HRR: humoral immune response

Question 1

__ receptors can bind to free floating antigens, while ___ receptors require antigens to be presented

Answer 1

B cell; T cell

Question 2

What are the steps involved in B cell maturation

Answer 2

1.Proliferation of immature cells
2.VDJ recombination of antigen receptor genes
3.Selection of lymphocytes with useful receptors

Question 3

Name the phases of the humoral immune response

Answer 3

1.Naïve IgM, IgD B cell waits for an antigen
2.The B cell becomes activated upon antigen recognition
3.The B cell proliferates
4.Without T cell activation, the B cell will make IgM. With T cell activation, there are other options. They can create memory B cells, do isotype switching, and affinity maturation

Question 4

Describe how B cells change with repeat exposure to antigen

Answer 4

They change quantitatively and qualitatively. Their infinity for antigen increases and their response is larger. This is why we do boosters in vaccines!

Question 5

If A B cell receives a T signal to switch to an isotype other than IgM, what happens?

Answer 5

The B cell will produce memory cells with the new isotype as the B cell receptors.

Question 6

What can an IgM to IgG ratio tell us?

Answer 6

If IgM is higher, it likely means it’s their first time being infected. If IgG is higher, it likely means it is a repeat or chronic infection

Question 7

Describe activation of B cells

Answer 7

Cross-linking of two or more B cell receptors is required for activation. This means a multivalent antigen is needed; this requires either two copies of the same epitope, or a clump of different epitopes

Question 8

What is the purpose/significance of costimulatory signals

Answer 8

It is the required second signal from the innate immune system that indicates danger, keeping B cells from responding to autoantigens

Question 9

List the two types of costimulatory molecules for B cell receptors

Answer 9

Iga and Igb; they have ITAMs that can be phosphorylated

Question 10

What are the kinases seen in B cell receptors for phosphorylating ITAMS?

Answer 10

Lyn, Fyn, and Blk

Question 11

What adaptors are used in signal transduction pathways for B cells?

Answer 11

Syk that binds to phosphorylated ITAMS, which then activates btk

Question 12

What transcription factors are relevant in B cells?

Answer 12

Myc, NFAT, NF-kb, and AP-1

Question 13

List the two costimulatory molecules and signals for B cells

Answer 13

CR2 stimulates C3d
stimulation of toll-like receptors expressed by B cells

Question 14

List 3 clinically relevant ways that secondary humoral responses differ from primary immune responses.

Answer 14

-High IgM in first-time infection allows to distinguish between a primary or secondary immune response

-Immunizing with T dependent antigens can protect from disease due to a faster and more robust secondary response

-Boosters (secondary) strengthen the memory immune response

Question 15

What changes are seen in antigen-activated B cells?

Answer 15

Antigen presentation of MHC II and increased expression of B-7, increased IL-2R and IL-4R and BAFF-R, increased CCR7, and generation of plasma cells

Question 16

What are plasma cells?

Answer 16

Terminally differentiated B cells that no longer have receptors and just make low levels of IgM for the rest of their life.

Question 17

Explain how and where T and B cells for the same antigen find each other and interact.

Answer 17

they migrate towards each other by changing their chemokine secretion. T cells increase CXCR5 and decrease CCR7, while B cells decrease CXCR5 and increase CCR7. This allows helper T cells and B cells to meet.

Question 18

Describe the molecular nature of T-cell “help.”

Answer 18

-A cell-cell contact via CD40 on B cell and CD40L on T cell occurs. The T cell will also make cytokines for B cell cytokine receptors.

-These signals can lead a B cell to switch isotype, undergo affinity maturation, or become memory B cells

Question 19

Describe the molecular basis of isotype switching

Answer 19

-A cytokine secreted from a helper T cell activates a switch region on the chromosome

-Activation induced deaminase causes two switch regions to come together, cutting ut the DNA in-between the two

-The VDJ region is closer to a C gene that codes for the isotype

-This occurs only in heavy chains!

Question 20

Is isotype switching permanent?

Answer 20

yes

Question 21

What are follicular dendritic cells?

Answer 21

Follicular dendritic cells: hold full antigen molecules on their surface

Question 22

What are T follicular helper cells

Answer 22

T follicular helper cells: stays in the follicle and waits for signal from the B cell and provides help to the B cell

Question 23

List the steps in affinity maturation and explain the role of follicular dendritic
cells and activation-induced deaminase (AID).

Answer 23

-Naïve B cells are activated by antigen and helper T cells in the follicle of a lymoh node

-B cells migrate to the germinal center

-B cells with high affinity membrane Ig bind antigen on the follicular dendritic cells and present it to T follicular helper cells. These will be able to survive and be mature.

-B cells that do not have high affinity for the antigen on follicular dendritic cells die

Question 24

List the steps of antigen-induced B cell maturation

Answer 24

-Activation and migration of T and B cells

-T and B cells interact

-B cell differentiation: isotype switching and Ig secretion

-Germinal center reaction: affinity maturation, plasma cells, isotype switching, memory B cells

Question 25

Explain the difference between T-dependent and T-independent antigens and provide examples.

Answer 25

T-dependent antigens have proteins, and T-independent antigens do not.

Question 26

What are haptens?

Answer 26

Small molecules that cannot induce immune response on their own, but can when they are conjugated to a protein

Question 27

Diagram the T-cell:B cell interaction during a response to a hapten-protein conjugate.

Answer 27

-A carrier protein containing a linear peptide binds to B cell receptors

-The B cell internalizes the carrier protein

-The carrier peptide binds to MHC II

-The MHC II with the carrier peptide can be expressed on the B cell membrane and be presented to a T cell!

Question 28

In what context are hapten-protein conjugated useful?

Answer 28

Conjugate vaccines!

Question 29

Explain how excess circulating antibody to an antigen downregulates the humoral immune response to that antigen

Answer 29

Secreted antibodies will form complexes with antigens. When this antigen encounters BCR, the cell will come in contact with both the antigen and Fc portion of antibodies. This interaction blocks B cell receptors signaling by shutting down the tyrosine kinase pathway in the B cell.