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31 Cards in this Set

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What is the key event in adaptive immunity?
The key event in adaptive immunity is the binding of T-cell to antigen.
What structures does the TCR recognize?
The TCR is responsible for recognizing a peptide of 9-16 amino acids in length that is derived from the antigen of interest. The TCR also recognizes the MHC molecule
What are the challenges to generating a repertoire of T-cell clones in adaptive immunity and how are these problems solved?
1. The great number of pathogens (somatic recombination). 2. Microbial pathogens can mutate around a sterotyped defense recognition system (alternative MHC molecules that bind different pathogen peptides). 3. Need to create T-cell clones prior to antigen encounter (use self proteins as surrogate molecules)
What determines the specificity of peptide binding?
The specificity of peptide binding is determined by the binding pockets of the MHC molecule that only bind certain amino acid side chains. MHC molecules are very polymorphic.
What are the two principles behind the large amount of diversity seen in MHC molecules?
MHC molecules are very polymorphic. The general strategy is the duplication of loci that code for the proteins and there are multiple alleles as well.
How many different loci are important in generating MHC molecules? How many alleles per loci are there?
6 different loci. HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DP, HLA-DQ. There are 100s of alleles per loci, thus the order of diveresity is 10^8
What is a potential problem in using self-proteins as a surogate for antigen in the production of T-cell clones?
The randomly generated T-cell clones could either be incapable of recognizing one's own MHC or strongly recognize self-peptides in self-MHC.
What are the two goals of clonal selection?
Production of T-cells that are non-reactive agains self, yet reactive agains non-self.
Describe what occurs during clonal selection in the Thymus.
1. Select clones that recognize self-peptide in one's own MHC molecules (+selection)
2. Eliminate clones that are overtly self-reactive with self-peptide in MHC molecules (-selection)
How do NK cells of the innate immune system play a role in thymic selection?
One of the roles of NK cells is to detect the decrease in the MHC portion of the self p-MHC.
What is a primary immune response?
Refers to T cell clones that have passed both positive and negative selection and are used by the immune system to then mount a response to non-self peptides that are analogously presented by self-MHC molecules and recognized by the TCR of the T-cell
Name the two fundamental classes of pathogens that the immune system must recognize and respond to.
Viral peptides on MHC I molecules
Bacterial peptides on MHC II molecules of APCs.
If a peptide is cytosolic what type of MHC molecule does it get presented on? If it is endocytosed or ingested what type?
Cytosolic peptides will be presented on class I MHC molecules and presented to CD8+ CTLs for killing. Digested or endocytosed peptides are displayed on MHC II molecules and presented to CD4+ T-cells
Describe the structure of the MHC Class I and MHC Class II molecules.
MHC I has 3 alpha and 1 B2 domains with alpha 1-2 binding cleft and closed ends. MHC II is symmetrical with 2 alpha and 2 beta, each with 2 globular domains. Alpha1 and beta 1 domains form the binding cleft
How do peptides bind to the MHC Class I molecules?
Peptides must be bound in the same orientation (L->R; amino->carboxy) every time. Side chains interact. Binds the 2nd and 9th amino acids and MHC I P2 and P9 are homologous amino acids
How do peptides bind to the MHC Class II molecules?
Side chains in the middle of the peptide (P4,P6) tether it to MHC II molecule with hydrogen, electrostatic, and van der Waals interactions. Peptides are free and length is variable, but same amino->carboxy orientation
What is polygeny and polyallelism and how do they relate to MHC molecules?
polygeny is the duplication of the gene locus resulting in multiple loci. it increase diversity on a individual level. polyallelism is the development of multiple alleles at a gene locus among individuals in a species. This accounts for MHC diversity on a population level
How does MHC diversity affect survival?
The individual with the rarest allele has the best chance to survive an infection
On what chromosome is the MHC gene located?
MHC gene is located on Chromosome 6.
What HLA loci produce alleles for MHC I and MHC II molecules?
HLA-A,B,C --> MHC Class I
HLA -DR, DQ, DP --> MHC Class II
A large number of immune self-peptides are used up to select and education the duplicated MHC alleles. What happens to the repetoire of each allele?
As the number of gene loci duplications increases the size of immune self increases and mandates more negative clonal selection across all repetoires during repetoire formation. This reduces the size of the repetoire for each allele.
What is the practical maximum of loci per for each MHC I and MHC II?
The practical maximum is about 3 loci for each class of MHC. Because both maternal and paternal alleles are expressed the total number is 12 HLA loci expressed.
What is genotype?
The collection of genes in an individual usually referring to a small segment of a chromosome
What are alleles?
The alternative forms of a gene found in different individuals
What are allotypes/allomorphs?
The different protein forms encoded by alleles
What is a haplotype?
The genes contributed by one parent usually referring to both class I and class II loci
What does linkage refer to?
Linkage refers to the genetic distance between loci
What is linkage disequillibrium?
certain alleles of a haplotype are found together significantly more or less frequently than expected by chance
What is the genetic unit of the HLA system?
The genetic unit is the allele with each defined by its own DNA nucleotide sequence. These alleles are grouped into specific families
In what genetic fashion are MHC molecules presented?
Co-dominant. Which is important in transplantation because a parent will always be a one-haplotype mismatch
In what type of transplantation do you have to worry more about haplotype matching versus blood antigen matching?
In bone-marrow transplants it is important to get haplotype matching because there is a strong role of hematopoetic cells in such transplantations procedures. Heart and liver rely more on immunosuppression so blood group matching is the primary concern