module 06 section 01 (primary/secondary immune responses)

Question 1

recall: what is clonal expansion?

Answer 1

• during the antigen-independent phase, as a result of VDJ rearrangement, each mature B-cell expresses an antigen-specific antibody on the cell surface prior to contact with an antigen
• during the antigen-dependent phase, there is clonal expansion of B-cells with a particular specificity
• if a B-cell does not encounter an antigen, it dies via apoptosis

Question 2

what does the primary immune response trigger in terms of B-cells?

Answer 2

the activation and differentiation of of naive B-cells into antibody-secreting plasma B-cells

Question 3

recall: what antibody is produced following the first exposure to antigen?

Answer 3

IgM

Question 4

after being produced, IgM can undergo:

Answer 4

class switching to other isotypes (primarily to IgG) which have higher antibody affinity

Question 5

as antibody concentration levels diminish towards the end of the primary response, what remains in circulation?

Answer 5

memory B-cells that are specific to the antigen

Question 6

what does the secondary immune response trigger in terms of B-cells?

Answer 6

antigen-specific memory B-cells are preferentially activated, resulting in a quick response

Question 7

what differs in terms of Ig production from the primary to the secondary immune response?

Answer 7

• secondary response displays rapid shift to the production of IgG (1-3 days) compared to the primary response (4-7) days (I.e. primary antibody of secondary response = IgG where IgM=IgG in primary)
• higher overall antibody concentration is sustained for a longer period of time compared to primary (i.e. higher overall antibody titer)

Question 8

describe the carrier effect

Answer 8

• when a host has been exposed to the hapten-carrier conjugate (primed) and re-exposed with the same carrier that was used during priming, there’s a secondary response to the hapten
• when the primed host is injected wih the hapten coupled to an unrelated carrier protein, a weaker immune response is observed
• *the MHC complex expresses the processed carrier protein and not the hapten

Question 9

recall: humoral immunity results in the differentation of naive B-cells into:

Answer 9

antibody secreting plasma cells that display memory

Question 10

what about memory B-cells can help explain why vaccines have such a long-lasting protective effect?

Answer 10

they have been found to survive in the bone marrow for an extended period of time

Question 11

what cytokines are involved in the plamsa cell survival niche in the bone marrow? (3)

Answer 11

IL-5, IL-6 and TNF-a (been shown to increase the long-term survival)

Question 12

explain plasma cell survival niche disorders using an example

Answer 12

• multiple myeloma - cancer of the plasma cells in the bone marrow
• associated with deregulations in the bone marrow microenvironment and the plasma cell survival niche

Question 13

what are morphological features associated with multiple myeloma? (3)

Answer 13

dutcher bodies
mott cells
russell bodies

Question 14

what are dutcher bodies?

Answer 14

inclusions that represent Ig accumulation in the perinuclear cytoplasm with subsequent invagination into the nucleus (giving appearance of being intranuclear)

Question 15

what are mott cells?

Answer 15

cells that have spherical (grape-like) cytoplasmic inclusions full of russell bodies

Question 16

what are russell bodies?

Answer 16

eosinophilic Ig-containing inclusions found in plasma cells undergoing excessive Ig synthesis

Question 17

what is antigenic sin (a.k.a. hoskins effect)

Answer 17

• (usually occurs following repeated exposure)
• antigenic shift and/or drift of virsuses poses a major challenge
• previous memory cells cannot bind to neutralize the pathogen as effectively
• memory cells specific to the origional virus can inhibit activation of B-cells specific to the newly altered virus
• also NO recruitment of naive memory B-cells to make new antibodies
• results in weak immune response to the newly altered virus (due to the immunological memory of the origional virus)
• e.g. influenza, HIV, dengue

Question 18

describe antigenic sin using an example

Answer 18

• the immune system encounters an antigen and develops memory B-cells against it (virus X1)
• later the immune system encounters the same virus, but it has undergone antigenic shift (virus X2)
• these memory cells will differentiate into plasma cells which make large amounts of anitbody specific to virus X1
• these antibodies inhibit activation of naive B-cells against virus X2
• the secondary immune response is mounted, led by the memory B-cells for virus X1
• the anti-X1 antibodies cross-react with the virus X2 antigen, but do not display as high of an affinity as a newly developed response would

Question 19

summary: compare the peak antibody concentration of the primary and secondary immune responses

Answer 19

• amount produced by primary is relatively low compared to the secondary
• overtime antibody levels will decline to undetectable levels in the primary
• conversly the secondary response will exhibit antibody levels that remain high for a linger period of time

Question 20

summary: compare the response time for primary vs secondary immune responses

Answer 20

• primary: following first exposure to antigen, lag period (4-7days) occurs where no antibodies are being made BUT activated B-cells are differentating into plasma cells (responding cells = naive B-cells)
• secondary: shorter lag period due to presence of memory b-cells and their ability to quickly respond (responding cells = memory B-cells)

Question 21

summary: compare the IgM:IgG ratio for primary vs secondary immune responses

Answer 21

• primary: IgM is produced at nearly the same level as IgG

- secondary: IgG production is far greater than IgM production, high IgG titer provides lasting protection

Question 22

class switching is a necessary part of which immune response (primary or secondary)

Answer 22

primary

Question 23

which immune response displays a higher affinity for the antigen (primary or secondary)?

Answer 23

secondary (more IgG)

Question 24

define the lag period

Answer 24

time when antigen processing, T-cell acitvation via cytokine induction, as well as proliferation and differentiation of B-cells occurs

Question 25

why is the lag period shorter for the secondary immune response?

Answer 25

because memory cells are already present - which already have VDJ rearranged and already have specificity to the antigen (thus they can respond quickly)