Term
| There are two main types of CD4 cells, what are their designations and functions? |
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Definition
TH1- activate tissue macrophage
TH2- stimulate B cells to make antibodies |
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Term
What structural domains make up the MHC I and MHC II molecules respectively.
Where do CD8 and CD4 bind? |
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Definition
MHC ClassI: α1,α2 and α3 and β-2 microglobulin
MHC Class II: α1 α2 and β1 and β2
CD8- α3 on MHC Class I
CD4-β2 on MHC Class II |
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Term
What are the professional antigen presenting cells and what do they express on their surface?
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Definition
Cells that express MHC Class II molecules are professional antigen presenting cells. They alert T-cells to the presence of extracellular infections.
- B cells
- Macrophages
- dendritic cells
- epithelial cells of thymus
What cells types don't express any MHC?
rbcs and neurons
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Term
| What facilitates the release of CLIP from MHC Class II and allows peptide to bind. |
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Definition
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Term
| After the proteosome breaks down viral proteins, how are the peptide particles are transported out of the cytosol into the ER. |
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Definition
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Term
| What chaperone proteins would be required to translocate newly synthesized MHC class I |
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Definition
Calnexin: retains partly folded heavy chain in ER lumen
calreticulin: similar to calnexin
tapasin: binds to TAP-1 subunit and positions the partly folded MHC molecule |
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Term
| What are the costimulatory molecules involved in MHC:TCR binding. |
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Definition
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Term
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Definition
| portion of an antigenic molecule bound by an antibody or T cell receptor |
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Term
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Definition
| antibody dependent cell-mediated cytotoxicity- antibody bound to an an antigen binds to NBK cell via FcR to trigger lysis of antibody target |
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Term
| What makes up the B cell receptor? |
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Definition
| immunoglobulin and two other transmembrane proteins Igα and Igβ |
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Term
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Definition
| Allergic reactions by activating mast cells present in the epithelial tissue. |
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Term
| During heavy chain somatic recombination, what two gene segments combine first? |
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Definition
| D and J. Subsequently VDJ join together. |
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Term
| What are the different gene segments in the immunoglobulin heavy locus gene? |
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Definition
1. Leader peptide
2. V region
3. D region
4. J region
5. C region |
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Term
| In the somatic recombination of the heavy chain of the immunoglobulin gene, why can the VH and JH gene segments be joined directly? |
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Definition
| Because they are flanked by the same RSS sequence i.e. the 12-23 rule |
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Term
| What are the proteins that bind the RSS called? |
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Definition
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Term
| What 3 processes generate antibody diversity? |
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Definition
1. somatic recombination
2. somatic hypermutation
3. isotype switching or class switch recombination |
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Term
| What kinds of nucleotides are randomly added into the coding joint between gene segments during somatic recombination? How are they added in? |
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Definition
P-nucleotides: cleavage of the DNA hairpin left by V(D)J recombinase by hairpin endonuclease at a random site yields nucleotides that were originally complementary in the double stranded DNA
N-nucleotides: enzyme terminal deoxynucleotidyl transferase adds nucleotides at random ends to the ssDNA ends. |
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Term
| What is allelic exclusion? |
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Definition
| The process of immunoglobulin gene rearrangement is tightly controlled so that only one heavy chain and one light chain is finally expressed. |
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Term
| What is somatic hypermutation and when does it occur? |
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Definition
| somatic hypermutation is the introduction of point mutations at a high rate in the V regions of heavy and light chain genes. It occurs after a B cell has been activated by antigen and occurs in the germinal centers of lymph nodes and spleen. |
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Term
| What is the difference between the generation of B-cell immunoglobulin diversity and T cell receptor diversity? |
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Definition
1. after stimulation of receptor, the genes encoding the TCR do not continue to diversify i.e. somatic hypermutation does not occur
2. the constant region in the T-cell receptor is less variable. only 1 C alpha and 2 C beta genes. |
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Term
| In the context of immunoglobulin generation, what is one cause of SCID i.e. Omenn syndrome? |
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Definition
| mutations in the RAG genes |
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Term
| What cause the condition that results in B cells that can not undergo somatic hypermutation and affinity maturation? |
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Definition
| Activation induced cytidine deaminase (AID) deficiency |
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Term
| What is affinity maturation? |
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Definition
| Process of mutation and selection continue in the germinal center so that over time the antigen binding efficiency is vastly improved |
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Term
| What is the first antibody produced in a B cell? |
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Definition
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Term
What part of the immunoglobulin would be
1. isotypic
2. idiotypic? |
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Definition
1. constant region
2. variable region |
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Term
| What stage of B cell development is the μ chain made? What is it expressed with? |
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Definition
| large pre-B cell stage, it is expressed with surrogate light chain |
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Term
| What stage of B cell development does H-chain D-J rearrangment occur? |
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Definition
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Term
| During what stage of B-cell development are the RAG genes temporarily turned off? |
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Definition
| large pre-B cell when the μ heavy chain is expressed on the surface with surrogate chain |
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Term
| What is the etiology for X-linked agammaglobulinemia? |
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Definition
| The lack of functional B-cell tyrosine kinase (Btk). B cells arrest in the pre B cell stage. |
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Term
| What is receptor editing? |
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Definition
| When an immature B cell expresses IgM that cross links to self antigen, it receives signals to arrest development. The about of B cell receptor is reduced and RAG activity is increased to give the B cell an opportunity to continue rearranged the light chain genes. |
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Term
| Clonal detection and clonal anergy prevent autoimmunity. How do these processes work? |
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Definition
clonal detection: the apoptosis of B cells that make self recognizing antibodies after receptor editing fails
clonal anergy: if surface IgM of an immature B cell binds to a soluble self antigen, it is inactivated but does not die. Most of the IgM is retained on the inside of the cell and IgD is expressed on the cell surface |
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Term
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Definition
| A subset of B cells that arise early in development and precede the development of "normal" B cells. B-1 cells express CD5 and no surface IgD. They may be important in rapid spontaneous production of Ig against carbohydrate antigens on microbes. |
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Term
What chemokines attract immature B cells to HEV and then subsequently into the lymph node.
What is the receptor that is expressed on immature B cells that are complementary to CCL21? |
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Definition
CCL21 attracts immature B cells to HEV. CXCL13 chemokine is released by follicular dendritic cell that attracts immature B cells to the primary follicle.
CCR7 is the receptor expressed on the immature B cells for CCL21. |
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Term
| Where in the lymph nodes do B cells encounter specific antigen? |
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Definition
| T cell areas, here they are activated by antigen specific C4 helper T cells. |
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Term
| What are the two types of B cells that result after T cell activation? |
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Definition
1. plasma cells that secrete antibody. These cease to divide, have a limited life span and no longer responsive to antigen and interaction with T cells
2.Memory B cells: Other activated B cells migrate to nearby primary follicle which change morphology to become secondary lymphoid tissue containing a germinal center. They become large proliferated lymphoblasts called centroblasts which mature into centrocytes. These undergo somatic hypermutation and isotype switching. Cells that survive affinity maturation become plasma cells or quiescent memory B cells possessing high affinity isotype switching receptors. |
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Term
| What proteins communicate the interaction of the B cell receptor to the interior of the cell? |
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Definition
| Igα and Igβ (they are attached to immunoreceptor tyrosine based activation motifs or ITAMs). |
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Term
| What three things are necessary for B cell activation? |
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Definition
1. crosslinking of antigen with the B cell receptor.
2. ligation of B cell coreceptors:CD2, CD19, CD81
3. help form CD4+ T cells that respond to the same antigen (cognate interaction). However there are T cell independent antigens that can stimulate antibody production. What are the properties of TI antigens?
a. large polymeric molecules with anitgenic determinants: bacterial products, lipopolysaccharide, dextran
b. TI primary antibody responses are weak and IgM
c. no affinity maturation |
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Term
| What syndrome is seen in patients with at a mutation in CD40L ? |
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Definition
| Hyper IgM syndrome because CD40:CD40L interactions are necessary for isotype switching |
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Term
| What cytokines induce B cells to become plasma cells? |
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Definition
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Term
| What CD marker do uncommitted progenitor T cells express on their surface? |
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Definition
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Term
| What cytokine activates uncomitted progenitor to become CD2 double-negative T-cell progenitor ? |
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Definition
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Term
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Definition
| function similar to innate immune response in that they traffic to sites of inflammation. they are a bridge between the innate and adaptive immune response |
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Term
| At what point does a thymocyte start to express CD4 and CD8? |
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Definition
| After the first round of proliferation and β chain rearrangement |
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Term
| α:β T cells undergo positive selection. Describe this process and where does it occur? |
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Definition
Cortical epithelial cells express self-peptides on their surface to double positive thymocytes. If TCR can not bind the MHC/peptide complex no survival signal is sent, the thymocyte dies.
If TCR can bind the MHC:peptide, the T cell lives
Positive selection also down regulates either CD4 or CD8 depending on whether the TCR interaction with the peptide occurred in the context of MHC class I or class II resulting in single positive T cells. |
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Term
| A cortical epithelial cell expresses a MHC class I molecule with self peptide bound. When a double positive thymocyte binds, is CD8 or CD4 downregulated in the thymocyte? |
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Definition
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Term
Where does negative selection occur in self reactive T cells?
What cells mediate the negative selection? |
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Definition
In the corticomedullary region of the thymus.
dendritic cells and macrophages. |
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Term
| If T cells only undergo negative selection in the thymus, why are they not self reactive to cells in other tissues? |
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Definition
Autoimmune regulator (aire) is expressed in the thymus which is a transcription factor that promotes the expression of many different genes in the thymus at low levels. What condition results from a mutation in the aire gene?
Autoimmune polyendocrinopathy candidiasis-ectodermal dystrophy |
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Term
| A patient receives a bone marrow transplant. Unfortunately delivery of the donor bone marrow infusion is mixed up. The donor and the recipient do not share any HLA allotypes. Explain why the patient will not be able to develop an adaptive immune response. |
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Definition
| The donor derived thymocytes are selected on recipient HLA allotypes. In contrast the antigen presenting cells will be presenting antigens with donor derived HLA allotypes. When antigen is presented by the APCs, there are no T-cells that are able to respond to those HLA allotypes. |
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