Adaptive Immunity and the Establishment of Memory Flashcards
What is a viral epitope?
T and B cells possess receptors on their surface that can recognize small portions of a viral protein (or three-dimensional facets of a protein) termed
epitopes .
What is an antigen?
protein made by pathogen that is responsible for inducing a host immune response
B cells can differentiate into plasma cells and secrete >2000 antibody molecules per second
How are unique antibodies created?
MHC2 exogenous antigen processing system
Variable region of receptors is changed by DNA rearrangements in the genome, and selected genes are spliced together during DNA recombination. This creates unlimited number of possible new variable regions
Thymus has quality control measures, so those without functioning antibody receptors are not released into circulation. This means only 2% of lymphocytes make it to bloodstream. This also helps eliminate any autoreactive lymphocytes, to prevent autoimmune disease
What MHC receptors do CD4 and CD8 receptors bind to?
CD4 - MHC II - APCs
CD8 - MHC I - found on most cell types in body
Immature T-cells leave the bone marrow without any receptors. They then mature in the thymus. They then develop both CD4/CD8 receptors, and then lose one of these receptors depending on what is required
CD8 T cells- cytotoxic
CD4 T cells - helper
Can be Th1 or Th2
What is the difference between Th1 and Th2 response?
APC present to naïve T cells and receptor interactions stimulate either Th1 or Th2 response
Th1 - produce IL-2, IFN - most important for controlling viral infections by causing inflammation, and activating CD8 cells to kill infected cells
Th2 - produce cytokines to stimulate antibody response - B cells into plasma cells
TNF-alpha is primary driver of inflammation
What are the four classic signs of inflammation?
redness
heat
swelling
pain
Due to increased blood flow, capillary permeability, influx of phagocytic cells and tissue damage
Viral infection
Why do patients often have lymph node swelling neck or groin?
Once APC presents to naive T cell, masive expansion of naive population increases
Expansion occurs in lymph nodes - usually the site local to infection
However neck and groin has high abundance of lymph nodes, so stimulation elsewhere in the body can cause proliferation at another site. E.g throat infection causing groin swelling - as lymph node in groin has been stimulated by total body response
What are the different types of IFN, and where are they produced?
IFN type 1 - alpha/ beta - all infected cells in body
IFN2 type 2 - gamma - NK/ T cells
IFN 3 type 3
Virus such as VZV infects via droplet mechanism
How does it then cause a skin rash?
Virus escapes local immune response in lungs, and travels in circulatory system to infect skin
Th1 cells and macrophages were activated in the lungs, they move to the secondary site of infection
There is aggressive immune response, resulting in significant vascular permeability, which can cause skin lesions
Immunity can be measured by antibodies levels
Cellular immune response is difficult to measure
What are methods of doing this?
Limiting dilution and Chromium release assay
Take CD8 T cells from infected person. Slowly dilute down until cellular immunity is not demonstrated
At each dilution check for two properties
- ability of foreign proteins and peptides to stimulate lymphocytes proliferation
- capacity of CD8 cells to lyse target cells
Target cells have Chromium–51 marker, and radiation measured to indicate cell lysis
This method is time-consuming, expensive, and technically demanding. But does give a quantitive measure of cellular immunity
Immunity can be measured either humoral and cellular immunity
Measuring humoral immunity usually involves counting antibody count, and inferring immunity from total antibody count
What is a better measure of immunity?
Neutralisation assays - plaque reduction assay
Culture virus in cell lines - they form plaques
Add diluting samples of antibodies, you keep diluting until you get 50% plaque reduction
Immunity can be measured either humoral and cellular immunity
Measuring humoral immunity usually involves counting antibody count, and inferring immunity from total antibody count
What is a better measure of immunity?
Neutralisation assays - plaque reduction assay
Culture virus in cell lines - they form plaques
Add diluting samples of antibodies, you keep diluting until you get 50% plaque reduction
Immunity can be measured either humoral and cellular immunity
How can we measure cellular immunity?
Limiting dilution and Chromium release assay
Viral culture in cells
Add CD8 T-cells and check for:
- ability of lymphocytes to proflieration
- ability of lymphocytes to lyse cells
Keep diluting until effect is lost
Provides quantitative effect of CD8 cells - although difficult to find standard measures of this as comparaters
This process is slow, expensive, and time consuming
