Virology 1 Flashcards
What are the main determinants of viral pathogenesis
- Factors from the virus, the host, and their interaction determine the outcome of an infection.
- Three requirements must be met to ensure successful infection in an individual host:
1) a sufficient number of infectious virus particles must be available to initiate infection.
2) the cells at the site of infection must be physically accessible to the virus, susceptible (bear receptors for entry), and permissive (contain intracellular gene products needed for viral reproduction).
3) local antiviral defences must be absent, or at least initially, quiescent. - Free viruses face a harsh environment and rapid dilution that can reduce their concentration.
- To remain infectious, viruses spread in contaminated water and sewage must remain stable in the presence of osmotic shock, pH changes, proteases, and sunlight.
- Host physical and immune defences, coupled with the complexity of the infection process, usually require the presence of many virus particles.
- Even those particles that have remained intact face difficulties:
1) may not encounter a target cell following entry into a host.
2) may adhere to a dead or dying cell.
3) may become attached to non-susceptible cells by non-specific protein-protein interactions.
4) may be swept away in the blood stream. - Populations of viruses often contain particles that are not capable of completing an infectious cycle. Defective particles can be produced by incorporation of errors during virus genome replication or by interaction with inhibitory compounds in the environment.
- Successful infections must modulate or bypass host defences including that of the skin, respiratory tract, alimentary tract, and urogenital tract.
Describe the intrinsic immune responses to viral infection
Intrinsic Responses
1) Apoptosis
- Programmed cell death.
- The result of a cascade of reactions that leads to nuclear membrane breakdown, chromatin condensation, loss of membrane integrity, and eventually DNA degradation.
- Blocks virus replication.
- Apoptotic cells can be detected by tissue-resident sentinel cells which can sensitise the adaptive immune system.
2) Autophagy
- Cells degrade cytoplasmic contents by formation of autophagosomes.
- It is evoked by stressors such as viral infection and can degrade whole viruses or viral genomes.
- Unlike apoptosis, it is a cellular effort to consolidate resources.
3) Interferons
- Signalling proteins secreted by virus-infected cells and uninfected sentinel cells as a warning.
- Induces an antiviral state.
- Can be recognised by infected cells which amplifies the antiviral response.
4) ISGylation (ISGs)
- Interferon-stimulated gene 15 is mainly expressed in monocytes and lymphocytes, and acts like a cytokine.
- Many ISGs have potent, broad-spectrum antiviral activity.
- Participate in signal transduction, chemokine action, antigen presentation, regulation of transcription, stress response, and control of apoptosis.
- Many are cytotoxic.
Describe how the IFN response is regulated
- Many gene products of the antiviral state are highly cytotoxic.
- The response needs to be suppressed once viral reproduction has been controlled.
- Accomplished by the actions of members of the suppressor cytokine signalling protein family which activate in a negative feedback loop to attenuate cytokine signal transduction.
Describe the innate immune responses to viral infection
1) Natural killer cells
- Can distinguish between infected and uninfected cells.
- MHC I protein molecules are self antigens. The natural killer cells detect when these are missing from the surface of body cells.
- Results in apoptosis of the target cell.
2) Complement
- Composed of three pathways called the classical pathway, alternative pathway, and lectin pathway.
- Detects viruses by using antibodies and mediates destruction of virus envelopes.
- Facilitates the phagocytosis of viruses.
Describe the inflammatory response to viral infection
- Infected cells produce cytokines and chemokines.
- Vasodilation and increased vascular permeability cause redness, heat, and swelling.
- Inflammatory cells migrate into tissue, releasing inflammatory mediators that cause pain.
- Chemokines recruit immune cells and pro-inflammatory cytokines promote immune cell activation.
- Anti-inflammatory cytokines suppress pro-inflammatory cytokines which ends the response.
Describe the adaptive immune responses to viral infection
1) Cell-mediated response
- Eliminates virus-infected cells without damaging uninfected cells.
- Carried out by cytotoxic T-lymphocytes (CTLs) which produce antiviral cytokines.
- T-lymphocytes clone and divide, producing killer T-cells.
- Killer T-cells directly kill viral infected cells by releasing perforin which directly kills the infected cells.
2) Neutralising antibodies
- Bind to and cause the elimination of free virus particles.
- Neutralises virus particles in the blood and prevent the virus from spreading.
- IgA antibodies block the entry of viruses at mucosal surfaces.
- Some are important for recovery from infection.
3) Humoral response
- Specific B-lymphocytes become activated by a specific virus (specific antigen).
- B-lymphocytes divide and clone to produce plasma cells.
- Plasma cells produce antibodies.
- Formation of antigen-antibody complexes.
- Phagocytosis of virus particles.
Explain immunological memory
- Due to the presence of memory B cells and memory T cells.
- Located in the spleen and lymph nodes.
- If the host is subsequently infected by the same virus, the secondary response will be rapid and much greater than the primary response.
What are some of the viral immune evasion mechanisms
Viruses can impair:
- antibody recognition of viral epitopes.
- presentation of viral peptides by major histocompatibility complex (MHC) class I and class II molecules.
- recruitment of immune effector cells.
- complement activation.
- apoptosis.
What is tissue tropism
- The spectrum of tissues infected by a virus.
- Can be determined by:
1) the distribution of receptors for entry (susceptibility).
2) a requirement for differentially produced intracellular gene products required to complete the infectious cycle (permissivity).
3) whether they can physically interact with the tissue (accessibility).
4) intrinsic and innate immune defences.
Describe haematogenous viral spread
- Virus particles reproduce at site of entry (skin, mucus membrane, respiratory tract, gastrointestinal tract).
- Virus particles move into lymph node and reproduces.
- Particles enter blood stream and transported to muscle, liver, spleen and blood vessels where they reproduce.
- Enter blood stream again and transported to skin, mucus membranes, lungs, kidneys, GI tract, and brain. Reproduce again.
- Virus transmitted to other hosts.
What are PRRs
- Pattern recognition receptors
- Intracellular detectors of viral infection.
- Recognise viral nucleic acids because their features and location are distinct from host nucleic acids.
