Assignment #11 --> B cell activation

Question 1

B cell activation –> in what tissue does the primary immune response occur?

Answer 1

occurs in the secondary lymphoid tissues

Question 2

B cell activation is initiated where in the secondary lymphoid tissues?

Answer 2

Outer areas of follicles

Question 3

what is the initiating stimulus for B cell activation?

Answer 3

antigen-induced crosslinking of mIg (immunoglobulins) in the B cell receptor complex

Question 4

What receptor is upregulated following crosslinking of the B cell antigen receptor

Answer 4

BR3

Question 5

BR3 ligand is BLyS and it is produced by and released from activated dendritic cells, monocytes, and macrophages. What is the significance of this interaction?

Answer 5

critical for B cell survival (escapes apoptosis)

Question 6

Class II MHC/peptide complex is recognized by activated CD4+ T cells and results in a T cell/B cell conjugate that is further stabilized by what adhesion molecules?

Answer 6

LFA-3 –> CD2
ICAM-1 –> LFA-1
ICAM-2 —> LFA 1

Question 7

what are the costimulatory molecules that facilitates several membrane bound ligand interactions

Answer 7

B7-1/CD 80 —> CD28

B7-2/CD86 —> CD 28

Question 8

What molecules are required for B cells to isotype switch?

Answer 8

CD 40 (B cells): CD40L/CD154 (T cells)

Question 9

what clinical disorder is associated with a mutation in CD40/CD40L/CD154 interaction?

Answer 9

Hyper IgM syndrome- patient only has IgM antibodies (isotype switching does not occur)

Question 10

Clonal expansion of activated B cells produces a population of B cells that will undergo different fates. Differentiation to the plasma cell stage occurs about 4 days after B cells interact with antigen. What antibody isotype is secreted by these plasma cells?

Answer 10

IgM antibodies

Question 11

B cells that have not undergone differentiation to plasma cells secreting IgM will undergo isotype switching and affinity maturation. What is the mechanism for isotype switching?

Answer 11

process by which cells expressing IgM and IgD are modified at the genomic level such that they produce antibodies of different isotypes (IgA, IgE, or IgG).

Question 12

Cytokines play a critical role in determining the isotype to which the B cell switches. Specify the cytokine required to isotype switch to IgE

Answer 12

IL-4

Question 13

what is isotype switching (switch recombination)

Answer 13

DNA encoding the mu and delta constant regions is excised, resulting in the juxtaposition of the heavy chain variable region to either an alpha,epsilon, or gamma heavy chain constant region.

Question 14

what is affinity maturation/somatic mutation?

Answer 14

process that leads to the gradual accumulation, with time after immunization, of higher affinity antibodies for the immunizing antigen.

Question 15

what is the significance of affinity maturation/somatic mutation in an immune response?

Answer 15

now there is production of an antibody with increase affinity for the immunizing antigen.

Question 16

Differentiation of activated B cells to memory cells occurs where?

Answer 16

in germinal centers, beginning approximately one week after antigenic challenge with a T dependent antigen.

Question 17

what is the fate of memory B cells?

Answer 17

some colonize the secondary lymphoid tissues

most join the pool of recirculating B cells that circulate the blood, lymph and tissues.

Question 18

BLyS (B cell stimulator), what is another name?

Answer 18

BAFF (B cell activating factor)

Question 19

What are the sources of BLyS?

Answer 19

monocytes/macrophages, dendritic cells, and some lymphocytes (LYS-DML)

Question 20

What is the stimuli for release of membrane bound BLyS?

Answer 20

Release of BLyS from monocytes/macrophages and dendritic cells is triggered by cytokines, or by crosslinking of FcgammaR by IgG an opsonin

Question 21

what is the effect of BLyS interaction with BR3 on activated B cells?

Answer 21

signaling via BR3 leads to B cell survival by preventing apoptosis

Question 22

What are three disorders in which abnormal production of BLyS has been documented?

Answer 22

Rheumatoid arthritis (RA)
Systemic Lupus Erythematosus (SLE)
Multiple Sclerosis

Question 23

Secondary immune responses (activation of memory B cells), explain lag time, antibody titer and site of activation

Answer 23

shorter lag time, lead to a higher antibody titer, secretion of antibodies of the new isotype, and can occur anywhere in the body .

Question 24

what are T-dependent antigens?

Answer 24

antigens that can induce naive (mature) B cell activation only when cognate interaction with CD4+ T cells, and cytokines derived from the T cells are available to the B cell

Question 25

what are T-independent antigens?

Answer 25

antigens that can induce naive (mature) B cell activation in the absence of cognate interaction with T cells (i.e this is called T cell help)

Question 26

Explain hapten, carrier molecule and carrier effect

Answer 26

small molecules (hapten), less than 5kd, become immunogenic when coupled to large proteins (carrier). this is called carrier effect

Question 27

Polyclonal activators are termed mitogens what is the role of these activators?

Answer 27

have the capacity to bind to, and trigger proliferation of many clones of lymphocytes.

Question 28

what are the B cell mitogens?

Answer 28

pokeweed, and high concentrations of lipopolysaccharides

Question 29

what are the T cell mitogens?

Answer 29

concanavalin (Con A), phytohemagglutinin (PHA), and pokeweed mitogen (PWM).

Question 30

what mitogens bind carbohydrate molecules?

Answer 30

Con A and PHA are plant glycoproteins, commonly referred to as lectins

Question 31

what is one class of oligoclonal activators?

Answer 31

superantigens; that are often bacterial products that activate subsets of T cells

Question 32

what region of the T cell receptor do superantigens bind to?

Answer 32

Vbeta

Question 33

what happens when there is activation of all T cell clones that express this Vbeta region?

Answer 33

excessive amount of cytokines being released

Question 34

What is cytokine storm?

Answer 34

effect of excess cytokines (again being secreted from these T cell clones)

Question 35

Mutations in this protein leads to X-linked agammagobulinemia?

Answer 35

Btk

Question 36

What does not have a germinal center?

Answer 36

``` somatic recombination (differentiation to plasma cells, affinity maturation, isotype switching, and memory cell formation ALL HAVE germinal centers) ```

Question 37

Expression of IgD ---->

Answer 37

mature B cell stage

Question 38

Tolerance Induction -->

Answer 38

immature b cell stage

Question 39

initial expression of CD19 --->

Answer 39

pro b cell stage

Question 40

initial expression of CD20 -->

Answer 40

pre- B cell stage

Question 41

Sam, a high school student, has been diagnosed with acute lymphocytic leukemia. Peripheral blood cells from the patient were incubated with anti-CD19 fluorescent antibodies. Flow cytometric analysis revealed a high intensity immunofluorescence, indicating enhanced expression of CD19, relative to controls. Cells that were detected must have been in the ??

Answer 41

Pro B cell stage or Pre B cell stage or immature B cell stage (answer: could be any of these)