Assignment #11 --> B cell activation Flashcards Preview

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Flashcards in Assignment #11 --> B cell activation Deck (41)
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1
Q

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

A

occurs in the secondary lymphoid tissues

2
Q

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

A

Outer areas of follicles

3
Q

what is the initiating stimulus for B cell activation?

A

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

4
Q

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

A

BR3

5
Q

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?

A

critical for B cell survival (escapes apoptosis)

6
Q

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?

A

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

7
Q

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

A

B7-1/CD 80 —> CD28

B7-2/CD86 —> CD 28

8
Q

What molecules are required for B cells to isotype switch?

A

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

9
Q

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

A

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

10
Q

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?

A

IgM antibodies

11
Q

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?

A

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).

12
Q

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

A

IL-4

13
Q

what is isotype switching (switch recombination)

A

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.

14
Q

what is affinity maturation/somatic mutation?

A

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

15
Q

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

A

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

16
Q

Differentiation of activated B cells to memory cells occurs where?

A

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

17
Q

what is the fate of memory B cells?

A

some colonize the secondary lymphoid tissues

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

18
Q

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

A

BAFF (B cell activating factor)

19
Q

What are the sources of BLyS?

A

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

20
Q

What is the stimuli for release of membrane bound BLyS?

A

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

21
Q

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

A

signaling via BR3 leads to B cell survival by preventing apoptosis

22
Q

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

A

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

23
Q

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

A

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

24
Q

what are T-dependent antigens?

A

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

25
Q

what are T-independent antigens?

A

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)

26
Q

Explain hapten, carrier molecule and carrier effect

A

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

27
Q

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

A

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

28
Q

what are the B cell mitogens?

A

pokeweed, and high concentrations of lipopolysaccharides

29
Q

what are the T cell mitogens?

A

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

30
Q

what mitogens bind carbohydrate molecules?

A

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

31
Q

what is one class of oligoclonal activators?

A

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

32
Q

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

A

Vbeta

33
Q

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

A

excessive amount of cytokines being released

34
Q

What is cytokine storm?

A

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

35
Q

Mutations in this protein leads to X-linked agammagobulinemia?

A

Btk

36
Q

What does not have a germinal center?

A
somatic recombination 
(differentiation to plasma cells, affinity maturation, isotype switching, and memory cell formation ALL HAVE germinal centers)
37
Q

Expression of IgD —->

A

mature B cell stage

38
Q

Tolerance Induction –>

A

immature b cell stage

39
Q

initial expression of CD19 —>

A

pro b cell stage

40
Q

initial expression of CD20 –>

A

pre- B cell stage

41
Q

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 ??

A

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