Immuno 5: MHC Flashcards Preview

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Flashcards in Immuno 5: MHC Deck (51)
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1
Q

What is the Major Histocompatability Complex?

A

A large cluster of genes encoding specialized glycoproteins; many functions
Initially identified through studies of transplant rejection. Has a role in antigen presentation to T cells.

2
Q

T/F: T cells ONLY recognize peptides bound to MHC molecules.

A

True

3
Q

MHC class I molecules are homo or heterodimers?

A

Heterodimer

4
Q

What is beta-2-microglobulin?

A

A protein that is not encoded within the MHC I complex gene that encodes the rest of the heterodimer but is found as one subunit (of 4) of the MHC I complex.

5
Q

How many domains are found in the alpha chain of the MHC I complex? (3 of 4 subunits).

A

3 (alpha1, 2, 3)

6
Q

What part of the MHC I complex anchors it into the cell membrane?

A

The alpha 3 domain, has transmembrane region that anchors the chain into the cell membrane.

7
Q

What secondary structure is characteristic of the peptide binding cleft of the MHC I complex?

A

extended alpha helices of alpha 1 & 2 domains

8
Q

What differentiates the MHC class II molecule from the class I molecule?

A
1- The MHC class II molecules are heterodimers that are composed of an alpha (1,2) and a beta (1,2) chain (MHC I has 3 alpha and a beta-2-microglobulin subunit. 
2- The ends of the binding clefts of class II molecules are open (hot dog in a bun model), class I are closed.
9
Q

Are both the alpha and beta chains encoded by the MHC Class II locus?

A

Yes.

10
Q

In the MHC class II molecule, what two domains come together to form the peptide binding cleft?

A

Alpha 1 and beta 1

11
Q

In the MHC class II molecule, what two domains have transmembrane regions that anchor the chains into the host cell membrane?

A

alpha 2 and beta 2

12
Q

What characteristic of MHC I and MHC II molecules makes them similar?

A

The alpha helices that make up the peptide binding domains and the alternating beta sheets that make up the floor of the peptide binding groove.

13
Q

What is the most important function of the MHC moletules?

A

To bind to peptides and present them to T cells

14
Q

T/F: MHC molecules bind to antigen peptides in a promiscuous fashion.

A

True

15
Q

T/F: MHC molecules bind to a limited number of peptides (they are very specific and picky).

A

False, remember, they are promiscuous! Sluts. MHC molecules are sluts.

16
Q

Regarding the MHC class I molecule’s peptide binding groove, how large of a peptide (in amino acids) will be accommodated by the groove?

A

peptides 8-10 amino acids in length

17
Q

What is the name for the amino acid residue with shared features among different peptides that will assist in locking the peptide into the peptide binding groove of the MHC molecule?

A

Anchor residue

18
Q

Do longer peptides bind to MHC class I or II molecules and why?

A

MHC class II. They have open ended peptide binding grooves that require a minimum of 13 AAs. The peptide will actually not fit completely within the binding groove.

19
Q

The MHC class I precessing and presentation pathway primarily presents antigens that are derived from intracellular or extracellular pathogens?

A

Intracellular pathogens

20
Q

The MHC class II precessing and presentation pathway primarily presents antigens that are derived from intracellular or extracellular pathogens?

A

Extracellular pathogens

21
Q

What is a proteosome?

A

A complex that takes up and degrades proteins that are targeted for destruction within the cytoplasm.

22
Q

What is the TAP transporter complex?

A

A complex that transports peptide products of the proteosome from the cytosol into the lumen of the ER.

23
Q

What is the significance of the TAP transporter complex in relation to immunology?

A

It participates in the process of loading peptides onto newly synthesized MHC class I molecules as it moves peptides (products of the proteosome) from the cytosol to the ER lumen.

24
Q

The TAP transporter complex associates with this complex that helps load the peptide from the proteosome onto the MHC molecule.

A

peptide-loading complex

25
Q

The TAP transporter can transport and assist in loading how many peptides at a time to the MHC with help of the peptide-loading complex?

A

One

26
Q

Are the MHC class I molecules stable if they have not been loaded with a peptide as they pass from the ER to the Golgi to the cell surface?

A

No.

27
Q

A deficiency of TAP transporter proteins will result in a person having very few cells that bear __________ on their surface.

A

MHC class I molecules

28
Q

In cells that are not antigen presenting to T cells but who do place MHC class I molecules with antigen peptides on their surface, what happens to them?

A

An effector T cell with specificity for that peptide can now potentially recognize the cell as an infected cell and effect its destruction via apoptosis.

29
Q

T/F: the vast majority of the peptides that are loaded onto MHC class I molecules are derived from pathogens.

A

False. The vast majority are derived from self proteins. Therefore, it is critical that all self-reactive T cells be removed from the T cell repertoire.

30
Q

Are MHC class II molecules loaded with cytosol-derived peptides as they are trafficked through the ER?

A

No.

31
Q

What blocks cytosolic peptides from loading into the MHC class II molecule?

A

The invariant chain protein. Part of this protein fits into the peptide binding groove of the MHC class Ii molecule and remains associated with the class II molecule until it has completed its passage through the ER and golgi app. and it resides in cytosolic vesicles. Once in the cytosolic vesicle, the invariant chain is cleaved leaving behind a short peptide called the CLIP fragment that continues the job of blocking cytosolic peptides.

32
Q

What provides the MHC class II molecule with an antigen peptide from the extracellular milieu for presentation to naive T cells?

A

a phagolysosome, containing materials collected from the extracellular milieu.

33
Q

The vast majority of all peptides ever loaded onto MHC class II molecules are derived from self or antigen proteins?

A

Self. Only during an infection will that be a source of non-self proteins for leading onto MHC class II molecules.

34
Q

Virtually all cells of the body express MHC class I except for these notable exceptions:

A

Erythrocytes- None

Neuronal cells- few

35
Q

MHC class II expression is restricted to ________________ .

A

professional antigen presenting cells

  • dendritic cells
  • B cells
  • Thymic epithelium
  • macrophages (some)
36
Q

CD4 T cells only recognize peptides bound to MHC class _____ proteins.

A

MHC class II proteins

37
Q

CD8 T cells only recognize peptides bound to MHC class ____ proteins.

A

MHC class I proteins.

38
Q

The primary role of the CD4 effector T cells is to:

A

Drive development of antibody responses

39
Q

__________ -mediated immune responses are usually the best for clearance of extracellular infections, and __________ T cells are required for priming acquired antibody responses.

A

antibody-mediated; effector CD4+ T cells

40
Q

Clearance of intracellular pathogens is mediated primarily by a ___ ____-mediated immune response.

A

T cell-mediated

41
Q

Intracellular pathogens’ antigenic peptides will be presented to ______ T cells by the MHC class ____ molecule.

A

CD8 T cells; MHC class I

42
Q

What is polygeny?

A

The existence in the genome of several different genetic loci encoding structurally similar proteins of identical function (isoforms).

43
Q

What is a polymorphism?

A

The existence of two or more forms (alleles) of a given gene within the population.

44
Q

T/F: both MHC class I and II expression is monogenic.

A

False. Both expressions are polygenic. The loci encoding MHC complex proteins are found in multiple genes.

45
Q

On each copy of chromosome 6 that a person inherits, there are (how many?) ____ loci that encode MHC class I molecules?

A
  1. HLA-(A, B, C)
46
Q

On each copy of chromosome 6 that a person inherits, there are (how many?) _____ loci that encode MHC class II molecules?

A
  1. HLA-(DP, DQ, DR)
47
Q

T/F: the MHC genes are the most polymorphic within the human genome.

A

True

48
Q

If a person inherits heterozygously at HLA-A, HLA-B and HLA-C, that person will express how many distinct isoforms of MHC Class I on all nucleated cells in their body?

A

6.

1 from each of 3 loci on each chromosome (2 total) inherited from mom & dad.

49
Q

Briefly describe the basis of transplant rejection.

A

Any particular person will only be tolerant to the MHC class I or MHC class II isoforms that they have inherited and express on their cells. Each person will have T cells in their repertoire that will recognize determinants derived from any MHC isoform that they do not express on their cells. Recognition by a T cell will initiate an immune response that is what we see clinically as “rejection”.

50
Q

Is it possible for alpha chains to pair with beta chains from a different locus?

A

No.

51
Q

Is it better to have a diverse array of isoforms of MHC class I & II?

A

Yes. The more isoforms you express, the higher the number of peptides that you will be able to present to naive T cells and the better your immune system will be at fighting infections.