Immunologie (Fach) / MD PhD (Lektion)

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Oxenius & Kopf

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  • NOD mice = Non-obese diabetic (NOD) mice • Develop spontaneously insulin-dependent diabetes mellitus (IDDM)  • The susceptibility to IDDM is polygenic:- MHC haplotype - NOD mice have a mutation in the CTLA-4 gene --> T-cells attack the insulin producing cells • The incidence of disease is linked to microbiome. 
  • Structure of MHC classes MHC class I- a chain- ß2 microglobulin MHC class II- Two chains (α and β) of roughly equal length. - CD4 binds to α2 Peptide-binding groove: - wall of two α helices and a floor of eight β pleated sheets - structurally similar - class I requires 8-11 amino acids- class II requires 13-25 amino acids - Alleles differ from one individual to another by 5-10% 
  • Cross-presentation - by dendritic cells and macrophages (not B-cells/fibroblasts) - correlated with a cells capacity to phagocytose  - can make pathogen visible that would otherwise have lysed a cell before presentation (eg NK) - if pathogen could avoid being phagocytosed by dendritic cells and macrophages it would be invisible to immune system without cross-presentation!
  • γδ T cells - not MHC restricted - They populate secondary lymphoid organs and tissues with epithelial linings - Specific for molecules produced in damaged cells (e.g. heat shock protein) - wound repair -γδ TCRs on cells produced shortly before or after birth are more diverse and have N nucleotides - not crucial for survival - Rearrangement of TCR α chain prevents TCR δ chain 
  • SCID (severe combined immunodeficiency) - mutation a common gamma chain of interleukin receptors, which are involved in the development and differentiation of T and B cellsIL-2R: ProliferationIL-4R: TH2 development, IgE/IgG productionIL-21R: NK developmentIL-7R: T and B cell developmentIL-9R: Mast cell development  --> complete failure of the immune system to develop and function, with low or absent T cells and NK cells and non-functional B cells - 'bubble boy'; very susceptible to infections
  • IL-6 - secreted by macrophages, dendritic cells, fibroblasts, endothelial cells after infection or tissue damage - Fever - Hematopoesis ↑ - Antibody response ↑, Th17 differentiation ↑, T cell memory ↑  - Acute phase response ↑  - Protection from neuronal cell death 
  • Tetramer staining - Purified MHC class I bound to biotin which form a tetramer with fluorecently-labelled streptavidin - bind exclusively to complementary TCRs - signal measured by flow cytometer --> measures memory/effector cells
  • RSS (recombination signal sequences) - flank V, D and J gene segments - RSS function as signal sequences for recombination process  - contains a palindromic heptamer and a conserved nonamer sequence - intermittent sequence of 12 or 23 bp (one or two DNA helix turns) - One turn RSS can only join with two turn RSS 
  • Immunoglobulins effector functions 1. Complement 2. Neutralization 3. Opsonisation--> promotion of phagocytosis 4. Antibody-dependent cytotoxicity--> promotion of destruction by NK, granulocytes 5. Transcytosis
  • CD4 - Help B cells in T-dependent antibody responses (class switch)  - help CD8 T cells in memory response  - Recruitment and activation of innate immune cells