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Karteikarten von ruby.white94, aktualisiert more than 1 year ago
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Erstellt von ruby.white94
vor etwa 11 Jahre
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| Frage | Antworten |
| PRRs | Pattern recognition receptors |
| PAMPs | Pathogen associated molecular patterns |
| Transcription factors turned on by MyD88 dependant and independant signalling | Dependant - NFkB, JNK, p38 Independant - NFkB and IRF3 |
| C-type Lectin receptors | Dectin 1, Dectin 2 and mannose receptors all recognise candida and all lead to Th17 adaptive immune response |
| Mincle | A C-type lectin receptor which recognises malassezia spp, recognises trehalose dymycolate from Mtb |
| RIG-1 like receptors | RIG-1 - recognises retinoic acid-inducible gene 1, ss RNA, short blunt end of dsRNA. MDA5 - melanoma differentiation associated genes, recognises dsRNA. |
| Th1 Tcell what activates it what response does it produce | IL-12 Produces IFN-y Macrophages increased phagocytosis CD8Tcell kill infected cells B cell make antibody to enhance phagocytosis |
| Th2 CD4 Tcells | IL-4 from APC Starts making IL4, IL5, IL13 Makes mast cell destroy worms CD4 Tcell produce more IL4, IL5, IL13 and Bcell make antibody to bind pathogen. |
| What does MyD88 independant signalling use instead of MyD88? | TRIF |
| Explain the structure of a BCR | Notes |
| Explain the structure of a TCR | notes |
| What are two other sources of variation for the Bcell receptor other than rearrangment? | 1. Exact point of splicing between V and D and D and J 2. extra nucleotide can insert at these joints called N region |
| RSS | Recombination single sequence Recognised by RAG-1 and RAG-2 for recommbination |
| RAG-1 and RAG-2 | Recognise RSS and cut both strands of DNA. |
| How is RAG-1 and RAG-2 cutting repaired? | Regular cellular machinary, Tdt by nonhomologous joining, the two ends are ligated to form a coding joint V-DJ on heavy chain and VJ on light chain |
| Allelic exclusion | One chromosome makes a defective BCR then the other one is used. If both defctive then death occurs. |
| Where does Negative and positive selection of Tcells occur | Thymus |
| Negative selection | Cells that bind MHC to strongly are killed |
| Positive selection | Cells that bind MHC at the right level survive Cells that don't bind enough, death by neglect |
| Features of cytokines | Souble intercellular signalling molecules picomolar and nanomolar concentrations acts through specific receptors Acts locally |
| Pleiotrophic | More than one effect, cytokines |
| Why are cytokines tightly regulated and how? | Extremely potent and through receptor expression |
| What does sustained of systemic production of cytokines lead to? | Pathogenesis and disease |
| IL-2, IL-6, TNFalpha | Proinflammatory cytokines |
| Endogenous pyrogens | Increase the thermoregulatory set point in the hypothalamus |
| What are effects of pro-infammatory cytokines | Endogenous pyrogens upregulate synthesis of pro-inflammatory cytokines Stimulate production of acute phase proteins attract inflammatory cells |
| Cytokine storm | Large quantities of cytokines released, uncontrolled high fever, local edema, severe swelling, septic shock |
| Anti-inflammatory cytokines | IL10, TGFbeta |
| IL-10 effects | Stops macrophage production of TNFalpha suppressive functions in the immune response |
| Chemokines | Proteins active over 1-100mg/ml concentration range stimulate and sustain inflammatory response short lived |
| Describe overall chemokine structure | Conserved cysteine residues that form disulphide bonds in tertiary structure |
| CXC chemokines | Bind to CXCR receptors produced mainly by macrophages primarily effect neutrophils |
| CC chemokines | Two adjacent cystienes Bind to CCR receptor Produced mainly by macrophages and t cells primarily attract monocytes Can also attract tcells, eosinphils and basophils |
| C chemokines | Only one cystiene bond bind to XCL receptors Attract pre cursor tcells in thymus |
| CX3C chemokines | Have cysteines separated by three amino acids Attract tcells and monocytes |
| Structure of a chemokine receptor? | All have seven span transmembrane proteins Signal through G-coupled receptor |
| IL-8 | CXCL8 Produced by monocytes, macrophages, fibroblasts, keratinocytes |
| Antigen specific | MHCI/II and TCR |
| Coreceptor | CD4/8 |
| Adhesion | LFA1 - ICAM |
| Co-stimulation | CD28/CD80 |
| What inflammatory signals does the APC give the Tcell? | IL-12 |
| CTLA-4 | Competes with CD28 to bidn with CD80 from APC |
| p-SMAC | The peripheral ring of contact all but ICAM and LFA are in this cirle |
| Describe the intracellular process of TCR activation | Notes |
| Outcome of TCR activation | Il-2 - Tcell proliferation Tcell cytotoxic function CD8 cytokines -> anitbody production IFNgamma activates macrophages |
| Th | T helper cell CD4 Tcell subsets |
| Tc | Cytotoxic Tcell CD8 subsets |
| What do CD4 Tcell subsets do? | Activate macropahges to make cytokine |
| What do CD8 Tcell subsets do? | Release perforins and granzymes Cell death of target cell |
| CD4 Th1 | IL-12 from APC activates them They create IFNy Increase macrophage phagocytosis, induce CD8 cells to kill infected cells, Bcells make antibody to enhance pahgocytosis Intracellular infection |
| CD4 Th2 | IL-4 activates them Make IL4, IL5, IL13 Mast cell and eosinohil destory worms, CD4 tcell produce more IL4,5,13 Bcell make antibody Worms and parasites |
| What can result from Th1 and Th2 if things go wrong? | Th1 - autoimmunity Th2 - allergies |
| IL-12 | IFN-y production |
| IL-23 | IL-17 production |
| Th17 immune cells | causes neutrophils, inflammation, CD4 tcells to make IL22, autoimmunity |
| Tfh | Stimulate B cells |
| Th9 | Activated by IL-4, TGFb Makes pro-inflammatory IL9 and Anti-inflammatory IL-10 |
| Type 1 response CD8 | IL-12 activated IFNy production |
| Type 2 responses CD8 | IL4 activated Makes IL4, IL5, IL13 |
| Non conventional Tcells | Within gut epithelium gamma sigma not alpha beta TCR Recognise antigen directly, innate like |
| Non convential Tcell NK | Natural killer cells Respond very fast express restricted alphabetaTCR and NK markers Recognise lipid antigen on MHC like molecules Innate like |
| What two types of transcription factors are needed in Tcell activation? | One to turn on genes STAT One to keep them on |
| Th1 | IL12 Activation STAT3 turn on genes Tbet keep genes on INFy produced |
| Th2 cells | IL4 activator STAT6 turns genes on GATA3 keeps genes on IL4, IL5 IL13 produced |
| Th17 cells | IL-23 activator STAT3 turns genes on RORyt keeps genes on IL17 produced |
| What are the five ways of keeping a tcell subset that subset? | 1. transcription of cytokine genes (positive feedback) 2. Inhibit expression of other cytokine receptors 3. Hisotne modifications to prevent other transcription factors binding 4. DNA methylations to prevent other genes being transcribed 5. micro RNAs HERITABILITY OF DIFFERENTIATION |
| What controls the speed of response? | Amount and availability of antigen costimulation cytokines |
| What controls the magnitude of a response? | The amount and availability of antigen costilumaltory molecules cytokines naive precursor frq |
| What drives the resolution of a response | decreased cytokines antigen/pathogen cease to bind decreased cytokines |
| Tregs | Suppress the Tcell activation, proliferation and differentiation |
| Natural Tregs | Develop in the thymus 10% of all CD4 T cells |
| Induced Tregs | Are induced in the periphery |
| What do Tregs express? | FoxP3 IL2 receptor and alpha chain CD25 Co-inhibiting molecule CTLA4 |
| Foxp3 | Expression in induced Tregs can be driven by TFGb Interferes with IL-2 production by uptaking and degrading it as well as stopping Tcells produce it |
| Foxp3 | Expression in induced Tregs can be driven by TFGb Interferes with IL-2 production by uptaking and degrading it as well as stopping Tcells produce it |
| Foxp3 | Expression in induced Tregs can be driven by TFGb Interferes with IL-2 production by uptaking and degrading it as well as stopping Tcells produce it |
| Foxp3 | Expression in induced Tregs can be driven by TFGb Interferes with IL-2 production by uptaking and degrading it as well as stopping Tcells produce it |
| IL-10 secretion by Tregs | Suppresses Tcell cytokine production and reduces MHC expression in APCs |
| TGFb expression by Tregs | Blocks Tcells cytokine production stops cell division and killing ability |
| CTLA-4 and Tregs | Binds with high affinity to CD80 on APC stopping binding with Tcells It also induces DC to porduce molecules that are toxic to Tcells |
| IPEX | Systemic autoimmunity Foxp3 mutation Will die within 1-2 years without treatment symptoms gut inflammation, autoimmunity, type 1 diabetes, thyroid disease, dermititis |
| M2 | Regulatory macrophages Produce TGFb Antiinflammatory promote wound healing and tissue repair |
| What do B cells do? | Secrete antibody act as APC Establish a memory population |
| Tcell dependant antibody production | Bcell takes up pathogen and presents it, Tcell bind, activate tcell to produce cytokines, B cell develops into a plasma cell |
| CD40L | Bcell uptakes pathogen, presents it and upregulates CD40L. Tcell activated and also upregulates CD40L which binds CD40L on Bcell Bcell develops into plasma cell |
| CD40L | Bcell uptakes pathogen, presents it and upregulates CD40L. Tcell activated and also upregulates CD40L which binds CD40L on Bcell Bcell develops into plasma cell |
| Spleen | Blood filter Red and white pulp |
| White pulp | Bcells and Tcells are organised into discrete regions of the white pulp. Bcells in follicles, Tcells in PALS Marginal zones contain macrophages and DCs |
| Germinal centres | Found in Bcell region of lymphnode or spleen Naive Bcells which encounter antigen moves to the boundary with Tcell areas Activated cells move to the follicle to form a germinal centre |
| Role of antibodies | Can neutralise toxins opsonisation to help ingestion by macrophage cause compliment activation |
| Somatic hypermutation | Occurs after antigen driven activation as part of the germinal centre response Point mutations, 50% of mutation in antibody at each division Requires AID |
| AID | Activation inducedcytidine deaminase |
| Affinity maturation | Good mutations then the Bcell survives Bad mutation apoptosis |
| Where does somatic hypermutation and antibody class switching occur | Germinal centres |
| Antibody classes | Different isotypes of constant regions of heavy chain |
| What three forms does antibody come in? | Monomer 2 sites dimer 4 sites pentamer 10 sites |
| IgM | 1st antibody after immunization strong activator of complement generally low binding strength |
| IgG | Monomer Can cross the placenta in blood, lymph and ecf major circulating antibody activate complement |
| IgD | Abdundant on Bcell surface like IgM Secreted function unknown |
| IgA | In blood, saliva, tears, breast milk, mucous dimers linked by jchain peptide |
| IgE | Most bound to receptors on granulocytes binding to Ige bound to mast cells causes degranulation and allergies |
| What drives class switching? | Tfh |
| What is initally produced in an immune response followed by what? | IgM IgA and IgG |
| What isotype do naive b cells express? | IgD and IgM |
| What is immunological memory? | Cells more specialised and more of them |
| Immunology memory is | A pool of specialised memory cells that develop during an immune response and persist without the antigen available naymore |
| Where do short lived plasma cells reside | lymph node or spleen |
| Long lived plasma cells reside in? | Bone marrow |
| What are long lived plasma cells a source | High affinity class switched antibody |
| Where do memory Bcells arise from? | The germinal reaction |
| Features of a memory Bcell | Express higher levels of MHCII and co-stimulatory molecules than naive Bcells Divide very slowly if at all Express surface IgG but do not secrete it Quickly regenerate antibody when they reencounter it |
| T memory cells | long lived cells that survive after the contraction of the effector phase |
| Features of T memory cells | Divide more frequently than naive t cells balance of proliferation and death dictates memory pool size IL7 and IL15 needed for survival |
| Why are T memory cell better? | They divide more and to lower antigen doses require less costimulation produce cytokine faster may be strategically positioned in tissue where infection might occur |
| Central memory | Express lymphnode homing molecules slower than effector memory cells to produce cytokine |
| Effector memory | Lack lymphnode homing molecule rapidly produce cytokine upon antigenic stimulation |
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