6 BL Immunopathology type IV

Question 1

Define Type IV immunopathology

Answer 1

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!

Question 2

Some examples where Type IV represents all or most of the mechanism:

Answer 2

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

Question 3

Tuberculin skin test aka “Mantoux skin test”

- what happens if you have Ab to TB?

Answer 3

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

Question 4

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.

Answer 4

You see a cellular infiltrate, not Th1.

○ Remember that one Th1 can attract 1000 macrophages? Yea …macrophages win.

Question 5

Explain why a person usually has no observed symptoms when first exposed to poison ivy.

Answer 5

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

Question 6

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.

Answer 6

• 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

Question 7

Abacavir

Answer 7

nucleoside reverse transcriptase inhibitor for HIV treatment

Question 8

Describe the problem that HLA-B*5701 people may have with the HIV drug abacavir

Answer 8

8% of people given abacavir develop abacavir hypersensitivity syndrome
○ Most people with this syndrome have HLA-B5701 allele
-HLA-B5701 allele is class I and works through CTLs → drug induced autoimmune rxn!
- Abacavir can bind to HLA-B57 and induce a conformational change

Question 9

Discuss in principle how T cell immunity could be measured in the laboratory.

Answer 9

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

Question 10

Differentiate between a first-set and second-set graft rejection.

Answer 10

First-set reaction:
• 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

Second-set reaction:
• 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)

Question 11

hyperacute rejection

- example

Answer 11

“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

Question 12

What are Autoimmune conditions?

Answer 12

T cells are involved in the pathogenesis.

Question 13

Discuss how autoimmunity can result from environmental exposure to tissues that cross-react with human organs.

Answer 13

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

Question 14

three requirements for graft-versus-host disease to occur.

Answer 14

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.

Question 15

graft-versus-leukemia phenomenon.

Answer 15

In leukemia, you are immunodeficient.

So get this: Graft vs Tumor (GVT) or “graft-vs leukemia” phenomenon:

• If Leukemia stopped responding to conventional therapy → give large drug doses or radiation (destroys bone marrow)→ then transplant marrow from best match allogenic donor  → Graft-versus-leukemia (GVL)  phenomenon

	- Graft-versus-leukemia (GVL)  phenomenon: Can see decreased relapse rate of leukemia after allogeneic bone marrow transplantation.
	- Due to a therapeutic immune reaction of the grafted donor T lymphocytes against the diseasedbone marrowof the recipient