Hiv what is your problem Flashcards
What is the best way of preventing a virus from infecting an individual
By stimulating the formation of neutralizing antibodies at the site of entry
In HIV this could include :
-vagina , anus /rectum ,penis
What is the best type of antibody in neutralization
think of where you can encounter the HIV - mucosal surface
Can you make an antibody to HIV before you acquire infection
yes, but it needs to encounter the HIV antigen before it can persist
Can you make neutralizing antibodies without acquiring HIV first
No, IgM is not good at neutralizing and you need class switching, which is not possible less there is an encounter
Summary of anti-viral infection response
The virus cannot be transmitted because the mucosae are covered with neutralizing antibodies and because specific antiviral factors are present
If the virus is transmitted and manages to infect a cell, the cell will sense it through pattern recognition molecules
If the pattern recognition molecules are upregulated, the infected cell will start producing interferons and prepare for death
The interferons will prime APCs in the environment to present to CD4+ T cells in a Th1 way
The CD4+ T cells will activate CD8+ T cells to kill virally infected cells
Any cells which escape CD8+ T cell killing will be killed by NK cells
There will be the generation of memory so that the virus will be killed the next time
There is resolution
What are the viral escape strategies
- Rapid mutation resulting in poor recognition by antibodies
- Inactivate TLR signaling by sequestration signaling molecules
- Prevent interferons secretion
- Prevent MHC class1 and class2 upregulation to prevent being killed by cell killing cells
- Prevent upregulation of the second signal,to prevent FAS effects
Which cells are susceptible to HIV infection
Cells that express CD4 receptors and chemokines receptors (CCR5 and CXCR4)
- macrophages
- Dendritic cells
- CD4 cells
Which cells are the earliest to be infected with HIV?
*Dendritic and macrophages
>when infected they move to the lymph node.
> HIV can also stick to pattern recognition receptors without being phagocytosed.
In the lymph node, these dendritic cells can pass the HIV on
How does HIV cause low-grade septicemia
*After infecting CD4 cells in the genitalia, it then migrates and infected CD4 cells in the GIT. This results in gaps forming in the GIT. Pathogens start to relocate from inside the GIT to the bloodstream
Where do the CD4 cells go?
> Some are infected with HIV and pop via virolysis
Some are targeted and killed by NK and CD* cells
CD8+ T cells will kill them if they express viral peptides in the context of MHC 1
NK cells will kill them if they downregulate MHC 1
Some are overexcited in general inflammatory background and then become exhausted
T/F: Eventually the immune system reached an equilibrium with the virus but the CD4 cells population will never reconstitute, even after the administration of therapy
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How does HIV affect the Th1 and Th2 response
> Th1 response is inappropriate : HIV patients are at risk of intracellular pathogens eg TB and cancer
> Th2 is completely inappropriate :
- There is an increased risk of fungal and bacterial infection
- secretion of non-specific antibodies resulting in non-specific autoimmune
What are the factors that influence whether a patient can control HIV
> Genetics
- Protective HLA classes
- Protective NK cell response
- Protective CD* T cells response
These patients have a lower level of inflammation and immune activation
What makes HIV difficult to cure
- Highly mutable ‘
- Heavily glycosylated (antibodies don’t bind)
- Infection does not result in sterility
- Infection does not result in sterility
A successful prophylactic vaccine requires :
- Neutralizing antibodies (most likely IgA)
2. Against conserved sites so that the sites cant be changed because the virus would lose its ability to infect)