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IMMUNOLOGY: CMOD-Week 2 > (06) MHC > Flashcards

(06) MHC Flashcards

1
Q

T or F: MHC plays a big role in transplant rejection

A

True

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2
Q

MHC

  • what chromosome?
  • What macromolecules make it up?
A
  • Chromosome 6

- Glycoproteins

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3
Q

What binds MHC?

A

T cells bind after the MHC presents the PEPTIDE

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4
Q

MHC class I structure:

  • Subunits
  • functional parts
  • encoding
A

Overall - Heterodimer

Alpha 1 and 2
- Creates binding cleft

Alpha 3
- contains transmembrane domain

Beta 2
- Not encoded in the the MHC complex

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5
Q

MHC Class II structure:

  • Subunits
  • Functional Parts
  • encoding
A

Overall - Heterodimer

Alpha 1 and Beta 1
- binding domains

Alpha 2 and Beta 2
- transmembrane domains

**All are encoded at the MHC locus

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6
Q

Why are MHC molecules able to present all 10^18 peptides that T cell receptors can recognize?

A
  • They binding in a promiscuous fashion, MUCH LESS SPECIFICITY
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7
Q 
How big are the peptide fragments presented by MHC class I? 
- what determines this cut-off?
A
  • 8-10 amino acids long
  • Bound peptide interacts with the edges of the binding pocket that contains invariant contacts with the N and C terminal ends of the peptide
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8
Q

What are anchor residues in MHC class I?

A
  • residues (usually 2?) that will be constant among one persons group of MHC class I’s, however they will vary from person to person (polygenics, and polymorphism)
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9
Q

How do the binding chacteristics of MHC class I vary form MHC class II?

A

MHC class II:

  • must be AT LEAST 13 amino acids long
  • Edges do not limit binding cleft

MHC class I:

  • must be NO MORE than 8-10 residues
  • Edges limit binding cleft
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10
Q

For what reason are MHC complexes so promiscuous?

A
  • binding pockets only require that 2-4 residues fall into a certain structural category of amino acids
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11
Q

T or F: MHC plays a vital role in telling the body whether its dealing with an intracellular infection or extracellular infection

A

True

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12
Q

How does the body use MHCs to determine where the pathogen lives?

A 
MHC class I 
- Processing and presentation of INTRACELLULAR pathogens 
MHC class II
- Processing and presentation of EXTRACELLULAR pathogens
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13
Q 
What is the MHC class I pathway? 
- what type of pathogen does this protect against?
A

Takes place IN the ER.

  1. MHC Class I is stabilized by Calnexin
  2. MHC Class I binds to Protein Loading complex and TAP
  3. TAP imports peptide fragments and PLP loads them to MHC
  4. MHC with bound peptide is exprelled to golgi then to cell surface
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14
Q

Suppose you have a patient who presents with very little MHC class I on their cells, yet their MHC class one gene is perfectly functional. why is this?

A 
TAP1/2 genes could be defective. 
- it presents this way because MHC class I is very unstable without being bound to peptides
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15
Q 
When is the MHC class I pathways occurring? 
- what are some possible reactions to presentation of antigen?
A
  • All of the time

Possible Outcomes:

  1. Nothing happens because the peptide is normal
  2. Abnormal peptide is presented on APC and Naive T Cells are notified
  3. Abnormal peptide is presented on regular cell and cytotoxic T-cells kill it
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16
Q

In general how does the MHC class II pathways work?

A
  • Extracellular Mileu is sampled and MHC class II is sent back out with parts of it
17
Q

MHC class II

  • where is it found?
  • What type of proteins does it bind?
A
  • ONLY antigen presenting cells
  • Binds BOTH host and pathogenic cells so MAJORITY of BOUND PROTEINS are HOST proteins
  • T cells must differentiate what’s pathogenic and what isn’t
18
Q 
MHC class II
- pathway
A
  1. MHC class II resides in ER bound to INVARIANT CHAIN
  2. MHC II vesicle Buds off then goes to golgi and invariant chain is degraded leaving CLIP behind in the binding cleft
  3. MHC class II binds to phagosome and HLA-DM dislodges CLIP and TProtein is bound
  4. MHC class II vesicle continues and combines with cell membrane
19
Q

T or F: there is some crossover between proteins loaded on MHC I and MHC II

A

True, the pathways are not 100% exclusive

20
Q

What is the only tissue to lack MHC I expression?

- why is this?

A

Erythrocytes

  • T cells can’t kill enucleate cells
21
Q

Explain why MHC I levels are the way they are on the:

  • Liver
  • Kidney
  • Brain
A

Low on these tissues because killing cells that are essential for survival is pointless

Especially Low in the Liver

22
Q

Where can you find MHC II expression in the greatest proportions?

A

APCs:

  • Macrophages
  • Dendritic Cells
  • B cells

Thymic Epithelium

23
Q

What is the difference in the type of T cell that is recruited by MHC class I and MHC class II?

A 
MHC class I
- presents to CD8
MHC class II
- presents to CD4
24
Q

What players are involved in the extracellular response?

A

MHC class II —> CD4 —> antibodies

**CD4 is critical for linking the extracellular sensory system with the extracellular response

25
Q

What is polygeny?

- what is an immune system example?

A
  • 2 or more proteins with similar structure having similar (identical) function existing at 2 Different parts of the genome
  • MHC I and MHC II
26
Q

What is polymorphism?

- what is an immune system example?

A
  • 2 or more varients of a gene in a population (alleles)

- MHC I and MHC II

27
Q

T or F: there is a tremendous clinical relevance for MHC class I and MHC class II being both polymorphic and polygenic.

A

True

28
Q

Polygenic Nature MHC class I and MHC Class two

A

3 loci encode for MHC class I isoforms

  • HLA-A
  • HLA-B
  • HLA-C

3 loci encode for MHC class II isoforms that WITHIN THEM have code for alpha and beta chains

  • HLA-DP
  • HLA-DQ
  • HLA-DR (can have 2 two different genes) ***
29
Q

Polymorphic Nature of the MHC genes

A

**each of the Loci for all MHC genes are super polymorphic (different individuals are likely to have different versions of the gene)

**Most polymorphic genes in the genome

30
Q

Where (in sequence) are most polymorphisms in MHC genes found?

A

in sequence that codes for the binding region of MHC molecules

  • This is why the binding regions are variable from person to person.
31
Q 
What is the largest and smallest number of different isotypes a person can express of MHC class I? 
- is the a result of polygenics or polymorphisms?
A

3 (homozygote)-6 isotypes possible on all nucleated cells

  • Polygenic

(variation from person to person = polymorphism)

32
Q

MHC class two

  • minimum number of isotypes
  • why
A

3 - 16
*greater number has to do with alpha and beta chains within genes expressing individual polymorphisms and being able to mix

33
Q

Is it better to inherit express the minimum or maximum amounts of isotypes?
- why

A

There are benefits to both:
- Minimum number of isotypes –> you will be more likely to be able to accept an implant

  • Maximum number of isotypes
  • -> you will probably be a little more immunologically protected
34
Q

What is the basic of transplant rejection?

A

MHC molecules of the host don’t match those of the organ donor

35
Q

Differentiate between transplant types

  • syngeneic (isograft)
  • allogeneic (allograft)
  • zenograft
A

Isograft
- genetically identical individuals

Allogeneic
- genetically distinct individuals

zenograft
- different species

IMMUNOLOGY: CMOD-Week 2 (11 decks)

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