Karteikarten
Immunogenetics
Karten in diesem Stapel (38)
- 1What 3 things do immune response genes control1 - immunity to infection
2 - response to vacc
3 - susceptibility to immune-mediated disease (autoimmune disease) - 2What are the immune response genes involved in innate immunity- toll like receptors (recognition of common microbial components)
- NRAMP1 (phagosome function)
- cytokines e.g. IL-12 and TNF-a - 3What are the immune response genes involved in adaptive immunity- MHC
- CTLA4 (tolerance)
- transcription factors e.g. Tbet, GATA-3
- cytokines e.g. IFN-Y, IL4 - 4Give 2 features of innate immune response genes and how does this occur1 = genetic variability in TLRs between species
- evolutionary adaptation to environmental microbial flora
-TLRs evolved to adapt to particular environment
2 = polymorphisms within species - 5How does polymorphisms within species occur- resistance vs susceptibilty to pathogens e.g. NRAMP1 and canine leishmaniosis
- response to vaccination (adjuvant effects)
- susceptibility to immune mediated disease e.g. TLR4/5 and IBD - 6What does MHC variability determine in adaptive immunity- whether or not the animal responds adequately to pathogen e.g. quantitative effect
- can influence balance of the immune response (Th vs Treg/TH1 vs TH2) e.g. qualitative effect - 7Give the mechanism of antigen presentation in MHC I- cell taking protein antigen in cytoplasm - intracellular
- degraded into peptides by proteosome
- peptides migrate to ER
- peptides loaded onto newly synthesised MHC I
- travels by golgi in secretory vesicles
- expressed on cell surface - 8Give the mechanism of antigen presentation in MHC II- protein antigen in extracellular fluid
- endocytosed into vesicles
- lysosomal digestion into peptides
- loaded onto newly synthesised MHC II
- complex transported onto cell surface for presentation - 9What is the structure of the MHC I- a 1,2,3 domains
- stabilised by B2m protein - not v variable = scaffolding protein
- junction between a1 and a2 = peptide binding groove - 10How does the structure of MHC II differ- encoded by 2 genes
- a1 and b1 subunits - 11Describe the surface view of the peptide binding groove- helical walls with B pleated sheet floor
class I = ends closed
class II = ends open - 12Describe the side view of the peptide binding groove- peptides anchored to MHC
- key residues that determine binding
- any peptides that has residues to it can bind
- determines T cell receptor interaction - 13MHC molecules must be able to present a wide variety of peptides from different pathogens. What 3 characteristics allow them to do this1 - polygenic - 3 x MHC I and 3 x MHC II loci
2 - co dominant expression - 3 from mother and 3 from father = 6 x MHC I and 6 x MHC II genes expressed
3 - polymorphic - lots of alleles, most individuals are heterozygous = 6 different MHC I and 6 different MHC II - 14What is the advantage of evolutionary drive to maintain heterozygosityincrease MHC repertoire
- 15What happens if there are less than 6 MHC I and MHC II molecules- more susceptible to infection
- 16What happens if there are more than 6 MHC I and MHC II molecules- autoimmune disease - overloading of the immune system
- 17What is the outcome if there are polymorphisms in MHC II exon 2- altered amino acid sequence at peptide binding groove
- variability predominantly at peptide binding groove
- alters amino acids - influences peptide that can bind - 18Give an example of an event that caused loss of MHC alleles and what are the implications of thisSpanish flu
= huge loss of MHC alleles
- unable to pass on alleles
- bottleneck effect - influence future generations
- takes hundreds of years to get diversity back - 19What do different MHC molecules bind todifferent sets of peptides containing specific binding motifs
- 20T/F there is flexibility in terms of where a peptide sitsT
- 21Why is MHC diversity important for protection against infection- important to prevent extinction
- change in 1 amino acid affects anchor residue
- simple mutation would cause evasion of detection from immune system
- if MHC diversity - single mutation wont prevent presentation - 22Give an advantage of MHC diversity- evolutionary survival mechanism - virus mutations which alter peptide structure can interfere with MHC binding and antigen presentation
- some individuals with particular MHC alleles might die
- large diversity in population ensures that some will always present and survive - 23Give a disadvantage of MHC diversity- individuals can carry MHC alleles that could make them relatively immunodeficient or hypersensitive
- 24What 3 things have we learnt from studying different animals1 - MHC genetics of different species can be different
2 - some rely on polygeny with less polymorphism
3 - some have less polygeny and rely more on polymorphism - 25What is found in modern dog breeds- phenotypic uniformity with a high degree of genetic homogeneity
- 26What 2 things do dogs have a unique combination of1 - interbreed diversity
2 - intrabreed uniformity - 27What are the 3 dog leukocyte antigen - MHC IIDRB, DQA, DOB
- 28What are the 4 consequences of lack of MHC diversity in dogs1 - poor gene pool of MHC molecules can lead to problems
2 - infection e.g. african wild dogs highly susceptible to distemper
3 - vaccination e.g. rottys have poor response to rabies vacc
4 - immune mediated disease e.g. cockers prone to developing autoimmune disease - 29What are the proposed theories behind rottys poor response to vaccine- breed only has 2 DLA haplotypes 1,3,4 snd 6,5,7 - poor gene pool of MHC alleles
- proposed theory - poor positive selection in thymus or poor antigen presentation - 30What can we learn from comparative MHC studies- evolutionary relationships between different mammal groups
- susceptibility to infectious disease in endangered species
- establishing breeding programmes to maintain diversity in endangered species - 31What similarities have been found between grey wolves and dogs- similar MHC alleles
- 32What are the consequences of MHC restriction in endangered species and give an example- when population become small - MHC gene pool diminishes
- increases susceptibility to infection
- example - serengeti lions (1993-97) - 1/3 of the lions in serengeti died from distemper - 33What are the reasons for studying mhc genes in the eu badger- will badger mhc genes play a role in immunity to bovine tb
- will badger mhc genes play a role in response to bcg vaccination
- what will influence mhc diversity in a badger population
- will selective culling influence mhc diversity - 34What is the link between ctla-4 and human autoimmune disease- ctl4 polymorphisms implicated in Grave's disease, autoimmune hypothyroidism, autoimmune addisons, type 1a diabetes mellitus
- SLE, rheumatoid arthritis, MS
- variability in breaking system - hyper responsive/hyper reactive - 35What are the effects of CTLA4 polymorphisms on autoimmunity- adverse effect on regulatory cells which constitutively express CTLA4
- soluble CTLA4 generated by splice variant
- sCTLA4 functions to inhibit CD80/86 and CD26 interaction
- reduced sCTLA-4 mRNA with susceptible alleles - 36Give the features of canine CTLA4- 15 single nucleotide polymorphisms (SNPs) in the promoter region
- no polymorphism in coding region
- association with susceptibility to diabetes in some breeds e.g. samoyeds
- association with susceptibility to hypoadrenocorticism in cockers - 37What are the implications of CTLA4 promoter polymorphism- haplotype 3 found in boxer - DIABETES RESISTANCE
- haplotype 8 found in samoyed - SUSCEPTIBLE TO AUTOIMMUNE AND DIABETES
- haplotype 8 found commonly in dogs with addisons - 38What is the role of CTLA4 in canine autoimmunity- some polymorphisms are located in areas that might affect transcription factor binding
- e.g. NF-AT
- differences in gene expression
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- BSc Pathology Karteikarten am Immunogenetics, erstellt von Teresa Richards am 05/12/2016.
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- Teresa Richards
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