Immunology Flashcards
Tumors that elicit strong host immune response
virally-induced (oncogenic viruses) Ex: HPV, EBV
mutations caused by carcinogens
tumor antigens expressed on normal cells
tumor-associated antigens
What supports immune surveillance as being tumor suppressive?
Virus-induced tumors occur frequently in immunocompromised patients
Vaccination to prevent tumors
HPV vaccine reduces cervical cancer risk
HBV vaccine to reduce liver cancer risk
oncofetal antigens
carcinoembryonic antigen (CEA)
alpha-fetoprotein (AFP)
proteins that are expressed in normal developing fetal tissues and in cancer cells
which tumor cells do NK cells kill?
Those with reduced expression of MHC Class I
those which express ligands for activating receptors of NK cells
What role might CD4 T cells play in tumor immunity?
provide cytokines for effective CTL development
may also secrete IFN-gamma or TNF to increase tumor cell MHC I expression and sensitivity to lysis by CTLS
How do tumor cells evade immune recognition?
decrease synthesis of MHC I
Decrease synthesis of beta2-microglobulin
decrease synthesis of antigen-processing machinery
Do not express MHC Class II or costimulators
Tumor antigens may be inaccessible to immune system
Vaccination with tumor antigens
used to enhance immune responses against the tumor being developed
Cell-based vaccine for advanced prostate cancer
Disadvantage: in order to eradicate tumor cells the immune response must be strong, which is difficult to induce
What type of vaccine is available for renal cancer?
cytokine and costimulator-enhanced vaccines
Why might IL-2 or GM-CSF be used to treat cancer?
these enhance adaptive and innate immune responses against tumors.
It is approved for malignant melanoma and renal cell carcinoma
How does BCG affect tumor growth?
It activates macrophages and promotes macrophage-mediated killing
Intravesicular BCG is used to treat cancer
What is adoptive cellular therapy?
transfer of cultured immune cells that have anti-tumor reactivity into the tumor-bearing host. These are expanded from the lymphocytes of patients with the tumor.
Ex: LAK cells
What inflammatory response increases risk of a urinary tract cancer?
prostatitis
manifests with skin rash, liver failure (jaundice), and/or diarrhea. T cells of the donor become active especially with cytokine stimulation from other inflammatory processes
acute GVHD
disease acts more like an autoimmune or immunodeficient state. There is a predominantly TH-2 immune response. Major risk is prior acute GVHD
chronic GVHD
What cell type mediates immune response to tumor cells?
major immune response to tumors comes from cytotoxic CD8 cells. Tumor cells often do not express costimulators or do not express class II MHC molecules that would aid in activation of CD4 helper cells, a tumor immune response is dependent upon tumor cell processing by APCs such as macrophages which present class I MHC molecules to the CD8 cells along with costimulators
What chromosome has the genes for HLA?
genes for the HLA system are located on chromosome 6
Review of MHC
MHC class 1 consists of the A, B, and C loci. MHC class 2 consists of the DR, DQ, and DP loci. One allele for each gene is inherited from each parent. The clinically relevant loci are A, B, and DR. Class 1 MHC molecules are found on all nucleated cells in the body. Class 2 molecules are found only on antigen presenting cells, such as dendritic cells and macrophages, and on B cells.
alternative complement pathway
Complement components are present in the blood plasma. C3 is constantly being hydrolyzed and destroyed and replenished. When a microbe is present, one component of hydrolysis, C3b, binds to the microbial surface and remains stable long enough for protein factor B to bind. Factor B is cleaved by factor D, leaving a component b that is an active protease which breaks down more C3 so that additional C3b is bound and cleaved. The resultant C3bbC3b complex acts as a “C5 convertase”. C5 is cleaved, yielding a C5a component that is a powerful chemoattractant. C5b binds C6, C7, C8, and C9 to form a “membrane attack complex” that punches a hole through the membrane in the microbe.
Classic complement pathway
Antibody coating a microbe will display Fc receptors that, if close enough, can cross-link C1 (of which C1q is a main component) to begin complement activation. The enzymatic action of the bound C1q cleaves C4 and then C2, leaving a C4bC2a complex that acts as a “C3 convertase” to cleave bound C3. The resultant C4bC2aC3b complex acts as a “C5 convertase”. C5 is cleaved, yielding a C5a component that is a powerful chemoattractant. C5b binds C6, C7, C8, and C9 to form a “membrane attack complex” that punches a hole through the membrane in the microbe.
Function of C5a
C5a component is a chemoattractant for neutrophils
Function of C3b
C3b component coats microbial agents and enhances phagocytosis because of C3b receptors present on phagocytic cells.
cytokine that activates NK cells
IL-12
