chapter 10 – immune responses against tumors and transplants lecture 10
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Chapter 10 – ImmuneResponses against
Tumors andTransplants
Dr. Hafez Sumairi
Learning outcomes
1.What are the antigens in tumors and tissuetransplants that are recognized as foreign by theimmune system?
2.How does the immune system recognize and reactto tumors and transplants?
3.How can immune responses to tumors and grafts bemanipulated to enhance tumor rejection and inhibitgraft rejection?
Immune responsesagainst tumors• Immune surveillance
Control and elimination ofmalignant cells by theimmune system
Tumor antigens• Malignant tumors
express various types ofmolecules that may berecognized by theimmune system asforeign antigens
Immune mechanisms of tumor rejection• The principal immune mechanism
of tumor eradication is killing oftumor cells by CTLs specific fortumor antigens.
• CTL responses against tumors oftenare induced by recognition of tumorantigens on host antigen-presentingcells (APCs)
• Cross-presentation or cross-priming, when one cell type (thedendritic cell) presents antigens ofanother cell (the tumor cell) andactivates (or primes) CD8+ Tlymphocytes specific for the secondcell type.
Evasion of immuneresponses by tumors• Immune responses often fail to check
tumor growth because tumors evolvein the host to evade immunerecognition or resist immune effectormechanisms.
• Tumors can grow rapidly• Tumor antigens are weakly
immunogenic.
• Tumor cells develop severalmechanisms of resistance to immunerecognition and destruction
Immunologicapproaches forcancer therapy• The main strategies for cancer
immunotherapy aim to
1. Provide antitumor effectors(antibodies and T cells) topatients
2. Actively immunize patientsagainst their tumors
3. Stimulate the patients′ ownantitumor immune responses
Immune responses against transplants
Donor is the individual that provides the graft
Recipient or host is the individual in whom thegraft is placed
Syngeneic are animals that are identical to oneanother (and grafts exchanged among theseanimals) isograft
Allogeneic (allografts) are animals (and grafts)of one species that differ from other animals ofthe same species
Xenogeneic (xenografts) are animals (andgrafts) of different species
Alloantigens & xenoantigens are the antigensthat serve as the targets of rejection
Alloreactive and xenoreactive are theantibodies and T cells that react against theseantigens
Transplantation antigens• The antigens of allografts that
serve as the principal targets ofrejection are proteins encoded inthe MHC
• MHC is called the humanleukocyte antigen (HLA) complex
• MHC genes are highlypolymorphic
• MHC proteins are the majorantigens that stimulate graftrejection
• Non-MHC antigens that inducegraft rejection are called minorhistocompatibility antigens
• Blood transfusion• Stem cell transplantation
Induction of immune responses against transplants
• Direct recognition (or directpresentation) T cells mayrecognize allogeneic MHCmolecules in the graft displayedby donor dendritic cells in thegraft
• Indirect recognition (orindirect presentation) Graftalloantigens may be processedand presented by the host′sdendritic cells
• Mixed lymphocyte reaction(MLR) is an in vitro model of Tcell recognition of alloantigens
Immune mechanismsof graft rejectionGraft rejection is classified into hyperacute,acute, and chronic, on the basis of clinical andpathologic features
• Hyperacute rejection occurs within minutesof transplantation, is mediated by circulatingantibodies and is characterized by thrombosisof graft vessels and ischemic necrosis of thegraft
• Acute rejection occurs within days or weeksafter transplantation, is mediated by T cellsand antibodies leading to vascular damage
• Chronic rejection is occur over months oryears, leading to progressive loss of graftfunction, manifested as fibrosis & graftarteriosclerosis
Prevention and treatment ofgraft rejection• The mainstay of preventing and
treating the rejection of organtransplants is immunosuppression,designed mainly to inhibit T cellactivation and effector functions
1. Block cytokine production2. Block lymphocyte proliferation3. Reduce inflammation4. Bind to & deplete T cell5. Inhibit T cell activation
Transplantation ofblood cells andhematopoietic stemcells (transfusion)• These antigens are expressed on
red blood cells, endothelial cells,and many other cell types
• Transfusion reaction
• Blood group antigens are sugars,they do not elicit T cell responses
• Rh antigen, which is a red cellmembrane protein
• Hematopoietic stem celltransplantation
• HLA matching
• Graft-versus-host disease
Maternal tolerance to fetal tissues
• The anatomy of the trophoblast and placenta plays a key role intolerance to the fetus
• Placenta• Does not allow T cells to enter• Actively suppresses immune responses by the action of abundant regulatory T cells or
immunosuppressive molecules
• Maternal trophoblast• Expresses low levels of conventional class I MHC molecules• Expresses unique atypical class I MHC molecules which likely prevent maternal NK cell
recognition and attack
Thank you