Immunology Flashcards
HIV gp____binds to the T-cells _____ receptors. The viral gp_____ then binds to the coreceptor_______ or _______. The gp______ then fuses with the cellular membrane and the HIV virus enters the cell.
HIV gp120 binds to the T-cells CD4 receptors. The viral gp120 then binds to the corecptor CCR5 or CXCR4. The gp41 then fuses with the cellular membrane and the HIV virus enters the cell.
What are opportunistic infections?
Infections that take advantage of a weakened immune system (ie - HIV) and cause many problems (ie - Pneumocystis carinii pneumonia). Under normal conditions, these infections would be quickly eradicated by the immune system.
What component in the blood is used to determine if someone has been infected with HIV? When is this compound present?
Antibodies produced against the HIV virus. This typically occur 2-3 weeks after infection.
What 2 tests are conducted to confirm if someone has an HIV infection?
- Commercial EIA (enzyme immunoassay) detect antibodies to multiple HIV proteins. (highly sensitive)
- Western Blot assay idenfies antibodies against specific HIV proteins.
A positive EIA test requires a second test (western blot) to confirm an HIV infection.
What is seroconversion?
Seroconversion occurs when an individual presents antibodies to an infections like HIV. Prior to seroconversion, the individual is in a seronegative window and is highly infectious.
What are the 2 major coreceptors HIV uses to gain access to the host cell? What are the names given to these viruses? What type is more prevelant
- CCR5 - macrophage tropic viruses (receptor is more prevelant on macrophages and langerhans dentritic cells)
- CXCR4 - lymphotrophic viruses (receptors are more prevelant on CD4+ lymphocytes)
- Some strains use both
- CCR5 is the more prevelant type of HIV infection.
Approx. 15% of caucasians have a heterozygous mutation to CCR5. 1% who are of european decent are homozygous. This can lead to a resistance to macrophage tropic HIV virions.
HIV may lay dormant in a CD4 T-cell for years. What can trigger the virus to suddenly spring to life?
An infection that causes the T-Cell to activate.
What is the viral setpoint? What causes it to be high or low? What is the prognosis for someone who has a high viral set point?
The viral set point is the amount of HIV virus established in the blood serum after the initial immune response. The viral set point is determined by the CD8+ response of the host towards HIV infected cells (CD4 cells). People with higher set points will have a more rapid fall of CD4 over time which is correlated with a more rapid progression of AIDS.
Describe the cell mediated immune response to HIV
During an acute HIV infection, CD4 T-cells are presented with HIV antigens. Those that react positively, will proliferate and attempt to help kill HIV. However, proliferating/active CD4 T-cells are the best targets of HIV. HIV infects, replicates, and kills the very cells that are most likely to clear the virus.
With the lack of HIV specific CD4 T-cells, CD8 T-cells (who rely on the CD4 cells) will not be able to function properly. Without CD8 t-cells, the virus will persist in infected cells.
Describe what occurs in a hots immune response after treatment with anti-retro viral treatment (ART).
- ART will decrease the level of viremia in the plasma
- This increases the levels of CD4+ cells (no virus to kill them)
- This improves immune response to opportunistic infections
- However, less virus–>less antigens–>less HIV specific CD4 T-cells
- HIV will remain dormant in memory T-cells (viral resovoir)
- Stopping ART will cause an increase in replication and an explosion of HIV viruses.
In HIV infected patients, what is the CD4 count an indicator of? What is a normal CD4 count? What is the count for someone with AIDS?
- The CD4 count is an indicator of immune system damage caused by HIV.
- Normal ~1000 cells/mm
- AIDS <200 cells/mm
On what chromosome are MHC molecules coded?
Chromosome 6
What is the purpose of MHC molecules?
For immune cells to distinguish self from non-self
What is an allogeneic transplant?
Cells or tissues are transplanted from one individual to another, need therapeutic intervention to prevent rejection
What is an autologous transplant?
An individual receives a transplant of cells or tissues from one’s self (common in bone marrow transplants), biologically equivalent to transplant from genetically identical individual (twin)
What are the structural differences between MHC class I and MHC class II molecules?
MHC class I: 1 chain (different for each isotype), 1 beta-2 microglobulin molecule (the same molecule for all isotypes
MHC class II: 1 alpha chain, 1 beta chain
On what cells in the body are MHC class I molecules present? MHC class II?
MHC class I: all cells in the body (except RBCs and neurons)
MHC class II: antigen-presenting cells (dendritic cells, macrophages, B cells)
What is an alloantigen? What are 2 examples?
Proteins that vary between members of the same species
Examples: HLA molecules and AB antigens on RBCs
Describe the endogenous (cytosolic) pathway.
What MHC class is used? What cells do they present to? Against what pathogen types is this pathway mostly used?
MHC class I molecules present antigens derived from proteins MADE IN CELL, therefore used mostly against viruses and tumor cells
- Intracellular proteins are broken down into peptides in proteosomes (protein complexes that degrade unneeded, damaged, or excess proteins in cells) in cytoplasm
- Peptides are loaded into empty MHC class I molecules in ER (transported there by transporter associated with antigen processing, TAP) and transported to cell surface
- Antigens are presented to CD8+ cytotoxic T cells
Describe the exogenous (endosomal) pathway.
What MHC class is used? What cells do they present to? Against what pathogen types is this pathway mostly used?
MHC class II molecules present antigen from peptides phagocytosed by APCs, therefore mostly used against bacteria
- Extracellular proteins are endocytosed by phagocytic cells
- Endosomes fuse w/ lysosomes and proteases degrade proteins into peptides
- MHC class II molecules in late endosomes are loaded with peptides and transported to cell surfaces
- Antigens are presented to CD4+ T helper cells to help other adaptive immune cells work better
What is HLA restriction?
There is a limited ability for peptides to fit into MHC molecules, and even when they do there will be a limited repertoire of T cells that recognize that specific peptide/MHC complex
What is the role of macrophages?
Macrophages stay in tissue, process and present antigen, and produce cytokines and chemokines to attract neutrophils to the site of infection
What is the role of dendritic cells?
Dendritic cells phagocytose debris, process and present Ag, and leave the site of infection to take antigen to lymph nodes
How do macrophages and dendritic cells recognize pathogens? What happens as a result?
Macrophages and dendritic cells use pathogen-associated molecular patterns (PAMPs), they contain receptors on their surfaces for molecules that are present on pathogen surfaces that aren’t present on human cell surfaces (LPS receptors, Toll-like receptors, mannose receptors, scavenger receptors, complement receptors)
As a result, dendritic cells upregulate MHC molecules and costimulatory molecules (B7 or CD80/86)
How do B cells internalize pathogens?
Receptor-mediated endocytosis
What is thymic education? When does the thymus work best?
Ability to generate a diverse repertoire of T cells that distinguish between self and non-self. The ability of the thymus to make new naïve mature T cells decreases w/ age.
What 4 cell types does the thymus contain?
Developing thymocytes
Thymic stroma (epithelial cells)
Dendritic cells
Macrophages
What cytokine is produced by thymic stromal cells and what does it do?
IL-7, initial step in thymocyte differentiation that commits a CD34+ progenitor cell to being a T cell
How do undifferentiated progenitor cells enter the thymus?
The express CD34
Describe the first rearrangement process that a T cell goes through.
Which chains rearrange? What are the two possible outcomes? How often does each happen?
Beta (B), gamma (y), delta (d) rearrangement
- If y and d chains rearrange successfully BEFORE B chain, the cell will expresses a yd T cell receptor. This cell is considered mature and naïve and it goes through NO ADDITIONAL MATURATION PROCESS. This happens in only 1-5% of T cells.
- If the B chain rearranges successfully first, gene rearrangement stops, the cells co-express CD4 and CD8 (double positive T cells), and the maturation process continues. This happens in more than 95% of T cells.
Describe the second rearrangement process that a T cell goes through.
Which chains rearrange? What are the two possible outcomes?
Alpha (a), gamma (y), delta (d) rearrangement only happens in uncommitted double positive cells that express B chain and CD4 and CD8 receptors
- If the y and d chains rearrange first, a yd T cell receptor is expressed (B chain is not expressed anymore).
- If the alpha chain rearranges first, the a and B chains are expressed together to make an aB T cell receptor
What segments rearrange in the beta chain of T cell receptors and in what order?
Beta chain undergoes rearrangement of V, D, J segments
- Specific D and J segments come together.
- V segment comes together with the DJ segment that already rearranged
What segments rearrange in the alpha chain of T cell receptors and in what order?
Alpha chain undergoes rearrangement of V and J segments
Describe the process of positive selection.
What cells undergo positive selection? Where does it occur? What is the outcome? What is the purpose?
T cells that express the alpha-beta T cell receptor undergo positive selection
Positive selection occurs in the cortex of the thymus
T cells interact w/ MHC molecules expressing self-peptides on surface of epithelial cells– if a strong interaction occurs, the cell survives; if a strong interaction does not occur, the cell dies. Most T cells are eliminated at this point.
A T cell that can’t recognize self-MHC is USELESS
During positive selection, if a double positive T cell had positive interaction w/ MHC class I, ______ is upregulated, ______ is downregulated, and the cell becomes ______.
During positive selection, if a double positive T cell had positive interaction w/ MHC class I, CD8 is upregulated, CD4 is downregulated, and the cell becomes a CD8+ T cell.
During positive selection, if a double positive T cell had positive interaction w/ MHC class II, ______ is upregulated, ______ is downregulated, and the cell becomes ______.
During positive selection, if a double positive T cell had positive interaction w/ MHC class II, CD4 is upregulated, CD8 is downregulated, and the cell becomes a CD4+ T cell.
