Immune cell plasma membrane Flashcards
identify immune cell surface membrane contribution to immunity and inflammation
What part of the T-cell receptor complex binds to the antigen in the MHC groove ?
Complementarity determining region 3 (CDR3) on the beta chain. NOT CD3 -cluster of differentiation 3.
What enzymatic actions does cd38, aka cyclic ADP ribose hydrolase, control ?
CD38-glycoprotein, multifunctional ectonucleotidase enzyme, cyclic ADP ribose hydrolase, synthesize NAADP from NAD(P)+, nucleosidase activity generatiing cyclic ADP-ribose. Opens Ca channels, participates in cell adhesion, B cell signalling pathway, signal transduction (IL-1, retinoic acid, estradiol, progesterone, insulin, H2O2), regulation of cytosolic calcium concentration. Surface marker for B lymphocytes.
What cellular membranes contain CD38 aka cyclic ADP ribose hydrolase ?
CD38 is found on external and basolateral plasma membrane, on intracellular bounded organelle membranes, extracellular exsomes, cell nuclear membrames, secretory granular membranes.
What are the cell membrane markers for HSC, hematopoetic stem cells?
Hematopoetic stem cells markers include: CD34,38,59, Thy1/CD90, C-kit/CD117, lin–
CD34-phosphoglycoprotein single pass transmembrane sialomucin, cell-cell adhesion factor ro extracellular matrix,stromal cells, necessary for lymphocytes to enter lymph nodes
CD38-glycoprotein, cyclic ADP ribose hydrolase, cell adhesion, signal transduction, calcium signaling. also found on CD4+,CD8+,B lymphocytes, NKC.
CD59-glycoprotein, MAC-inhibitory protein(MAC-IP., membrane attack complex), glycophosphatidylinositol (GPI) anchor, prevents C9 from forming C’ attack complex
CD117-receptor tyrosine kinase, Mast/stem cell growth factor receptor (SCFR), proto-oncogene c-Kit, KIT gene product.
CD90-immunogloglobulin superfamily, GPI anchor, N-glycosylated,=Thy-1 on thymocytes and neuron axons.
Lin- Lack of expression of mature blood cell markers
What are the cell membrane markers for granulocytes ?
+surface markers for granulocytes: CD11B, CD24, CD45, CD55, CD114, CD182.
CD11B - complement receptor 3 (CR3)
CD24: cell adhesion molecule, MAP kinase activity, crosslinking results in apoptosis
CD45 - Protein tyrosine phosphatase,receptor type C. Signaling molecule important in cell growth, differentiation, mitotic cycle, and oncogenic transformation.
CD55 - tetrasaccharide, aka CD15s, Sialyl Lewis stage -specific embryonic antigen 1..
CD114: hamatopoietin receptor family, aka G-CSFR (granulocyte colony stimulating factor receptor).
CD182: Interleukien 8 receptor, responsible for angiogenesis of intestinal endothelial cells.
What are the cell membrane markers for monocytes?
monocytes plasma membrane contains CD11a, CD11b, CD14, CD16, CD91, CD45, CD114,CD11a - product of gene ITGAL, integrin alpha L (ITGAL), lymphocyto function-associated antigen 1, alpha polypeptide. involved in cellular adhesion and costimulatory signaling.
CD11B - integrin alpha M (ITGAM), complement receptor 3 (CR3), macrophage-1 antigen (Mac-1), one subunit of integrin alpha M beta 2,
CD14 - monomeric bent solenoid with hydrophobic amino terminal. product of CD14 gene, found free in plasma (sCD14, or shedding from mCD14) and GPI membrane bound to membranes (plasma, and Golgi). Involved in TLR pathways, opsnization, phagocytosis, endocytosis, cytokine secretion, Type 1 inferferon requllation, response to heat and electrical stimulation, NF-kappa B signaling.
CD16 - Immunoglobulin super family-Fc fragment of IgG, 2 nearly identical genes. 2 Fc receptors - FcyRIIIa {CD16a, gene FCGR3A) and FcyRIIIb (CD16b, gene FCGR3B ). Signal transduction, Antigen dependent cytotoxicidy, membrane bound CD16 combines with CD2 to acrivate natural killer cells.
CD45 - Protein tyrosine phosphatase,receptor type C, product of gene PTPRC, LCA-leukocyte common antigen,
CD91: gene low density lipoprotein receptor 1 (LPR1), or alpha-2-macroglobulin receptor (A2MR) or apolipoprotein E receptor (ALOER). Involved in lipoprotein metabolsim, neurodegenerative diseases, atheroaclerosis, and cancer.
CD114: hamatopoietin receptor family,G-CSFR (granulocyte colony stimulating factor receptor.
What are the cell membrane markers for T lymphocytes ?
T lymphocytes stain positively for CD3, CD45
T helper cell: CD3, CD4, CD45.
cytotoxic T cell: CD3, CD8, CD45.
regulatory T cell: CD4, CD25, and Foxp3
CD45 - Protein tyrosine phosphatase,receptor type C, product of gene PTPRC, LCA-leukocyte common antigen,
CD3 - composed of 3 immunoglobulin superfamily proteins CD3d, CD3e, CD3g Delta, episolon, and gamma. Part of T cell receptor along with TCR-alpha and beta chains, and zeta chains.
CD4 - immunoglobulin superfamily, 4 domains, interacts with beta 2 chain of MHC class II molecule on antigen presenting cell.
CD8 - transmembrane glycoprotein that binds lymphocyte to class I MHC on presenting cell. Product of CD8-a and CD8beta genes forming a heterodimer. Downstream effects of binding include generation of NFAT, NF-kB, and AP-1.
CD25 - interleukin -2 receptor alpha chain, product of IL2RA gene. The complete receptor also contains IL2RB and IL2RG chains which regulate receptor affinity.
Fosp3 - Forkhead box P3 gene codes for forkhead/winged-helix family of transcriptional regulators that generate regulatory T cells.
What are the cell membrane markers for B lymphocytes ?
B lymphocytes stain positively for CD45, CD19, CD20, CD22, CD24, CD38.
CD45 - Protein tyrosine phosphatase,receptor type C, product of gene PTPRC, LCA-leukocyte common antigen,
CD20 - phosphorylated glycoprotein, product of MS4A1 (membrane spanning 4 domains) gene, role in differentiating B cells into plasma cells.
CD22 - SIGLEC (Sialic acid-binding immunoglobulin-tyoe lectin) family, prevents overactivation
CD24 - sialoglycoprotein, heat stable antigen, adhesion molecule, GPI anchor, found on neuroblasts and neutrophils as well.
CD38 is a multifunctional ectonucleotidase enzyme, cyclic ADP ribose hydrolase, found on external and basolateral plasma membrane, on intracellular bounded organelle membranes, extracellular exsomes, cell nuclear membrames, secretory granular membranes.
What are the cell membrane markers for thrombocytes?
Thrombocytes stain positively for CD16a and b, CD30, CD31, CD38, CD45, CD56, CD61, CD3-(neg).
CD16a and b aka FcyRIIIa and b, low affinity receptor of Fc fragment of IGg involved in ADCC, killing by NKC.
CD30 - Tumor Necrosis Factor Recptor superfamily 8 (TNFRSF8), on active T and B cells but not resting ones. Regulator of apoptosis protecting against autoreactive CD8 effector T cells.
CD31 - Platelet endothelial cell adhesion molecule (PECAM-1), active in removing aged neutrophiles.
CD38 is a multifunctional ectonucleotidase enzyme, cyclic ADP ribose hydrolase, opens Ca++ channels, on external and basolateral plasma membrane, intracellular bounded organelle membranes, extracellular exsomes, cell nuclear membrames, and secretory granular membranes.
CD45 - Protein tyrosine phosphatase,receptor type C. Signaling molecule important in cell growth, differentiation, mitotic cycle, and oncogenic transformation.
CD56 - Neural cell adhesion molecule (NCAM), glycoprotein, most strongly assoc with NKC.
CD61 (integrin beta-1, ITGB3 gene product)CD3 - composed of 3 immunoglobulin superfamily proteins CD3d, CD3e, CD3g Delta, episolon, and gamma. Part of T cell receptor along with TCR-alpha and beta chains, and zeta chains.
What is the role of IgD?
IgD results from alternate splicing of IgM mRNA and may be important in B cell interaction with mast cells and basophils. This stimulates release of B cell homeostatic factors. Knockout mice have suppressed IGE levels and defective primary IgG1 response. Circulating IgD interacts with basophils through a calcium-fluxing receptor to produce cathelicidin, pentraxin-3, IL-1, IL-4, and BAFF. IgD armed basophils may play a role in autoimmunity and orchestrating normal immune response.
cathelicidin- antibacterial polypeptides in lysosomes of polys, and macrophages.
pentraxin-3; pattern recognition domain of innate immunity.
BAFF; BLyS receptor 3, TNF receptor superfamily 13C, required for mature B-cell survival.
What are the differences between B1 and B2 lymphocytes?
B-1 cells have more IgM than IgG on the surface with low antigen avidity responding mostly to polysaccharides. They are present in the plural and peritoneal cavities. B-2 cells are intended when B cell is otherwise unqualified.
What is the main function of M1 macrophages, what stimulates their development .and what do they produce?
M1 macrophages are inflammatory and respond to INFg, GM-CSF, lipopolysaccharide, DAMPS(damage associated pattern molecules). M1 macrophages produce IL-1,, 6 , 12, 23, TNFσ, NO, and reactive O2 species. Also produce low levels of IL-10.
IL-1 - interleukin 1 refers to 17 types of agonists to related receptors that alter gene expression via NK-kappaB, AP-1, JNK, and p38 MAPK.
IL-6 - product of IL6 gene is an antiinflammatory myokine and proinflammatory cytokine.
IL-12 - heteero or homohimer formed by 2 ge.nes IL-12A and IL-12B. Stimulates T cells and NK cells to produve TNF-alpha, INF-gamma, Reduces IL-4 suppression of INF-gamma. CD30 acts as a coreceptor to increase acrivity. Has 2 receptors IL-12R-beta1 and beta2. Jak STAT pathway mediates promotion of Th2 pathway.
What is the main function of M2 macrophages, what stimulates their development .and what do they produce?
M2 macrophages phenotypically are resident macrophages, and are equiped to clean up damaged cells with an overall anti-inflammatory effect. They generate IL-4,10,18, M-CSF, TGFß1, VGEFA low levels of IL-12. They are needed for revascularization, and epithelialization.
M2 macrophages are up regulated by stimulating CD86 (CD28,CTLA4), CD14, CD209, CXCR4, and CD206. acetylglucosamine, fucose CD209 (C type lectin receptor), cxcr4 (CD184), fusion, binds SDF-1 (stromal derived-factor-1 or CXCL12), HIV binding site on T cells.
M2 macrophages are associated with tumors and seem to promote tumor growth. They are down regulation of CD25, TLR2, CD127, CD64, CCR7, CD16, and CD36.
M2 macrophage function is variable and further functional classification is likely.
What do Th3 cells do?
Th3 cells promote mucoaI immunity by favoring non complement fixing IgA secretion managed by TGFß and IL-10. Intestinal dendritic cells produce TGFß. Th3 cells Inhibit TH1 and TH2 cells.
What glycoprotein expressed on T cells interacts with a C type lectin on B cells, and what is the result?
CD5 is a transmembrane glycoprotein, expressed mostly on T cells and some B1 cells. Interacts with CD72, a C type lectin, on B cells (pro B to mature). Stimulation of CD5 by CD72 increases intracellular calcium, cell proliferation, and receptor mediated endocytosis.
CD5-495 residues, 67 kDa, glycosylated at two sites, serine occurs at 5 sites
What are some of the major surface receptors on macrophages?
Macrophage plasma membrane may contain:
CCR7 (C-C chemokine receptor type 7), CD14 (coreceptor with TLR4 for lipopolysaccharide),
immunoglobulin receptors: CD16 (Fc IgG receptor,) CD64 (monomeric IgG Fc receptor),
cytokine receptors: CD25 (alpha chain IL-2 recptor), CD127 (IL-7 receptor subunit alpha),
CD86 (ligand for CD28 and CTLA4), cd206 (c type lectin, mannose receptor), CD36 (thrombospondin receptor),
What is the role of M1 and M2 macrophages in atherosclerosis?
M1 macrophages induce subintimal inflammation.
M2 macrophages ingest cholesterol which when oxidized induces apoptotic foam cells.
How many different types of T cells are there ?
Cell sorting by surface receptor first, then permeabilized cells for intracellular cytokines, mRNA, etc. is used to identify T cells.
Tn: naive T cell : CCR7+,CD167, CD132
Tcm : Central memory T cells : found in lymph nodes: CCR7+ CD45RO+ CD62L (L selectin)+ CD44+ CD4+ or CD8+ ,
Tem:: Terminally differentiated effector memory T cells, antigen experienced: found in peripheral circulation and tissues not lymph nodes: CD45RO+ CD62L (L selectin)-, CD4+ or CD8+ CCR7-
Trm: Tissue resident memory T cells: skin, lung, GI: integrin alpha e beta7, lipid metabolism genes++Tvm: virtual memory T cells: homeostatic proliferation of antigen inexperienced T cells, CD4 or CD8
Tfh: follicular helper- CD4+ CXCR5+ CD40L+
Th-1: Thelper type 1: stimulates cytotoxicity: STAT4 T-bet transcription factors,->INFgamma
Th-2 T helper type 2: stimulates antibody generation: STAT6 and GATAs transcription factors,
Treg: Regulatory T cells: produce IL10, Tr3 produce TGFbeta.Treg17.
Th-17 stimulated by bacterial antigens presented by gut dendritic cells, Formation stimulated by TGFbeta, IL-6, IL-21, IL-23 via differentiating transcription factors include STAT3, RORγ, RORa,l Related to Treg and inhibit Th1 and Th2 pathways.
IL17 nTreg: CD4+ CD25bright, FoxP3+
iTreg: induced T reg: CD4+ CD25- Foxp3+, outside thymus
Treg17 ? CCR7 (CD197), binds CCL19-homing, CCL21, CD25 alpha chain
NKT cells): Natural killer T cells recognize ag on CD1d
MAIT: Mucosal associated invariant T cell: has MR1 MHC class1 like protein receptor.
I
How are sub types of T cells identified?
Identification by cell sorting stains surface receptor first, then cells are permeabilized and stained for intracellular cytokines, mRNA, etc.. Precise identity is in state of flux.
Naive T cell (Tn)- CCR7+CD45RA+
Central memory T cells (Tcm): CCR7+CD45RO+CD44-CD62L+ CD4+ or CD8+
Terminally differentiated effector memory T cells (Temra): CD45RA ?+CD62L-, CD4+ or CD8+ CCR7-
Temra- ?CD4+ or CD8+, CD45RA+, CCR7-
Regulatory T cells (Tr1): produce IL10, Tr3 produce TGFbeta.Treg17.
Tissue resident memory Tcell (Trm): integrin aebeta7
virtual memory T cells: CD4 or CD8
Tfh (follicular helper) CD4+CXCR5+CD40L+
Th-1 STAT4 and T-bet transcription factors,->INFg
Th-2 STAT6 and GATAs TF
Th-17 STAT3, RORg, RORa,
IL17 nTreg CD4+CD25brightFoxP3+
iTreg CD4+CD25-Foxp3+, outside thymus
Treg17 CCR7 (CD197), CD25 alpha chain
Natural keller T cells (NKT cells): recognize ag on CD1d
Mucosal associated invariant:
IL-2 receptor CD40L= CD154
CCR7 binds CCL19-homing, CCL21,
CD44-lectin binding Hyaluronic acid receptor, binds collagen mmp
CD45 (PTPRC, protein tyrosine phosphatase receptor type C, leukocyte common antigen), type 1 transmembrane protein used to differentiate lymphocytes from carcinomas. CD45RA longer isoform, appears on naive T cells. The CD45RO isoform is on active and memory T cells. the largest CD45 isoform B220 appears on B cells and antigen presenting cells.
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. iTreg (induced Treg) nTreg (natural T reg) STAT3 (Signal transducer and activator of transcription), downstream form tyrosine phosphatase growth factors STAT4 downstream from IL-12 and JAK kinase. STAT6 downstream
IL-6 Tcm (central memory T cell)
Tem (effector memory), stimulated Tcm produce Tem Temra (terminally differentiated Tem cells) Tfh (T follicular helper) Th1 (T helper type 1 ) Tn (naive T cell)
CCR7: appears on Tn, Tcm, Tem, Treg1. Ligands include ccl19 mostly produced in thymus and lymph nodes attracting dendritic cells and antigen-engaged B cells.
How many types of selectins does CD62 aka L selectin refer to, and what does it do ?
CD62 refers to L (leukocyte) selectin transmembrane adhesion molecules that contain a calcium dependent Ca binding domain, EGF domain. Other subtypes serve different functions in different cell types.
What proteins make up the T cell receptor complex?
TCR alpha and beta chains ( 95%) or epsilon and gamma (5%). 3 additional dimeric signaling molecules are associated, 2 types of CD3 (one chain each of CD3E (epsilon), CD3Z (Zeta), CD3D (delta), and CD3G (gamma)), and CD247 (zeta chain dimer).CD3 chains belong to the immunoglobulin superfamily. The transmembrane portion is negatively charged but associates with the positively charged TCR complex. Intracellular portion contains ITAM (immunoreceptor tyrosine-based activation motif) structure, which accounts for downstream T cell signaling.
what is CD45 , LCA-leuocyte common antigen, do ?
CD45 - Protein tyrosine phosphatase,receptor type C, product of gene PTPRC, LCA-leukocyte common antigen. Signaling molecule important in cell growth, differentiation, mitotic cycle, and oncogenic transformation.
What is CD11a and CD11b produced by ITGAL and and ITGAM genes ?
CD11a - product of gene ITGAL, integrin alpha L (ITGAL), lymphocyto function-associated antigen 1, alpha polypeptide. involved in cellular adhesion and costimulatory signaling.
CD11b - integrin alpha M (ITGAM), complement receptor 3 (CR3), macrophage-1 antigen (Mac-1), one subunit of integrin alpha M beta 2. Dysfunction is suspected as predispoaing to infection by Trophorema Whippilei.
How does CD14 regulate innate immunity?
CD14 - monomeric bent solenoid with hydrophobic amino terminal. product of CD14 gene, found free in plasma (sCD14, or shedding from mCD14) and GPI membrane bound to membranes (plasma, and Golgi). Involved in innate immunity- TLR pathways, opsnization, phagocytosis, endocytosis, cytokine secretion, Type 1 inferferon regullation, response to heat and electrical stimulation, NF-kappa B signaling.
Presence helps to identify monocytes.
What is CD16, the gene product of FCGR3A and B ?
CD16 - Immunoglobulin super family-Fc fragment of IgG, 2 nearly identical genes. 2 Fc receptors - FcyRIIIa {CD16a, gene FCGR3A-Fc fragment of IgG, low affinity IIIa, receptor) and FcyRIIIb (CD16b, gene FCGR3B ). Signal transduction, Antigen dependent cytotoxicidy, membrane bound CD16 combines with CD2 to acrivate natural killer cells.
Found on surface of NKC, neutrophils, granulocytes, monocytes, and macrophages.
What is CD91 aka LRP1 ?
CD91: gene low density lipoprotein receptor 1 (LRP1), or alpha-2-macroglobulin receptor (A2MR) or apolipoprotein E receptor (ALOER). Involved in lipoprotein metabolsim, neurodegenerative diseases, atheroaclerosis, and cancer. Knockout mice show increaased apoptosis and increased inflammatory macrophage accumulation in atherosclerotic lesions.
Present on monocytes, vascular smooth muscle, hepatocytes, neurons.
What is CD114 aka G-CSFR ?
CD114: hamatopoietin receptor family, G-CSFR (granulocyte colony stimulating factor receptor). Activates JAK, Lyn, STAT, and Erk1/2.
Used to identify monocytes.
What is CD34 a sialomucin ?
CD34-glycoprotein single pass transmembrane sialomucin, cell-cell adhesion factor ro extracellular matrix,stromal cells, necessary for lymphocytes to enter lymph nodes.
Found on hematopoetic stem cells.
What is CD59 aka MAC-inhibitory protein(MAC-IP) ?
CD59-glycoprotein, MAC-inhibitory protein(MAC-IP, membrane attack complex), glycophosphatidylinositol (GPI) anchor, prevents C9 from forming C’ attack complex. Mutation results in paroxysmal nocturnal hemoglobinuria.
What is CD117 aka Mast/stem cell growth receptor (SCFR) ?
CD117- Mast/stem cell growth receptor (SCFR), receptor tyrosine kinase, Mast/stem cell growth factor, proto-oncogene c-Kit, KIT gene product.
There are 58 receptor tyrosine kinase genes in the human genome generating 20 classes of receptor kinases by 2018.
