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Molecular Immunology > Antigen recognition (9) > Flashcards

Antigen recognition (9) Flashcards

1
Q

How was the Major Histocompatibility complex discovered?

A

Research into graft rejection.

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2
Q

What chromosome is the Major Histocompatibility complex found on in humans?

A

6.

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3
Q

What can MHC also be known as in humans?

A

HLA molecules - human leucocyte antigen.

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4
Q

Is the HLA-A, HLA-B or HLA-C locus most polymorphic?

A

HLA-B.

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5
Q

How many alleles are there for the HLA-A locus?

A

More than 1400.

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6
Q

HLA alleles are very polymorphic. How many amino acids substitutions can they differ by?

A

20 a.a.

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7
Q

What type of response does the MHC complex have a major role in activating?

A

The T cell response.

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8
Q

When can T lymphocytes recoginse an antigen?

A

When it is in complex with self MHC molecules.

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9
Q

How were mice used experimentally to show that T cells can only recognise antigen that are bound to self MHC?

A

Two inbred mice ( A and B) are immunized with virus B however only T cells from mouse A can kill infected A cells as T cells from B to not recognise A’s self molecules.

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10
Q

Does the MHCI or MHCII structure include B2-microgloblin?

A

MHCI.

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11
Q

Does the MHCI or MHCII structure contain a beta chain?

A

MHCII.

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12
Q

Is the MHCI or the MHCII protein completely polymorphic?

A

II.

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13
Q

What part of MHCI is invariant?

A

B2- microglobulin.

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14
Q

What domains of the MHC proteins are Ig like?

A

Membrane proximal domains.

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15
Q

What domains of the MHC proteins bind peptide?

A

Membrane distal domains.

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16
Q

Do the membrane proximal or membrane distal domains of MHC proteins contain polymorphisms?

A

Distal.

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17
Q

What is the length of peptides that MHCI can bind?

A

8- 10 amino acids.

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18
Q

What is the length of peptides that MHCII can bind?

A

13-25 amino acids.

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19
Q

How do peptides bind to MHCI?

A

The N and C termini bind to the invariant pockets at the end of the peptide binding groove via two or three anchor residues found on the peptide itself.

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20
Q

What forms the specificity pockets in the MHC proteins?

A

Polymorphic residues.

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21
Q

How does MHCII bind peptides?

A

Peptide backbone interacts with invariant residues whereas side chains interact with specificity pockets found at the base of the peptide binding groove.

22
Q

The specificity pockets in MHCI and MHCII peptides are found in different places in the peptide binding groove. Where are they found?

A

In MHCI they are found at the end of the peptide binding grove whereas in MHCII they are found at the base.

23
Q

Does a particular MHC molecules bind to specific peptides or a wide range of peptides?

A

A wide range of peptides.

24
Q

What two key points regarding antigen recognition were determined by XRC?

A
  1. MHC binds peptide.

2. TCR recognises complex of peptide + self MHC.

25
Q

MHC molecules have a broad specificity for peptides. What is this type of specificity also known as?

A

Degenerate specificity.

26
Q

How fast do bound peptides dissociate from MHC?

A

Very slowly.

27
Q

Where do peptides associate with MHCII?

A

Endocytic/ vesicular compartments.

28
Q

Is peptide binding essential for MHCI or MHCII cell surface expression?

A

MHCI

29
Q

What ATP driven transporter drive peptides to the ER to be associated with MHCI?

A

TAP (transporter associated with antigen presentation).

30
Q

Where are peptides produced that need to be presented via MHCII?

A

Phagolysosome.

31
Q

Where do peptides need to be processed in order to be presented via MHC1?

A

The proteosome.

32
Q

Why are co receptors needed with the TCR?

A
  1. Stabilise interactions

2. Facilitate signalling.

33
Q

What state do ITAMS have in resting cells?

A

Unphosphorylated.

34
Q

What leads to TCR ITAM phosphorylation?

A

Binding of MHC ligand to the TCR.

35
Q

What phosphorylates ITAMS in the TCR when MHC ligand binds?

A

Receptor associated tyrosine kinase.

36
Q

Once MHC ligand has bound to the TCR the TCR ITAMS are phosphorylated via a receptor associated tyrosine kinase. What happens next?

A

ZAP 70 binding to the phosphorylated signalling (zeta) domain ITAMs and is itself phosphorylated by Lck.

37
Q

What is Lck?

A

Tyrosine kinase.

38
Q

How are MHC genes expressed and why?

A

Co- dominantly in order to increase the number of different MHC molecules expressed.

39
Q

What is a major consequence of MHC polymorphism?

A

Graft rejection.

40
Q

Why is the variability of MHC molecules small compared to the variability of TCRs?

A

As all variability is inherited.

41
Q

What is MHC restriction?

A

The fact that an individuals T cell response is determined by their MHC type.

42
Q

MHC restriction means individuals can be classed into two types. What are these types?

A

Responders and non responders.

43
Q

What 6 key processes do MHC proteins function in?

A
  1. Graft rejection.
  2. Antigen presentation to T cells.
  3. T cell activation.
  4. Self/ non self recognition.
  5. Autoimmune disease.
  6. Development of T cell repertoire in the thymus.
44
Q

What HLA stereotype is associated with MS?

A

DR2.

45
Q

What HLA stereotype is associated with RA?

A

DR4

46
Q

What HLA stereotype is associated with Insulin Dependant Diabetes Mellitius?

A

DR3 and DR4.

47
Q

T cells undego thymic selection. What states is the T cell present in in the thymus before it leaves the thymus to enter the peripheral lymphoid tissue?

A
  1. Double negative
  2. Double positive
  3. Single postive
48
Q

What does positive selection in thymic selection involve?

A

Removal of T cells that do not bind self MHC via apoptosis

49
Q

What does negative selection in thymic selection involve?

A

Removal of T cells that bind self MHC and self peptide via apoptosis.

50
Q

Does positive or negative selection in thymic selection occur first?

A

Postive.

51
Q

Is positive or negative selection in thymic selection most imporant?

A

Negative.

52
Q

What is it also thought MHC proteins can be involved in?

A

Mate choice.

Molecular Immunology (9 decks)

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