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5. Immunity to viral infection
immunity to viral infection
49
Immunology
Professional
11/11/2014

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Term
There are two kinds of immunity to viral infections. WHAT ARE THEY!?
Definition
Innate and adaptive
Term
What's involved in innate immunity to viral infections?
Definition
structural protection
IFN-alpha and beta
Term
What's involved in adaptive immunity to viral infection?
Definition
-antibody
-cytotoxic T cells (CD8+ T cells)
Term
Explain the structural protection aspect of innate viral immunity
Definition
tight junctions hold cells together to prevent anything from coming down into the cell and into the lamina propria.

This means, anything trying to get in would have to go through the cell or through active transport
Term
IFN alpha and beta are consider an __ __ system
Definition
early warning
Term
Explain the importance of the IFN produced by the infected cells.
Definition
When a cell is infected it produces IFN alpha and beta. This has no effect on the infected cell but it is an early warning sign (you gonna get infected) to surrounding uninfected cells that have receptors for IFN alpha and beta.
Term
What's the deal with the Jak/Stat pathway?
Definition
IFN alpha and beta signal through a Janus kinase (Jak) to signal transduction and activation of the Stat pathway. This leads to gene transcription and functional change in the infected cell
Term
How does the Jak/Stat pathway protect uninfected cells from the virus?
Definition
1. Inactivates protein translation (this doesn't prevent infection, but it makes the cell inhospitable for replication)

2. Induce RNAse activity (breaks down RNA viruses, but if it's a DNA virus it has to produce RNA to make protein)

3. Destroy virus and Host cell (virus can't replicate and produce infectious virions, but the cell also needs protein and RNA to survive so it dies too)
Term
If a virus gets into a cell, then you burst it open, there are no infectious virions inside.

What happens in order to make the infectious virions?
Definition
replication!
Term
Explain main points of adaptive (antibody) immunity to viruses
Definition
1. Block attachment
2. Aggregate for phagocytosis
3. Activates complement for MAC attack
Term
Explain blocking of attachment in adaptive immunity to virus
Definition
antibodies bind to the virus to prevent viral penetration --> we call this neutralizing antibody
Term
Explain aggregating for phagocytosis in adaptive immunity to virus
Definition
it will clump a bunch of viral particles together that then get removed from circulation by monocytes and myeloid cells
Term
Explain Activation of complement for the MAC attack in adaptive immunity to virus
Definition
Some, but not all, viruses are susceptible to antibody mediated complement activation via the classical pathway
Term
What is the main way we fight viruses?
Definition
Cell mediated immunity
Term
If you have an antibody deficiency you'll still be able to fight against __ infections, but not __ infections
Definition
viral, bacterial
Term
If you have a cell mediated deficiency (ex: low T cells) you'll have problems with __ infections.
Definition
viral
Term
Why do people who have cell mediated deficiencies (ex: HIV) have problems with cancer?
Definition
because some cancers are virally induced
Term
Describe the first step of activation and killing of viruses by cytotoxic T cells. How does this happen?
Definition
Some virus must be killed and taken up by dendritic cells.

(virus gets in, uncoats, tries to replicate but it can't b/c the cell is inhospitable for replication, so virus AND host cell die... host cell bursts and a bunch of cellular and viral antigens get released into the local area, dendritic cells are around to pick them up).
Term
Describe the second step of activation and killing of viruses by cytotoxic T cells.
Definition
dendritic cells process the viral antigen and take the viral antigen to the local draining node
Term
What happens in step two that is different from bacterial infection?
Definition
The bug bits get taken into a phagosome, they merge with a lysosome
THEN bug bits get released into the cytoplasm

This has to happen b/c Class I MHC constantly samples cytoplasm contents and brings it to the surface to present to CD8+ T cells.
Term
CD8+ Cytotoxic T cells recognize peptide in the context of __ __ __
Definition
Class I MHC!
Term
Class I MHC picks up peptide in the cytoplasm through a __.
Definition
proteasome
Term
Explain cross presentation.
Definition
It is the process of taking in antigen externally and processing it through the proteasome, through a molecule called Tap, get into the ER so it can get stuffed into the groove of Class I MHC
Term
__ __ are the only cells that can do cross presentation.
Definition
dendritic cells
Term
Cells that are NOT dendritic cells, that take antigen in from the outside in an endosome, can only process and present in Class _ MHC, not Class _
Definition
II, I
Term
Where are CD8+ T cells that respond to the viral infection?
Definition
in the node! (not at the site of the viral infection)
Term
Describe the third step of activation and killing of viruses by cytotoxic T cells.
Definition
The dendritic cells present the antigen to the cytoxic T cells in the context of Class I MHC!
Term
What goes on in step three?
Definition
The cytotoxic T cell binds to the peptide in context of class I MHC presented by the dendritic cell.
CD8 (on the surface of the Cytotoxic T cell) binds to the MHC as well.
Co-stimulation occurs!
Term
What is the result of activation of CD8+ T cells in the node?
Definition
1. Activation of the cell
2. Proliferation of CD8+ T cells
3. The CD8+ T cells exit the node via the blood
Term
Describe the fourth step of activation and killing of viruses by cytotoxic T cells.
Definition
Activated cytotoxic t cells need to become activated
Then they leave the node
Then they travel to the site of infection
Then they recognize infected cells (the infected cell contains the antigen that they recognized on the surface of the dendritic cell)
Term
Describe the fifth step of activation and killing of viruses by cytotoxic T cells.
Definition
The cytotoxic t cells then kill the virally infected cells
Term
When CD8+ T cells leave the node, and got to the site of inflammation they are no longer __.
Definition
naive! it is now a killer
Term
How has the cytotoxic t cell changed since leaving the node?
Definition
It has undergone morphological changes in it's cytoplasm
- more granulated
- has different receptors on its surface
- it's a killer!
Term
The kiss of death is another name for _ _ _ _
Definition
This is the name for Cytotoxic T lymphocyte (CTL) killing
Term
Explain the kiss of death
Definition
The cytotoxic t-lymphocyte does up to the infected cell, forms a lip shape seal on its surface then delivers toxic material called perforin and granzyme
Term
What do perforin and granzyme do?
Definition
perforin perforates the cell
granzymes - an enzyme in a granuole, they go through the holes and activate the caspase pathway

--> this leads to apoptosis of the cell
Term
True or false: Cytotoxic t lymphocytes kill virally infected cells.
Definition
Yes, but indirectly. They actually influence the cell to kill itself through apoptosis
Term
What is the backup plan to the kiss of death?
Definition
Fas-FasL interaction
Term
What type of cells have FasLigand on their surface?
Definition
CD4 and CD8 T cells
Term
What is the result of Fas (on infected cell) binding to FasL on T cell?
Definition
Activation of the capsase pathway (slightly diff. pathway than that of the kiss of death, but same end result) which leads to apoptosis
Term
TNF binds to the TNF receptor on cancer cells, it activates the __ pathway.
Definition
Caspase
Term
How do viruses strike back against the immune system?
Definition
1. They down-reguate Class I expression (b/c they know their viral proteins are going to be their downfall... they know Class I MHC will sample their proteins in the cytoplasm)

2. Produce immune regulatory proteins
Term
Explain why viruses down regulated class I expression
Definition
- It prevents expression of viral proteins in MHC I
- It allows virus infected cells to hide from CTL
Term
What is the problem with down-regulation of Class I expression?
Definition
Natural killer cells recognize cells that have low levels of Class I MHC!

Natural killer cells also have perforin/granzyme killing ability
Term
Natural killer cells (do/don't) recognize specific antigens.
Natural killer cells are (lymphocytes/t cells)
Definition
don't
lymphocytes (not T or B)
Term
How do viruses produce immune regulatory proteins?
Definition
- Some viruses have stolen the IL-10 gene from human cells and incorporated it into the viral genome
- Then they produce it any time they want
- production of IL-10 down-regulates CTL activity
Term
Human T lymphotropic virus 1 and 2 affect _ cells
Definition
T cells
Term
HIV infects and kills __ __ __
Definition
CD4+ T cells
Term
Why is it worse to have a virus that kills CD4+ T cells?
Definition
First of all, there's no antibody production.

Second:
CD8+ T cells can still do their job in the absence of CD4+T cells

But CD4+ T cells produce cytokines (IL-2) that help CD8+ T cells be much better at their job
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