Download 32_Immune responses to viruses BA

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
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 genes and proteins of HIV-1
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
Antiviral drugs rapidly clear virus from the blood
and increase the number of circulating CD4 T cells
Broadly neutralizing antibodies recognize four epitopes
of the HIV envelope glycoprotein that trimerizes
to form the viral spike