immunology original Flashcards
What is the difference between anti-receptor antibodies in Graves’ disease and in autoimmune thyroiditis.
Anti-receptor antibody stimulate in Graves’ disease and block the receptor in autoimmune thyroiditis.
what cytokines do CD4+ Th1 cells secrete?
TGF beta, interferon gamma, IL-3, IL-10, ?IL-2 absent IL-4 and IL-5.
What cytokines do CD4+ Th2 cells secrete?
IL-4, IL-5, IL-6, IL-10, IL-13Th2 response relies on B cells to produce IL-4-5-6-10-13 thus stimulating antibody class switching and neutralizing antibody production. IL-4 Starts the process which auto stimulates itself and other cytokines. IL-10 Inhibits IL-2 and interferon gamma.
What cytokines do CD4+ Th17+ cells secrete?
TNF alpha, IL-17. IL-17 recruits monocytes and neutrophils to inflammatory sites and stimulates the production of IL-6, G-CSF, GM-CSF, IL-1 beta, TGF-beta, and TNF alpha as well as many chemokines, and prostaglandins.This pathway is active in psoriasis, autoimmune uveitis, juvenile idiopathic arthritis, rheumatoid arthritis, and Crohn’s disease.IL-23 (heterodimer containing IL-12 from macrophages, dendritic cells) stimulates the production of IL-17.
How do autoantibodies in Hashimoto’s thyroiditis stimulate apoptosis and CD4+ Th1 cell cytotoxicity.
Autoantibodies stimulate epithelial cell HLA type II expression which increases presentation of thyroid antigens to T cells. FAS ligand appears on epithelial cells so that lymphocytes with FAS can induce cell death. Antithyroid antibody producing B cells can present antigen to T cells. Some antibodies fix complement.
Type I interferon consists of what interferons?
Interferons that stimulate the INF alpha receptors, R1 and R2 and consist of INF alpha, INF beta, and INF Omega (~20 kd). Interferon alpha is coded by 13 genes on chromosome 9, and is strongly produced by plasmacytoid dendritic cells. They are the proximal cause of prostaglandin E2 release, fever, and stimulate the mu receptor causing analgesia.
What is the major difference in immune pathogenesis between lupus and Sjogren’s syndrome?
Both show similar autoantibodies but lupus tends to develop immune complex disease whereas in Sjogren’s syndrome damage occurs by lymphocytic infiltration.
What additional membrane receptors occur on memory B cells infiltrating the salivary glands in Sjogren’s syndrome?
CXCR4+(CD184, stromal derived factor receptor causing chemotaxis, HIV receptor), CXCR5+(CD185, 7 transmembrane receptor for b cell mitogen), CD27+ (TNF receptor family, cd70, proliferation and Ig synthesis)
What immune mechanisms cause glandular damage in Sjogren’s syndrome?
Perforin/granzyme A, FAS/FAS ligand, cytokines, autoantibodies, metalloproteinases.
what is LFA-1?
Lymphocyte function-associated antigen 1 is a heterodimer integrin CD11a (integrin alpha L, p189) and CD18 (integrin beta-2). This is present on both T and B cells and binds to ICAM-1 (CD54) on antigen presenting cells.
What type of lymphocyte infiltrates salivary glands in Sjogren’s syndrome?
75% are T cells Helper/inducer CD4+ which coexpress LFA-1.
What does IL-5 do?
IL-5 is a Th2 cytokine similar to granulocyte stimulating factor. Eosinophiles have high concentration of IL-5 receptors which increases their numbers and ability to infiltrate. Asthma and allergic rhinitis depend on IL-5.
what is CXCR4?
CXCR4 is a chemokine receptor which causes circulating cells to home to the bone marrow. It is also the major HIV receptor on lymphocytes.
What is CXCR5 ?
CXCR5 is a 7 transmembrane G protein-coupled receptor for CXCL13, secreted by T cells. CXCR5 is important in B cell migration. CD4+ CXCR5+ T cells protect against tuberculosis.
What cell types promote Th1 and Th2 type responses?
Macrophages promote Th1, B cells Th2.
What immune activity results from Th1 response?
Cellular immunity with activated macrophages, increased CD8 cytotoxic T cells, opsonizing antibody production.
What immune activity results from Th2 response.
Increase in T helper cells, B cell proliferation, increased neutralizing antibodies, promote antibody class switching,
What plasma components are increased by IL-6?
IL-6 increases complement levels, acute phase protein synthesis, and myelopoeisis. IL-6 stimulates prostaglandin synthesis in the hypothalamus..
What sort of immune reaction characterizes rheumatoid arthritis?
Type 3, immune complex complement mediated hypersensitivity. Th17 induced inflammation.
What cells respond in Th17 mediated stimulation?
Neutrophiles and IgM,IgA B cells
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 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 is CD4?
CD4, the product of the CD4 gene, is a membrane-bound glycoprotein with 4 immunoglobulin domains, 2 variable and 2 constant. The D1 (variable) domain interacts with the Beta 2 domain of MHC class 2 molecule thus accounting for MHC class 2 restriction.
How many binding sites must connect to stimulate T helper cell activation?
2.The beta chain of the T cell receptor must recognize the antigen in the MHC class 2 groove and CD4 must associate with the T cell receptor and bind to the beta-2 domain of the MHC class 2 complex.
How strong is the attachment of the T cell receptor to the immunogen on the MHC molecule?
The binding is weak permitting easy on easy off interrogation of multiple receptors. Additional binding such as CD4 and presence of appropriate cytokines determines the T cell response.
What is the protein domain structure of MTOR?
MTOR consists of 2549 amino acids. Domains from N terminal consist of HEAT repeats, FAT, FRB, serine/threonine kinase (PI3K/PI4K) domain, then FATC.HEAT= Huntingtin, Elongation factor 3, a subunit of protein phosphatase 2A, TOR1.FAT= FRAP-ATM-TRRAP.FRAP=K506 Rapamycin Associated Protein.ATM= Ataxia Telangiectasia Mutated.TRRAP= Transformation/Transcription domain Associated Protein.FRB= FKBP12-rapamycin binding.FATC= FAT domain at the C terminal end.
What are the 2 downstream effector complexes containing mTOR?
mTORC1 controls protein synthesis, and contains mTOR, RAPTOR, mLST8, DEBTOR, and PRAS40. Raptor and mLST8 are positive regulators, Debtor and PRAS40 are negative. mTORC2 regulates cytoskeleton and contains mTOR, RICTOR, mLST8, DEBTOR, and mSIn1.mTORC1 :RAPTOR = Regulatory Associated Protein of mTORmLST8 = mammalian Lethal with SEC13 protein 8, G protein beta subunit likeDEBTOR = DEP domain-containing mTOR interacting protein. The DEP domain contains 80 amino acids important in G protein signaling initially found in disheveled (Dsh) transduction, Egl-10 (nervous system G protein signaling), and Pleckstrin domain.PRAS40= Proline-rich AKT1 substrate 1The Pleckstrin homology domain contains 120 amino acids that form attachment sites to membranes which then attract phosphatidylinositol lipids, heterotriimeric G proteins, and protein kinase C.mTORC2:AsRICTOR = Rapamycin-insensitive companion of mTORmSin1 = mammalian stress-activated interacting protein kinase 1.
What is composition of the IL-12 family?
IL-35 is a dimer containing p35 (IL-12 alpha) and EBI3 (Ebstain Bar virus Induced 3) chain that binds to gp130 .IL-27 is a dimer containing P28 (IL-27)and EBI3. IL-12 is a dimer containing p35 (IL-12 beta 2) and p40 (IL-12 beta1).IL-23 is a dimer containing p19 (IL-23), and p40 (IL-12 beta 1 ).The chains associate via Jak and Tyk motifs which phosphorylate STAT 3 and 4 transcription factors.
What is the difference between anti-RNP antibodies and anti ribosomal P protein antibodies
Anti-RNP antibodies are directed against a ribonucleic (RNA) protein of the splisosome, common in mixed connective tissue disease. Ribosomal P protein is a protein on the 60s ribosomal subunit and antibodies to it are highly specific for SLE.
How does mTORC1 inhibit autophagy?
Activated mTORC1 phosphorylates Atg 13 (autophagy related protein 13) which prevents autophagosome construction at the plasma membrane.
How does mTORC1 increase production of reactive oxygen species?
mTORC1 increases cytosolic glycolysis and decreases oxidative phosphorylation thus lowering O2 demand and allowing excess O2 to form reactive oxygen species.
How do tuberous sclerosis proteins affect mTOR?
TSC2 (tuberin, tuberous sclerosis 2) is a peripheral membrane protein that combines with TSC1 (hamartin, peripheral membrane protein) in cells to become a cytosolic dimer, GTPase activating protein (GAP) that inhibits mTORC1. The TSC1/TSC2 heterodimer is a sensitive to upstream signals that result in increased or decreased mTOR activation and can function as a tumor suppression gene..
what is the B7 lymphocyte membrane protein?
B7-1 is CD80 and B7-2 is CD86, present antigen presenting cells, which bind to CD28 or CD152 (CTL A-4) on T cells. T cells without CD80/CD28 binding are anergic.
What are regulatory B cells?
Regulatory B cells (Bregs) secrete IL-10 and and TGF-beta.
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 does the alpha chain of the IL-2 receptor (CD25) do?
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.
What is CD5?
CD5 is on B-1 cells and serves to lower B cell responsiveness so that only strong stimuli become immunogenic.
What cytokines are included in the IL-10 superfamily?
IL-10 (CSIF cytokine synthesis inhibitory factor) family includes IL-19, IL-20, IL-24, IL-26, and sometimes IL-28 and IL-29. IL-10 down regulates Th1 responses, MHC class !! expression, and costimulatory molecules on macrophages. It downregulates TNF alpha, interferon, and GM-CSF. It upregulates IL-6 in muscles during exercise.
