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MFMII > Humoral Immunity I - Activation of B cells > Flashcards

Humoral Immunity I - Activation of B cells Flashcards

1
Q

classes of Ab

A

MAGED

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2
Q

mechanisms of antibodies

A
  1. neutralization
  2. opsonization
  3. antibody dependent cell cytotoxicity
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3
Q

how do Ag flow into lymph node?

A

afferent lymphatics

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4
Q

what do follicular DC do? (FDC)

A

capture, concentrate and slowly release Ag (in follicles of lymph node) so B cells have a better chance of seeing Ag

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5
Q

what is a BCR crosslink

A

when a cluster of BCR engage with Ag which have repeats of epitope

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6
Q

what are the signaling molecules of BCR

A

Ig-alpha and Ig-beta

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7
Q

what occurs when BCR are activated?

A

Ig-alpha and beta ITAMs are phosphorylated by Src kinases

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8
Q

what occurs once ITAMs are phosphorlyated

A

Syk binds to ITAMs (acts like ZAP70 inT cells)

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9
Q

what does Syk binding do?

A

PLC and Ras pathways are activated and TF are bound to B cell DNA

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10
Q

what does Syk in B cells correspond to in T cells?

A

ZAP70 = Syk

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11
Q

what are components of B cell co-receptors?

A
  1. CR2 aka CD21
  2. CD19
  3. CD81
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12
Q

what does CR2/CD21 do

A

recognizes iC3b and C3d derivatives of C3b fragments

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13
Q

what is CD19

A

signaling chain of co-receptor

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14
Q

benefit of co-receptor activation in B cells?

A

increases BCR signaling events by 1,000-10,000

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15
Q

what occurs if patient lacks functional B cell co-receptor CD19 or 81?

A
  1. low levels of serum Ab
  2. limited isotype switching
  3. poor response to infections and vaccinations
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16
Q

unique characteristics of FDC

A
  1. extensive surface for large quanitities of Ag
  2. lack phagocytic activity
  3. Ag capture are preserved for months/years
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17
Q

how do FDC tether Ag

A

on CR1 and CR2 to be screened by naive B cells

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18
Q

what occurs first in B cell activation

A
  1. proliferation of B cell army

2. increased antiapoptotic factors like BCL

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19
Q

what occurs 2nd in B cell activation

A
  1. upregulated MHC I and II expression

2. increased B7 (CD80/CD86) which allows engagement with T cells

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20
Q

what occurs 3rd in B cell activation

A

increased cytokine receptors IL-2R, IL-4R, IL-5R, IL-21R

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21
Q

what occurs 4th in B cell activation

A
  1. CCR7 is upregulated (move to paracortex)

2. decreased CXCR5

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22
Q

what T helper cells reside near follicles

A

TFH (t follicular helper cells)

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23
Q

what do TFH do

A

promote Ab production

24
Q

where do pre-TFH live

A

interfollicular zone, so they have CCR7 and CXCR5 (localizes to paracortex)

25
Q

how are pre-TFH activated

A

DC engagement by presenting CD40, which makes secrete IL-2,IL-4,IL-5

26
Q

what does binding of DC to pre-TFH do?

A
  1. proliferation
  2. anti-apoptotic factors
  3. IL2,4,5
  4. other cytokines by signal 3
27
Q

what do activated pre-TFH cells do ?

A

engage activated B cells in the interfollicular zone to induce B cell proliferation and AID

28
Q

what does CD40 ligation between pre-TFH and B cell do

A

induces AID and makes pre-TFH fully differentiate into TFH

29
Q

which cytokines produced by TFH promote differentiation of B lymphoblasts into PC

A

IL-5
IL-6
IL-10

30
Q

describe B cell clonal expansion (primary focus)

A

B cells turn into B lymphoblasts which turn into plasma cells secreting IgM

31
Q

primary focus of B cell clonal expansion

A

turn into PC: in medulla, B and TFH cells divide and B cells become PC

32
Q

secondary focus of B cell clonal expansion

A

make a secondary follicle:
some B lymphoblasts leave medulla attached to TFH and go to primary follicle. the proliferation of these in primary make a secondary follicle

33
Q

what are centroblasts

A

rapidly dividing B cells with downregulated BCR (lost surface Ig)

34
Q

secondary focus of B cell clonal expansion again

A

make a germinal center:

TFH cells undergoing slower differentiation, so centroblasts push them and naive B cells out to form germinal center

35
Q

what does germinal center represent

A

B cell responses to specific Ag

36
Q

what TFH cytokines initiate proliferation

A

IL-2
IL-4
IL-5

37
Q

what sustains proliferation??

A

FDC cytokines

38
Q

what promotes somatic hypermutations

A

AID

39
Q

what induces more AID?

A

interactions of centroblasts with TFH cells in germinal center

40
Q

where do mutations occur on light and heavy chain

A

variable region

41
Q

benefit of somatic hypermutation

A

Igs with varying affinities for Ag, improves

42
Q

what are centrocytes

A

aka germinal center B cells, centroblasts that have completed a somatic hypermutation and now express a BCR

43
Q

what is affinity maturation

A

centrocytes engage FDC via BCR and CR2/CD21, and the centrocytes with the highest affinity BCR for Ag survive

44
Q

what occurs once centrocytes (GC B cells) win affinity maturation?

A

they engage TFH cells and differentiate into PC and also undergo isotype switching

45
Q

what signaling promotes proliferation and differentiation of GC B cells into PC

A

IL-10

IL-21

46
Q

what occurs if GC B cells and TFH don’t interact?

A

phagocytosed by tingible body macrophages

47
Q

what occurs if centrocyte and FDC don’t interact

A

phagocytosed by tingible body macrophages

48
Q

what plasma cells are generated first?

A

short lived to produce IgM, and undergo apoptosis as the long lived Pc are generated

49
Q

where are long lived PC localized?

A
  1. inflamed/infected tissues

2. bone marrow

50
Q

what do long lived PC do at inflamed tissue

A

secrete high levels Ig – long term, but undergo apoptosis once Ag levels go down

51
Q

what do long lived PC do in bone marrow?

A

is a memory plasma cell, don’t migrate, but they constantly secrete low levels of Ig *** this is what we want vaccines to do

52
Q

what are memory B cells?

A

non Ab producing B cells, serve as a reservoir for memory B cell responses and have a BCR.

53
Q

where are memory B cells?

A

remain in blood circulation or reside in lymphoid organs

54
Q

what induces memory B cell formation?

A

IL-4

switch of TFH cytokine production from IL-10 and IL-21 to IL-4 and IL-21

55
Q

what induces plasma cell formation

A

IL-10

IL-21

56
Q

what are immune complexes

A

secreted Ig that bind Ag

57
Q

how is Ig production regulated

A

Immune complexes form and bind to B cells on their Fc receptor. this activates phosphatase which removes phosphate from BCR signaling proteins to shut down Ab production in plasma cell

MFMII (29 decks)

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