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THE IMMUNE RESPONSES TO VIRUSES Replication of Ebola Virus http://www.microbiologyinfo.com Mechanisms of induction of type I interferons by viruses Cellular and Molecular Immunology, 7th ed., 2012 Elsevier Major functions of the type I interferons Biologic actions of type I interferons Cellular and Molecular Immunology, 7th ed., 2012 Elsevier Activation of NK cells by receptors of innate and adaptive immunity Antibody Dependent Cellular Cytotoxicity (ADCC) Induction of T cell responses to virus-infected cells Cellular and Molecular Immunology, 7th ed., 2012 Elsevier Cytotoxic CD8 T cells can kill several infected target cells in succession Viral infections are blocked by neutralizing antibodies Kinetics of various anti-viral mechanisms Cellular and Molecular Immunology, 7th ed., 2012 Elsevier Innate and adaptive immune responses against viruses Cellular and Molecular Immunology, 7th ed., 2012 Elsevier Evolution of new influenza variants by antigenic drift Evolution of new influenza virus variants by antigenic shift Generation of new influenza virus strains by genetic recombination (antigenic shift) Cellular and Molecular Immunology, 7th ed., 2012 Elsevier Mechanisms by which viruses inhibit antigen processing and presentation Cellular and Molecular Immunology, 7th ed., 2012 Elsevier The immunopathogenesis of HIV infection Global summary of the AIDS epidemic 2014 36.9 million [34.3 million – 41.4 million] 34.3 million [31.8 million – 38.5 million] 17.4 million [16.1 million – 20.0 million] 2.6 million [2.4 million – 2.8 million] Number of people living with HIV Total Adults Women Children (<15 years) People newly infected with HIV in 2014 Total 2.0 million [1.9 million – 2.2 million] Adults 1.8 million [1.7 million – 2.0 million] Children (<15 years) 220 000 [190 000 – 260 000] AIDS deaths in 2014 Total 1.2 million [980 000 – 1.6 million] Adults 1.0 million [760 000 – 1.8 million] Children (<15 years) 150 000 [140 000 – 170 000] The number of people living with HIV infection worldwide is still increasing, but seems to be reaching a maximum The virion of human immunodeficiency virus The life cycle of HIV After infection with HIV there is a gradual extinction of CD4 T cells CD4+ T CELL DEPLETION IN HIV INFECTION 1. Direct cytopathic effect of HIV – lytic cycle in activated CD4+ T cells 2. Killing by virus-specific CD8+ T lymphocytes – CD4+HIV+ targets 3. Syncytia formation – gp120 of infected T cells binds to uninfected T cells fusion The natural course of an HIV infection and the immune response against it Some opportunistic infections that kill patients with AIDS Candida infection in oral cavity and esophagy Receptors and co-receptors CCR5 co-receptor on monocytes, macrophages and memory T cells In initial infection CXCR4 co-receptor on activated T cells In late infection Current world-wide frequency distribution of CCR5-Δ32 allele frequencies 20% of the Caucasian population is heterozygous for a mutation in the CCR5 gene, which results in an unfunctional protein People homozygous for an inherited defect of the CCR5 gene are resistant to HIV infection – 1% of the Caucasian population Three main transmission routes for HIV have been identified Sexual The risk of female-to-male transmission is 0.04% per act and male-to-female transmission is 0.08% per act. Blood products Blood transfusion, intravenous drug users, piercings, tattoos Mother-to-child The risk of transmission is 20-33 %. Perinatal > intrauterin > breast feeding The cause of HIV variability Enzyme Mistakes DNA-Polymerase 1 Mutation in 108 bp Reverse Transcriptase 1 Mutation in 105 bp THE VIRAL REVERSE TRANSCRIPTASE LACKS PROOF READING MECHANISMS OF TYPE POSSESSED BY CELLULAR DNA NEW VIRAL VARIANTS (quasi species) CO-EXIST IN AN INDIVIDUAL NEGATIVE SELECTION OF NEUTRALIZING AND CYTOTOXIC EPITOPES Broadly neutralizing antibodies recognize four epitopes of the HIV envelope glycoprotein that trimerizes to form the viral spike