Type IV immunopath Flashcards
Type IV Immunopathology
aka delayed hypersensitivity
Injurious/deletirious T-cell mediated events
Describe the cellular and molecular events that take place in a positive skin test for tuberculosis
1) preparation of M. tuberculosis antigen (purified protein derivative) is injected intradermally
2) antigen is taken up by APC and presented on MHC Class II
3) If the subject has been exposed to the antigen previously, memory anti-tuberculosis Th1 cells will be stimulated and attract macrophages to the site
–> Result = firm raised portion of the skin at the injection site
Explain why positive TB test is called delayed-type hypersensitivity
Because area of inflammation resulting from activation of memory T cells is visible 6-12 hours following injection and peaks after 24-48 hours
why a person usually has no observed symptoms when first exposed to poison ivy
By the time, dendritic cells with the poison ivy antigen presented on their MHC II reach the lymph nodes and activate Th1/Th17 cells, the antigen is no longer present on the skin (it has been washed or worn away).
Thus, Th1 cells have no more antigen to bind and recruitment of macrophages does not take place.
INITIATION PHASE
Discuss how a chemical or small peptide might not need to be processed through an antigen- presenting cell to be presented by that cell to T cells.
Processing of antigen is required to reduce the antigen to an epitope-sized particle capable of interacting with the MHC.
If the antigen is already reduced to the size of the epitope, as with small chemicals or peptides, it may associate directly with the MHC without processing
Discuss in principle how T-cell mediated immunity could be measured in vitro.
Whole blood or WBCs is incubated with antigen in cell culture
Cell proliferation, cell size, DNA synthesis (assessed with radiolabeled DNA precursors), or cytokine release can by used to measure T-cell immune response.
Explain why TB skin tests can be administered repeatedly to the same subject
dose of antigen required for the TB skin test is far lower than the dose required to immunize a patient
antigen remains local and no memory cells or B cell antigen are generated
First set graft rejection
Graft rejection in 10-20 days due to 5-10% of recipient T cells recognize foreign MHC that look like self MHC plus antigen.
Boost anti-graft Th1 and CTLs
Second set graft rejection
graft rejection in 5-10 days to a second skin graft due to T cell memory recognize graft and more quickly increase response
HIGHLY SPECIFIC
hyperacute reaction
Responses to grafts resulting in graft rejection before the graft has even healed in.
Caused by repeated graft attempts and the development of antibodies to the graft’s histocompatibility antigens
Assoc with donors of diff species because humans have pre-existing antibody against carb epitopes on other species
how autoimmunity can result from environmental exposure to tissues that cross-react with human organs.
Brain is antigenic, not immunogenic so anti-brain T cells exist in everyone- just not stimulated since brain is well protected
Because there is no contact, the brain is considered foreign to the immune system.
If a person’s immune response is exposed to brain “antigen” from the environment, it will be presented on APC and trigger the proliferation of “anti-brain” T-cells.
These T-cells can then enter the brain and cause an immune response and encephalitis.
requirements for graft-versus-host disease
- The graft must contain immunocompetent T-cells
- There must be at least one antigen in the host that the graft’s T cells recognize
- The host must be relatively immunoincompetent (or else the graft would be rejected by the host before the graft could reject the host)
Graft vs host
when T cells from a graft attack the host
graft-versus-leukemia phenomenon
leukemia patients that receive bone marrow from themselves (T-depleted) have a higher rate of leukemia relapse than those who receive the marrow from someone else (with T cells)
assumed that graft-versus-leukemia actually plays an important role in the success of bone marrow transplant.
Examples of Type IV
1) rejection of allografts
2) graft vs host
3) positive tuberculin skin test
4) resistance to TB
5) resistance to fungal infections
6) contact dermatitis
