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06. HDM Test 2 > 3. Humoral Immune Responses > Flashcards

3. Humoral Immune Responses Flashcards

1
Q

What broad class of antigens is T Dependent for B Cell antibody production?

A

Protein antigens

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2
Q

What class of antibody is produced in greater numbers during the secondary antibody response?

A

IgG

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3
Q

Which complement system is often activated by the presence of polysaccharides?

A

Alternative pathway

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4
Q

What is the function of CD81?

A

Ensures normal CD19 expression, and forms a complex with CD19 as well.

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5
Q

What is required for T Follicular Helper Cell (Tfh) activation?

A

Sequential activation by dendritic cells, then by activated B Cells

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6
Q

What disease has been linked to a polymorphism in FcγRIIb?

A

Systemic lupus erythematosus

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7
Q

What is the function of the CD19 B Cell co-receptor

A

Acts as the dominant signaling component of B Cells.

Works with CD21 to lower the antigen threshold for B Cell activation (positively regulates B Cell activation)

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8
Q

Where would you find high affinity B Cells?

A

In the light zone of the germinal center with the follicular dendritic cells.

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9
Q

What class of antibody is produced in greater numbers during the primary antibody response?

A

IgM

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10
Q

How does somatic hypermutation lead to more specific antibodies?

A

Mutations occur in the V region while the B Cells are in the germinal center. Antigens contact the B Cells, and if they can internalize and present the antigen to Tfh cells, they are rescued from apoptosis. The B Cells with more specific antibodies are more likely to survive, ala Darwinian Evolution.

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11
Q

How does the activation of Helper T Cells by B Cells promote B Cell proliferation and differentiation?

A

Helper T Cells that are activated by B Cells begin to produce CD40L, which binds to CD40 on the B Cell and triggers differentiation.

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12
Q

What are two examples given for tyrosine phosphatases recruited by phosphorylated ITIMs?

A

SHP and SHIP

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13
Q

What is C3d?

A

A fragment of C3b, that is left on the antigen when C3b is degraded.

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14
Q

What do you find in the dark zone of the germinal center?

A

Proliferating B Cells

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15
Q

How to marginal zone B Cells shuttle antigens to the follicular region?

A

They bind immune complexes coated in compliment fragments with their compliment receptors (CRs) “in a manner independent of B Cell receptor specificity.”

Follicular dendritic cells then compete for binding and present to the follicular B Cells. The marginal zone B Cells then go back to the marginal zone.

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16
Q

Why are the germinal centers a location for “tremendous apoptosis?”

A

Because most B Cells are out competed by higher affinity B Cells

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17
Q

What are the three receptors involved in the B Cell co-receptor complex?

A

CD19, CD21, CD32

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18
Q

What is the function of Syk?

A

Phosphorylates BLNK, and recruits BTK and PLC-γ, which continue the B Cell receptor signal

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19
Q

What chemokine attracts naive B Cells to the lymphoid follicles?

What cell produces these chemokines?

A

CXCL13

Dendritic cells

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20
Q

How do phosphorylated ITIMs continue their inhibitory signal?

A

They recruit an SH2 domain-containing tyrosine phosphatase, which attenuates immune receptor signaling.

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21
Q

What is the function of IL-21?

A

Generates B-cell responses in germinal centers

Results in isotype switching, affinity maturation, and antibody production.

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22
Q

Which antibody response, primary or secondary, releases antibodies with a higher average affinity?

A

Secondary

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23
Q

What are the characteristics of a secondary antibody response, relative to the initial response?

A

Faster response (1-3 days instead of 5-10)

Peak response is higher (more antibodies)

More heavy chain isotype switching

Higer average affinity

pg 150

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24
Q

Where might memory B Cells be found?

A

Some may remain in the lymphoid organ in which they were produced.

Others recirculate between the blood and lymphoid organs

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25
Q

What causes activation of the B Cell receptor?

A

Cross Linking

The B Cell must have multiple receptors activated at one time

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26
Q

What cytokine promotes expression of IgA?

A

TGF-β

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27
Q

What is the function of the CD21 B Cell co-receptor?

A

It is a compliment receptor (aka CR2)

Works with CD19 to lower the antigen threshold for B Cells

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28
Q

By what mechanism is CD40 essential for B Cell isotype switching?

A

CD40 induces Activation-Induced Deaminase (AID) which is necessary for isotype switching.

29
Q

What kind of antigen can be presented to marginal zone B Cells by marginal zone macrophages?

A

Polysaccharide antigens

30
Q

How might one create a vaccine against a polysaccharide, since TI B Cells don’t create memory cells?

A

Create a hapten-carrier conjugate vaccine by linking a foreign protein to the polysaccharide.

31
Q

What happens to the B Cells after B-T interaction?

A

The B Cells become short lived plasma cells, mainly producing IgM, and head to the germinal centers for affinity maturation, isotype switching, and memory B Cell / long lived plasma cell generation.

32
Q

Which subset of B Cell antigens is typically multivalent?

Why does this matter?

A

T Independent (TI) antigens

(eg. polysaccharides)

Multivalency leads to additional cross linking, which helps amplify the B Cell’s intracellular signaling since it doesn’t have T Cell help.

33
Q

What is the function of follicular dendritic cells?

A

They retain immune antigen-antibody complexes on their surface for long periods so they can contact B Cells.

Drives antibody affinity maturation.

34
Q

What cell causes a B Cell to undergo isotype switching?

A

Tfh cells

35
Q

What three receptors are used by follicular dendritic cells to retain antigens?

A

FcγRIIb (Fc receptor)

CR1 and CR2 (aka CD21 - compliment receptors)

36
Q

Where does B Cell isotype switching typically occur?

A

Inside the germinal centers

37
Q

What mechanism makes TLR signaling in B Cells an interesting topic for vaccine design?

A

TLR stimulation can cause proliferation of B Cells and differentiation into plasma cells, which means TLR signaling has an adjuvant effect in immunization.

38
Q

What isotype of antibody is promoted by IFN-γ?

A

IgG (involved in intracellular pathogen blocking)

39
Q

What kinase is responsible for phosphorylating ITIMs to inhibit B Cell responses?

A

Src kinases

40
Q

How might a Tfh cell induce apoptosis in a B Cell not presenting an antigen?

A

Some Tfh cells produce FasL to recognize Fas on a B Cell and induce Fas mediated apoptosis.

41
Q

When B Cells are activated, what receptor induces migration toward the T Cell zone?

A

CCR7

42
Q

What are “natural antibodies” and what produces them?

A

Antibodies that are produced without prior exposure to the antigen

Produced by T Independent B Cells

43
Q

Are Follicular B Cells T Dependent or Independent?

What about Marginal Zone B Cells and B1 Cells?

A

Follicular B Cells are T Dependent

Marginal Zone and B1 B Cells are T Independent

44
Q

What subset of T Cells primarily responds to protein antigens?

A

Follicular T Cells

45
Q

What do marginal zone B Cells primarily respond to?

A

Polysaccharides

46
Q

How do larger antigens get presented to follicular B Cells?

A

They are consumed by APCs and carried there.

47
Q

Why might a B Cell lymphoma be likely to occur?

A

Because the DNA breaks associated with somatic hypermutation and isotype switching facilitate incorporation of oncogenes.

48
Q

What do you find in the light zone of the germinal center?

A

Follicular Dendritic cells

49
Q

Where are the B-1 cells produced, and when?

A

They are produced in the fetal liver, by the eighth gestational week.

50
Q

How does activation of CD21 (CR2) lead to phosphorylation cascades inside the cell?

A

By bringing CD19 in proximity to BCR associated kinases, causing CD19 to become phosphorylated, and recruiting Lyn kinase to phosphorylate ITAMs.

51
Q

What anti-apoptotic protein is produced by memory B Cells that allows them to survive for so long?

A

BCL-2

52
Q

What part of the B Cell receptor complex contains ITAMs?

A

Igα and Igβ

53
Q

What are the functions of SHP and SHIP?

A

They remove phosphates from PIP3 and thus inhibit PI3-kinase activity in lymphocytes NK cells and innate immune cells

54
Q

What process might randomly create a self-reactive B Cell after it’s already been activated by a non-self antigen?

A

Somatic hypermutation

55
Q

What is the funciton of Tfh cells?

A

Secretion of IL-21 to assist in the germinal reaction (production of plasma cells)

Secretion of IFN-γ and IL-4 to control isotype Th1/Th2 switching

56
Q

What might cause a microbial antigen that has been opsonized by C3d to have a greatly enhanced B Cell activation?

A

The antigen-C3d complex can activate the B Cell receptor and CD21 (CR2) simultaneously.

57
Q

What is the relationship between PAMPs and B Cell activation?

A

B Cells produce TLRs to recognize PAMPs, and simultaneous PAMP recognition by BCR and TLRs may contribute to B Cell activation.

58
Q

How do small antigens get delivered to B Cells in follicles?

A

They are washed directly into the follicles by the subcapsular sinus, where they meet B Cells without an APC.

59
Q

What might induce T Independent B Cells to switch isotypes (even though this doesn’t happen very often)?

A

Specific antigens (Eg: Pneumococcal capsular polysaccharide induces IgG2)

TGF-β (induces IgA at mucosal sites)

BAFF produced by DC and Macrophages can induce AID synthesis

60
Q

What is the function of the CD32 (FcγRIIB) B Cell co-receptor?

A

Contains an ITIM and negatively regulates BCR signaling

61
Q

What class of antigen is more likely to elicit a secondary immune response?

A

Protein antigens

62
Q

What is the function of fyn, lck, and blk?

A

Activate Syk kinase

63
Q

What motif will you typically find on inhibitory receptors?

A

ITIMs

64
Q

What part of the genome controls the Class-Switch Recombination (CSR)?

A

The “Switch” (S) Sequence

65
Q

What happens when an antigen binds to a BCR, but an already secreted antibody bound to that antigen binds to FcγRIIb?

A

The phosphatases associated with FcγRIIb prevent the B Cell from being activated, despite the association with the BCR.

66
Q

What is the main mechanism of defense against encapsulated bacteria?

A

Humoral immunity (antibodies)

67
Q

How does affinity maturation occur?

A

Over time, in the germinal center, less and less antibody is available for binding. As a result, only the B Cells with the highest affinity / specificity for their antigen are able to survive.

68
Q

What sort of pathogen is likely to be captured by plasmacytoid dendritic cells and delivered to marginal zone B Cells in the spleen?

A

Blood borne pathogens

69
Q

When high affinity Ig - containing B Cells are selected for and become long lasting plasma cells, where do they go?

A

The bone marrow.

06. HDM Test 2 (9 decks)

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