Lymph prot on immune cell membrane

Question 1

what is the B7 lymphocyte membrane protein?

Answer 1

CD80 (B7-1) on antigen presenting cells is the initial costimulatory ligand based on its more abundant and earlier expression. It interacts with CD 152 (CTLA-4) to maintain immune tolerance. CD86 (B7-2) participates later following antigen-presenting cell activation, binds to CD28 promoting T cell responses. CD86 may also bind CTLA-4 for attenuation of regulation and cellular disassociation.

Question 2

What does the alpha chain of the IL-2 receptor (CD25) do?

Answer 2

The alpha chain of the IL-2 receptor is present on activated T and B lymphocytes, thymocytes, myeloid precursors, and oligodendrocytes. It associates with CD122 (beta chain of IL-2R) and the GAMMA chain (CD132) to form a high affinity IL-2 receptor, commonly expressed on Treg cells as well as resting memory T cells. CD122 has JAK 1 , and gamma chain JAK3 kinase capacity. The complex stimulates JAK-STAT, PI3K, and MAP kinase pathways. CD132 also participates in 6 other receptors: IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21.

Question 3

What is CD5?

Answer 3

CD5 is a 67 kD 495 aa, glycoprotien on B-1 cells (IgM without terminal deoxynucleotidyl transferase (TdT)) and has an ITIM motif which serves to lower B cell responsiveness so that only strong stimuli become immunogenic.

Question 4

Where are TLR-2, TLR-3, TLR-7, And TLR-9 located and what are their endogenous and exogenous ligands?

Answer 4

TLR-2 located on the plasma membrane, is stimulated by HMG B-1 (high mobility group box chromosome protein 1) and by lipoteichoic acid, and peptidoglycan.TLR-3, located on the endolysosome, is stimulated by cellular dsRNA, viral dsRNA.TLR-7, on the endolysosome is stimulated by ssRNA, bacterial ssRNA and viral ssRNA.TLR-9, on the endolysosome, is stimulated by cellular dsDNA, unmethylated CpG sequences as well as bacterial dsDNA.

Question 5

What is ROR?

Answer 5

ROR (retinoid-related orphan receptor) is a transcription factor whose activation results in naïve T cells transforming to promote proinflammatory Th17 cells.

Question 6

What is DAXX?

Answer 6

DAXX (death domain-associated protein) 740 aa, resides in cytoplasm, and nucleus, associated with multiple proteins including Fas, centromere protein C, erythroblastocysts virus E26 oncogene homolog 1 (ETS1) transcription factor, sumoylated transcription factors resulting in apoptosis, and tumor suppression. Often modified by sumoylation, phosphorylation, and polyubiquination.
Sumoylation adds SUMO proteins (small ubiquitin like modifier) to target proteins inducing post translational modification. The sumo protein C terminus is cleaved by 5 amino acids, leaving a glycine which then forms an isopeptide bond with lysine on the target protein.

Question 7

What is CD45?

Answer 7

CD45 is a heavily glycosylated glycoprotein about 200 kd, with many isoforms present on T cells. The cytoplasmic domain is a phosphatase that activates Lck.CD45 is a marker of hematopoietic (vs mesenchymal) stem cells.

Question 8

What is CD21?

Answer 8

CD21 is the C3b complement receptor Cr2 from CR2 gene.This is a marker for dendritic cells.

Question 9

What lactosamine carbohydrate mediates phagocytosis?

Answer 9

CD30 is TNFRSF8, present time activated but not resting T and B cells and is a positive regulator of apoptosis.

Question 10

What sort of lactosamine is CD15?

Answer 10

CD15 is 3-fucosal-N-acetyl-lactosamine, a carbohydrate found within glycoproteins, glycolipids, and proteoglycans. It mediates phagocytosis chemotaxis and is a marker for Reed Sternberg cells, diagnostic of Hodgkin’s disease.

Question 11

What C type lectin serves as a signal transducer on NK cells?

Answer 11

CD69 is a transmembrane C type lectin that appears early on T lymphocytes and natural killer cells (NK cells) during activation. It serves signal transduction in NK cells and platelets.

Question 12

What does CD1a (a MHC like glycoprotein) do ?

Answer 12

CD1a on chromosome 1 associates with beta 2 microgolbulin and presents lipid and glycolipid antigens to T cells. It is expressed on cortical thymocytes and some lymphoid neoplasms. Negative on macrophages.

Question 13

What is CD8?

Answer 13

CD8 is usually a heterodimer from 2 separate genes, immunoglobulin class, 34 kDa, 114 aa, recognizes a flexible loop on the alpha 3 portion of class 1 MHC and holds T cell receptor close to antigen. Cytosolic domain binds lck tyrosine kinase via Zn linkage, activating the T cell. CD8 binding activates the T cell which then release cytotoxins perforins, granzymes, and granulysin. Granzymes Use serine proteases to trigger the caspase cascade. FAS ligand (FasL) is also expressed.I

Question 14

What are some members of the IL-1 receptor family?

Answer 14

ILR (IL-1R like receptors) family includes signaling molecules (TIR8/Sig1RR, IL-1RAcPb, DIG1RR), + orphan receptors (no known ligand), as well as decoy receptors (IL-1R2, IL-18BP). Accessory proteins (AcP (accessory protein for IL-1α, beta, -18, -33, -36 ) are also included.

Question 15

What is the signaling domain on Toll and IL-1 receptors?

Answer 15

TIR (Toll IL-1) domain is on signaling IL-1 receptor and Toll-like receptors which then begins signaling pathways that generate NF-kB, JNKs, ERKs, and mAPKs transcription factors.

Question 16

What is the receptor for MICA on NK cells?

Answer 16

NKG2D (KLRK1 Killer cell Lectin like Receptor subfamily K type 1- approved name) receptor on NK cells that mediates NK cell killing of virus infected cells through its adaptor protein DAPK1. DAPK1 (death-associated protein kinase 1) mediates gamma-interferon induced programmed cell death. It is a calmodulin dependent serine-threonine kinase, 160 kD, 8 ankyrin repeats, and a tumor suppressor candidate.MICA is one of the ligands.

Question 17

What does the CD40-CD40L system do?

Answer 17

CD40 is a costimulatory protein on antigen presenting cells that binds to CD40L (CD154) on Th cells. CD40 is also present on dendritic cells, B cells, endothelial cells, smooth muscle cells, fibroblasts, epithelial cells, tumor cells-lymphoma, myeloma, and carcinoma. CD154 on B cells stimulates antibody class switching and differentiation into plasma cells. CD154 on T cells stimulates macrophages to produce reactive oxygen species and nitric oxide.

Question 18

What is CD44 hyaluronic acid binding protein ?

Answer 18

cd44 is a cell surface glycoprotein (ch 1, cd44 gene), expressed on many cell types, that is a receptor for hyaluronic acid as well a collagen, MMPs, and osteopontin. Many post translational modifications alter function. Plays a role in lymphocyte maturation in thymus, splice variants occur in neoplastic markers.

Question 19

What is CD62 selectin cell binding domain?

Answer 19

CD62 contains a calcium dependent Ca binding domain, and an EGF like domain. Subtypes L selectin (leukocyte), E selectin (endothelial), and P selectin (platelet) serve different functions in different cell types.
Selectins bind to glycoproteins and are considered a type of lectin.

Question 20

What is the CD 138 plasma cell marker?

Answer 20

cd138 is a transmembrane heparin sulphate proteoglycan of the syndecan family that participates in cell binding, signaling, and cytoskeletal functions. Serves as a marker for blood derived plasma cells.Required for internalization of HIV-1 tat protein. Variants occur as tumor cells.

Question 21

What interferon receptors respond to types 1, 2 and 3 interferons?

Answer 21

Type 2 IFN utilize IFNGR1 and IFGAR2 combination receptor, which utilize JAK2 and JAK1 cytoplasmic tails to stimulate STAT1. Type I INF utilize IFNAR 1 and 2 with TYK2 and JAK1 tails. Type 3 INF use IL-10R2 and IFNLR1 receptors the same tails as Type 1 to phosphorylate STAT1 and 2 which elicits a different cascade from Type 2 IFN.

Question 22

What is CD71 ?

Answer 22

CD71 is the transferrin receptor which adsorbs iron by internalizing its receptor-transferrin complex.

Question 23

What is a type 1 cytokine receptor?

Answer 23

Type 1 cytokine receptors respond to cytokines that contain 4 alpha chains. Receptor contains wsxws motifs close to the cell membrane.They respond to interleukins and colony stimulating factors.

Question 24

What is ICOS?

Answer 24

ICOS (inducible T cell costimulator, CD278) is expressed on activated T cells especially Th2 cells.

Question 25

What immunoreceptor regulates immunosuppression in T and B cells?

Answer 25

TIGIT is a T cell immunoreceptor with IG and ITIM domains, also found on NK cells. It binds to CD155 (PVR-polio virus receptor) on dendritic cells and macrophages and also on CD112 (PVRL2). When stimulated by CD155 it increases IL-10 secretion and decreases IL-12 and inhibits T cell activation.

Question 26

What is the formyl peptide receptor?

Answer 26

The formyl peptide receptor (FPR) is a G protein-coupled receptor that responds to bacterial and host products similar to met leu phe. Multiple pathways are activated including PI3, MEK. Receptors primarily on polys, less so on macrophages and glial cells, effects cytokine secretion, degranulation, and apoptosis.

Question 27

What are the major HLA class I antigens?

Answer 27

``` HLA antigens A,B, and C are the major class I MHC genes on chromosome 6 that form heterodimers with beta-2 microglobulin (chromosome 15). There are over 2400 HLA-A genes coding for over 1700 proteins and 117 null proteins. There are over 2800 HLA-B genes. HLA-C genes have changed the least since evolving from apes, and recognize various members of the leukocyte immunoglobulin like receptor family (LILRA1). HLA-B and HLA-C genes are classified by serotype then genotype. ```

Question 28

What are the minor HLA class I antigens?

Answer 28

There are three minor HLA class I genes; HLA-E, HLA-F, and HLA-G. HLA-E is a class 1 MHA heavy chain/beta-2 micoglobulin surface receptor that presents a TAP (transporter associated with antigen processing) transported protein to the CD94/NKG2 receptor of NK cells. This usually inhibits NK cell damage. HLA-F molecules binds a restricted subset of peptides derived from the leader peptides of other class I molecules. HLA-G is expressed on fetal derived placental cells instead of HLA-A and HLA-B, and is ligand for NK cell inhibitory receptor (KIR2DL4), protecting cell from NK attack. Replaces major MHC class I antigens A, B, and C for the placenta.

Question 29

What is BAFF?

Answer 29

BAFF also known as BLyS, CD257 and tumor necrosis factor ligand and superfamily member 13B, encoded by the gene TNFSF13B. 285 aa transmembrane glycoprotein, natural ligand for BAFF-R (BR3,TNFRSF13C), TACI (transmembrane activator and calcium modulator and cyclophillin ligand and interacter,TNFRSF13B), and BCMA (B cell maturation antigen,TNFRSF17 ). These 3 receptors are expressed on mature B lymphocytes and expression varies on B cell maturation stage. TACI Also found on T cells, BCMA on plasma cells. BR3 binding activates classical and noncanonical NF-kB signaling pathways important for B cell survival.

Question 30

What is APRIL (proliferation inducing ligand), and how does it differ from BAFF?

Answer 30

APRIL(proliferation inducing ligand) product of TRFSF13, a cytokine that also binds to TACI and BCMA. Promotes survival of plasma cells in bone marrow. Does not bind to BR3- TNFRSF13C.

Question 31

How do BAFF and APRIL interact?

Answer 31

BAFF also known as BLyS, TALL1 (TNF and APOL-related leukocyte expressed ligand), CD257, product of TNFSF13B (tumor necrosis factor ligand and superfamily member 13B), is 285 aa transmembrane glycoprotein cytokine, natural ligand for BAFF-R (BR3), TACI, BCMA. Mutations cause common variable immunodeficiency, IgA def 2. APRIL(proliferation inducing ligand) product of TRFSF13, a cytokine that also binds TACI and BCMA. Promotes survival of plasma cells in bone marrow. TACI (transmembrane activator and CMAL(calcium modulator and cyclophillin ligand) and interacter), encoded by TNFRSF13B , CD267, 293 aa. Binds BAFF and APRIL. Mediates calcineurin activation of NF-AT, NF-kB, and AP-1. Stimulates B and T cell fx, regulates humeral immunity. Interacts MYD88. BCMA (B cell maturation antigen) encoded by TNFRSF17 binds BAFF. Activates NF-kB, MAPK substrate ELK1, JNK, p38(MAPK14). cytoplasmic tail associates with TRAF1,2,and3. BAFFR, BR3, TNFRSF!3C bins BAFF. mutation results in common variable immunodeficiency 4. Over expression in mice results in SLE. Activates classical and noncanonical NF-kB signaling pathways important for B cell survival. Does not bind APRIL Receptors are expressed on mature B lymphocytes and expression varies on B cell maturation stage. TACI Also found on T cells, BCMA on plasma cells.

Question 32

What are the major types of TNF superfamily proteins?

Answer 32

Super family of genes producing tumor necrosis factors TNFA (TNF alpha), 212 aa, type II transmembrane protein, released by ADAM17 to form a 51 kDa trimeric bioactive sTNF. Binds to TNFR1, CD120a, expressed in most tissues responding to soluble and bound TNF, and TNFR2, CD120b, found on immune cells responding only to membrane-bound TNF. TNFB/LTA-(lymphotoxin, TNF-C), 205 aa, Chr 6, 2LTA+1LTB=active trimeric ligand or lymphotoxin-beta receptor. necessary for Peyer's patches and lymph node development. TNF/LTB (anchors trimer with LTA to cell surface. 244 aa, normal development of lymphoid tissue). TNFSF4 (OX40L, CD252, expressed dendritic cells, binds CD134, 153 aa, associated SLE). TNFSF5 (CD40L, CD154, also binds integrins a5b1 and a2bb3. stimulates T follicular helper cells (Tfh). Defect results in inability for Ig class switching. TNFSF6 Fas ligand, CD95L, homotrimeric type II transmembrane protein on cytotoxic T lymphocytes, cleaved by MMP-7 to produce soluble Fas ligand. TNFSF7 (CD70 ligand for DC27, expressed on activated lymphocytes especially lymphoma cells. ARGX-110 is monoclonal antibody to CD70 TNFSF8 CD153 ligand for CD30 TNFSF9 CD137, 4-1BB ligand, type 2 transmembrane protein on activated T cells TNFSF10 TRAIL (TNF-related apoptosis-inducing ligand), CD253, 281 aa, causes apoptosis in tumor cells TNFSF11 RANKL (receptor activator of nuclear factor kappa B ligand) or DF (osteoclast differentiation factor) TNFSF13 APRIL (a proliferation-inducing ligand) CD256, may be able to induce apoptosis, important and long-term survival of lymphocytes, TNFSF13B BLys EDA ectodysplasin-A, cleaved by turin to produce a secreted form, important in development of ectodermal organs, mutation results in X-linked hypohidrotic ectodermal dysplasia.

Question 33

what is the B7 lymphocyte membrane protein?

Answer 33

CD80 (B7-1) on antigen presenting cells is the initial costimulatory ligand based on its more abundant and earlier expression. It interacts with CD152 (CTLA-4) to maintain immune tolerance. CD86 (B7-2) participates later following antigen-presenting cell activation, binds to CD28 promoting T cell responses. CD86 may also bind CTLA-4 for attenuation of regulation and cellular disassociation.

Question 34

What is the CD138 plasma cell marker?

Answer 34

cd138 is a transmembrane heparin sulphate proteoglycan of the syndecan family that participates in cell binding, signaling, and cytoskeletal functions. Serves as a marker for blood derived plasma cells.Required for internalization of HIV-1 tat protein. Variants occur as tumor cells.

Question 35

What are the surface markers for CD20?

Answer 35

CD20 is a glycosylated membrane spanning phosophprotein on the surface of pro-B cells CD45R +, CD117+

Question 36

What does the CD40-CD40L system do?

Answer 36

``` CD40 is a costimulatory protein on antigen presenting cells that binds to CD40L (CD154) on Th cells. CD40 is also present on dendritic cells, B cells, endothelial cells, smooth muscle cells, fibroblasts, epithelial cells, tumor cells-lymphoma, myeloma, and carcinoma. CD154 on B cells stimulates antibody class switching and differentiation into plasma cells. CD154 on T cells stimulates macrophages to produce reactive oxygen species and nitric oxide. CD154 tumor necrosis factor family member on surface of T cells that bind CD 40 as well as a5 betaI integrin and a IIb beta 3. Especially important on T follicular helper cells Tfh. ```