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Flashcards in Memory and vaccines Deck (54)
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1

What are the key features of a secondary immune response?

1) Faster
2) Stronger
3) More effective

2

What is the basis for vaccines?

Immunological memory; memory can be lifelong, meaning patient may not show any symptoms upon repeated exposure.

3

What is the basis for vaccines?

Immunological memory; memory can be lifelong, meaning patient may not show any symptoms upon repeated exposure.

Vaccine immunise patients with benign form of pathogen to induce immunological memory against disease.

4

What was Edward Jenner famous for?

1780: vaccination against small pox (using cowpox)

5

What was Louis Pasteur famous for?

1880: Developed vaccines for chicken cholera, rabies and anthrax.

6

What are mechanisms of immunological memory 1?

1) Long lived Plasma cells which produced continual low level circulation of specific antibodies.
2) Generation of memory lymphocytes during adaptive response

7

What are the characteristics of memory cells?

1) They are long lived

8

What are the characteristics of memory cells which make them more efficient than naive Lymphocytes?

1) They are long lived; they survive even in complete presence of antigen
2) They are more sensitive to low doses of antigen than naive B/T cells

9

What is essential for the survival of B cells?

prdm1 is the gene that encodes a transcription factor Lymph1 needed for survival.
No gene, means there is no memory cell marker called CD38; memory cell proliferation is low. When antigen (NP) added to knockout the response of memory cells is lower.

10

Describe an experiment to show memory cell sensitivity.

-purify naive and memory T cells
-immuno-labelling using Ab against T cell marker and conjagated Ab with gold particles
-stained cells with gold Ab
-visualised by electron microscopy
The memory cells have more clustered TCR, therefore more effective T cell activation

11

What are the three characteristics of memory cells which make them more efficient than naive Lymphocytes?

1) They are long lived; they survive even in complete presence of antigen
2) They are more sensitive to low doses of antigen than naive B/T cells
3) Their response is faster and stronger

12

Describe an experiment to show memory cell sensitivity.

-purify naive and memory T cells
-immuno-labelling using Ab against T cell marker and conjagated Ab with gold particles
-stained cells with gold Ab
-visualised by electron microscopy
The memory cells have more clustered TCR, therefore more effective T cell activation
-increased activation shown by CD25 or secretion of T cell cytokine IFN-gamma.

13

Why are memory cells faster and stronger?

1) There is higher frequency of antigen-specific memory cells as a result of previous clonal proliferation; There is more!
2) They have already undergone isotype switching so memory cells are primed to make correct antibodies with the best affinity for antigen (hypermutation) and so more effective
3) It is only memory cells that take part

14

Why are memory cells faster and stronger?

1) There is higher frequency of antigen-specific memory cells as a result of previous clonal proliferation; There is more!
2) They have already undergone isotype switching so memory cells are primed to make correct antibodies with the best affinity for antigen (hypermutation) and so more effective for T cell binding.
3) It is only memory cells that take part to save time activating a naive B cell, when tried and tested B cell awaits.

15

Describe the mechanism involved in secondary immune response.

Only emery cells participate.

-naive B cells bind to pathogen-Ab complex. Negative signal to naive B cell so it is not activaed, there is no production of its low affinity initial IgM Ab

16

Describe the mechanism involved in secondary immune response.

Only emery cells participate.

-naive B cells bind to pathogen-Ab complex. Negative signal to naive B cell so it is not activaed, there is no production of its low affinity initial IgM Ab

-memory B cell binds to pathogen-Ab complex. Memory cell activated into plasma cell which makes correct (rearranged) Ab immediately.

17

Describe the mechanism involved in secondary immune response.

Only emery cells participate.

-naive B cells bind to pathogen-Ab complex. Negative signal from Fc-gammaRIIb (FcyRIIB) to naive B cell so it is not activaed, there is no production of its low affinity initial IgM Ab

-memory B cell binds to pathogen-Ab complex. Memory cell activated into plasma cell which makes correct (rearranged) Ab immediately other than IgM.

18

What is FcyR2B?

Inhibitory receptor which binds to IgG on naive B cells that prevents their involvement in the secondary response.

The receptor has ITIM as a signalling motif

FcyRIIB is downregulated on memory cells so these are not inhibited.

19

Why are memory cells faster and stronger?

1) There is higher frequency of antigen-specific memory cells as a result of previous clonal proliferation; There is more!
2) They have already undergone isotype switching so memory cells are primed to make correct antibodies with the best affinity for antigen (hypermutation) and so more effective for T cell binding.
3) It is only memory cells that take part to save time activating a naive B cell, when tried and tested B cell awaits.
4) They are hypersensitive to antigen.

20

Describe the mechanism involved in secondary immune response.

Only memory cells participate.

-naive B cells bind to pathogen-Ab complex. Negative signal from Fc-gammaRIIb (FcyRIIB) to naive B cell so it is not activaed, there is no production of its low affinity initial IgM Ab

-memory B cell binds to pathogen-Ab complex. Memory cell activated into plasma cell which makes correct (rearranged) Ab immediately other than IgM.

21

What is FcyR2B? How does it work?

Inhibitory receptor which binds to IgG on naive B cells that prevents their involvement in the secondary response.

The receptor has ITIM as a signalling motif; ITIM phosphorylated, so it recruit/docks phosphatases when which act to dephosphorylate signalling molecules and inhibit B cell activation.

FcyRIIB is downregulated on memory cells so these are not inhibited.

22

What experiment involving PKD can be used to show inhibitory FcyRIIb effect?

protein kinase PKD enzyme when activated in absence of FcyRIIB it autophosphorylates itself; activity measured in kinase assay.

PKD is blocked by engagement of the FcyRIIb receptor, despite initial autophosphorylation; activation signals are switched off over time.

Shows that negative ITIM dominates activation via BCR in naive B cell.

23

Why are memory cells faster and stronger?

1) There is higher frequency of antigen-specific memory cells as a result of previous clonal proliferation; There is more!
2) They have already undergone isotype switching so memory cells are primed to make correct antibodies with the best affinity for antigen (hypermutation) and so more effective for T cell binding.
3) It is only memory cells that take part to save time activating a naive B cell, when tried and tested B cell awaits.
4) T memory cells are hypersensitive to antigen.

24

What experiment involving PKD can be used to show inhibitory FcyRIIb effect in naive B cells?

protein kinase PKD enzyme when activated in absence of FcyRIIB it autophosphorylates itself; activity measured in kinase assay.

PKD is blocked by engagement of the FcyRIIb receptor, despite initial autophosphorylation; activation signals are switched off over time.

Shows that negative ITIM dominates activation via BCR in naive B cell.

25

What features of memory T cells make them more sensitive?

1) enrichment of Oligomeric T cell receptor complexes

26

What features of memory T cells make them more sensitive?

1) enrichment of Oligomeric T cell receptor complexes
2) They splice out CD45 mRNA so they express a different isoform

27

What is the role of CD45 in T cells?

It is a phosphatase which dephosphorylates certain inhibitory sites on kinases so they become active.

Therefore, it is important for positive regulation of TCR signalling

28

What are the 2 isoforms of CD45?

-CD45RO: on effector and memory T cells. This CD45RO causes increased TCR signalling.

-CD45RA: on naive T cells

29

What features of memory T cells make them more sensitive?

1) enrichment of Oligomeric T cell receptor complexes
1) They splice out CD45 mRNA so they express a different isoform; they express CD45RO isoform which has lower activation threshold, stronger TCR signalling, and more rapid up-regulation of CD40L

30

What are the 2 isoforms of CD45?

-CD45RO: on effector and memory T cells. This CD45RO causes increased TCR signalling, and activating kinases.

-CD45RA: on naive T cells