Immunology Block: Imm # 10 - Alloantigens And Transplantation Biology

Front 1

what are the basic kinds of rejection and what's the principle mediator of each?

Back 1

Hyperacute reaction - this is very rapid and is mostly an antibody/complement/innate leukocytes (PMN's, macrophages).

Acute rejection - this can take up to a couple of weeks to set in - and this is T-cell mediated (recognition of foreign HLA's). Note that the "second set" reaction is in this previous graft attempt builds up memory T cells, etc.

Chronic rejection - both T cells and antibodies mediate it.

Front 2

how can you test for chronic rejection, and what does it cause?

Back 2

test function of the transplanted organ to see it.

generally the immune response causes INTERSTITIAL FIBROSIS (collagen deposition/scarring), and narrowing of blood vessels.

Front 3

let's review the 4 kinds of hypersensitivity here:

Back 3

Type 1: allergy/atopic (mediated by IgE and mast cells).

Type 2: Cytotoxic reactions, driven by antibody and complement and ADCC. Blood type problems, etc.

Type 3: Complex driven. Frustrated PHAGosomes.

Note that types 1 through 3 are antibody driven.

Type 4: delayed, cellular. This is about lymphocytes, and it's the main player in acute/chronic rejection of organs.

Front 4

what does the HLA complex look like?

Back 4

remember, there are 3 kinds.

HLA type 1 comes in A, B and C. It's a tri-alpha chain thing with a weird globulin thing.

Class II: can be DR, DQ, and DP.

Class III: complement something or other.

Front 5

what's a synogenic graft?

what's the fundamental difference in risk between a kidney and a bone marrow transplant?

Back 5

from an identical twin.

kidney transplant will lead to host-vs-graft disease (host recognizes foreign HLA"s and t-cells go kill them).

in bone marrow transplants, reallyw worry about graft vs. host disease, where the grafted cells contain T-cells and they attack the host.

Front 6

in skin grafts, what kinds of rejection might you see?

Back 6

these are considered small grafts without vascular anastomoses.

can have primary (first set) rejection - takes a couple weeks, gets necrotic.

Second set - tried before, get rejected faster. Can lead to "white graft" - it just never takes.

Front 7

so, imagine an APC with a "foreign" antibody just presented to a TH cell. how what?

Back 7

If the Th cell gets sprayed with IL-12, it'll become a Th1 cell and present to cytoxic T cells, spewing out IFN-gamma and IL2.

If it gets hit with IL-4 from a presenting B cell (presenting to Th2 cells), then it's likely to go producing all kinds of IL2, IL4, IL5, etc and make lots of antibodies.

Front 8

talk about hyperacute, acute, and chronic rejection - what are the hypersensitivity reaction types associated with each?

Back 8

acute rejection is mostly about Type 4 - it takes a couple weeks to set in 'cause it's all about T cells.

Hyperacute, remember, is type II because it's about preformed antibodies and complement-driven destruction.

Chronic is a combination of antibodies and cells, and seems to be involving type 4 and type 2.

Front 9

what's a potential paradoxical medaitor of chronic rejection?

Back 9

TGF-beta, the anti-infalammatory cytokines that comes from T-regulatory cells.

Chronic inflammation is caused by the implanted organ, and the body eventually tries to calm this down. Makes TGF-beta, which helps deal with inflammation by encouraging fibrosis and scar formation - this of course damages the organ.

So inflammation is bad, resolving inflammation is bad. This is why all organs eventually end up getting rejected.

Front 10

what are the major drugs involved and what should we know?

Back 10

organ transplantation drugs:

1. Corticosteroids - these are immunosuppressive and block IL1 production, stopping all sorts of stuff.
also, don't forget how they stop the production of pro inflammatory things like arachadonic acid derivatives (both leukotrienes and prostiglandins).


2. Azothioprine, cyclophosphamide, and methotrexate - these are all inhibitors of DNA synthesis and screw up any rapidly proliferating cells, including T cells.

3. Cyclosporine, tacromolius, seroliums - these all inhibit IL2 production by messing with calcinurin in CD4 cells, so you don't get much T cell differentiation.

Front 11

bone marrow transplantation - what percentage end in GVHD?

Back 11

all of them get this to some degree.

unless it's isografting.

T cells in the graft react with self antigens.

Front 12

for this class, what are the actions of corticosteroids?

Back 12

immunosuppressant that works by decreasing the secretion of pro-inflammatory cytokines (including TNFalpha, IL1, and others) and by lowering arachadonic acid derived inflammation mediators.

AKA NFkappaB-dependent transcription

Front 13

what's the danger of being a 99% match, rather than an 80% match?

Back 13

can get donated HLA molecules presenting to your own T cells, which can increase the immune response more than if you were a slightly less-good match.

Front 14

chronic rejection is a lot like other rejections, but what makes it different?

Back 14

it can involve anti-inflammatory cytokines, like TGF-beta, and causes fibrosis/scarring/smooth muscle proliferation.

Front 15

what are typical symptoms of GVHd?

Back 15

skin problems, GI problems, liver, and lung.

Front 16

briefly, describe the interferons and their functions. this is review.

Back 16

alpha and beta are part of the innate response and are released by virally infected cells, which will help their neighbors stave off invasion. Up MHC1.

gamma is the main activator of macrophages, and it encourages the expression of MHC 1 and II on cells to better mount an adaptive response. only weakly anti-viral.