Immunology - Final - Part 1

davidwurbel7's version from 2015-12-14 02:11

Transplant Immunology

Question Answer
The immunologic destruction of transplanted organs or tissuesGraft Rejection
Rejection usually occurs within 10 daysFirst Set Rejection
Rejection occurs within 1 weekSecond Set Rejection
These proteins play the major role in the acceptance or rejection of a transplant, with the proteins encoded by the DR locus being especially importantMHC Class II
The most especially important protein encoded by this loci in acceptance or rejection of a transplantDR Locus
Occurs due to direct allorecognitionHyperacute Rejection
Graph between identical twinsSyngeneic graft
Graph, usually skin, from the same individualAutograft
Graph between non-identical individualsAllograft
Graph between different speciesXenograft
Pre-formed antibodies reactive with vascular endothelium activate complement and trigger rapid intravascular thrombosis and necrosis of the vessel wallHyperacute Rejection
Rejection that occurs within minutes-first 24 hoursHyperacute Rejection
These are required for hyperacute rejectionPre-Formed Antibodies
CD8+ T lymphocytes reactive with alloantigens on endothelial cells and parenchymal cells mediate damage to these cell types. Alloreactive antibodies formed after engraftment may also contribute to vascular injuryAcute Rejection
Rejection that occurs within the first few days to weeks but can be up to 3 monthsAcute Rejection
These are required for acute rejectionCD8+ T Lymphocytes
Cells that do most of the killing of the allograft cellsCD8+ Cytotoxic T Cells
Rejection with graft arteriosclerosis, injury to the vessel wall leads to intimal smooth muscle cell proliferation and luminal occlusion. This lesion may be caused by a chronic delayed type hypersensitivity(DTH) reaction to alloantigens in the vessel wallChronic Rejection
These cells are required for chronic rejectionTh1 Helper T Cells
Rejection that occurs within months to yearsChronic Rejection
Antigen-antibody complexes activate the complement system to result in an intense infiltration of neutrophils. Vascularization of the graft is prevented due to obstructing blood clots within the capillariesHyperacute Rejection
Tissue destroyed due to massive infiltration of macrophages and CD8+ lymphocytes suggestive of CD4+ T cell activationAcute Rejection
Mechanisms include both humoral and cell-mediated responses by the recipient. The main pathological finding is arteriosclerosis of vascular endotheliumChronic Rejection
Recognition that occurs when T cells bind directly to an intact allogeneic MHC molecule on a graft (donor) antigen-presenting cell (APC)Direct Alloantigen
Recognition that occurs when allogeneic MHC molecules from graft cells are taken up and processed by recipient APCs, and peptide fragments of the allogeneic MHC molecules containing polymorphic amino acid residues are bound and presented by recipient (self) MHC moleculesIndirect Allogantigen
Develops when immunocompetent grafted lymphocytes attack cells in an allogeneic recipient whose immune system is compromisedGraft-versus-Host Disease (GVHD)
Infusion of horse or rabbit-derived antibodies against human T cells which is used in the prevention and treatment of acute rejection in organ transplantation. rATG in particular effects large reductions (through cell lysis) in the number of circulating T-lymphocytes, hence preventing (or at least delaying) the cellular rejection of transplanted organsAnti-Thymocyte Globulin
Drug used to reduce the graft-versus-host reactionCyclosporin
Graft-versus-host reactions often develop after this transplantation into an irradiated immunocompromised patientBone Marrow Transplantation
An in vitro determination of the compatibility of the class II proteins. The mixture of donor and recipient lymphocytes are incubated together to permit DNA synthesis as measured by incorporation of tritiated thymidine. The greater the amount of DNA synthesis in the responder cells, the more foreign are the class II MHC proteins of the donor cells. The MLR does determine the degree of allogenicity of the MHC molecules on the two populations of lymphocytes being tested.Mixed Lymphocyte Reaction (MLR)
The more [H^3] thymidine present in a tissue graft, the more mismatches that are present here between the donor and recipientMHC Class II
A group of procedures that determines the type of histocompatibility antigens on a person's cells or tissuesTissue Typing
Involves placing recipient serum (potentially containing donor-specific anti-HLA antibodies) onto donor lymphocytes (containing HLA antigens). A cytotoxic reaction (deemed ‘positive’) suggests the presence of pre-formed donor-specific AbsCross Matching
Highly polymorphic set of genes on chromosome 6 that code for self-antigensMajor Histocompatibility Complex (MHC)
: Minor Histocompatibility Complex (mHC)
Question Answer
Cells from the donor and recipient are reacted with a battery of antibodies, each one specific for a different class I and class II protein. Complement is then added, and any cell bearing an MHC protein homologous to the known antibody will lyseSerologic Assays
Determines the haplotype for the class I and class II alleles on both chromosomes. Current method involves PCR amplification of donor and recipient HLA alleles to use as probes for an HLA gene array. This approach is highly specific and sensitiveHLA Typing

Immunosuppressive Medications and Treatment

Question Answer
Drugs that inhibit IL-2 synthesis following Ag-receptor bindingCyclosporin A and Tacrolimus (FK506)
Drug that interferes with signal transduction following IL2 - IL2 receptor interactionRapamycin
Binds to B7 on the APC preventing T cell activation and inducing anergyCTLA-4 Immunoglobin
A reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH) in purine biosynthesis, which is necessary for the growth of T cells and B cells. Other cells are able to recover purines via a separate scavenger pathway and are thus able to escape the effectMycophenolate Mofetil (MMF)
A purine analogue which inhibits DNA synthesis: blocks T cell divisionAzathioprine
Anti-inflammatory; inhibits cytokine production and accumulation of immune cells in the graftCorticosteroids
Made by a fungus and bacterium - bind to calcineurin to inhibit T cell function mainly by inhibiting IL-2 and IFN-gamma productionCyclosporin A and Tacrolimus (FK506)
Binds to CpN and together inhibits calcineurin (CaN) preventing calcineurin (CaN) from dephosphorylate the cytoplasmic component of the nuclear factor of activated T cells (NF-ATc), and thereby the transport of NF-ATc to the nucleus and the binding of NF-ATc to the nuclear component of the nuclear factor of activated T cells (NF-ATn)Cyclosporin A
Binds to FKBP and together inhibits calcineurin (CaN) preventing calcineurin (CaN) from dephosphorylate the cytoplasmic component of the nuclear factor of activated T cells (NF-ATc), and thereby the transport of NF-ATc to the nucleus and the binding of NF-ATc to the nuclear component of the nuclear factor of activated T cells (NF-ATn)Tacrolimus (FK506)
Binds to FKBP and together binds to the mammalian target of rapamycin (mTOR). The SRL–FKBP–mTOR complex inhibits biochemical pathways that are required for cell progression through the late G1 phase or entry into the S phase of the cell cycleRapamycin

Cancer Immunology

Question Answer
Altered self cells that have escaped normal growth-regulating mechanismsCancer
Antigens unique to tumor cells; arise from mutations creating an altered self peptideTumor-Specific Antigens (TSAs)
Antigens not unique to tumor cells e.g., expression of oncofetal proteins on fully differentiated tumor cells, or high level expression on tumor cells of normally low level expressed proteinsTumor-Associated Antigens (TAAs)
Antigens found on human tumors normally expressed in fetal but not in adult human cellsOncofetal Antigens
Normally found in the intestine, liver, and pancreas in months 2 to 6 of gestation. Found at high levels pancreatic cancers (90%), colon cancers (70%), breast cancers (35%), and 5% of normal persons (increases during pregnancy)Carcinoembryonic Antigen (CEA)
Is the normal a-globulin of embryonic and fetal serum. Present at elevated levels in the sera of patients with hepatoma, cirrhosis, and hepatitisAlpha Fetoprotein (AFP)
These may be mutated forms of normal self proteins, products of oncogenes, overexpressed, aberrantly expressed self proteins or products of oncogenic viruses which are recognized by tumor-specific CD8+ T cellsTumor Antigens
When tumor cells arise in a tissue a number of immune cells recognizes and eliminate themElimination Phase
Variant tumor cells arise that are more resistant to being killed and over a variety of different tumor variants developImmunoediting Phase
One variant may escape the killing mechanism or recruit regulatory cells to protect it and so spreads unchallengedEscape Phase
CD8+ T cell responses to tumors when tumor cells or tumor antigens are taken up, processed, and presented to T cells by professional antigen-presenting cells (APCs)Cross-Priming (Cross-Presentation)
Starts with antibody binding to tumor cells leading to the following modes of killing - Attachment of Fc receptors on macrophages and neutrophils, followed by phagocytosis. Attachment of Fc receptors on null (NK or killer) cells, followed by lysis by antibody-dependent cell-mediated cytotoxicity (ADCC). Activation of the complete complement sequence causing tumor cell lysis. Activation of the complement sequence to produce C3b on the tumor-cell surface, reacts with C3b receptors on macrophages and neutrophils to enhance phagocytosisHumoral Immunity to Tumor Cells
Production of lymphokines by TH cells which mobilize and activate macrophages against tumor cells. Production of monokines by activated macrophages (e.g. TNF-α + IL-1). Activation of CD8+ CTLs that recognize TSAs on virally-transformed cells in association with class I major histocompatibility antigens. Spontaneous killing of tumor cells by NK cells without previous sensitizationCell-Mediated Immunity to Tumor Cells
Activation of these cells due to recognition of TSAs on virally-transformed cells in association with MHC class I antigensCD8+ CTLs
A type of cytokine produced primarily by monocytes and macrophages. Examples include interleukin 1 and TNF-αMonokine
Therapy using of lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL) lymphocytes (NK cells and CTLs) recovered from a surgically removed tumor are activated by IL-2 and returned to the patientAdoptive Cellular Therapy
(Insert 12.15)
Question Answer
Tumors that lose expression of all MHC class I molecules are susceptible to killing by these cellNK Cells
This was used as a vector to cure a girl with acute lymphoblastic leukemia by introducing TCR genes into her T cells specific for CD19Disabled HIV Virus
These which are specific for human tumors are used to identify specific tumor antigensCloned CTL Line
DNA from melanoma gene libraries is transfected into these cellsClass I MHC-Expressing Target Cells
Enhanced tumor immunogenicity by transfection of tumors with the genes for these so that the tumor cell provide the activation signal for the immune systemB7 or GM-CSF
This is expressed on healthy red blood cells and blocks the immune system from destroying them as they circulateCD47
CD47 is expressed in high level in new cells of this typeRBC
This is overexpressed on the surface of all human solid tumor cells, as well as leukemias and lymphomasCD47
Therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis by activating macrophages to phagocytize cancer cellsAnti-CD47 Antibody Therapy
The antibody shrunk or cured human breast, ovary, colon, bladder, brain, liver, and prostate tumors that had been transplanted into miceAnti-CD47 Antibody Therapy
The quadrivalent Human Papillomavirus Virus-Like Particle vaccine (HPV-VLP vaccine) is prepared from the highly purified virus-like particles (VLPs) of the recombinant major capsid (L1) protein of HPV Types 6, 11, 16, and 18Gardasil