Flashcards in Type IV Immunopathology Deck (14)
Define Type IV Immunopathology
Type IV immunopathology is also called delayed response or T-cell mediated immunopathology. These reactions do not require antibodies or B-cells, though they may be involved in the overall pathology since actual diseases frequently combine several "Types" of immunopathology.
What are the events that follow the administration of tuberculin antigen in a TB skin test?
The antigen will be taken up by macrophages and DCs, which then present it on MHC Class II molecules. If a person has been exposed to active TB the Th1 cells from the TB clone will recognize the antigen/MHC II complex and become activated, producing IFN-g and attracting up to 1000 M1 macrophages to he site of the test.
Why is a positive TB skin test considered a sign of delayed hypersensitivity?
The reaction takes 24 to 48 hours to peak, unlike other hypersensitivity reactions which are much more rapid.
What sort of cells would be visible in a biopsy of a positive TB test site?
The site would be predominantly composed of macrophages.
Why does a person typically display no symptoms when first exposed to poison ivy?
The first exposure to urushiol causes the creation of the initial clone. Due to the time required for clonal expansion, the urushiol oil is typically washed away or otherwise removed from the skin, offering no target for the clone to attack and cause a reaction.
How might a chemical or small peptide evade processing by an APC and end up directly on the MHC molecule?
The chemical may attach directly to the MHC molecule, or attach to another molecule which is then processed by the APC and expressed on its surface with the other molecule still attached.
What is the complication caused by the interaction of abacavir and HLA-B5701?
Abacavir, an antiretroviral drug, induces a conformational change in MHC I causing it to take up other "self" proteins not normally expressed on the surface. Because these are not upregulated by AIRE in the thymus, there is no negative selection against T-cells specific for them, and those CTL cells may become activated and trigger cell death. Thus, abacavir + HLA-B5701 cause localized auto-immune response "Abacavir Hypersensitivity Syndrome"
How can T-cell immunity be measured in the laboratory?
Whole blood or isolated WBC containing T-cells and APCs can be collected and incubated with antigen in cell culture, causing activation of clones. One could then count cell numbers for proliferation, look at cell size for activation (blast transformation), at DNA synthesis using radio labeled precursors, or quantify cytokines.
Why can TB tests be administered repeatedly to the same subject?
The volume of TB antigen used in the test is sufficient to stimulate a response if there is an extant clone, but not enough to be immunogenic in the absence of an established clone.
What is the difference between first-set and second-set graft rejection?
A first-set reaction occurs after the first grafting from one individual to another in approximately 10-20 days and represents the recognition of the graft MHC by 5-10% of the host T-cells. This expands a large number of clones. Second-set graft rejection occurs after another graft from the same donor to the same individual and occurs in 5-10 days due to the expanded clones in the recipient.
What are hyper acute or "white graft" rejections?
White Grafts occur when the rejection is so rapid that the graft never receives blood supply. It is caused by the development of antibodies to the histocompatibility antigens. It may also occur in xenografts, where antibodies to the foreign antigens are already circulating.
How can autoimmunity result from environmental exposure to tissues that cross react with human organs?
The aerosolization of other tissues (e.g., mammalian brains) allows those particles to be taken up by APCs which, in turn, activate T-cells which have never been exposed to brain antigens before. Activated T-cells can cross the BBB, and may then cause neuropathies.
What are the three requirements for graft-versus-host disease?
1) The graft must contain immunocompetent T-cells 2) There must be at least one antigen in the host that the graft T-cells can recognize (grafts between ID twins do not cause GvHD) 3) The host must be immunocompromised or genetically unable to recognize the graft T-cells, or else it would overpower them.