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MIMM 214 > B Cells 1 > Flashcards

B Cells 1 Flashcards

1
Q

describe the inactivation of T cells by Tregs

A

if a Treg recognizes p:MHC on an APC, the APC is presenting self-peptides

then Tregs will secrete cytokines that inhibit AUTOREACTIVE T cells which recognize self-peptides:MHC

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2
Q

what are the 3 signals of B cell activation?

A

signal 1: p:BCR
signal 2: TCR:pMHCII, CD40L:CD40
additional signal: cytokines from Tfh

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3
Q

what type of T cell activates B cells?

A

Tfh

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4
Q

where do antibodies exert their effects?

A

at the site of infection

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5
Q

what are the 3 roles of antibodies?

A
  1. pathogen neutralization
  2. opsonization
  3. complement activation
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6
Q

what cytokines does Tfh secrete for B cell activation?

A
  1. IL-21
  2. type 1 (INFgamma), type 2 (IL-4), type 3 (IL-17)
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7
Q

what do the type 1/type 2/type 3 cytokines cause?

A

activate B cells to produce specific types of antibodies

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8
Q

what is IgM?

A

antibody class that acts as a receptor on naive B cells

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9
Q

where do B cells arise?

A

in bone marrow

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10
Q

are B cells specific or non-specific?

A

specific

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11
Q

what does it mean for B cells to be clonotypic?

A

each B cell has specificity to a unique antigen, then undergoes clonal expansion once it meets the antigen

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12
Q

B cells are progenitors for which types of cells? (2)

A
  1. antibody-producing plasma cells
  2. plasmablasts
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13
Q

what are plasma cells? what is their function?

A

activated and differentiated B cells

they are the main antibody-secreting cells

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14
Q

where are plasmablasts located?

A

B cells in a lymph node

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15
Q

what are plasmablasts?

A

B cells before they are plasma cells, show some features of plasma cells but cannot secrete Ab

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16
Q

describe the location of BCR?

A

inactivated B cell: membrane-bound

activated B cell: secretes BCR as antibody

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17
Q

describe the general process of clonal selection and expansion

A
  1. stem cell undergoes gene rearrangement for unique specificity
  2. meets antigen, proliferation
  3. differentiation
  4. plasma cell can secrete antibodies
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18
Q

why can naive B cells easily reach the lymph node?

A

naive B cells circulating in the periphery regularly pass through the lymph nodes and spleen

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19
Q

how do naive B cells enter the lymph node?

A

through the HEV

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20
Q

what happens if a B cell doesn’t encounter an antigen in the lymph node?

A

leaves via EFFERENT lymphatics

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21
Q

what happens if a B cell doesn’t encounter an antigen after a few months?

A

dies via apoptosis

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22
Q

what happens if a B cell does encounter an antigen in the lymph node?

A

provides survival signal - SIGNAL 1

23
Q

do B cells search for p:MHC?

A

no, B cells search for an antigen

24
Q

what are the 3 ways that antigen can end up in the lymph node?

A
  1. Ag from pathogens arrive in lymph node via afferent lymphatics by chance
  2. Ag opsonized by complement proteins
  3. Ag transported via activated conventional DCs and transferred to follicular/residential DCs in lymph node
25
Q

what type of cells become involved once opsonized antigens enter the lymph node?

A

subcapsular sinus macrophage (SCS macrophage)

26
Q

what type of macrophages are subcapsular sinus macrophages?

A

resident macrophages

27
Q

what do subcapsular sinus macrophages do?

A

they express complement receptor on their surface which binds the complement protein on the opsonized antigen, allowing the antigen to retain in the lymph node

28
Q

why are subcapsular sinus macrophages different than normal macrophages?

A

they have low endocytic and degradative activity –> won’t phagocytose the antigen, will just retain the antigen on their surface

29
Q

what do we mean by “antigen”

A

piece of a pathogen or the whole antigen

30
Q

are all antigens bound to subcapsular sinus macrophages?

A

no, they can be free floating in the lymph node

31
Q

what happens to the antigen bound to subcapsular sinus macrophages?

A

B cells can enter the lymph node and encounter the antigen, specifically binding the EPITOPE of an antigen via BCR

32
Q

where can antigens in lymph node be transferred? what is this important for?

A

antigens can transferred onto surface of follicular dendritic cells –> this is important for later stages in B cell differentiation

33
Q

describe the 2 potential parts of antigen binding to B cell

A

BCR binds antigen (sufficient by itself)

B cell expresses CD19 and CD21 co-receptors which bind complement (not necessary but can enhance signaling and activation)

34
Q

what are the signaling subunits of BCR?

A

Ig-alpha and Ig-beta

35
Q

describe the 2 steps of BCR signaling

A
  1. ITAM motifs on Ig-alpha and Ig-beta are phosphorylated
  2. multiple signaling pathways are activated
36
Q

what is an extra way for signaling to occur that is not necessary but is helpful?

A

co-receptor complex with CD19 and CD21 binding complement proteins

37
Q

what are the 3 main outcomes of BCR signaling?

A
  1. TFs activated, translocate, affect gene transcription
  2. survival signal via anti-apoptosis proteins
  3. cytoskeletal reorganization
38
Q

what is the purpose of cytoskeletal reorganization?

A

endocytosis of BCR-antigen once signaling begins

39
Q

describe the 3 steps of internalization and presentation of antigen by B cell

A
  1. antigen binds BCR, leads to signaling (exogenous)
  2. BCR-Ag complexes are internalized
  3. internalized Ag are processed and presented on MHC II
  4. this pMHC can interact with TCR on T cell
40
Q

what are the names for the 2 types of signal 2

A
  1. Thymus-dependent antigens (TD antigens)
  2. Thymus-independent antigens (TI antigens)
41
Q

which type of signal 2 is more common?

A

thymus-dependent antigens (TD antigens)

42
Q

what provides signal 2 for thymus-dependent antigens?

A

activated CD4+ Tfh cell

43
Q

what does signal 2 from thymus-dependent antigens lead to? (2)

A
  1. produces specific antibodies
  2. provides memory
44
Q

what provides signal 2 for thymus-independent antigens (TI antigens)? how does this work?

A

TLR signaling

TLR on B cells binds PAMP with the same antigen as the B cell

45
Q

what type of antigens are typically thymus-independent?

A

highly repetitive molecules that we are constantly exposed to, like LPS and crosslink on the BCR

46
Q

do all B cells provide signal 2 for thymus-independent antigens?

A

no, only some B cells

47
Q

does signal 2 from thymus-independent antigens cause antibodies or memory?

A

no

48
Q

what are the 2 signals that occur during signal 2 of B cell activation?

A
  1. signal from pMHC that has bound to TCR and co-receptors on Tfh
  2. signal from CD40 on B cells bound to CD40L on Tfh
49
Q

what does signal 2 directly result in?

A
  1. signaling
  2. activation of TFs
50
Q

what does signal 2 lead to?

A

activation, proliferation, differentiation –> for antibody secretion

51
Q

what is a common cytokine involved in B cell activation?

A

IL-21 from Tfh for B cell proliferation

52
Q

what is the difference in the peptides that TCR and BCR recognize?

A

BCR recognize epitope on full antigen

TCR recognize small pieces of antigen on MHC of APC

53
Q

what does linked recognition mean?

A

epitopes recognized by B cell and Tfh must be from the SAME ANTIGEN

but the actual peptide recognized by each may differ and recognition occurs differently for each cell type

54
Q

what is the purpose of linked recognition?

A

once Tfh and B cell have each recognized their epitopes, the Tfh can effectively activate the B cell

MIMM 214 (33 decks)

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