Flashcards in 6 BL Immunopathology type IV Deck (15):
Define Type IV immunopathology
T cell-mediated events that are undesirable or injurious
○ Only type of immunopathology not requiring antibodies or B cells
○ Was known as: delayed-type hypersensitivity (DTH) → No mas!
Some examples where Type IV represents all or most of the mechanism:
1. poison ivy (contact dermatitis)
2. TB test +
3. Chronic beryllium disease
4. Abacavir in hiv patients
5. Graft rejection (allograft rejection)
6. GvH disease (allograft rejects host)
7. Resistance to Mycobacterium/fungus
8. autoimmune diseases
Tuberculin skin test aka "Mantoux skin test"
- what happens if you have Ab to TB?
Inject 0.1mL of purified protein derivative (PPD), aka a std prep of M. tuberculosis antigens, intradermally → see skin "bubble" → local macrophages or dendritic cells take up antigen → present on MHC Class II
you have expanded number of anti-tuberculosis Th1 memory cells → Th1 memory cells get stimulated → produce IFN-γ → attract M1 macrophages → after 48 hours, you see red/raised induration
Characterize the cells that would be seen in a 48-hour biopsy of the TB test site with regard to whether T cells or macrophages predominate.
You see a cellular infiltrate, not Th1.
○ Remember that one Th1 can attract 1000 macrophages? Yea …macrophages win.
Explain why a person usually has no observed symptoms when first exposed to poison ivy.
Thanx to our Immunization phase of immune response! (initiation phase)
□ Skin first gets exposed to oil of Toxicodendron radicans → oil contains urushiol → penetrate skin and binds to MHC (or binding peptides that eventually get presented on MHC) → dendritic cell w/ MHC goes to lymph node → presents MHC + antigen to Th0 precursors → develop into Th1 and Th17 → divide and voila! you are immunized and ready to respond . . . Next time
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.
• Chemicals or Small peptides can associated directly with MHC type II without having to be processed
○ If then mixed with pt's T cells → target cell death in hours
nucleoside reverse transcriptase inhibitor for HIV treatment
Describe the problem that HLA-B*5701 people may have with the HIV drug abacavir
8% of people given abacavir develop abacavir hypersensitivity syndrome
○ Most people with this syndrome have HLA-B*5701 allele
-HLA-B*5701 allele is class I and works through CTLs → drug induced autoimmune rxn!
- Abacavir can bind to HLA-B57 and induce a conformational change
Discuss in principle how T cell immunity could be measured in the laboratory.
T CELL-MEDIATED IMMUNITY IN VITRO
• Whole blood or isolated WBCs (as long as it has T cells AND APCs) are incubated with antigen in cell culture → observe for:
○ Proliferation: Count cell numbers
○ Activation ("blast transformation"): Look at cell size
○ DNA synthesis
○ Cytokines released
Differentiate between a first-set and second-set graft rejection.
• Skin graft from mouse strain A is inserted into mouse strain M → rejected in 10-20 days
• Recipient (M mouse) has differing MHC to A mouse. So recipient's response to mouse A histocompatability antigens become boosted → develops more anti-A Th1 and CTL
• Another A skin graft is placed on same M recipient → rejected in 5-10 days (faster the second time around!)
• Secondary response results from T cell memory developed during first exposure (anti-A Th1 and CTL)
"White graft" reaction:
Hyperacute rejection → due to preexisting Ab
• If you keep putting A grafts onto B, eventually they will rejected even before they heal, that is, they stay white and bloodless.
○ This is due to the development of antibodies to histocompatibility antigens.
• Common when xenografts (from another species) are attempted.
○ Due to human pre-existing antibodies to ubiquitous carbohydrate epitopes which are present in the foreign species
What are Autoimmune conditions?
T cells are involved in the pathogenesis.
Discuss how autoimmunity can result from environmental exposure to tissues that cross-react with human organs.
If there is an antigen that is similar enough to a self-protein, exposure to the foreign antigen could create an immune response that ends up targeting self-protein as well
three requirements for graft-versus-host disease to occur.
1. The graft must contain immunocompetent T cells (even bone marrow has mature T cells in it).
2. There must be at least one antigen in the host which the graft’s T cells can recognize
- No worries with identical twins.
3. The host must be relatively immunoincompetent or unable for genetic reasons to recognize the graft’s MHC antigens, otherwise the graft would be rejected too rapidly.