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Definition
| type of immunity that involves the production of antibody molecules in response to an antigen and is mediated by B-lymphocytes. |
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| type of immunity that involves the production of cytotoxic T-lymphocytes, activated macrophages, activated NK cells, and cytokines in response to an antigen and is mediated by T-lymphocytes. |
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Definition
the specific name for human MHC complex (human leukocyte antigen); (first discovered on human leukocytes), cell biology of these products contribute to class I and class II gene expression.
All species of mammals have a MHC; |
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Definition
| abundant dendritic cells in the skin that are part of immunity, they interact with Ag, engulf it, and phagocytose and then give the Ag peptides to helper t cells ; how does it find the t cell? It has to move; it migrates from the hypodermis to the lymphatic system in the lymph nodes, and then within the lymph node, that APC cell interacts with a t helper cell. |
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| NO they tend not to, thus they need cells to come to them, and there is the secondary lymphatic system (sites where there are organized numbers of lymphocytes) |
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| In the lymph node, there are many _______ and ________, so there is a greater opportunity for APC cell to find a helper t cell |
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Definition
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Term
| when langerhans cell first encounters Ag, it is said to be in what state? |
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Definition
quiescent state
if you look at factors that LH uses to activate t cell, some factors are reduced on the membrane surface in terms of their expression; however once Langerhans activates, it can then activate t cells much more efficiently |
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Term
| What is the density of a quiet langerhans cell in comparison to one that is active/trafficking to lymph node? |
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Definition
| Quiet Langerhans cell has certain density of class 2 molecules (relatively low), but as it trafficks on its way to lymph node, the class 2 signals are upregulated and then they can better signal helper t cells once they get into the lymph system (for antigen-specific stimulus) |
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Term
| what are 2 examples of secondary signals? |
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Definition
-Soluble-cytokines
-Receptors and ligands give more complete activation of lymphocytes |
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| Pattern recognition receptors are involved with with what type of immunity? |
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Definition
| membrane surrounding intact bacteria immediated after it has been engulfed into the APC |
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| once endosome immediately forms, what happens after? |
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Definition
that endosome migrates to interior of cell (certain changes occur to break down bacteria- pH drops and acid proteases degrade the Ag) general class of acid proteases are cathepsins.
Lipids, carbs and other structures in Ag are degraded by other enzymes but lets just focus on the proteins being degraded. |
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Definition
| general class of acid proteases inside the endosome |
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Term
| what are the genes specific to the MHC class II molecules? |
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Definition
1) HLA-DP3
2) HLA- DQ7
3) HLA-DR4
loci |
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Term
| How are the HLA-DP3 ,HLA- DQ7 and HLA-DR4 loci in class 2 MHC structured? (appearance/formation) |
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Definition
End terminal domain - alpha 1
Proximal domain - alpha 2
End terminal domain - beta 1
Proximal domain - beta 2 |
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| what is the structure of a class II molecule? |
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Definition
| a alpha chain w two extracellular domains and a beta chain with two extracellular domains |
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| professional APC’s consist of what types of cells? |
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Definition
| Macrophages, dendritic cells, b cells |
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| What are the 3 loci that encode MHC class II? |
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Definition
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| How are the MHC genes inherited? |
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Definition
Each person inherits one set of these genes from our mother (haplotype) and one from our father (haplotype) we express all of these , so it is codominant expression of all of these genes per each individual
(these genes that serve as basis for graft rejection) |
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Term
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Definition
| array of genes expressed on a particular chromosome that you inherit from mom, and they one from dad, expressed codominantly |
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Term
| what type of configurations can occur in gene regulation of MHC class II genes? |
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Definition
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Term
| How do you know if you inherited a DP haplotype from your mother and not your father? |
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Definition
-Use polymorphisms and numerically tag the molecules
Over many years we produce antibodies that interact with these polymorphisms
-also in terms of medicine, You can use sequence specific oligonucleotide typing to see if the donor has the same polymorphisms (so wont reject the graft) |
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Term
| Why do we need polymorphisms? |
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Definition
(to activate t helper cells);
-new pathogens are emerging all the time, if we all had the same APC type and they didn’t recognize one specific Ag then we could all be eliminated. Thus there is more genetic diversity to protect our human race |
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Term
| How do MHCs know how to recognize a peptide antigen a second time? |
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Definition
| (thymus expresses the antibodies) the t cells are educated to our own MHC type by the antibodies. |
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Definition
| these are proteins that cover up the peptide binding sites in the ER lumen so it doesn’t bind to things that it shouldn’t bind to (so it only binds to appropriate antigen) ; blocks binding site of newly synthesized class 2 molecules that are not ready to function yet |
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Term
| When you isolate class 2 molecules from ER and use gel electrophoresis what do you see? |
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Definition
separated by charge and size...
you can see one polymorphic spot for alpha chain and one for beta chain (different spots on the gel of electrophoresis)- and one keeps showing up on the same spot: this is the invariant chain. |
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Term
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Definition
| class 2 associated invariant peptide: piece of invariant chain that is bound in peptide binding site of class 2 MHC sites as the vesicle breaks off of the ER to fuse with the endosome. |
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Term
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Definition
| complex when the endosome fuses with the ER vesicle and their contents mix |
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Term
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Definition
| Found in endosomal vesicle, which removes CLIP from class 2 molecules, encoded in MHC and removes clip from MHC molecules (it DOES NOT transport molecules to the surface) (thus when the endosome and ER vesicle fuse, this molecule is able to take off CLIP from MHC complex |
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Term
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Definition
Peptides derived from native Ag will bind as long as the appropriate AA’s are present. Those unique AA’s that allow binding are called this....
this allows peptides from Ag to bind to MHC molecules) |
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Term
| Are there different types of MHCs in each APC cell? |
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Definition
| There are thousands of types of MHC types in each APC cell. Therefore that polymorphism allows for different peptides to be expressed on MHC molecules |
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Term
| If you are homozygous for any of the MHC class II loci, what happens to the variability of the peptides? |
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Definition
| you reduce the complexity/heterogeneity of these peptides |
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Term
| When does the invariant chain get processed ? |
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Definition
as ER vesicle fuses with endosomal vesicle;
CLIP’s get clipped off by HLA-DM, and the MHC molecules are free to bind to peptides in the MIIC complex |
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Definition
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Definition
| B cells, macrophages, dendritic cells |
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| MHC class one is encoded by 3 loci named: |
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Definition
1) B locus which encodes an alpha chain
2) C locus which encodes an alpha chain
3) A locus which encodes an alpha chain |
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Term
| if you crystallize class I and class II MHC's how would they look in comparison to one another? |
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Definition
| they look almost superimposable, however they are both very different ( virtually identical looking in structure, but actually they are very different in terms of components) |
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Term
| what is the very small domain called located on the class I structure? |
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Definition
beta2 microglobulin
(associated with each of the alpha chains encoded by A, B, and C loci)
For each alpha chain to fold properly, it must have an associated beta2microglobulin |
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Term
| what is the function of the beta2microglobulin structure in the class I MHC? |
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Definition
| This allows each alpha chain to fold properly. Without this chain, the MHC class I would not function properly |
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Term
| What region of the molecule do Ag proteins actually bind to for class II MHC structures? |
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Definition
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Term
| what structural domain do the Ag proteins bind to in class I MHC? |
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Definition
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Term
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Definition
- this is found in all cells, part of pathway of which proteins are degraded, (part of gene regulation of normal healthy cells) and if normal proteins are made abundantly, then extras are degraded by this structure and recycled for later use. This is a multicatalytic structure (tube like) and the degrading parts are in inside of the tube; chops up components into small peptides
Enzymes are directed to interior of tube |
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Term
| what class MHC is the proteasome located in? |
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Definition
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Term
| TAP (transporter associated with antigen processing/presentation) |
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Definition
| in class I MHC molecules, this is a transporter that allows cytosolic peptides to go into the ER lumen using some ATP |
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Term
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Definition
| transporter associated with antigen processing/presentation |
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Term
| in class I MHC producing cells, what happens once the degraded peptides are trasported into the ER? |
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Definition
| A vesicle pinches off from the ER and goes to the plasma membrane of the cell. The class I MHC bound to the peptides waits at the surface while waiting for the cytotoxic c cell recognition. |
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Term
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Definition
this prevents peptides from binding in ER lumen in class II MHC cells
called CLIP |
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Term
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Definition
| in class II MHC cell, once ER vesicle fuses with the peptide-containing endosome, then the CLIP invariant chains get clipped off by what enzyme (that had been in the endosome)? |
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Term
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Definition
| intracellular antigens (ex. virus) enters cell, proteins are made and proteins of Ag are processed/degraded in the proteasome. Peptides generated by proteasome go from cytosol to ER lumen by TAP protein (heterodimer in ER membrane) peptides brought into ER lumen through TAP to the class I molecules. Then an ER vesicle releases the complexes to the plasma membrane surface where Class I MHC is bound to the Ag peptide at the plasma membrane surface waiting to serve as signal |
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Term
| how big are class II molecules? |
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Definition
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Term
| how big are class I molecules in length? |
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Definition
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Term
| give more detail on how class II molecule looks like? |
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Definition
Floor of binding group of molecule is antiparallel. Side of floor is alpha helix,
Forms a super domain (2 alpha-helical sides)
Peptide binds right in the midde; open binding site (ends are NOT closed off)
(like a hot dog in a bun with the dog sticking out on both sides) |
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Term
| give a little more information about structure of class I molecule |
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Definition
ends are closed off, which limits size of peptide, peptide binding groove is smaller
(like a hot dog in a bun but with the dog staying well within the bun parameters) |
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