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22 Cards in this Set
- Front
- Back
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Immune Responses against Tumors and Transplants--common features
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-Reactions to human cells perceived as foreign
-Antigenic targets can be expressed elsewhere in the body -Requires special mechanisms for induction/control of these response -Central to the immune response in both cases is the CTL |
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Evidence for Immune Responses against Tumors: 3
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Describe Tumor Antigens:
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-“Self-ish”
-To trigger immunity they must be “seen” as non-self *Mutations in surface PROs *Overexpression of a cell surface marker *Aberrant expression (location or timing--embryonic expression) of cell surface PROs. |
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Types of Tumor Antigens recognized by T cells: 4
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-melanoma
-BCR/ABL -HPV, EBV |
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3 examples of how Immunodeficiencies highlight development of tumors in infectious settings:
2 examples of how Inflammation contributes to the development of cancer in chronic infections: |
Immunodeficiency:
HPV - cervical carcinoma EBV driven leukemia following transplantation HIV - Kaposi sarcoma Inflammation: Hepatitis B -hepatocellular carcinoma Helicobactor pylori - gastric carcinoma |
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Are tumor antigens intracellular or extracellular?
Tumor antigens are presented on which class of MHC molecule? Which subset of T cells will recognize these antigen-MHC complexes? What is the mechanism of action for these T cells? |
-intracellular
-MHC class I -CD8+ -Cytotoxic killing |
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How do you induce a CD8 T Cell Response against Tumors?
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3 Strategies to Enhance Anti-Tumor Immunity?
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1) Engage the APCs
-Antigen processing and presentation on MHC II -Costimulatory molecules -Cytokines 2) Vaccinate against tumor antigens 3) Combination therapies: Chemo + Immuno *IL-2* -Damage vasculature of tumor, improve access -Inflammation (caused by chemo, radiation) -Initial tumor cell death “feeds” APCs |
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-Most well-known FDA-approved monoclonal Ab for treating cancer?
How does it work? |
-rituximab
-binds to CD20 on tumor cell -acts by ADCC |
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Evidence for Immune Responses to Transplants: 3
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Syngeneic
Autologous Allogeneic Xenogeneic |
Syngeneic - from identical individual/ same species
Autologous – same individual is both donor and recipient Allogeneic - from different individual/ same species Xenogeneic - from different species |
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How many MHC I molecules are there?
How many MHC II molecules are there? |
6: HLA-A, -B, -C ; one allele from each parent
6: One HLA-DQ and –DP, One or more HLA-DR |
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Describe polymorphism in HLA genes:
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-MHC genes are highly polymorphic
*350 HLA-A, 620 HLA-B genes *HLA-C is of limited polymorphism -Six MHC Class II Molecules *90 HLA-DQ, 400 HLA-DR genes *HLA-DP is of limited polymorphism *There are also Minor Histocompatibility Proteins -Allelic forms of normal cellular proteins -Important in blood transfusion and BMT |
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Components of the Anti-MHC Immune Response:
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-T cell receptors evolved to recognized MHC
-CD4 and CD8 T cells are positively selected *Allo MHC bearing allo-antigens look like self MHC bearing foreign antigens *Many T cell clones specific for different foreign peptides bound to one self MHC may cross-react with any one allo MHC *Every MHC molecule on each allo graft cell may be recognized as foreign *Makes a rejection a significant challenge |
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Describe direct vs. indirect recognition of organ allografts:
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Recognition of Allogeneic MHC:
-normal -allorecognition |
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Three Classes of Graft Rejection:
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-Hyperacute
Occurs in minutes Thrombosis of graft vessels, necrosis of the graft -Acute Occurs in days or weeks Cell damage, inflammation -Chronic Occurs over months or years Fibrosis, arteriosclerosis, & gradual loss of function of grafted tissue |
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Left to Right: Hyperacute, Acute Cellular, Acute Humoral, and Chronic Graft Rejection
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Prevention and Treatment of Graft Rejection:
-prevention -treatment -future therapies |
-Prevention
Major histocompatibility match Minor histocompatibility match -Treatment Immunosuppression T cells, T cells, T cells (interfere with T function) -The Future Tolerance induction Specificity for graft to avoid over-immunosuppression |
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Treatments for Graft Rejection: 8
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Transplantation of Blood and Marrow:
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-Transfusions
*The “original” transplant *Limited by blood group antigens ABO *Expressed on RBCs, endothelial cells, and others *Express one, tolerant to it but sensitive to the other *Pre-formed antibodies react against transfused blood -Transfusion Reaction *Severe, immediate *Avoided by matching donors |
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Hematopoietic Stem Cell Transplantation:
-clinical applications -sources of donor stem cells -preparation of the pt -preparation of the transplant |
-Clinical applications
Correct hematopoietic defects Restore marrow damaged by cancer treatments -Sources of donor stem cells Collection of bone marrow cells Mobilization of stem cells collection by leukopheresis -Autologous vs allogeneic transplant -Preparation of the patient Matching Making space Immunosuppressive therapy -Preparation of the transplant Stem cell enrichment T cell depletion Purging of malignant cells |
