Immunological memorry

Question 1

4 differnet kinds of immunity?

Answer 1

Sterilising, against symptomatic infection, against persistence, and against diseases severity.

Question 2

Example of immunity against symptomatic infection?

Answer 2

When you have an infection, but initial infection is very quickly controlled. Zoster booster?

Question 3

Example of immunity against persistence?

Answer 3

When you have no symptomatic infection, may generate Ab against but don’t show chronic infection. May also target latent virus.
e.g. SIV vaccines.

Question 4

Examples of immunity against severe disease?

Answer 4

Not controlling initial infection, just limits severity/ death. e.g. BCG vaccine.

Question 5

The traditional view of memory looks at cells, what other views can you take of memory? And what additional cells could this involve?

Answer 5

View memory as the functional response, so can include other cells that are modified by prior exposure, e.g. memory NK cells, innate-like T cells, innate imprinting.

Question 6

How is T memory improve qualitative response?

Answer 6

Selection of hihger affinitty t cell clones. And development e.g. of T resident memory cells that have increased functionality.

Question 7

Persistence of antigen not required for memory cell formation, what effects could it have though?

Answer 7

May effect the quality of the memory response- e.g. more differentiated memory cells or exhaustion.

Question 8

Differences in effector molecules between TEM and central memory cells?

Answer 8

Tcm have lower levels of effector moleules, more naive and quiescent.
Teff, higher levels of effector molecules like perforin and granzymea nd low levels of IL-7R but high levels of klrg1 (inhibitory receptor)

Question 9

What markers for naive T cells?

Answer 9

CD45RA+ CCR7+ CD62L+ (L-selectin).
In mice CD44 is the activation marker.
CCR7 and CD62L home to lymph nodes.

Question 10

Markers for Tcm cells and Tem cells?

Answer 10

CD45RA- (CD45RO+) switch to this isoform to allow formation of immune synapse.
CD62L+ CCR7+

Tem CD45RA+ CCR7- CD6L low.

Both have high CD28+

Question 11

TEMRA cell markers?

Answer 11

these can be CCR7- CD62L low that reexpressed CD45Ra.

Also low CD28+

Question 12

T resident memory cell markers?

Answer 12

CD45R- CCR7- CD62L- but higher expression of effector molucles and co inhibitory molecules.
As well as cytokines!

they are highly responsive.

Question 13

TF marker fo memory cells?

Answer 13

Bcl2?

Question 14

How to identify Trm?

Answer 14

Use parabiosis of congenic mice. This will mix lymphocyte populations, but you see that the persistence of T resident memory cells.

Or in organ transplants, see the persistence of donor Trm cells with MHC mismatch antibody.

Or stain with antibodies that will stain in circulation and sacrifice. Trm don’t have access to the circulation and won’t be marked.

Question 15

Tem cells have high CX3CR1 expression and Tcm and Trm cells have CX3CR1- expression. What is expression of transitional cells?

Answer 15

intermediate population between these cells (CX3CR1 intermediate) peripheral memory cells.

Question 16

What does conventional memory populations look like?

Answer 16

Larger more highly proliferating Tcm cells (CX3CR1-) which give rise to a small population of intermediate cells that give rise to a small population of Tem.

In memory inflation, the Tem population is inflated, because of the increase in proliferating intermediate cells?

Question 17

When might you see memory inflation in infection? what populations and epitopes involved?

Answer 17

In chronic CMV infection. Tcm populations often against an epitope that isn’t presented.

Chronic presentation of antigen due ot exposure, or non-classical APC presentation, expands Tem cells which are against a different epitope that is present.

Question 18

What might the CX3CR1 intermediate memory cell population explain?

Answer 18

Provide an intermediate for Trm cells and for inflationary Tem populations.

Question 19

what other unconventional T cells and innate cells might have memory?

Answer 19

MAIT cells (recognise MR1), iNKT cells (CD1(d)), yD T cells (recognise butyrophilin) and innate T cells (recognise CD1a lipids)

Question 20

MAIT cells are somewhat preset with memory markers, like?

Answer 20

CCR7- CD62L- and CD45RO+.

Question 21

How might the expansion of MAIT cells be considered memory? Same is seen for yD cells.

Answer 21

They expand with age in response to commensal bacteria (not seen in germ free mice) and TCR diversity becomes more restricted.

Question 22

Example for NK cell memory evidence? Mice

Answer 22

in response to infection, some NK cells with receptors e.g. Ly49H are expanded and contract like T cells and maintain a higher population of NK Ly49H+ cells.

Question 23

Example of NK cell memory in humans?

Answer 23

In CMV+ patients you only see the NKG2C+ population that is expanded.