Immunity mediated by B cells and antibodies Flashcards

1
Q

B cell activation requires ___

A

2 signals

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2
Q

What 2 signals are required?

A
  1. Antigen binding B receptor
  2. Helper T Cell delivers 2nd Signal – CD40

Cytokines also help

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3
Q

Describe the Antigen Binding signal

A
  1. B cells become cross-activated when receptors are linked
  2. Clustering allows receptor ass. kinases to Phs. ITAMs
  3. Syk binds double P’d ITAMs, is activated
  4. Changes in gene expression
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4
Q

3 B Cell components of Co-receptor complex

A

CR2
CD19
CD81

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5
Q

What does CR2 bind?

A

C3d

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6
Q

What is the purpose of the coreceptor complex?

A

To lower the threshold of B cell activation

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7
Q

Four Activities Following B Cell Activation

A

Proliferation
Somatic Hypermutation (Affinity Maturation)
Isotype Switching
Dev. of Memory and Plasma cells

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8
Q

What B cells are present in the Mantle Zone?

A

Naive Unactivated

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9
Q

What B cells are present in the Germinal Centers?

A

Active, Proliferating

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10
Q

What do B Cells need to enter the LN (via afferent lymphatic)

A

Actual Antigen

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11
Q

Antigen goes from the afferent lymphatic into the ______

A

Subcapsular Sinus

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12
Q

How does antigen get from the subcapsular sinus into the Node?

A

Macrophage pickup using CR2

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13
Q

How do Peyer’s Patches/Tonsils let in antigen?

A

Specialized epithelial cells for transport

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14
Q

Steps of Naive B Cell Activation

A
  1. Naives look for their antigen on FDC
  2. Antigen Activated Bs go to Boundary region
  3. AA Bs present ant to effector T-fh cells - form pair
  4. Bound pairs migrate to medullary cords, EXPANSION
  5. Bound pairs migrate to Primary Follicle, 2dary EXPANSION
  6. Expansion of Primary Follicle generates Germinal Center
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15
Q

Germinal centers are full of what cell?

What does this cell do?

A

Follicular Dendritic Cell

CR1 and CR2 on FDCs holds antigen in place for several months

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16
Q

How is a follicular dendritic cell different than a DC?

A

Fibroblast lineage, Not from BM

No MHC II

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17
Q

How does somatic hypermutation work?

A

Activated B cell mutates V regions
Different versions of the B cell compete for binding to the antigen on the Folicular cell
No Binding = Death, Higher Affinity Bs bind, receive anti-apoptotics from helper T.

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18
Q

Two important signals a B gets from a T helper

A
  1. CD40 triggers isotype switching

2. Cytokines afterward influence what switching will occur

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19
Q

IFN-gamma drives what B cell type expression?

A

IgG2a, IgG3

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20
Q

TGF-beta and IL-5 trigger what diff in B cells

A

IgA, IgG2b

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21
Q

Il-4 triggers what kind of differentiation?

A

IgE, IgG1

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22
Q

Antigen selected centrocytes will tend to become plasma cells if exposed to _____ or memory cells if exposed to _______>.

A

Plasma – IL-10

Memory – IL-4

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23
Q

Mutation of CD40L will cause…

A

Hyper-IgM syndrome

Lack of Isotype Switching

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24
Q

Inheritance of Hyper-IgM syndrome?

A

X linked

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25
Q

What is seen in the blood of a Hyper-IgM syndrome patient

A

No IgG, IgA

Increased IgM

26
Q

How do TI-1s activate B cells?

A

Via a non Ig receptor, for example using TLR4 to activate upon exposure to LPS

27
Q

How to TI-2s activate B cells

A

Chains of epitopes that cause extensive cross linking signaling of Ig on B cell surface

28
Q

What do TI-2s tend to target?

A

Polysaccharids, sometimes proteins

29
Q

Why is it important that TI-2s can act without help from T cells?

A

Ts recognize peptide fragments.

Polysachharide aren’t processed that way, so no CD4s

30
Q

T-dependent, TI-1, TI-2. Who is present in athymic people?

A

TI-1, TI-2

31
Q

T-dependent, TI-1, TI-2. Who does idotype switching?

A

Only T-dep

32
Q

T-dependent, TI-1, TI-2. who makes memory cells?

A

Only T dep

33
Q

T-dependent, TI-1, TI-2. Who works in infants?

A

Tdep and TI-1

34
Q

How do conjugate vaccines work?

A

Polysaccharide target is bound to a peptide toxoid
B cell binds antigen, toxoid is presented to Thelper
Activated B differentiates into plasma cell against polysac.

35
Q

Three bacteria targeted by Conjugate polysaccharide vaccines?

A

Haemophilius influenzae
Streptococcus pneumoniae
Neisseria meningitidis

36
Q

What is streptococcus pneumoniae?

Gram? Symptoms? Serotypes?

A

G+
Upper Resp. Inf, Otitis Media, Pneumonia
Over 90 serotypes

37
Q

Problems with using a vaccine against only the most common disease types?

A

Increases in prevalence of non-vaccine types

38
Q

Unique movement of IgA and IgG?

A

IgA – Across Epithelials into Mucosal Secretions

IgG – Across Endotheliams into Extravascular Space and across placenta

39
Q

What receptor mediates IgA travel across epithelial cells?

A

Polymeric Immunoglobulin Receptor

40
Q

What receptor mediates IgG travel across endothelial cell

A

Brambell Receptor (FcRB

41
Q

How does IgA get across epithelial cells?

A

Binding to poly-Ig rec. on the basolateral face
Endocytosis + Transcytosis
Receptor Cleaved
IgA bound to Mucus through Secretory Piece

42
Q

Poly-Ig receptor can transfer which two antibodies

A

IgA and IgM (but almost always does A)

43
Q

How big is A1 hinge region? A2?

A

26 aa

13 aa

44
Q

Role of secretory componeny in IgA dimer?

A

Wraps around J Chain – May help prevent protease activity

45
Q

IgA2 is most found…

A

In the digestive tract (esp. Ileum+Colon)

Shorter chain makes harder to cleave there

46
Q

How does IgG get across endothelial cells?

A

Binding to FcRB, transcytosis

Mostly active transport

47
Q

At birth, what antibodies does an infant have?

Which come along later?

A

Maternal IgG and Fetal IgM

Fetal IgA and IgG

48
Q

Name three effector functions of antibodies.

A

Neutralization
Opsonization
Complement Activation

49
Q

Who expresses Fc-gamma receptors?

A

Neut, Mac, B Cells, FDCs, NKs

50
Q

Purpose of Fc-gamma receptors?

A

Opsonization and Antibody-dependent cell-mediated cytotoxicity

51
Q

Purpose of Fc-epsilon receptors? Who expresses them?

A

Important in allergic reactions

Expressed on Mast Cells and Basophils

52
Q

FcR1 is on _____ and has a high affinity for ___

Describe its action.

A

Mac and Neut. IgG1 and IgG3
FcR1 binds the lower hinge/CH2 of Ig, Ig binds antigen
More efficient phagocytosis

53
Q

Which Fc has the strongest relative binding strength to IgG1?

A

Fc-gamma R1 (CD64)

54
Q

Which Fc-gamma receptors are inhibitory

A

RIIIB2, RIIIB1

CD32

55
Q

How does antibody dependent cell mediated cytotoxicity work?

A

Antibody binds target
Fc receptors of NK cells recognize Ab
Crosslinked Fc receptors signal NK cell to kill the target
Apoptosis

56
Q

Describe the relationship of IgE and Mast Cells

A

IgE binds onto Fc-gammaR1 on mast cells

On second exposure, antigen binding to bound antibodies will trigger degranulation

57
Q

IgG3 is unique for…

A

Long Hinge
Large Heavy Chain + many disulfide bonds
Very susceptible to clevage, so short half-life
Great ability to activate complement

58
Q

What is IgG4 good at?

A

Allergen Response

59
Q

How long do untriggered naive B cells live?

A

3-8 weeks

60
Q

Short lived plasma cells in the medulla generate….

A

IgM for approx. 5 days

Forms initial response to infection

61
Q

What happens in secondary response if Naive B binds to a path coated in antibody?

A

Negative signal is given to naive B

Activation prevented

62
Q

What happens in secondary response if Memory B cell binds a pathogen coated in Ab?

A

Memory B is activated
Becomes a plasma cell
Produces high-affinity IgG, A, and E