TYPE IV IMMUNOPATHOLOGY Flashcards
Type IV
T-cell mediated. Do not require antibody or B cells.
Initiation
phase of an immune response following first exposure to the antigen. (immunization phase). Poison Ivy example. urushiol compound is what causes it. MHC gets the antigen. Common in contact immune responses. MHC on dendritic cells (either by binding directly to MHC, or by binding peptides which then get presented on MHC). The dendritic cell travels to the draining lymph nodes, where it presents its MHC plus antigen to the appropriate Th0 precursors, which develop into Th1 and Th17 cells.
elicitation
of a reaction in a person who is already immunized (effector phase). memory T cells from the expanded clones are throughout the body, and get activated. They secrete interferon-γ which attracts and activates a large number of macrophages. , because of all the cellular events that need to take place, begins to be visible in 6 to 12 hours, and peaks at 24 to 48 hours, thus earning the label ►delayed- type hypersensitivity. Th1 –> IGN-Gamma–> M1. NOTE: 1 th1 can recruit 1000 macrophages!
Memory T cells
are persisting cells in a clone that was expanded by contact with antigen. key thing is that there are more of them than in a naïve person. They also ►have a lower activation threshold, so that it takes less antigen for elicitation of a reaction than it did to immunize in the first place.. Tho–>Th1, so more easily triggered.
Tuberculin skin testing
The Mantoux skin test is most commonly used in the USA. In it, 0.1 mL of PPD—purified PROTEIN derivative, a standardized preparation of M. tuberculosis antigens—is injected intradermally. (It is necessary to see a skin “bubble,” because if not the injection has gone subcutaneously, and will diffuse away before the reaction can get established.) The antigen is taken up by local macrophages and dendritic cells, and presented on MHC Class II. If the subject has an expanded number of anti-tuberculosis Th1 memory cells, they will come by and get stimulated, produce IFNγ, and attract macrophages. The test is read at 48 hours, and the diameter of the induration (firm raised part) is measured; 15 mm is always positive, and 10 or even 5 mm can be called positive under certain conditions, for example if a person is partly immunosuppressed. TB skin tests are not immunizing, and they can be repeated regularly without the subject becoming positive since it is a miniscule dose. In some countries kids get vaccined with Bacill Calmette Guerin (BCG)
Immunization to TB antigens
normally happens during a primary infection, which is usually unapparent to the patient, so a positive routine skin test usually comes as a surprise
T-Cell mediated immunity in Vitro
TESTING: Whole blood or isolated white blood cells (you need both T cells and APCs like monocytes) may be incubated with antigen in cell culture, and activation observed: one could count cell numbers for proliferation, look at cell size for activation (“blast transformation”), or at DNA synthesis using radiolabeled precursors.
T-cell testing quantiferon-TB GOLD
test is new, very nice, and is preferred (2010, CDC) to skin testing when the subject has had BCG immunization. Purified M. tuberculosis (human-specific) proteins are added to a sample of whole blood, and after incubation, interferon-γ is measured in the medium by an ELISA assay. Unlike the skin test, it remains NEGATIVE in people vaccinated with BCG, (no cross-reactive antigen with BCG,) allowing you to distinguish infection from previous immunization.
Cytotoxic T lymphocytesin DTH
They probably take part in many manifestations of T cell-mediated immunity, and are quite important in many autoimmune diseases, tumor immunity, and transplant rejection
Contact dermatitis
Also called contact hypersensitivity or contact sensitivity or, INCORRECTLY, contact allergy; ‘allergy’ should be reserved for IgE-mediated events. The classic example of this is poison ivy, but many other chemicals can cause it; the main requirements are that they pass through intact skin to reach antigen-presenting cells, and they associate with MHC Class II. Treat with avoidance, and topical steroid creams or ointments. Example LATEX gloves are starting to go away in clinics.
HLA and T cell Reactions
HIV example and learning objective) Up to 8% of people who are given ABACAVIR, a nucleoside reverse transcriptase inhibitor, for HIV, develop abacavir hypersensitivity syndrome which is quite awful and difficult to diagnose correctly. Nearly all people with the syndrome are HLA-B*5701. We now TEST for this allele before offering the drug, a good example of “personalized medicine”. This is a Class I proble and the syndrom is actualy a drug induced autoimmune reaction
Graft rejection
Rejection is a complex phenomenon eventually involving most or all of the specific immune and nonspecific amplifying elements of the immune system. Allograft immunity shows specificity and memory:. First (10-20 days) and SECOND set reactions (5-10 days). Point it is faster the second time!
Hyperacute or “white graft” reactions
If you keep putting A grafts onto B, eventually they will rejected even before they heal in, that is, they stay white and bloodless. This is due to the development of antibodies to histocompatibility antigens. Common with xenografts. DUE TO PREEXISTING ANTIBODY.
Autoimmune diseases
any conditions are clearly autoimmune, and T cells are involved in the pathogenesis. Some of these conditions also involve autoantibodies, and thus there is both Type II and Type IV immunopathology
Multiple sclerosis
the demyelinating disease in which T cell (t1/t17) reactivity to an autoantigen (myelin basic protein) was first shown, responds to therapies directed at T cells, such as the humanized monoclonal antibody natalizumab. But it also responds to the B cell-depleting monoclonal rituximab.