Tumor and Transplant Immunology Flashcards
(35 cards)
What is “rejection”?
When T-cells and antibodies are produced to attack antigens on the new (donated) tissue/graft.
What is the main cause of the difference between the donated tissue and the patient? (aka what causes the immune response against the donated tissue?)
The major antigenic differences between the host and the graft cause the attack… These differences are the result of different HLA genes
What is an allograft?
When tissue is recieved from a member of the same species
What is a xenograft?
When tissue is received from a different species ( ie pig vasculature used in humans)
What are the two types of immune reactions to a graft?
1) direct pathway of allorecognition
2) indirect pathway of allorecognition
What is the direct pathway of allorecognition?
Antigen Presenting cells (APCs like dendritic cells) from the donor directly present antigens to the host CD4+ and CD8+ t-cells… (theres always gunna be some transfer of donor dendritic cells with transfer of tissue)
**think of this one as mostly CD8+ cells that get stimulated!!*
Summary: Direct = CD8 (mostly), Donor APCs, Acute Rejection (DAD8)
What is the indirect pathway of allorecognition?
When HOST APCs up-take some of the donated tissue and present to CD4+ only cells… not unlike the normal immune response… DCs pick up foreign material and present to T-cells. (note there is NOT CD8+ activation in this case… ONLY CD4+)
*Chronic Rejection
Summary: Indirect = CD4, host APCs, chronic rejection (IHC4)
What are the 3 types of allograft rejection?
1) Hyperacute
2) Acute
3) Chronic
What is a hyperacute rejection?
Occurs when preformed anti-donor antibodies are present in the circulation of the recipient!
Occurs within minutes/hrs of transplantatino and is NOT cell-mediated but rather a HUMORAL response of pre-formed antibodies. Patient likely has had previous transplantations or prior blood transfusions, or multiparous women (cuz these all give the opportunity to make the antibody)
What is acute rejection? (recall 2 different types!)
Occurs a few days after transplantation… may occur after stopping immunosuppressive therapy!
Is either humoral OR Cell-mediated!!!
Mostly CD8+ cells doing the work with some CD4+
Acute cellular rejection (T-cell mediated) usually presents with interstitial and infiltration into the tubules of the kidney and vasculitis!
Acute antibody-mediated rejection usually presents with damage to the glomeruli and small blood vessels
What is chronic rejection? (also 2 types)
Occurs months to years after transplantation
Also either humoral or cell-mediated but its mostly mediated by CD4+ (NOT CD8+)
What is an autograft?
graft from within the same person
What is an isograft?
graft from an individual to a syngenetic recipient (aka monozygotic twins)
What is an allograft?
Graft from a member of the same species
What is xenograft?
Graft between members of different species
When do you try to match HLAs and what HLAs do you want to match when looking for a transplant?
ONLY with a kidney transplant, do you acutally try to match HLAs… and you want to match HLA-A HLA-B and HLA-DR
With liver, lung, and heart transplants HLA matching is usually not even done!
What are the HLA genes for professional APCs and every other cell?
Professional APCs have both MHC class 1 & 2… every nucleated cell has MHC 1.
MHC class 1 genes = HLA-A, HLA-B, HLA-C MHC class 2 genes = HLA-DR, HLA-DP, HLA-DQ
Talk to me about MINOR histocompatibility complex
Coded by genes outside of HLA and NOT detectable by standard tissue typiing.
Causes rejection in up to 1/3 of transplants!!!
What are 2 potential immune responses to a transplant?
1) Recipient rejects donor stem cells (HVGD)
2) Donor cells respond against recipients MHC antigens (GVHD) (Major Problem!)
How do you prepare a donor for stem cell transplant?
No longer need to actually poke through the bone… Now you can simply mobilize the HSCs out of the marrow via stem cell growth factors to push into peripheral blood
What is the mechanism of damage in Graft vs Host Disease? and what is particularly vulnerable in chronic vs acute GVHD?
When donor T-cells recognize recipients MHC antigens resulting in activated DONOR T-cells –> cytokines –>inflammation –> tissue destruction!
Epithelia is particularly vulnerable to acute GVHD (epi of skin –> skin rash, epi of liver –> jaundice, epi of GI tract –> bloody butt pee)
Solid organs are more vulnerable in chronic GVHD
So if T-cells are the cause the damage with transplantation… why not just remove them prior to putting the organ in the patient?
It made things WORSE! The incidence of graft failures INCREASED when they removed the T-cells suggesting that they have some sort of protective effect.
So if immunosuppressive therapy helps to tone down the immune response in GVHD… why not just put them on a shitload of steroids indefinitely?
Infections are a big problem with those receiving immunosuppressive therapy… Specifically cytomegalovirus… CMV-induced pneumonitis can be fatal!
What is the biggest problem with xenografts (ie getting a transplant from a pig)?
Actually… humans do not have a strong T-cell response to pig (or any foreign) MHC antigen!…
However, people often have natural or pre-formed antibodies to carbohydrates expressed on the donor’s (pigs) endothelial cells which leads to complement activation and HYPERACUTE rejection.
There is also the possibility of introducing weird viruses and shit
