Download Host-pathogen interactions: An Overview Course instructor: Sumana

Host-pathogen interactions: An Overview
Course instructor:
Sumana Sanyal
email:
[email protected]
[email protected]
Co-evolution and adaption between viruses and humans are often portrayed as a
zero-sum biological arms race. Viruses enter host cells equipped with an array of
mechanisms to evade the host defense responses and replicate. The rapid rate of
mutation of viruses permits evolution of various methodologies for infection. The host
immune system has likewise evolved highly effective mechanisms to deal with the
constant challenge of pathogen invasion and restrict infection. Thus the study of hostpathogen interactions has illuminated essential functions of the immune system,
particularly in the area of virus infections, antigen presentation and responses by T and
B lymphocytes. In this short course we will cover basic concepts of innate and adaptive
immunity, virology and strategies that viruses have evolved to evade the host immune
system.
9th October; 5:00 – 7:00 p.m.
Basic principles of immunology:
• Concepts of innate and adaptive immune responses
• Role of phagocytes in innate immunity
• Humoral and cell-mediated immune responses
• B lymphocytes and production of antibodies
• Professional antigen presenting cells and MHC-II complexes
• Function of helper T cells and cytotoxic T cells
• Role of CD4+ T cells and CD8+ T cells
• Inflammatory responses and cytokine production
Basic concepts in virology
• Discovery of viruses and their classification
• Viral genomes and their organization
• The infectious life cycle of viruses
• Detecting viruses: The plaque assay
• Measurement of viruses by end-point dilution assay
• Multiplicity of infection
• Commonly used techniques for detection of antigens or antibodies by ELISA,
Western blotting, immunostaining
10th October; 5:00 – 7:00 p.m.
Pathogenesis and Immunity during viral infections
• Viral pathogenesis and acute infections
• Antigenic variation as a cause for recurring acute infections
• Host innate sensors of viral genomes
• Innate immune defenses
• Adaptive immune defenses: generation of antibodies
• Virus neutralization by antibodies
• The complement system
11th October; 5:00 – 7:00 p.m.
Insights into Influenza virus and its replication
• Structure of the influenza virus
• Influenza virus RNA genome
• Translation of influenza virus RNA into proteins
Entry into cells:
• Influenza virus attachment to cells
• Role of different sialic acids in influenza attachment to cells
• Release of influenza virus ribonucleoproteins into cells
• Influenza virus HA cleavage is required for infectivity
Replication and RNA synthesis:
• Influenza viral RNA synthesis
• The error-prone way of RNA synthesis
• The quasi-species concept
• Viral quasi-species and bottlenecks
12th October; 10 a.m. – 12 noon
Intracellular assembly of Influenza virus:
• Intracellular trafficking of influenza virus proteins
• Packaging of the segmented RNA genome: evidence for selective versus nonspecific packaging
• Consequences of antigenic drift versus antigenic shift
• Reassortment of the influenza virus genome
• Influenza virus reassortment: Past and current species
Propagation and measurement of Influenza:
• Influenza virus growth in eggs
• Influenza hemagglutinin inhibition assay
• Influenza microneutralization assay
Pathogenesis:
• Production of cytokines
• Gut microbes influence defense against influenza
• The D225G change in 2009 H1N1influenza virus
• Transformation of 2009 H1N1 influenza to highly pathogenic strain
• Influenza virus transmission
• Viruses and the respiratory tract
• Seasonality of influenza
• Innate immune defenses against influenza virus
• The inflammatory response against influenza virus
• Adaptive immune defenses: generation of antibodies
• Neutralizing antibodies against influenza
13th October; 10:00 a.m. – 12 noon
Prevention and control
• Efficacy of the influenza vaccine
•
•
•
•
•
•
•
•
Influenza vaccine of 2009: A case study – reasons for its failure and the pandemic
The concept of universal influenza vaccines
Emergence of Oseltamivir resistant influenza virus
Protection against 2009 influenza H1N1 by immunization with 1918-like and classical
swine viruses
Reinfection with 2009 influenza H1N1
Influenza neuraminidase inhibitors
Tamiflu-resistant pandemic influenza H1N1virus selected by prophylaxis
Ongoing research on H5N1 and H7N9
Reading material:
1. Bouvier, N. M., and Palese, P. (2008) The biology of influenza viruses. Vaccine 26,
D49–D53
2. Palese, P., and García-Sastre, A. (2002) Influenza vaccines: present and future.
Journal of Clinical Investigation 110, 9–13
3. Garcia-Sastre, A. (2006) Type 1 Interferons and the Virus-Host Relationship: A
Lesson in Detente. Science 312, 879–882