Bridging Innate And Adaptive Immunity

Front 1

How are γ:δ T cells different from α:β T cells?

Back 1

While derived from same precursors, they don't undergo positive and negative selection, limiting TCR diversity. Their main role instead is to react with common pathogens, mostly in the gut.

Front 2

What is special about γ:δ T cells?

Back 2

They recognize unique determinants - phosphoantigens (not phosphoproteins humans make). They then circulate directly to infected tissues. When activated they kill infected cells, or even mature to become APC to α:β T cells.

They can also react with MIC (stress induced protein family).

DISTINCT AND LIMITED RECEPTOR REPERTOIRES (analogous to Toll receptors in that they recognize common antigens)

Front 3

MIC is semi-homologous to what?

Back 3

MHC Class I. Has similar function - to activate T cells

Front 4

What is a common marker unique for NK cells?

Back 4

CD56. Also, all NK cells express NKG2D receptor (an activating receptor).

Front 5

T/F NK cells rearrange Ig and TCR genes

Back 5

false

Front 6

How do NK cells balance inhibitory and activating signal?

Back 6

The inhibitory signal allows NK cell to spare healthy cells.
Activating receptors bind things expressed by infected cells (like MIC:NKG2D)

The inhibitory signal predominates.

Front 7

What does a healthy cell look like to NK cells?

Back 7

Expresses a normal level of MHC Class I molecules and does NOT express MIC.

Front 8

What does an unhealthy cell look like to NK cells?

Back 8

Expresses a reduced level of MHC Class I molecules and expresses MIC. Indicates cell is undergoing stress.

Front 9

What is NKG2D?

Back 9

An activating receptor on NK cells. It binds to MIC to become activated.

Front 10

What is a common feature of infected cells?

Back 10

Expression of MHC Class I molecules is perturbed.

Front 11

What is NKG2A?

Back 11

An inhibitory receptor on NK cells that (indirectly) monitors overall level of MHC Class I (via HLA-E)

Front 12

How is NKG2A:CD94 monitoring accomplished?

Back 12

Indirectly.

It detects complexes of peptide bound to non-polymorphic class I HLA-E. HLA-E ONLY binds to peptides produced by intracellular degradation of leader sequences of HLA-A,B, and C molecules. Because an HLA-E needs to bind that leader peptide in order to be present on cell surface, the amount of HLA-E is a measure of the amount of the other HLAs being made by cell.

Front 13

What is HLA-E and what is special about it?

Back 13

It provides an indirect way for NK cells to see how much HLA is being expressed by the cell.

HLA-E ONLY binds to peptides produced by intracellular degradation of leader sequences of HLA-A,B, and C molecules. Because an HLA-E needs to bind that leader peptide in order to be present on cell surface, the amount of HLA-E is a measure of the amount of the other HLAs being made by cell.

Front 14

Interaction with MHC/HLA Class I is always a ___________ signal to NK cells

Back 14

Negative/inhibitory

Front 15

What is significance of killer-cell Ig-like receptors (KIRs?)

Back 15

Unlike CD94:NKG2A interaction they have narrower specificities. More able to detect loss of expression of individual HLAs (not just all of them thru HLA-E indirect measurement).

they bind to the same face of the MHC Class I molecule as the TCR.

Front 16

How do NK cells "decide" whether to express KIR or CD94:NKG2A?

Back 16

First they express the more general CD94:NKG2A and then KIR.

Then two things can happen.

A) If none of the KIRs reacts with self MHC I, CD94:NKG2A is retained as receptor for self MHC I.

B) If 1 (or more) KIRs reacts with self MHC Class I, expression of CD94:NKG2A is turned off.


So it's going from general to more specific in terms of recognizing HLA.

Front 17

What is the "missing self" hypothesis?

Back 17

Inhibitory receptors for self MHC Class I make NK cells tolerant to self and responsive to loss of MHC Class I (they're activated by ABSENCE of self).

Front 18

T (CD4 and CD8) cells recognizing lipid antigens protect against ______________ infection

Back 18

mycobacterial (e.g., TB, leprosy)

Front 19

What is significance of CD1d?

Back 19

Expressed by epithelial cells. Expresses lipid antigens from wide variety of pathogens. Presents to a subset called NKT cells, hybrid of NK and T cells that express α:β TCRs. BUT they can rapidly respond to infection, and do not generate memory response.

Front 20

What are NKT cells?

Back 20

Hybrid of NK and T cells that express α:β TCRs. BUT they can rapidly respond to infection, and do not generate memory response.

Therefore they're considered innate immunity responder.


They differ from conventional αβ T cells in that their TCRs are far more limited in diversity and in that they recognize lipids and glycolipids presented by CD1d molecules, a member of the CD1 family of antigen presenting molecules, rather than peptide-MHC complexes.

Front 21

What are similarities of γ:δ T cells and NK cells?

Back 21

1) Both have limited repertoires
2) When gene rearrangement is seen, fewer V regions will be used

Front 22

What are B1 B cells?

Back 22

Analogous role to γ:δ T cells and NK cells. Limited repertoire. Attack common pathogens.

(B2 cell is "classical" B cell).

Front 23

What are the three cell types that express NKG2D receptors, and thus recognize MIC?

Back 23

1) γ-δ T cells

2) subset of CD8 expressing αβ T cells

3) NK cells

Front 24

B1 B Cells are most analogous to what type of T cell?

Back 24

γ:δ T cells