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Immunology-Nicole > Assignment #11 --> B cell activation > Flashcards

Assignment #11 --> B cell activation Flashcards

1
Q

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

A

occurs in the secondary lymphoid tissues

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2
Q

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

A

Outer areas of follicles

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3
Q

what is the initiating stimulus for B cell activation?

A

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

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4
Q

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

A

BR3

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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)

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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

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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

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8
Q

What molecules are required for B cells to isotype switch?

A

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

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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)

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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

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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).

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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

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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.

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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.

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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.

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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.

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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)

Immunology-Nicole (20 decks)

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