Exam 3 Lecture 17: Viral Immunity Flashcards
What is a virus
Infectious agent that lacks the ability to replicate outside of a host cell: typically consists of nucleic acid in a protein coat, comes in many different shapes and size
What are the major steps in the viral lifecycle?
- Viral adherence to host cell
- Cell entry
- Uncoating: shedding envelope and capsid
- Replication of genetic material: forcing host cell to make viral proteins and glycoproteins
- Assembly of new viral particles
- Viral egress: through lysis or budding
What are the 4 major components of antiviral immunity?
- Production of pro-inflammatory cytokines (esp. type 1 interferons)
- NK cell mediated killing
- T cell mediated killing and activation
- Antibodies
What is the purpose of Type I interferon (IFN⍺/β) production?
Activates and induces proliferation in NK cells
Activates macrophages and dendritic cells to produce Interferon Stimulated Genes (ISGs) with antiviral properties
How do NK cells and T cells contribute to antiviral immunity?
NK cells: kill infected cells through release of lytic granules
CD8: kill virus infected cells through kiss of death
Th1: help macrophages to suppress intracellular infections
Tfh: Help B cells activate, switch isotype, increase antibody affinity
Which antibody classes are effective against viruses?
Dimeric IgA: neutralization/blocking viral entry, esp. at mucosal surfaces
(IgG, IgM to lesser extent)
IgG: enhance phagocytosis of viral particles through Fc gamma receptors (opsonization)
IgM: enhance agglutination of viral particles
What is antigen drift
Error-prone RNA polymerase leads to accumulation of small mutations over each replication cycle > some of these mutations alter epitopes that are targeted by the immune system > these strains will cause greater disease because individuals will not carry antibodies to these new epitopes > mild outbreaks
How does influenza evade host immunity?
Antigen Shift:
Influenza genomes are made up of 8 ssRNA segments.
The segmented genome allows for genomic mixing following co-infection of two different strains within 1 host
Genetic reassortment leads to new strains carrying entirely new proteins that no one has immunity against -> can cause a big epidemic or a pandemic
What is viral latency
A form of dormancy or non-replication
How does herpesvirus evade host immunity?
Following primary infection, herpesvirus stops being lytic and becomes dormant in the presence of immune pressure
The virus only reactivates if the host becomes immunocompromised (stress, aging, immunosuppressive drugs)
How is SARS-CoV-2 transmitted? What cells does it infect?
Spread by aerosol, droplet formation, and droplet contamination of surfaces (fomites)
Transmitted by respiratory route and infects ACE-positive cells: nasal mucosa, lungs, small intestine, secretory goblet cells, type II pneumocytes, absorptive enterocytes
What immune features distinguish mild from severe disease?
Speed and efficacy of the 3 different immune arms: innate immunity, T cells, and antibodies
Generic disease: fast innate response followed by T cells and antibody production
Average Covid-19: small innate response followed by T cells and antibody production
Severe Covid-19: delayed early response and a paradoxical hyper-inflammatory late response
What are strategies for SARS-CoV-2 immune evasion?
Inhibits initial interferon production > associated with severe and critical disease as well as an overexuberant pro-inflammatory (IL-6, TNFa) response that leads to tissue pathology
How do viral mutations evade immunity?
- Mutations alter the epitopes recognized by antibodies and prevent antibody binding and neutralization
- Mutations could also change the peptides recognized by T cells
How do COVID-19 vaccines elicit protection?
Vaccines generate spike-specific effector T cells, memory T cells, memory B cells, and plasma cells
