Term
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Definition
| intracellular proteins produced inside the cell in the cytosol |
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Term
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Definition
| extracellular proteins picked up by pinocytosis, endocytosis, and phagocytosis |
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Term
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Definition
| invariant polypeptide that is common to all MHC Class I molecules. 2nd protein in MHC 1 dimer |
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Term
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Definition
| "chaperon" protein. Keeps heavy chain folded properly until beta2-microglobulin can bind to the peptide |
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Term
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Definition
| Replaces calnexin. Also a "chaperon" protein that has the same function as calnexin |
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Term
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Definition
| (transporter associated with antigen processing). Heterodimeric protein that takes peptide from proteasome in cytosol to the ER |
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Term
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Definition
| associates the MHC class I heavy chain with TAP and does the enzymatic step to get the peptide fragments in the peptide groove |
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Term
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Definition
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Term
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Definition
| monster-protein recycle station in the cytosol and is in every cell of the body |
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Term
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Definition
| protein that plugs up the MHC Class II antigen- binding groove |
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Term
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Definition
| small peptides that were cleaved from the invariant chain |
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Term
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Definition
| releases CLIP and pops in a peptide from the endosome digest |
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Term
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Definition
| Human Leukocyte Antigen. Genes that code for MHC Class I and MHC Class II |
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Term
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Definition
| more than one gene encodes MHC Class I and II molecules |
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Term
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Definition
| hundreds of different alleles of the MHC genes (HLAs) exist in the human population. Genes vary from person to person but not randomly like BCR and TCR |
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Term
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Definition
| means "other gene". Refers to HLA typing and tissue typing |
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Term
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Definition
| response to a foreign allele that is viewed as antigenic |
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Term
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Definition
| antibodies produced following the introduction of allotissue from a donor |
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Term
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Definition
| Graft vs Host Disease. Rejection of donated tissue. Body fights of graft |
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Term
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Definition
| signals and causes burst of proliferation of pre-B cells. It is composed of μ heavy chain, VpreB, λ5, Igα, Igβ |
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Term
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Definition
| mimics Ab light chain. A combination of VPreB and λ5 |
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Term
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Definition
| recombination-activating genes. Recognize RSS's and make dsDNA cuts to initiate recombination |
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Term
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Definition
| cell-adhesion molecules. Proteins on the cell surface involved in binding to other cells |
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Term
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Definition
| antibody that can bind to multiple structurally related species but at a low affinity to each |
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Term
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Definition
| occurs in mature B cells when the BCR (IgM) is cross-linked by self antigen and still exhibits self reactivity even after receptor editing. The self reactive B cell undergoes apoptosis. |
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Term
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Definition
| when immature Bcells can bind soluble self antigen (self Ig) but do not react. They treat self Ig as “normal” and are not activated. |
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Term
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Definition
| LymphoToxin. Produced by immature B calls and provides life signal to FDC when these cells are interacting in follicles of LNs |
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Term
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Definition
| produced by FDC that provide life-saving maturation signal to immature B cells |
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Term
| Primary Lymphoid Follicle |
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Definition
| where immature B cells interact with FDC to receive maturation signals. B cells enter the PLF after the T cell area of the cortex |
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Term
| Secondary Lymphoid Follicle |
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Definition
| primary follicle where activated B cells form a germinal center |
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Term
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Definition
| in the lymphoid follicle; concentration of proliferating B cells. |
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Term
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Definition
| fully differentiated B cells that produce massive amounts of antibody. It can migrate to lymph nodes (secrete Ig into lymph), red pulp in spleen or bone marrow (secrete Ig into blood), GALT and sit directly under epithelial |
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Term
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Definition
| large activated B cells that proliferate |
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Term
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Definition
| matured centroblasts; small non-proliferating cells that are isotype switched and have undergone somatic hypermutation. |
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Term
| Double-negative thymocyte |
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Definition
| immature T cell in the thymus that expresses neither CD4 nor CD8 |
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Term
| Double-positive thymocyte |
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Definition
| T cell in an intermediate stage of development in the thymus. It expresses both CD4 and CD8 |
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Term
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Definition
| a late stage of T cell development in the thymus and characterized by the expression of either CD4 or CD8 co-receptor on the cell surface. |
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Term
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Definition
| the surrogate alpha chain that combines with the T cell receptor beta chain to form the pre-t cell receptor |
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Term
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Definition
| immunity that is mediated by antibodies and can be transferred to a non-immune recipient by serum. |
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Term
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Definition
| adaptive immune response in which antigen-specific effector T cell dominated. It cannot be transferred to a naïve recipient with serum antibody. |
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Term
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Definition
| molecule on antigen presenting cell (APC) that delivers signals to a naïve lymphocyte that is required in addition to the antigen-binding signal for the lymphocyte to respond. |
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Term
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Definition
| B71 and B72 proteins, which are co-stimulatory molecules present on the surface of professional antigen-presenting cells. |
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Term
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Definition
| low-affinity receptor on T cells that interacts with B7 co-stimulatory molecules to activate T-cell activation. |
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Term
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Definition
| T cell must receive a minimum of two signals to respond to antigen. This includes a primary signal through the TCR binding cognate expressed in self-MHC and co-stimulatory signal through a co-stimulator molecule on APC surface. |
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Term
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Definition
| high affinity inhibitory receptor on T cells that interacts with B7 co-stimulatory molecules. |
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Term
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Definition
| dendritic cells. cells of bond marrow origin. Present antigen to T cells in secondary lymphoid tissues |
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Term
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Definition
| Follicular Dendritic Cells. Embryo-derived stromal cells. They require lymphotoxin for differentiation and bind immune complexes and hold them on the surface for a long time. They also provide the antigen source for affinity maturation of B-Cells. |
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Term
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Definition
| They are formed from binding of antibody to antigen |
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Term
| Which T cell co-receptor molecule associates with what MHC Class? |
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Definition
MHC Class I: CD8
MHC Class II: CD4 |
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Term
| Usual source of peptide presented in MHC Class I and II |
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Definition
MHC Class I: endogenous proteins (produced from the cytosol)
MHC Class II: exogenous proteins (picked up by pinocytosis, endocytosis, phagocytosis) |
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Term
| General structure of peptide-binding groove of MHC Class I |
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Definition
| 2 α-helices of the Class I heavy chain and a floor made by an antiparallel β-sheet. This binding groove is described as a pita pocket, where the ends of the α-helices are pinched towards one another. 8-10 aas |
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Term
| General structure of peptide-binding groove of MHC Class II |
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Definition
| 2 α-helices and an antiparallel β-sheet floor, however the α-helices are from the α chain and β chain. Resembles a hot dog bun with open ends allowing for peptide fragments to overhang. 13-25 aas |
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Term
| Identify the body cells that do not express MHC Class I |
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Definition
| Erythrocytes because they do not have a nucleus or a mitochondria |
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Term
| 3 professional antigen-presenting cells and describe how they obtain the antigen they present |
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Definition
Dendritic: only activate naive T lymph
B lymph: soluble antigens endocytosed bound to BCR. Antigen-specific to B lymph. Looking for help from CD4+ T lymph
Macrophage: phagocytosed bacteria, yeast to activate CD4+ T cells |
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Term
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Definition
| loading of exogenous peptides into a MHC Class I molecule to stimulate CD8 cytotoxic T cells in response to a virus |
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Term
| Inheritance of HLA halotypes and # of Class I and Class II isoforms |
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Definition
Every person inherits a complete halotype from each parent.
Class I: min=3 max=6 alleles
Class II: min=3 max=8 alleles
Most idiv. express 6 Class I and 6 Class II isoforms |
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Term
| Describe why transplantation of solid tissue or bone marrow cells from one human to another requires HLA typing and “matching”, and the 2 possible adverse consequences of mismatches. |
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Definition
| ransplantation of solid tissue requires matching because of organ/tissue transplant compatibility and disease susceptibility prediction. HLA mismatches lead to graft rejection (e.g. kill the kidney) or graft versus host disease. which is a bone marrow transplant that creates a whole immune system for host and if host is not compatible, it will attack the host very painfully. |
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Term
| Degenerate Peptide Binding |
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Definition
| allows MHC class 1 and 2 to bind to multiple types of Antigens, by only requiring the “Anchor Residues” to bind through a NON-covalent bond. This allows a high level of variability in what can bind to the MHC class 1 or 2 molecule. |
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Term
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Definition
| The 2 or 3 amino acids that MUST be bonded to within the MHC binding groove in order for the antigen to bind. |
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Term
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Definition
| binds peptides of Class I leader fragments and presents them to inhibitory receptors on NK cells. MHC molecules will not move to surface of cell without binding peptide. So, it binds self peptide and move to surface to show NK cells that it is a normal non infected cell and thus avoids being killed. |
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Term
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Definition
| found only in fetal cells during fetal development. Fetal cells do not have HLA-A or HLA-B so it is thought that HLA-G aids in presenting a normal NK ligand so NK cells do not kill the normal fetal cell. |
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Term
| Properly order the cell stages that occur during B cell development |
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Definition
| Stem cell, pro-B cells, pre-B cell, Immature B cell, Mature B cell |
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Term
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Definition
| in bone marrow. both heavy and light chain are in germline and no Ig status |
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Term
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Definition
| Heavy chain D-J → V-D-J rearrangement occurs. Still no Ig status and no light chain change |
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Term
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Definition
| cells with productive heavy chain rearrangement. Transiently express rearranged μ heavy chain with surrogate light chain. cells with productive heavy chain rearrangement. Transiently express rearranged μ heavy chain with surrogate light chain. |
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Term
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Definition
| have surface expression of productively rearranged μ heavy chain plus rearranged light chain. It has IgM expressed on the surface |
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Term
| why it is advantageous for a pre-B cell to undergo a burst of proliferation following signaling through the pre-BCR |
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Definition
| Pre B cells transiently express rearranged mu heavy chain with surrogate light chain. Efficiency of effort you’re getting the numbers out there and you’re not losing anything. Each one of them paired up with a different light chain rearrangement so antigen specificity of that pool is still diverse. |
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Term
| Role of Stromal Cells in B cell development and location |
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Definition
Stromal cells provide two important signals for developing B Cells: cell contact through adhesion molecules (CAM’s) and membrane-bound growth factor (answer to question below)
Location: bone marrow |
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Term
| 2 growth factors that support B cell development the bone marrow |
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Definition
| SCF (Stem Cell Factor) and soluble cytokine factor interleukin-7 (IL-7) |
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Term
| what percent of developing B lymphos successfully make it through heavy chain rearrangements? |
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Definition
|
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Term
| what percent of developing B lymphos successfully make it through light chain rearrangements? |
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Definition
|
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Term
| what percent of developing B lymphos are successful? |
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Definition
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Term
| 2 CD markers that when used in combination can identify B-1 lymphos |
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Definition
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Term
| Average life-span of a B lymphocyte after it exits the bone marrow and enters circulation |
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Definition
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Term
| Identify the cell that provides necessary periodic survival signals to a naïve B lymphocyte, where this cell is located, and what molecule it produces that provides the survival signal. |
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Definition
| Follicular dendritic cells provide survival signals for the B cells, located in primary lymphoid follicles. BAFF from FDC provides life saving maturation to B cell |
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Term
| Explain what cell interaction triggers isotype switching and somatic hypermutation. |
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Definition
| When The B cell enters the “T Cell area” in the cortex of the lymph node, in this region it will pick up an antigen and endocytosis it. The B cell then presents that to a CD4+ T cell, and the T Cell then binds to it and becomes activated. The T Cell starts to secrete cytokines that influence the B Cell’s isotype to the most useful type of antibodies that will combat the pathogen. The T cell also triggers somatic hypermutation in the B cell. This strengthens and raises the overall affinity of the antigen receptors of the B cell population responding to that antigen. |
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Term
| Identify the main function of a plasma cell and the 4 locations where it may reside in the body. |
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Definition
| secrete as much antibody as fast as it can. The four locations where it may reside in the body are in the lymph node medulla, spleen red pulp, bone marrow, and GALT (under epithelium in the lamina propria). |
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Term
| List the 3 main options for what a B lymphocyte can do functionally (what it can become) after it is activated by antigen. |
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Definition
| Become a memory cell for future infection,Become IgM-secreting plasma cell,Become an IgG-secreting plasma cell |
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Term
| Identify what receptor/ligand interaction triggers commitment of an uncommitted lymphoid progenitor to the T lymphocyte lineage and where this interaction occurs. |
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Definition
| Notch one receptor on progenitor binding to delta one ligand in thymus, commits the progenitor to T cell lineage. |
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Term
| what cells are found in the cortex |
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Definition
| cortical epithelial cells, thymocytes, and macrophages |
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Term
| what cells are found in the medulla |
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Definition
| medullary epithelial cells, dendritic cells, and macrophages |
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Term
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Definition
| Thymic involution is when the thymus atrophies. Typically occurs around age 30. This means the Tcell pool is completed by age 30. Though it occurs “early” in life, thymic involution does not affect T cell immunity which means naive T lymphocytes live much longer than naive B lymphocytes. |
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Term
| List the proteins that compose the pre-TCR. |
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Definition
| Two zeta chains, CD3 complex ( consisting of ε and δ chains), γ and ε chains, along with a pTα. |
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Term
| Identify whether a pre-T cell would be a double-negative thymocyte, a double-positive thymocyte, or a single positive T cell. |
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Definition
| A double-negative thymocyte has yet to turn on CD4 or CD8. Double-positive thymocytes express CD4 and CD8 but have not decided on which it will ultimately express. Single-positive thymocytes have either CD4 or CD8. |
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Term
| Identify the normal proportion of to T cells produced after birth. |
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Definition
90%-alpha- beta
10% gamma-delta |
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Term
| Describe the purpose of “positive selection” |
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Definition
| Positive selection is the checkpoint where Tcells are checked to make sure they can bind to MHC I or MHC II containing self antigen and not become activated. This occurs in the inner cortex. |
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Term
| Describe the purpose of “negative selection” |
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Definition
| the check point in Tcell development where Tcells that are reactive to self antigen are removed. γδ Tcells do not undergo negative selection |
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Term
| Identify what cell(s) mediate positive selection and negative selection of T cells. |
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Definition
Positive Selection: cortical epithelial cells
Negative Selection: dendritic cells, macrophages, thymocytes |
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Term
| Describe the function of dendritic cells and macrophages in the thymus |
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Definition
Dendritic cells contribute to negative selection by presenting antigen to T-cells in the thymus. A T-cell with either too much or no binding will then subsequently die by apoptosis.
Macrophages remove the cells that die via apoptosis. Macrophages can also express antigen, just at a much lower level than Dendritic cells. |
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Term
| Identify the AIRE protein, what cell expresses it, and whether it is important in positive or negative selection. |
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Definition
AIRE stands for autoimmune regulator element. It’s a general transcription factor that causes several hundred tissue-specific genes to be transcribed by a subpopulation of epithelial cells in the medulla of the thymus. The proteins are chopped up and expressed on MHC Class 1. The proteins can also be picked up through pinocytosis and expressed by MHC Class 2. This enables the developing T-cell population to become tolerant of antigens that normally function only outside the thymus.
Medullary epithelial cells express AIRE. It is important in negative selection. |
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Term
| Describe the difference between central tolerance and peripheral tolerance in regards to T cells, and whether each is achieved by either anergy or apoptosis. |
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Definition
Central Tolerance is induced by negative selection in the Thymus, which leads to deletion of self-reactive T lymphocytes preventing autoimmune diseases. This is done through apoptosis.
Peripheral tolerance is done by regulatory T Cells that go around and suppress CD4+ T cells through the release of suppressive cytokines (IL-10 and TGF-Beta). |
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Term
| Define Treg and describe their cellular characteristics and the role they play in tolerance. |
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Definition
| Treg cells are CD4+ Tcells that suppress the T activation of other CD4+ cells. They suppress CD4+ cells that become activated in the periphery by self antigen. They allow for peripheral tolerance. |
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Term
| Identify the 3 main effector T cells and the important role that each has in the immune system. |
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Definition
CD8+ Cytotoxic T-cell - Kill infected cells by releasing cytotoxins
CD4+ T-helper 1 - Cell-mediated immunity, helps macrophages, and facilitates cytotoxic T-cell proliferation
CD4+ T-helper 2 - Humoral immunity - Stimulates B-cells to proliferate and induces antibody class switching |
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Term
| 2 ways that foreign antigen can reach the secondary lymphoid tissue to activate an adaptive immune response |
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Definition
| attaching to a dendritic cell or just entering in the lymph fluid itself to lymph node through the afferent lymph |
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Term
| role of selectins in lymphocyte trafficking |
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Definition
| provide low affinity adhesion that causes cell to roll along blood vessel walls within HEV or activated endothelium of inflamed tissues they bind to such as vascular addressins which are glycoproteins on endothelium that bin selectins |
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Term
| role of integrins in lymphocyte trafficking |
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Definition
| provides high strength binding that allows firm attachment and squeezing between endothelial cells and extended contact between lymphocytes and APC. |
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Term
| Identify the primary antigen type (bacteria, yeast, virus, soluble protein) that DC, macrophages, and B cells specialize in presenting. |
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Definition
DC- virus
Macrophages- bacteria, yeast?
B-cells- soluble protein, toxins, viruses |
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Term
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Definition
| primary signal that provides MHC with antigen peptide groove that triggers TCR and has to provide a costimulatory signal which maintains and amplifies autocrine IL-2 production |
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Term
| Discuss what factors can influence the choice of a naïve CD4 T cell to a functional subset choice (Th1, Th2…), and which of these factors appears dominant. |
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Definition
| T cell subset choice is influenced by: 1. TCR affinity 2. APC co-stimulatory molecules 3. Concentration of Ag 4. Cytokines in vicinity (most dominant!) |
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Term
| What cytokines do Th1, Th2, and Treg secrete and what transcription factors are responsible for activating this secretion in each cell type? |
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Definition
| Treg secretes TGF-beta and IL-10 and the trans factor is Fox P3. TH1 secrets IL-2 and IFN-gamma and the transfactor is T-bet. TH2 secretes IL-4 and IL-5 and the trans factor is GATA-3. |
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Term
| Describe the 3 ways in which naïve CD8+ T cells can be fully activated to differentiate into Tc effector cells. |
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Definition
1. Dendritic Cell with high co-stimulatory molecule expression triggers an optimal IL-2 response
2. APC activates CD4+ T Cell, which in turn activates APC to express necessary co-stimulator molecules to activate CD8+ T Cells
3. APC activates CD4+ T cell to secrete IL-2, which in turn binds to unregulated IL-2 receptor on CD8+ T cell |
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Term
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Definition
| CAM. Expressed on Effector T cells and binds to the adhesion molecule VCAM-1 on the endothelial cells of blood vessels in inflamed tissues |
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Term
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Definition
| CAM. Expressed on Effector T cells and binds LFA-3 |
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Term
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Definition
| cytotoxic T-cells and induces apoptosis of any target cell expressing Fas |
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Term
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Definition
| used by Th1 and Th2 cells to activate macrophages/ B- cells. Allows for max. activation of both macrophages and B-cells |
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Term
| Identify the three major proteins found in Tc lytic granules and the functions of each protein. |
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Definition
1. perforin - forms pore in target cell membrane to contribute to cell killing
2. granzymes - induces apoptosis of target cell
3. granulysin - works with perforin to make pore in target cell membrane |
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Term
| Describe how interferons (IFN’s; IFN-G, IFN-A, IFN-B) are especially important to fight viral infections. |
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Definition
They inhibit replication of viruses in infected cells
- Increase processing and presentation of viral antigens in Class 1 (by increasing LMP2/LMP7 in proteasome to cleave smaller peptides)
- Activate bystander macrophages to phagocytize apoptotic cells |
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Term
| List the 3 main cells that accomplish cell-mediated immunity |
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Definition
| Cytotoxic T cells, Th1 cells, macrophages |
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Term
| List the 3 CD proteins that form the B cell co-receptor complex, and the functions of each of the proteins (if known). |
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Definition
CD21 (CR2) - binds iC3b and signals through CD19
CD19 - gets signal from CD21 to increase BCR signal 1000-10000 fold
CD81 - function not yet known |
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Term
| List the 4 cell types that are minimally required to allow a T-dependent antibody response to occur in a secondary lymphoid tissue and the relative physical location of each cell within the secondary lymphoid tissue. |
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Definition
1. Dendritic cell exhibiting antigen in MHC II located in the Tcell zone surrounding HEV.
2. T cell (CD4+) leave HEV and interacts with DC in Tcell zone
3. B cell phagocytizes the pathogen and displays the SAME antigen in MHCII as the DC. This also takes place in the Tcell zone
4. Follicular Dendritic Cells and B-T cell cognate interact in the germinal center of the secondary follicle. |
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Term
| List the cell(s) that are normally located in the dark zone, light zone and mantle zone of a germinal center (include centroblasts, centrocytes, FDC and T helper cells in your list). |
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Definition
Dark Zone: Centroblasts
Light Zone: FDC, B cells, CD4+ T Cells, Centrocytes, Th Cells
Mantle Zone: Unactivated B Cells |
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Term
| Identify as many important functions of FDC as you can, and predict the ultimate effect on the immune system if FDC were absent from secondary lymphoid tissues. |
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Definition
FDCs :-provide the antigen source to allow B-cells to undergo affinity maturation.
-bind immune complexes
If FDCs were absent, B-cells would not be able to stay alive and die via apoptosis. |
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Term
| Identify the cytokine that is required for differentiation of FDC. |
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Definition
FDC requires lymphotoxin (LTalpha and LTbeta) for differentiation and follicles don’t form in absences of lymphotoxins.
Without one there’s no phenotype and without both there’s no germinal center in lab animals. |
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Term
| Explain the 2 signals a B cell requires in a germinal center to maintain activation, and the consequence if it does not receive these signals. |
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Definition
| 1: bind antigen held on FDC 2: antigen is processed and presented by the B cell to CD4+ T cell that provides second signal through CD40 =linked recognition=cognate interaction. |
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