German - B Cell Mediated Immunity Flashcards

1
Q

What chemokine attracts immature B cells to the HEV?

A

CCL21

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2
Q

What chemokines attract B cells into lymph nodes?

A

CCL21

CCL19

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3
Q

What chemokine attract B cells into the primary follicle?

A

CXCL13

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4
Q

Immature B cells are high in Ig__ and low in Ig__.

Mature B cells are high in Ig__ and low in Ig__.

A

IgM

IgD

IgD

IgM

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5
Q

T/F - Mature B cells recirculate b/t lymph, blood, and secondary lymph tissues.

A

TRUE

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6
Q

________ and ________ _________ _________ display antigen to B cells.

A

Macrophages

Follicular dendritic cells

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7
Q

B cell activation drives what 3 things?

A

Clonal expansion

Class switching

Somatic hypermutation

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8
Q

________ is bound to _______ in antibody crosslinking.

A

Antibody

Antigen

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9
Q

Tell me about signal 1: Antibody Crosslinking

A

Antibody is bound to antigen

Clustering and aggregation

Igalpha and Igbeta signaling

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10
Q

Signal 2: B cell co-receptor signaling does what?

A

Ensures target is pathogenic

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11
Q

What does signal 2: B cell co-receptor signaling do (detailed)?

A

Prevent anergy

Distinguishes b/t foreign and self-antigen

Initiates clonal expansion

Co-receptor signals are diverse (Play the “Co-receptor” role)
—CR2, CD19, CD81, complement, TLRs, CD40

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12
Q

What co-receptor signals are b-cell co-receptor complex?

A

Complement

CR2, CD19, CD81

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13
Q

What co-receptor signal are pattern recognition receptors?

A

TLRs

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14
Q

What co-receptor signals are CD40?

A

CD4 T cells

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15
Q

Signal 3 is what?

A

Cytokine signaling

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16
Q

What is involved with signal 3: cytokine signaling?

A

Tfh cells are most common source of cytokines during B cell activation

Local cytokines can provide signals in the absence of T cell-mediated activation

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17
Q

What re the 4 roles of cytokine signaling?

A

Survival and proliferation

Class switching
-Same epitope binding, different heavy chain

Somatic hypermutation
-Increases antibody specificity

Differentiation
-Produces plasma cells and memory B cells

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18
Q

B and T cells form cognate pairs where?

A

At the follicle boundary

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19
Q

What happens at the primary focus?

A

Produce IgM expressing plasma cells for several days

NO class-switching or somatic hypermutation

*In the medulla

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20
Q

What happens at the secondary focus?

A

Enormous proliferation and plasma/memory cell production
-Germinal center

Class switching and somatic hypermutation

Selection of most specific plasma cells

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21
Q

Cognate pairs first form ________.

A

Centroblasts

  • Form germinal center dark zone
  • Proliferating source of new B cells
  • Create centrocytes
  • DO NOT EXPRESS SURFACE IMMUNOGLOBULIN
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22
Q

What do centrocytes do?

A

Form light zone

Divide slowly

Express surface immunoglobulin

CanNOT class switch or hypermutate

Programmed to die

Interact with follicular dendritic cells

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23
Q

T/F - Class switching and somatic hypermutation improve antibody specificity.

A

TRUE

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24
Q

What are the 2 antigen types that B cells face?

A

Thymus-dependent antigen

Thymus-independent antigen

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25
Q

Tell me about thymus-dependent antigen.

A
  • Protein
  • Protein-associated antigen
  • Th cell interaction required
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26
Q

Tell me about thymus-independent antigen.

A
  • PRR-detected antigen

- Complement-bound antigen

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27
Q

B cell activation involves at least 2, sometimes 3 signals. What are they?

A

1 - Antibody crosslinking
—Activation

2 - Co-receptor signaling
—Survival and proliferation

3 - Cytokines
—Differentiation, class switching, somatic hypermutation

SIGNALS 1 AND 2 ARE REQUIRED

*Signal 3 happens some of the time

28
Q

TD antigen corresponds to what B cell activation antigen type?

A

Thymus-dependent antigen

  • Protein
  • CD4Tfh cells are needed*
29
Q

TI-1 and TI-2 antigens correspond to what B cell activation antigen type?

A

Thymus-independent

*Independent of T cell signals

30
Q

_______ cells drive B cell activation, proliferation, enhanced specificity, and differentiation into plasma and memory cells.

A

Tfh

31
Q

T/F - Tfh cell activation is the most common, but not sole pathway of activation.

A

TRUE

*TI activation

32
Q

T/F - Tfh activation typically yields a larger population of plasma and memory cells.

A

TRUE

33
Q

Tfh cells interact with which MHC?

A

MHC II

34
Q

T/F - Tfh cells aid in B cell activation.

A

TRUE

35
Q

Tell me about Tfh cells aiding in B cell activation.

A

MOST COMMON B CELL ACTIVATION PATHWAY

B cell first activated by antigen binding

B cell presents antigen to Tfh cells

CD40 induces survival and proliferation

Cytokines

  • Differentiate to plasma or memory
  • Isotype switch in germinal centers
36
Q

Class switching and somatic hypermutation improve what?

A

Antibody specificity

37
Q

Tell me 4 things with class switching.

A

RAG proteins deactivated

Change heavy chain Fc region

Cytokine induced

Classes dictate effector fxs

38
Q

Tell me about somatic hypermutation.

A

Mutations happen in hypervariable regions

Single nucleotide insertions and substitutions

Produces new epitope binding region

As centroblasts divide, more mutation are produced

Increases antibody affinity

39
Q

T/F - Only centrocytes that bind FDCs bind Tfh cells.

A

TRUE

-FDC = Follicular dendritic cell

40
Q

What secretes antibody?

A

Plasma cells

41
Q

Naive B cells have what 2 intrinsic things and 3 inducible things?

A

Intrinsic

  • Surface Ig
  • Surface MHC II

Inducible

  • Growth
  • Somatich hypermutation
  • Isotype switch
42
Q

Plasma cells have what intrinsic factor?

A

High-rate Ig secretion

43
Q

What are the four effector fxs of antibodies?

A

1 - Virus and toxin NEUTRALIZATION -> Prevents pathogen-host binding

2 - OPSONIZATION -> Phagocytosis

3 - COMPLEMENT -> Phagocytosis or lysis

4 - ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY (ADCC) -> NK-induced apoptosis

44
Q

Give me an overview of B cell activation Part 1

A

Naive, mature B cell

  • Circulates
  • Antigen browsing

If activated by an antigen, 3 signals occur

  • IgD antigen binding
  • Co-receptor signaling
  • Cytokine

OR, it differentiates into a plasma cell

  • TI activation
  • Local cytokine-induced class switching
45
Q

Give me an overview of B cell activation Part 2

A

Most common pathway

  • B and Tfh cell form a cognate pair —> Cognate pair primary focus (In medulla of lymph nodes)
  • IgM plasma cells can come from this

OR

Cognate pair goes to secondary focus (Germinal center) —> Centroblasts (Secondary focus)

  • Clonal source
  • Rapid proliferation
  • Class switching
  • Somatic hypermutation
46
Q

Give me an overview of B cell activation Part 3 (Final part)

A

After centroblasts —> centrocytes (secondary focus)

  • FDC selection
  • Proliferation (relatively limited)
  • Differentiation

—> Plasma cells

Memory B cells formed and circulate periphery, LNs, and bone marrow

47
Q

Cognate pairs first form ________.

A

Centroblasts

  • In germinal center of dark zone
  • No immunoglobulin expressed
  • Somatic hypermutation
  • Proliferating source of new B cells
  • Class switching
  • -Create centrocytes*
48
Q

Centrocytes form ______ _______ and ________ ________.

A

Plasma cells

Memory B cells

  • Form in the light zone
  • Slowly divide
  • Express immunoglobulin
  • No class switching or hypermutation
  • Interact w/ and selected by follicular dendritic cells
  • Programmed to die
49
Q

IgA good for what?

IgE good for what?

IgD good for what?

A

IgA - Mucosal surfaces

IgE - Parasite immunity, receptor

IgD - B cell receptor

IgM - Good in the vasculature
—Complement fxs

50
Q

Which Ig is good at crossing barriers?

A

IgG

51
Q

Fc receptors allow adaptive immunity for what?

A

To enhance innate immune cell specificity and fx

52
Q

Fc receptors bind _____ and provide adaptive _______ to innate cells.

A

Antibodies

Specificity

53
Q

T/F - Fc receptors are widespread and diverse.

A

TRUE

54
Q

Tell me about Fc receptors.

A

Monomeric and dimeric

Often req dimerization

Majority of them IgG, IgE, IgA

Enhance innate immunity

Stim and inhibit effector fxs

  • Cytokine production/release
  • Phagocytosis
  • Degranulation
  • Targeted killing
55
Q

T/F - Fc receptors facilitate IgG transport into tissues.

How?

A

TRUE

Endocytosis
-low pH of vesicles causes IgG to associate with FcRn (protects it from proteolysis)

Reaches basolateral face of endo cell, and basic pH of ECF dissociated IgG from FcRn

56
Q

_________ of IgA protects mucosal surfaces.

A

Transcytosis

57
Q

What is the PIgR?

A

Poly-Ig receptor

-Binds Fc

58
Q

What is transcytosis?

A

Binding of IgA to receptor on basolateral surface of epithelial cell

Leads to receptor-mediated endocytosis of IgA

T-port of IgA to apical face of epi cell

Receptor cleaved and IgA is bound to mucus

59
Q

What is one method of preventing pathogen establishment?

A

Neutralization

*DONE BY IgA and IgG

60
Q

__________ clear agglutinized antigens in the _________.

A

Erythrocytes

Spleen

*Via CR1, C3b, and RBC carries immune complex to SPLEEN or liver and macrophaged

61
Q

T/F - Opsonization leads to phagocytosis.

A

TRUE

62
Q

What Ig makes mast cells, basophils, and eosinophils competent?

A

IgE

  • Targeted degranulation
  • Important in allergy
63
Q

What two Igs initiate the classical complement pathway?

A

IgM

IgG

64
Q

What gives the innate system some specificity (in terms of broad effector fxs)?

A

ADCC

-Antibody-dependent cellular cytotoxicity

65
Q

Tell me about ADCC.

A

Anti-CD20 antibody binds CD20 on surface of B cell lymphoma

Fc receptors on NK cell recognize bound anti-CD20 antibody

Fc receptors signal NK cell to kill B cell lymphoma

B cell lymphoma dies via apoptosis

66
Q

Ig_ provides passive immunity during gestation, while Ig_ protects infant mucosal surfaces via the breast milk.

A

IgG

  • Crosses the placenta
  • Provides immediate immunity out of the womb and has a 20-30 day 1/2 life

IgA