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Immunology > 7 - Adapt 1: Antigen Recognition > Flashcards

7 - Adapt 1: Antigen Recognition Flashcards

1
Q

The adaptive immune system is capable of distinguishing how many antigens/epitopes?

A

Millions

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2
Q

Which immune response is specific?

A

Adaptive

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3
Q

The adaptive response relies on ____ of receptors on T lymphocytes.

A

pre-existing diversity

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4
Q

How many antigen receptors are expressed on each clone?

A

Only one specific antigen receptor.

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5
Q

How many antigen receptors are expressed on lymphocytes as a population?

A

> 5 x 10^7 different antigen receptors

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6
Q

The acquired immune response relies on ____ and ____ of clones that express the antigen receptors that can bind the specific relevant antigen.

A

selection and expansion

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7
Q

What are the four basic elements of clonal selection theory?

A
  1. Selection - Antigen selects pre-existing cell surface receptor made by a single cell.
  2. Clones - Selection of a precursor gives rise to clones that all make the same receptor.
  3. Origin of receptor genes - Randomized receptor that is subject to mutation that is transmitted by somatic inheritance to all descendants.
  4. Self/nonself - Self-reactive cells are killed upon interaction with self antigen early in life.
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8
Q

What is an antigen?

A

Any molecule that can be recognized by the adaptive immune system (ex. can be bound by a T cell receptor).

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9
Q

What do antigens bind to?

A

Both MHC molecules and TCRs.

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10
Q

What is an immunogen?

A

Something that initiates an immune response.

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11
Q

Most immunogens are …

A

proteins.

(Pure proteins, lipoproteins, or glycoproteins).

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12
Q

In general, proteins are very good…

A

immunogens.

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13
Q

List the 5 properties of antigens.

A
  1. Foreignness
  2. Molecular size
  3. Chemical nature and composition
  4. Physical form
  5. Degradability
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14
Q

Describe how foreignness is a property of antigens.

A

An antigen must be a foreign substance. Autologous (self antigens) are ordinarily not immunogenic, but under certain circumstances may act as auto-antigens. Not all foreign things are immunogenic.

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15
Q

Describe how molecular size is a property of antigens.

A

Active immunogens have high a molecular mass (>14kDa).

E.g., tetanus toxoid, egg albumin, thyroglobulin are highly antigenic. Insulin (5.7kDa) is either non-antigenic or weakly antigenic.

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16
Q

Under what circumstance might self-antigens become immunogenic?

A

Thyroglobulin (don’t ask how this is all it said).

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17
Q

Describe how chemical nature is a property of antigens.

A

The more chemically complex and organic the substance is, the more immunogenic it will be (mainly proteins).

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18
Q

Describe how physical form is a property of antigens.

A

Particulate antigens are more immunogenic than soluble ones.
Denatured antigens are more immunogenic than the native form.

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19
Q

Describe how degradability is a property of antigens.

A

Antigens that are easily phagocytosed or degraded (proteases) are more immunogenic.

E.g., T-dependent antigen requires to be phagocytosed, processed and presented to helper T cells by APC.

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20
Q

How do T cells see pathogens?

A

T cells can only “see” antigens in the context of other cells. They interact with other cells (infected cells, B cells, and phagocytes) and recognize pathogen-derived antigens in the context of MHC molecules with antigen specific receptors.

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21
Q

What cells do not express MHC?

A

Red blood cells.

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22
Q

Describe the peptide binding region of class I and II MHC molecules.

A

The peptide binding region exhibits polymorphism, meaning there is lots of variation in the peptide sequence.

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23
Q

How many allelic variants of MHC are there in humans?

A

Several hundred, one copy is inherited from each parent.

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24
Q

How many class I MHC molecules are expressed per person?

A

Up to 6

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25
Q

How many class II MHC molecules are expressed per person?

A

About 12

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26
Q

How does the limited group of MHC molecules present the vast diverse array of possible antigen peptide fragments?

A

A given MHC molecule can bind numerous different peptides, and some peptides can bind to several different MHC molecules.

Also gene polymorphism.

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27
Q

What are anchor residues?

A

The amino acids that are within the binding site of an MHC molecule.

28
Q

What cell types do class I MHC molecules present to?

A

CD8 T cells

29
Q

What do anchor peptides do?

A

They “anchor” peptides into the MHC binding groove.

30
Q

What type of molecules do class I MHC proteins present?

A

Peptides derived from endogenous intracellular proteins.

31
Q

What type of molecules do class II MHC proteins present?

A

Extracellular antigens or phagosomal pathogens

32
Q

What cell types do class II MHC molecules present to?

A

CD4 T cells

33
Q

What do MHC class III genes encode for?

A

Complement and inflammation proteins. These genes are within the MHC locus but are not expressed on MHC molecules.

34
Q

What molecules are expressed on the MHC locus?

A
  • Class I MHC genes
  • Class II MHC genes
  • Class III MHC genes
35
Q

How many major classes of molecules are encoded on the MHC locus?

A

3

36
Q

Do humans and mice have the same layout of MHC genes?

A

NOOOOO

37
Q

How many sets of MHC class II genes do humans have?

A

Humans = 3 sets

38
Q

How are allelic forms of MHC genes inherited?

A

They are inherited in linked groups called haplotypes.

39
Q

How many haplotypes of MHC genes does every individual inherit?

A

One haplotype from each parent.

40
Q

How are MHC alleles expressed?

A

Codominantly.

Both maternal and paternal MHC genes are expressed in offspring cells.

41
Q

What is the benefit of codominant MHC expression.

A

It gives the best chance for an organism to have SOME capability of presenting all the possible antigen peptides it encounters.

42
Q

What are the differences in the peptide binding domain between class I and II MHC molecules?

A

Class I = α1/α2
Class II = α1/β1

43
Q

What are the differences in the nature of the peptide binding groove between class I and II MHC molecules?

A

Class I = Closed at both ends
Class II = Open at both ends

44
Q

What are the differences in the size of bound peptides between class I and II MHC molecules?

A

Class I = 8 to 10 aa
Class II = 13 to 18 aa

45
Q

What are the differences in the nature of the bound peptides between class I and II MHC molecules?

A

Class I = Extended structure in which both ends interact with MHC groove but middle
arches up and away from MHC molecule
Class II = Extended structure that is held at a constant elevation above the floor of the MHC groove

46
Q

What are the differences in the motifs involved in peptide binding between class I and II MHC molecules?

A

Class I = Anchor residues at both ends of peptide; generally hydrophobic at carboxy-terminus
Class II = Conserved residues distributed along the length of the peptide anchor

47
Q

How do MHC alleles affect transplants?

A

It can also make transplantation somewhat difficult, as humans are heterozygous at each locus.

Nonmatching MHC patterns will result in rejection of transplanted tissues.

48
Q

The MHC region is …

A

polygenic.

49
Q

MHC molecules present both ___ and
___ antigens.

A

intracellular and extracellular

50
Q

Which class of MHC molecules presents self-proteins?

A

Class I

51
Q

How can the immune system check if cells are self and generally healthy?

A

Class I MHC presents intracellular antigens.

Can show which cells have been infected with viruses or are abnormal and display those peptides on class I and activate CD8+ T cells.

52
Q

Which class of MHC molecules help direct a response against threats?

A

Class II

53
Q

Where is MHC class I expressed?

A

Throughout the body on all nucleated cells.

54
Q

Where is MHC class II expressed?

A

Antigen presenting cells: macrophages, B cells, dendritic cells.

55
Q

What kind of processing does MHC class I require?

A

Cytosolic or endogenous.

56
Q

What kind of processing does MHC class II require?

A

Exogenous processing.

57
Q

Describe the endogenous pathway of antigen processing and presentation. (sorry)

A
  1. Peptides are transported from the cytosol to the rough endoplasmic reticulum (RER)
  2. Transporter associated with antigen processing (TAP) molecules in the RER membrane move the fragments
  3. MHC class I molecules synthesized on ribosomes on the RER anchor in the RER membrane after their translation
58
Q

MHC class I binding depends on how many amino acids?

A

As few as two amino acids.

59
Q

What molecules help peptide/MHC class I assembly?

A

Chaperones

60
Q

What trims long peptides to a suitable size for MHC class I grooves?

A

ER aminopeptidase ERAP1

61
Q

Peptides are generated from internalized antigens in …

A

endocytic vesicles.

62
Q

Where are MHC class II molecules produced and exported to?

A

Produced in the ER
Exported in vesicles to the Golgi

63
Q

What is the function of invariant chain (Ii, CD74)?

A
  • It guides transport of class II MHC molecules to endocytic vesicles.
  • It prevents peptides from binding to the groove too early in the ER.
  • It uses sorting signals to direct the MHC class II vesicles that contain molecules to endocytic compartments.
64
Q

What is Ii (invariant chain) degraded to?

A

Class II-associated invariant chain (CLIP)

65
Q

Where does degradation of Ii (invariant chain) occur?

A

In endocytic compartments by proteolytic activity.

66
Q

What is the function of HLA-DM?

A

It exchanges CLIP out of the groove for a peptide fragment.

67
Q

What happens in an MHC II late endosome?

A

The invariant chain is digested, leaving only a portion behind (CLIP).

Once the extracellular peptides enter that endosome, clip can be removed and the peptides can become bound to the MHC.

Immunology (18 decks)

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