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Immunology Exam 1, Part 5
Antigen Presentation and the MHC
38
Immunology
Professional
02/02/2012

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Cards

Term
Define HLA
Definition
Human Leukocyte Alloantigen- discovered in the 1960s to be the same thing as the MHC complex
Term
Define MHC
Definition
Major Histocompatibility Complex, Closely linked genetic loci on the short arm of chromosome 6 which encode for the alloantigens of major importance in allograft compatibility (MHC = HLA Complex).
Term
List the three Class I HLA proteins
Definition
HLA-A, HLA-B, HLA-C
Term
List the three Class II HLA proteins
Definition
HLA-DR, HLA-DQ, HLA-DP
Term
What is the role of Class I HLA proteins?
Definition
Presentation of antigen directly to CD8+ T cells
Term
What is the role of Class II HLA proteins?
Definition
Presentation of antigen directly to CD4+ T cells
Term
Define Class III HLA proteins
Definition

Soluble antigens including several Complement components, Tumor Necrosis Factor, etc

 

 Not transplantation antigens and not directly involved in immune regulation

Term
List the Class I Accessory HLA proteins
Definition
HLA-E, HLA-G, HLA-F
Term
List the Class II Accessory HLA proteins
Definition
HLA-DM, HLA-DO
Term
What is the role of Class I HLA accessory proteins?
Definition
Form ligands for NK cells

(Except HLA-F, function unknown)
Term
What is the role of Class II HLA accessory proteins?
Definition
Regulate peptide loading on HLA-DR, -DP, and -DQ
Term
Define haplotype
Definition
The unit of closely-linked alleles on each chromosome that expresses HLA antigens
Term
Describe how parental haplotypes are expressed
Definition
Each individual inherits a maternal haplotype and a paternal haplotype and, because the HLA genes are co-dominant, expresses all of the inherited HLA antigens

Each individual expresses 12 HLA specificities.
Term
Define HLA typing
Definition
Determining the HLA antigens possessed by an individual using DNA analysis
Term
What are some uses of HLA typing?
Definition
Transplantation — histocompatibility testing

Paternity testing

disease associations

anthropology
Term
What are the odds of sharing both haplotypes with a sibling?
Definition

25% (based on Mendelian genetics)

50% chance of sharing just 1 parent haplotype

25% chance of sharing none

Term
What are the odds of sharing haplotypes with an unrelated donor?
Definition
1:20,000-25,000
Term
Where are MHC Class I proteins found?
Definition
Surface of all nucleated human cells

(as many as 106 molecules/cell)
Term
What are the principle antigens recognized in allograph rejection?
Definition
MHC Class I proteins
Term
Describe the pathway that Class I MHC proteins take to present immunogens
Definition
1. Virus infects cell
2. Viral proteins synthesized in cytoplasm
3. Fragments bind to MHC in ER
4. Transport to cell surface
5. Cytotoxic T cell recognizes complex and kills infected cell
Term
What are the two proteins within the MHC class I complex?
Definition
HLA Glycoprotein (MW 44,000)

b2 Microglobulin
Term
How many types of MHC Class I molecules are expressed per individual?
Definition
6: 2 each of HLA-A, HLA-B, HLA-C

(one type of each from each parent)
Term
What protein domain of MHC I does CD8 react with?
Definition
α3
Term
Where are MHC Class II proteins found?
Definition
Primarily on the surface of antigen-presenting cells (APC)

Monocytes/macrophages, B cells, dendritic cells
Term
What is the main role of class II MHC?
Definition
Generating helper T cell function that is essential for most immune responses
Term
Describe the protein chains in MHC II
Definition
Heterodimer, each with 2 extraceullar, transmembrane, and intracellular segments.

First domain of each chain (a1+b1) form the protein-binding site.
Term
How many types of MHC Class I molecules are expressed in an individual?
Definition
6: 2 each of HLA-DP, HLA-DQ, HLA-DR

(one type of each from each parent)
Term
What protein domain of MHC II does CD4 react with?
Definition
β2 domain
Term
Define antigen presenting cell
Definition
Cells that express MHC class II proteins and present antigens to CD4+ T cells.

These are sometimes called “professional APCs"
Term
Are phagocytes more important in primary or secondary immune responses?
Definition
Secondary responses, because opsonized particles are much more efficiently phagocytosed
Term
What is the most important APC in the primary immune response?
Definition
Dendritic cell- it is highly efficient and highly dispersed, motile, and spread throughout the body to present to T cells
Term
Are B cells more important in primary or secondary immune responses?
Definition
Secondary, since they capture specific immunogens then multiply during further exposure
Term
What is the name of the pathway of MHC I presentation?
Definition
Cytosolic pathway
Term
What is the name of the pathway of MHC II presentation?
Definition
Endocytic pathway
Term
List the steps in the pathway for MHCII to present to helper T cells
Definition
1. APC takes up pathogen
2. Pathogen is taken apart
3. Pathogen proteins are cut
4. Peptides bind to MHC and go to cell surface
5. CD4 receptors bind to MHC II
Term
List the steps in the endocytic pathway for B cells to be activated by helper T cells
Definition

1. Surface IG bind bacteria

2. Cell engulfs and degrades

3. Peptides bind to MHC II in endocytic vesicles

4. Transport to cell surface

5. Helper T recognizes complex and activates B cell

Term
Define MHC restriction
Definition
T-cell receptors for the specific complex of a particular peptide bound to a particular MHC molecule.
Term
How is MHC and disease susceptibility related?
Definition
There is a statistical association between the susceptibility (or resistance) to some diseases — infectious and especially autoimmune—and the occurrence of HLA alleles.

The association is never 100% and the mechanism(s) of the relationships are unknown.
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