5.7 Immunopath 2

Question 1

Graft Rejection

Answer 1

Hyperacute, Acute, Chronic

Question 2

Hyperacute is malpractice bc

Answer 2

hyperacute rejection is based on ABO matching bc those are the Abs we have just floating around to produce and immediate response (everything would take time to develop a response), so if you have hyperacute rejection, you know there was a mess up in protocol where they skipped the blood type matching

Question 3

What is the proximal cause of hyperacute rejection

Answer 3

the endothelial cells are targetting and damaged so you have exposure of collagen, thrombosis, and you infarct the organ –> ischemia of the organ

Question 4

Acute graft rejection

Answer 4

happens if you do not have a perfect match

Question 5

Chronic graft rejection

Answer 5

tends to happen anyway, it can be really bad or take years to develop, it is mostly vascular where you get thickening of the vessel and slow ischemia

Question 6

What does hyperacute rejection look like on a slide

Answer 6

dead tissues – coagulative necrosis due ti infarct

Question 7

What does acute rejection look like

Answer 7

you see lots of lymphocyte infiltration (not neutorphils) bc rejection is autoimmunity mediated by your lymphocytes

Question 8

What does chronic rejection look like

Answer 8

you see less infiltrating lymphocytes and more scar tissue and vessel thickening

Question 9

Mechanisms of graft rejection

Answer 9

Dircet, Indirect, Antibody, CD8 kill/ Ab-complement

Question 10

Direct rejection

Answer 10

APCs in the graft think your body is foreign

Question 11

Indirect rejection

Answer 11

your body’s apc’s present the graft as foreign

Question 12

Indirect vs Direct rejection

Answer 12

indirect takes time and reaction to other peptides occurs, direct more associated with initiation and acute rejection, indirect more associated with late acute and chronic, Ab associated with both, Data not conclusive with great amount of overlap

Question 13

BM transplans are good for

Answer 13

cancer chemotherapy, metabolic deficiencies , and immune deficiencies

Question 14

Graft vs host

Answer 14

BM transplant is putting immunocompetent cells into an immunosuppressed pt creating the possibility of graft vs. Host

Question 15

Acute GVH

Answer 15

takes days and occurs in the skin, liver, intestins and reamining immune system, manifests as rash, destruction of small bile ducts, GI ulcers, and bloody diarrhea, enhanced infections esp CMV, but mostly don’t see acute bc it is well managed

Question 16

Chronic GVH

Answer 16

insideous, skin effects similar to systemic sclerosis, jaundice from chlestasis, severe GI strictures, devastation of the immune system, can be managed by immunosuppressive therapy

Question 17

in a biopsy of liver with acute GVH what would you see

Answer 17

big dialated small bile ducts full of bile bc the distal bile ducts have been closed and scarred

Question 18

Therapeutic intervention to prolong graft survival

Answer 18

tissue matching, azathioprine and other modified nucleosides, steroids, cyclosporin

Question 19

what organ do you not worry about tissue mathing

Answer 19

heart transplant, you just try to manage it

Question 20

Effect of Steroids

Answer 20

shut down all interactions of macs, DC,s T cells

Question 21

what is an ideal immuno suppressant

Answer 21

something that stops you from reactin to the graft leaving everything else in tact__..or at least something that stops you from interactin with new ag bc you ben exposed to most thing in childhood anyway

Question 22

Effect of Cyclosporin

Answer 22

inhibits Il2 signaling so you don_t get presentation of new ag, and don_t get new B cell T cell interaction, but B cells can still secrete low affinity ab’s without Tcells —but steroids would knock this functionout

Question 23

CD4 cells

Answer 23

help CD8s via th1 and B-cells via Th2

Question 24

What is the down side of Cyclosporins

Answer 24

they are renal toxic

Question 25

Autoimmune Diseases

Answer 25

Autoimmune reaction, Evidence that reaction is not secondary–meaning disease is directly related to immune system atacking self, no other cause of disease

Question 26

Tolerance

Answer 26

prevention of immune responses to self antigens, also Suppressor T cells help

Question 27

Central tolerance

Answer 27

clonal deletion and re-editing of self-reactive lymphocytes in thymus and bone marrow

Question 28

Peripheral tolerance

Answer 28

elimination of later developing self reactive clones

Question 29

central tolerance develops

Answer 29

in thymic epithelium for T cells that are positively selected if they don_t respond to self (if they do respond to self we kill them), and B cells are selected in BM, they have a chance to rearrange their Ab genes so they are not self reactive

Question 30

Peripheral tolerance

Answer 30

Clonal deletion — FasL expression on T cells is increases when you have a clone that recognizes self and it undergoes apoptosis due to burn out, Clonal anergy — APCs only upregulate costimulatory molecules when they are presenting ag on MCHII, but costimulatory molecules are not expressed when presenting self peptides, and without the costimulation the clone is turned off–possibly forever

Question 31

Suppressor T cells

Answer 31

CD4 Tcells constitutively expressing CD25 (the alpha chain fo IL2) are suppressive of immune reactions, possibly suppression via secretion of IL10 and TGF beta, gene called Foxp3 required for development of CD4+ and CD25+ cells, mutation in Foxp3 causes severe autoimmunity, polymorphisms in CD25 correlate with Multiple Sclerosis and autoimmune diseases

Question 32

Tolerance Failure

Answer 32

peripheral tolerance broken, not central tolerance; complex interplay of environmental, genetic, and microbial and immunologic mechanisms

Question 33

Clonal Deletion Breakdown

Answer 33

Fas or FasL knockout mice all develop severe autoimmune disease similar to Lupus

Question 34

T cell anergy

Answer 34

B7-1 expression in sites of infection and presence of auto-reactive T-cells, Murine model of Type I diabetes –transgenic mice express both a viral ag and B7-1 under insulin promoter

Question 35

Loss of suppressor cells

Answer 35

attractive hypotesis but least understood, selective IL10 secreting Th2 cells isolated from man and mouse

Question 36

Molecular Mimicry

Answer 36

post-streptococcal rheumatic heart disease, Myelin basic protein/viral cross reacting T-cells in MS – This is autoreactivity, your heart has ag that cross reactive with the strip ag

Question 37

Polyclonal lymphocyte Activation

Answer 37

LPS induce polyclonal activation, bacterial superantigens, A polyclonal activator will hit averything and activate it so if you hit a self reactive clone you’ll get autoimmune disease

Question 38

Exposure to Sequestered Ag

Answer 38

anatomic and molecular sequestration

Question 39

Genetic Factors

Answer 39

familial nature of many autoimmune diseases, induction of autoimmune disease by HLA–B27 placed in rats transgenically, Association of rheumatoid arthritis with MHC II HLA-DR4 and 1, many with these genes do not develop autoimmune diseases