Lecture 8- T cell memory

Question 1

what type of pathogens does the immune system have to deal with?

Answer 1

-viruses
-bacteria
-yeast and fungus
-parasites

Question 2

how are CD4 T cells the centre of the universe?

Answer 2

-Help B cells
-Regulate/help to resolve immune responses
-Control virus infections
-Get rid of gut worms
-Activate cells of the innate immune system to control bacteria and fungi

bt there are different types that are required for these cells to mediate their different functions

Question 3

what are thelper 1 cells and what do they do?

Answer 3

Bacteria and viruses cause DCs to make IL-12

Signature cytokine: Interferon-γ
Make cytokines to attract and activate innate cells
Macrophages exposed to IFN-γ are better at phagocytosing and destroying pathogens

Question 4

what are thelper 2 cells and what do they do?

Answer 4

Parasites cause low level activation of DCs eh Helminths
Cells exposed to parasites make IL-4

Signature cytokines: IL-4, IL-13
Make cytokines to attract and activate innate cells
Th2 cytokines key to expelling gut worms

Question 5

what are thelper 17 cells and what do they do?

Answer 5

bacteria and yeast are often triggers of Th17 responses
that DCs and damaged cells are important in driving Th17 responses; and that Th17 cells make IL17 that can help support neutrophil responses

IL-6 made by damaged cells
TGF-β – many potential sources

Make cytokines to attract and activate innate cells

Question 6

T follicular helper cells help B cell responses in the germinal centre…

Answer 6

1- Inside germinal centres, B cells proliferate and become better cells:
change the nucleotide sequence of their BCRs: somatic hypermutation
change their constant region: class switching

2. The mutated B cells compete for antigen
3. B cells with the highest affinity pick up the most antigen; they present to Tfh cells in the GC
4. The B cells that get help from Tfh cells either turn into memory B cells or plasma cells
5. Plasma cells make high affinity class switched Ab that clears the infection
   Memory B cells will protect the host from subsequent infections

Question 7

what is the subsets versus spectrum?

Answer 7

Thelper subsets display
Plasticity: one subset can change to express cytokines associated with another subset
Mix phenotype: express cytokines associated with more than one subset at one time

T cells don’t live in boxes – but exist in a continuum

Question 8

what are Tfollicular helper cells?

Answer 8

driven by interactions with B cells

T cells are first activated by mature dendritic cells in the paracortex/ T cell zone
Some activated T cells move towards the B cell follicle

If they interact with activated B cells they become committed Tfh cells
These Tfh cells move to B cell follicles to form the germinal centre response

Question 9

how are memory cells important?

Answer 9

T cell proliferate reaching a peak around day 10. This is followed by a contraction phase where most of the activated T cells die by apoptosis. Some of the activated T cells survive as memory T cells and these can respond quickly in response to a re-infection/re-exposure to antigen. In comparison to the primary response, the secondary response is larger, and peaks in less than a week.

Question 10

how do some activated T cells survive into the memory pool?

Answer 10

80-90% of the activated T cells die

after activated T cells proliferate, many of these die (by apoptosis) leaving memory cells to protect the host

Question 11

what are memory cells?

Answer 11

remember their training from the first response
Memory CD8 T cells rapidly make cytotoxic molecules to kill infected cells

Rapidly control virus and bacterial infection
Rapidly control worm infections
Rapidly control bacteria and fungi
Rapidly help B cells make antibody

Question 12

where are memory T cells found?

Answer 12

1. Memory T cells in tissues can be reactivated at the site of infection – Tissue resident memory T cells

Peripheral tissues

2. Memory T cells in the blood can get to new sites of infection quickly - Effector memory T cells

Secondary lymphoid organs

3. Memory T cells in the secondary lymphoid organs rapidly proliferate to make more effector T cells – Central memory T cells

Question 13

how are memory T cells are ‘better’ than naïve T cells?

Answer 13

1. after a primary response, there are more of the Ag-specific memory T cell than there were when these cells were naïve
2. some memory T cells are found in non-lymphoid tissue to response more quickly to pathogens
3. memory responses are faster as these cells remember the training they had during the primary response.