Immunity to Viruses Flashcards
How do viruses infect cells
Viruses bind to the Cell surface molecule / Virus receptor; the virus receptor preferred by a virus determines its tropism
Once it enters it can begin replicating by transcribing and translating enzymes required to begin replication of genes then synthesis of capsid proteins
Tropism of virus
Ability of different viral strains to infect different cell types or tissues
How do viruses leave cells
Cytolytic - Breaking the surface membrane and bursting out
Enveloped - Taking a piece of the membrane as an envelope
Anti-viral effects of antibodies
Antibodies bind to viral receptors and prevent them from binding/penetrating host cells (neutralising antibodies)
They cannot cross plasma membranes but can activate intra-cellular degradation using TRIM21 for viruses that have not yet been degraded which tells the proteosome of host cells to digest the lyse the virus
Activating complement pathway and disrupting the structure of the virus and envelope
Antibody bound to infected cells (NK Cells)
Antigenic shift and drift in viruses
Seen in influenza
Evasion mechanism whereby they mutate the genes that encode their surface proteins (Haemagglutinin and neuraminidase). This can change their antigenic properties and leave someone originally protected be no longer protected
Antigenic drift is a more drastic and bigger shift that can be caused by an animal being infected by two similar strains at once that exchange genetic material.
Seen in spanish flu
Describe release of IFNα, IFNβ, TNFα, IL-12, NK Cell mediated killing of infected cells and T cell mediated killing of infected cells throughout viral infection as an immune response to limit the viral spread
IFN
Group of signaling proteins made and released by host cells in response to the presence of several viruses
Type 1 Interferons
IFN Alpha, Beta
Their stimuli are viral infections; they “interfere” with and block viral replication. Pattern recognition molecules in cell cytoplasms that interact with nucleic acids in viruses like Toll-like receptor 3 which binds to viral double stranded RNA
These recognition molecules that recognise PAMPs trigger signals that cause type I IFN production and their secretion
Secreted IFN binds to receptors on neighbouring cells to produce an antiviral state in them that stops viruses from being able to replicate into them
What does the binding of IFN on cells cause?
The anti-viral state
Production of cells of enzymes that can degrade viral mRNA and other viral proteins that directly inhibit transcription and translation
Also enhances expression of HLA Class I proteins which enhances NK cell activation
Compare IFN response of SARS-CoV-2 to other viruses
Covid-19 has weak IFN responses compared to other viruses, potentially contributing to its high pathogenesis
Which cells express HLA Class I proteins
Pretty much all cells so that any infected cell can be a target to be killed by cytotoxic T cells
Other word for NK Cell
Large Granular Lymphocyte
Antibody Dependent Mechanism for NK Recognition
They have Fc Receptors that bind to IgG antibodies
IgG molecule binds to antigen (Fab site) on surface of cell and Fc region of antibody binds to NK Cells’ Fc receptor
How can cells have full viral antigens expressed on their surface and not just peptides
One way is with enveloped viruses::
As the H and N of the envelope are being produced, they are inserted into the cell’s membrane; gradually the virus is formed and makes up the rest of the viral cell so it can bud off; cells that can recognise the viral proteins though can equally recognise the same proteins on the cell’s membrane
NK Mechanism of Target Cell Recognition
NK Cells express two types of surface receptors that combine to other cells’ surfaces. One can bind to other molecules on cell surfaces that activates NK cells to kill them (killer activating receptor)
The other receptor binds to other receptors on normal cells which sends an inhibitory signal to the NK cell so that it does not kill body cells (this is dominant in normal cell) (killing inhibitory receptor)
Killing Inhibitory Receptor binds to HLA Class I proteins on cell surface; NK cells are not interested in the antigen that is presented though, they are more interested in a molecule in the side of the HLA molecule.
In a virally infected cell, there is less HLA class I expression for many reasons, e.g. the cell machinery is occupied or certain viruses inhibit this. This reduces the activation of cytotoxic T cells but actually leads to a lack of an inhibitory signal being sent to NK cells, causing the cell to be eliminated
There may alternatively still be HLA class I molecule but increased expression of molecules that NK killing receptors bind to, tipping the scale and causing murder
