Pathogens (Jeremy Lecture 3) Flashcards
Describe the characteristics of the innate immune response to a virus
1) Does not require previous viral exposure
2) Activated and responds in minutes to hours following infection
3) Involves pattern-recognition receptors and other innate signalling pathways
What components produce the antiviral state and how does this occur?
- Interferons
- Produced by innate immune activation
- Secreted interferons (INF) bind to INF receptors on uninfected cells
- Binding causes synthesis from over 1000 genes (ISG: INF stimulated genes)
- Interferons induce the cellular antiviral state
How do viruses inhibit interferon activation and function?
1) Prevention of signalling pathway activation (blocking interferon activation)
- dsRNA binding proteins, such as influenza virus NS1
2) Inhibition of signalling pathway
- PKR inhibitors
- STAT inhibitors
What are the main products of the innate immune system that cause inflammation?
Cytokines
- TNF-alpha in main early stage cytokine causing inflammation
What do cytokines cause?
- Increased blood flow (vasodilation)
- Increased blood vessel permeability (endothelial cell tight junctions)
- Influx of immune cells from blood to tissue
What are the main disease symptoms caused by inflammation?
- Redness
- Pain
- Heat
- Swelling
Why do viruses inhibit the inflammatory response?
Inflammation inhibits viral replication and infection
What is the name for viruses that do not cause an inflammatory response?
Non-cytopathic viruses
- Harder to cure
Describe the characteristics of the adaptive immune response in relation to viral infection?
- Activated days after initial infection
- Activated by innate immune system
- Cell mediated and humoral immunity
- Memory response
What are the effectors of cell mediated immunity and what does each do?
IFN-gamma secreted by Th and CTLs induces antiviral state
Cytotoxic T cells destroy virus infected cells
NK cells and macrophages destroy virus infected cells too
What are the effectors of humoral immunity and what does each do?
Primary secondary IgA - inhibits virion attachment
Primary IgG - inhibits fusion of enveloped viruses to PM
IgG and IgM antibodies - Opsonisation and complement activation
What is immunopathology?
Immune response to a disease
Name some viruses associated with CD8+, CD4+ and B-cell mediated immunopathology
CD8+:
- HIV-1
- Hepititis B
CD4+:
Measles
Herpes simplex
B-cell mediated:
Dengue virus
Name the different responses in viral-induced immunopathology
- Innate immunity killing
- Inflammation
- CD4+ cell mediated
- CD8+ cell mediated
- B cell mediated
- Molecular mimicry/autoimmunity
- Immunosuppression
How and what free radicals are produced during the inflammatory response?
- Nitric oxide (NO) is produced by nitric oxide synthase, a IFN-inducible enzyme
- Superoxide (O2-) is also produced
- Low NO is protective, high NO causes tissue damage