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Immunology 18


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Three types of transplantation
human: allogenic, syngeneic, autologous
nonhuman: xenogeneic
1st set rejection
occurs within 7-10 days occurs if donor MHC is different from host MHC; host mounts an immune response to donor tissue
2nd set rejection
occurs within 2-3 days; adaptive immune response of memory lymph
"Full match"
Matching of the 6 major HLA types (A,B,C,DR,DP,DQ)
Two ways to initiate a response?
direct allorecognition - Donor's APCs initiate an alloreactive T cell response without antigen processing
Indirect allorecognition- HOST APC's initiate an alloreactive T cell response by processing foreign antigen from donor cells
Three types of rejections seen in human transplant
Hyperacute, Acute, and Chronic
Describe Hyperacute rejection
occurs in minutes to hours following transplantation. due to pre-sensitization of recipient to foreign HLA and development of pre-existing antibodies. Both antibody and complement are activated. ADCC can develop. Not applicable to bone marrow or stem cell transplant
Describe Acute rejection
Most common occuring in days to wekks following transplantation. Alloreactive T-cells recognize HLA disparity. Some humoral antibody response. Leads to massive destruction of tissue, inflammation, thrombosis. can be responsive to immunosuppressive drugs
Describe Chronic rejection
occurs months to years following transplant. difficult to treat because of chronic inflammation, fibrosis, and arteriosclerosis. More of a Th2 response as wells as a result of cytokines produced by macrophages and monocytes.
Rejection prevention
1. HLA matching.
2. Calcineurin inhibitors, Ionsine monophosphate dehydrogenase Inhibitors, mTOR Inhibitors, Steroids, Anti-inflammatory
Central tolerance
T cells educated in thymus; positive and negative selection occurs; some of the T cells selected to survive in the thymus will become regulatory cells and will suppress self reactive immune cells in the periphery
Peripheral tolerance
Clonal anergy - host APC does not present co-stimulatory molecules correctly to T cell, from production of IL-10 and TGF-B
Clonal deletion - results from interaction with immune regulatory cells derived from central tolerance; activation-induced apoptosis occurs
How do you condition a host prior to stem cell transplant.
Irradiaton. To cause immunosuppression
How do you measure the response to stem cell transplantation?
monitor WBCs, PMNs, Platelets. Determine chimerism (what percentage of cells are donor vs recepient or use FISH for x/y chromosome in sex-mismatch)
Graft vs. Host Disease. opposite of rejection donor cells react against normal host recepient cells. Limiting side effect to allogeneic transplant. Affects mucosa, liver, infections. Chronich GVHD is like autoimmune disease.
What are the 3 criteria for acquisition of GVHD?
immuno-depressed host, infusion of competent donor T cells, HLA disparity
What are the three types of GVHD
Hyperacute, Acute (affects skin, liver, gut, results in high bilirubin) and Chronic
Risk factors for GVHD
High HLA disparity
Bone marrow or cord blood donor genetically unrelated to recipient, older donor, sex mismatch (particularly in female who has had kids) CMV incompatibility, Immune suppression.
How do you reduce likelihood of GVHD
T cell depletion donor graft or administer prophylactic drugs

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