Flashcards in Immunology 4 (Kyle) Deck (72)
What is the Major Histocompatability Complex?
A large cluster of genes encoding glycoproteins. They were initially identified through studies of transplant rejection.
How do T-Cells recognize antigens?
T Cells only recognize peptides bound to MHC molecules.
MHC Molecules come in Type 1 and Type 2
What is the major difference between type 1 and type 2 MHC molecules?
While both are heterodimers Class one is an MHC protein with a B2 microglobin where as type two is a heterodimer with two MHC complexes.
Describe the peptide binding to type 1 MHC molecules.
The binding cleft of MHC class 1 molecules is closed.
How is peptide bonding stabilized in class 1 MHC molecules?
Peptide binding is stabilized by contacts between the aminoterminal and carboxyterminalends of the peptide and invariant sites found at the ends of the binding proteins.
Can MHC molecules bind to different proteins?
Yes Each MHC molecule can bind to many different peptides.
Do MHC class one and MHC class two have different peptide binding characteristics?
Yes MHC class one and MHC class 2 have different binding characteristics.
Describe the binding cleft of MHC class 2 molecules.
MHC class 2 molecules have an open binding cleft. The ends of the peptide can hang over the edge of the cleft like a hot dog in a bun.
How is binding stabilized in MHC class two MHC molecules?
Peptide binding is stabilized by contacts between the peptide backbone and conserved residues that line the MHC class 2 binding groove.
Compared to MHC class 1 the ability of MHC class 2 to bond to peptides is
Less Restricted because it can accept peptides of much bigger lengths.
What is the TAP transporter complex?
Transports degraded proteins from the cytosol into the endoplasmic reticulum.
What is the source of the peptides that get loaded on the mHC class 1 molecules?
The peptides are derived from endogenous peptides.
What happens when a MHC class one is not loaded with a peptide?
Without a peptide the mHC class 1 molecule will become largely unstable and be degraded rapidly and recycled.
When will nonself peptides be loaded on MHC type 1 molecules?
At a time of infection when many nonself peptides are present in the body.
Where do MHC class 1 molecules bind with their peptides?
In the Endoplasmic reticulum. It is then passed to the golgi and is displayed on the cell surface via a secretory vesicle.
Where do MHC class 2 molecules bind to their peptides?
The MHC class 2 molecule leaves the ER and goes to the GOLGI where it is packaged and secreted in an excretory vesicle which fuses with an phagosome containing degraded antigen peptides where they bind and get transported to the cell surface.
How are MHC class 2 molecules prevented from binding peptides in the Endoplasmic reticulum?
The binding site is blocked by an invarient chain .
Where is this invarient chain degraded?
The invariant chain is degdaded in the phagosome leaving a clip fragment which prevents binding of peptides in the vesicle
How is the Clip fragment released?
HLA-DM facilitates CLIP removal which will allow peptides to bind the MHC molecule.
What cells are MHC class 1 molecules expressed.
All nucleated cells in the body however are relatively low in neural tissue. Neural cells do not regenerate so you do not want them being attacked unless completely necessary.
What cells to MHC class 2 cells present to?
Helper-T (CD4-T cells) so MHC class 2 molecules are only present in antigen presenting cells,
CD8-T cells recognize peptides bound to ________________ ?
MHC Class 1 cells.
CD4-T cells recognize peptides bound to _________ ?
MHC class 2 Molecules.
_____________ immune responses are best for clearance of Extracellular pathogens.
Ab-Mediated Immune response
____________ immune responses are best for clearance of intracellular pathogens.
T-Cell mediated immune responses
What is a polygeny?
The existance in the genome of several different genetic loci encoding structurally similar proteins of identical function ( isoforms)
What is a polymorphism?
(Genetic) : The existence of two or more forms (alleles) of a given gene within the population (variatne alleles occure at a frequency of at least 1%)
How many MHC class 1 genes are there on each chromosome?
3 ( HLA-A HLA-B HLA-C)
How many MHC class 2 genes are there on each chromosome?
3 ( HLA-DP HLA-DQ HLA-DR )
Are MHC Class 1 and 2 genes polygenic?
Yes The more peptides that MHC molecules that are expressed the more peptides you will be able to present to T-Cells resulting in a more functional immune response.
What is the maximum number of MHC molecules expressed per person?
6 different MHC Class 1
48 Different MHC class 2 molecules
What are the minimum number of MHC molecules that can be expressed?
3 Different MHC class 1 ( you would be homozygous at the three loci for MHC 1)
3 Different MHC class 2 ( There are six different MHC class 2 loci )
What are the differences in MHC class 1 polymorphisms?
The peptide binding groove.
What chromosome are MHC class 2 molecules located on?
What is body odor a function of ?
MHC haplotype. Women are attracted to men with body odor that is most different from theirs. Thus the MHC haplotype is most different and the offspring will have the strongest immune system.
What are the two chains that compose MHC Class 1 molecules ?
In MHC Class one molecules what is the Alpha Chain responsable for?
The alpha domain contains the binding domain for the antigen and the portion of the molecule that spans the membrane.
Describe the structure of MHC Class 2 molecules.
The MHC Class 2 molecules consist of an Alpha Chain and a Beta Chain. Both are glycosylated transmembrane proteins that have two domains.
What is the difference in the binding grooves of the MHC 1 and MHC 2 molecules?
The binding groove of MHC 2 molecules is open at both ends. MHC 1 molecules are closed on both ends.
Describe the specificity of MHC molecules to bind to peptides?
MHC molecules must be able to bind strongly to a diverse array of peptides. The binding is so strong that when purified they often associate together.
By what mechanism to peptides bind to the binging region of MHC molecules?
MHC molecules bind peptides by recognizing general features of the peptide. The binding cleft of MHC moleculeshave pockets where amino acid residues of a particular structure can "Anchor" the peptide to the MHC molecule.
What is more important for MHC binding, the sequence or the anchor residues?
The anchor residues.
What MHC molecule is most promiscuous in its binding to peptides?
MHC Class 2, because it can accommodate longer peptides due to its open binding cleft.
What stabilizes peptide binding to MHC Class 1 molecules?
Binding is stabilized by contacts between Amino Terminal and Carboxy Terminal ends of the peptide and invariant sites found at the ends of the binding groove?
How is peptide binding in MHC Class 2 molecules stabilized ?
MHC Class 2 molecues do not have invariatn sites at the C terminal and A terminal ends of the binding groove (IT IS AN OPEN BINDING GROOVE) The peptide is anchored in place by interactions between the protein side chain and the binding pockets in the groove.
What is antigen processing?
The degradation of proteins into peptides that can bind to MHC molecules for presentation to T cells. All antigens must pe processed into peptides before they can be presented via MHC molecules.
Where does antigen presentation take place?
In the 1. Cytosol and 2. endocytic vesicles
What degrades a cytosolic antigen into peptide fragments?
After the antigen is degraded by the proteosome how does it make it to the MHC molecule?
Peptides produced by the proteosome are actively transported to the lumen of the endoplasmic recitulum where they bind to MHC Class 1 molecules.
How does the fragment get transported from the cytosol to the ER ?
TAP Transport complex
Can antigens be degraded by proteosomes when they are confined to endocytic vesicles?
No, they are degraded by endosomes and lysosomes
Peptide fragments within endocytic vesicles bind to what type of molecules?
They bind to MHC class 2 molecules and are transported to the cell surface.
What is the invariant chain in the MHC 2 molecules?
The invariant chain (same in everyone) associates with the newly synthesized MHC 2 molec. and prevents peptides that are in the ER from binding to the binding groove of the MHC 2.
What happens to the invariant chain?
The invariant chain +MHC2 complex travels to an acidified vesicles where the invariant chain is degraded leaving only a clip (Class 2-associated invariant chain peptide)
What happens to the CLIP protein?
The CLIP, which is attached to the binding groove, interact with the vesicle membrane protein the clip peptide is released.
When the CLIP protein is released from the binding cleft what must happen to prevent the MHC molecule from being degraded.
A peptide must bind to the cleft of the MHC 2 molecule. This must happen quickly to prevent the molecule from being degraded.
What are the 3 steps of the processing of intracellular pathogens?
**Viruses Bacteria Pathogens in ANY Cell
1. Processed by proteosomes in the cytosol of the infected cell.
2. Peptides bind to MHC class 1, and the complex are transported to the cell surface.
3. Antigens are presented to CD8+ cells
What are the three steps for the processing of intracellular pathogens?
***Pathogens are endocytosed by Dendritic Cells Macrophages or B cells.
1. Endocytosed antigen processed within endocytic vesicles
2. Peptides bind to MHC 2 molecules and the MHC peptide complex is displayed on the cell surface,
3. Peptides are presented to antigen-specific CD4+ cells.
MHC Class 1 molecules present peptides derived from pathogens in the ________ ? And present them to __________ cells.
Cytotoxic Killa Cells (CD8+)
MHC 2 molecules present peptides derived from ( ? ) and present them to ( ? )
Peptides derived from endocytic vesicles and presents them to CD4+ Helper T Cells
What type of cells display MHC Class 2 molecules?
Antigen presenting cells ( macrophages, dendritic cells, and B cells) because their primary role of Helper T cells is to activate other cells of the immune system.
What organ has MHC 2 molecules in it and what role do they serve?
Thymic cortical epithelial cells. They participate in the positive selection of MHC-binding thymocytes during the thymic maturation process.
What cells have MHC 1 molecules ?
All nucleated cells, this is important because CTL's are programmed to kill any cell that presents their cognate antigen via MHC class 1 molecules.
What is the most polymorphic gene in the mammalian genome?
MHC 1 and 2 genes.
Are there rearrangement or somatic alterations in MHC genes?
No The MHC class 1 and 2 are encoded on conventially stable genes.
What is an allele?
A naturally occuring variant of a particular gene
What is an isoform?
The different forms of a protein that are encoded by the alleles of a gene or by different by closely related genes.
What is a haplotype?
For a linked set of polymorphic genes the set of alleles carried on a single chromosome 6
How many isoforms of MHC 1 molecules are there.
There are six distinct MHC 1 isoforms
What are the MHC 1 molecules that present peptide antigens to T cells ?
HLA-A, HLA-B, HLA-C.
How many isoforms of MHC 2 molecules are there?