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VMPM (Immunology) > Lecture 9 > Flashcards

Lecture 9 Flashcards

1
Q
A
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2
Q

What does MHC stand for?

A

Major histocompatability complex

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3
Q

What are the two major subdivisions of T cells (based on the sequence of the T cell receptors)?

A

Alpha beta

Gamma delta

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4
Q

What does TCR stand for?

A

T cell receptor

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5
Q

What are the subtypes of Alpha beta T cells?

A

CD4+

CD8+

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6
Q

CD4+ T cells recognize antigens presented on which molecule?

A

MHC II

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7
Q

CD8+ T cells recognize antigens presented on which molecule?

A

MHC I

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8
Q

What is meant by the term “antigen presentation”

A

An antigen-presenting cell chops up an antigen and presents it on an MHC molecule

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9
Q

True or False: A single T cell can detect multiple antigen types.

A

FALSE

T cells are specific to only one antigen

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10
Q

If a CD4+ T cell encounters its antigen, what will it differentiate into (i.e. what kind of effector cell will it become)?

A

T helper cell

Subclasses: Th1, Th2, Th17, Treg, and Tfh

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11
Q

What differentiates the different CD4+ effector cells?

A

The kinds of cytokines they can secrete.

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12
Q

What is the CD8+ effector cell (i.e. what kind of cell does it differentiate into once it encounters its antigen)?

A

Cytotoxic T cells

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13
Q

How many genes for MHC I does an individual inherent from its parents?

A

6

3 from the mother and 3 from the father.

Note that in inbred animals, the individual may not inherit 6 different genes.

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14
Q

True or False: T cells can recognize free-floating antigens in the same way that B cells can.

A

FALSE

T cells must have an antigen presented on an MHC molecule in order to detect it.

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15
Q

What molecule are we looking at here?

A

MHC class I

Note that there is only one transmembrane region, and that only one chain contributes to the groove at the apical surface.

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16
Q

What molecule are we looking at here?

A

MHC class II

Note that there are 2 transmembrane regions, and that both chains contribute to the groove at the apical surface.

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17
Q

How many MHC II chains does an individual possess?

A

6 alpha chains and 6 beta chains.

These can make different combinations of 2 chains, resulting in 10-15 different dimers that are expressed.

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18
Q

Which molecule class (protein, lipid, etc.) do TCRs recognize?

A

Only peptides

Must be bound to an MHC

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19
Q

Do B cell receptors (BCRs) require an MHC for immune recognition?

A

No

BCRs can recognize intact antigens.

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20
Q

Name the four major receptors of the immune system.

A

MHC I

MHC II

TCR

BCR

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21
Q

The immunoglobulin superfamily is a broad class of molecules, many of which are important receptors of the immune system. What do they all have in common?

A

110 amino acid homology domains (remember from lecture 7!)

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22
Q

Which cells have MHC I molecules?

A

All nucleated cells

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23
Q

How many peptide chains contribute to the apical groove in MHC I?

A

1

Formed by 2 domains of the same alpha chain

24
Q

How many transmembrane regions are found on MHC I?

A

1

25
Q

How long are the peptides that get presented on MHCI?

A

8-10 amino acids

26
Q

Suppose a peptide gets presented on MHC I. Where did this peptide come from?

A

Somewhere in the cytoplasm.

MHC I is important for sampling intracellular proteins to insure that the cell is not cancerous or expressing viral proteins.

27
Q

Describe how a T cell will interact with a peptide presented on MHC I.

A

CD8 interacts with MHC 1, and the TCR interacts with the peptide.

If the peptide is recognized, results in T cell mediated cytotoxicity

28
Q

Do red blood cells in mammals have MHCs?

A

No

MHC I is found on all nucleated cells. Recall that red blood cells are not nucleated in mammals.

29
Q

How many transmembrane regions are found on the MHC II molecule?

A

2

30
Q

How many chains contribute to the MHC II apical peptide binding region?

A

2

31
Q

Suppose a peptide gets presented on an MHC II molecule. Where did it come from?

A

Outside the cell via the exogenous pathway.

MHC II is important for detecting extracellular pathogens.

32
Q

Which cells express MHC II?

A

Antigen presenting cells

Sometimes epithelial cells during inflammation

Not found on all cells in the body

33
Q

Which cell type is the only cell that can present to naive T cells?

A

Dendritic cells

All other antigen presenting cells present to memory T cells.

34
Q

Describe how a T cell will interact with a peptide presented on MHC II.

A

CD4 recognizes MHC II molecule, TCR recognizes the peptide.

If the T cell recognizes the peptide, it will release cytokines.

35
Q

What is meant by the term “immunological synapse?”

A

The area of contact between an antigen presenting cell and a lymphocyte. Within the synapse, cell surface molecules are signaling between the cells.

36
Q

Suppose a macrophage phagocytizes an extracellular bacterium.

  1. Through which presentation pathway will it be processed?
  2. Which MHC will peptides be presented on?
  3. What kind of T cell will recognize the peptide?
A
  1. Exogenous pathway
  2. MHC II
  3. CD4+ (helper) T cell
37
Q

Suppose a virus is replicating within a cell and producing viral proteins.

  1. Through which presentation pathway will these proteins be processed?
  2. Which MHC molecule will they be presented on?
  3. What kind of T cell will recognize the proteins?
A
  1. Endogenous pathway
  2. MHC I
  3. CD8+ (cytotoxic) T cell
38
Q

True or False: Both foreign (e.g. viral) and native cellular proteins can be presented on MHC I

A

TRUE

The endogenous pathway takes a random sampling of all cytoplasmic proteins to present on MHC I molecules.

39
Q

What is the role of ubiquitin in the endogenous pathway?

A

Tags a protein for digestion by the proteasome

40
Q

What is the proteasome?

A

An organelle that degrades proteins into peptides around 8-15 amino acids in length.

41
Q

What is the TAP molecule and what is its role in the endogenous pathway?

A

Transporter for Antigen Processing (TAP)

Binds peptides from the proteasome and transports them to the lumen of the ER.

42
Q

The ER trims peptides received from TAP down to the appropriate length for attachment to MHC I. How long are these peptides?

A

9 amino acids long

43
Q

Describe the steps involved in the endogenous presentation pathway.

A
  1. Protein is tagged with ubiquitin for digestion by the proteasome.
  2. After digestion, peptides are transported to the ER by TAP.
  3. The ER trims peptides to 9 amino acids in length and attaches them to MHC I.
  4. MHC I and peptide are moved to the Golgi, where they are transported to the cell membrane in exocytic vessicles.
  5. MHC I and peptides are now visible to CD8+ T cells.
44
Q

The endogenous pathway regularly presents self proteins onto the cell surface. Why are these cells not destroyed by cytotoxic T cells?

A

T cells that recognize self are destroyed during the maturation process.

45
Q

What is the role of the lysosome in the exogenous pathway?

A

Digests antigens into short peptides

46
Q

What is the role of the invariant chain molecule in the exogenous pathway?

A

The invariant chain fills the peptide groove in MHC II to insure that MHC II does not bind to any cytoplasmic proteins

47
Q

List the steps involved in the exogenous presentation pathway.

A
  1. APC ingests an extracellular antigen.
  2. Antigen is digested by lysosome into small peptides.
  3. MHC II is synthesized in the ER. The peptide groove is filled with the invariant chain to keep it from binding to cytoplasmic proteins while moving through the Golgi.
  4. MHC II is transported to the phagolysosome, where the invariant chain is digested and the antigen peptide can bind to the groove of MHC II.
  5. MHC II and antigen are transported to the membrane, where they can be recognized by CD4+ T cells.
48
Q

Why do modified live viral vaccines elicit a stronger immune response than killed viral vaccines?

A

Killed viruses do not replicate in the cell, and so are not presented on MHC I and are not recognized by CD8+ cells.

49
Q

What is an ISCOM and how does it improve vaccine responses?

A

ISCOM - immune stimulatory complex

Lipid micelles with peptides trapped in the center. Can enter the cell, dumping the contents inside. Thus, peptides will be presented on MHC I and recognized by CD8+ T cells.

Great way to improve the immune response to killed virus vaccines.

50
Q

What is the major difference between T cell and B cell antigen recognition?

A

B cells can recognize intact antigen. T cells can only recognize peptides.

Only linear sequence, not 3D structure, matters to T cells.

51
Q

What are the major differences between peptide binding on MHC I and MHC II molecules?

A

MHC I

Groove is closed on each end - peptide cannot move.

Peptides are 9 amino acids in length

MHC II

Groove is open - peptide can slide around freely

Peptide is 13-20 amino acids in length, but only 9 are in the groove at any one time.

52
Q

What process is being depicted here?

A

An ISCOM - an antigen wrapped in a micelle - is dumping its contents into a cell.

ISCOMs are a good way to improve the immune response to killed virus vaccines by using the endogenous pathway.

53
Q

I lost a bunch of my skin and need a transplant. What properties must my donor have for the transplant to be successful?

A

Must match all MHC genes

54
Q

Why do parents make bad matches for tissue transplants into their children?

A

Each parent contibutes MHC genes to the offspring, so the likelihood of a match between parent and child is low. (Unless the kids are inbred!)

More likely to find a match with a sibling. Even better, an identical twin.

55
Q

What is meant by the term “heterozygote advantage” in terms of immunity?

A

Heterozygotes will have more diverse MHC molecules. A heterozygote will have 6 different MHC I genes, while an inbred animal may only have 3.

VMPM (Immunology) (15 decks)

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