ‘-azido-3' -deoxythymidine (AZT) Viral protease inhibitors have been developed that block the processing of precursor proteins into mature viral capsid and core proteins New triple-drug therapy, HAART (highly active anti-retroviral therapy) Such vaccines include nonvirulent recombinant hybrid viruses composed of part SIV and part HIV sequences or viruses that have been attenuated by deletions in one or more parts of the viral genome, such as the nef gene live –attenuated virus vaccines CTL-mediated immunity is the use of live recombinant non-HIV viral vectors carrying HIV genes DNA vaccines are composed of combinations of structural and regulatory genes of SIV or HIV packaged in mammalian DNA expression vectors Recombinant protein or peptide subunit vaccines that elicit antibodies