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
What is seen in the blood of a Hyper-IgM syndrome patient
No IgG, IgA | Increased IgM
26
How do TI-1s activate B cells?
Via a non Ig receptor, for example using TLR4 to activate upon exposure to LPS
27
How to TI-2s activate B cells
Chains of epitopes that cause extensive cross linking signaling of Ig on B cell surface
28
What do TI-2s tend to target?
Polysaccharids, sometimes proteins
29
Why is it important that TI-2s can act without help from T cells?
Ts recognize peptide fragments. | Polysachharide aren't processed that way, so no CD4s
30
T-dependent, TI-1, TI-2. Who is present in athymic people?
TI-1, TI-2
31
T-dependent, TI-1, TI-2. Who does idotype switching?
Only T-dep
32
T-dependent, TI-1, TI-2. who makes memory cells?
Only T dep
33
T-dependent, TI-1, TI-2. Who works in infants?
Tdep and TI-1
34
How do conjugate vaccines work?
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
Three bacteria targeted by Conjugate polysaccharide vaccines?
Haemophilius influenzae Streptococcus pneumoniae Neisseria meningitidis
36
What is streptococcus pneumoniae? | Gram? Symptoms? Serotypes?
G+ Upper Resp. Inf, Otitis Media, Pneumonia Over 90 serotypes
37
Problems with using a vaccine against only the most common disease types?
Increases in prevalence of non-vaccine types
38
Unique movement of IgA and IgG?
IgA -- Across Epithelials into Mucosal Secretions | IgG -- Across Endotheliams into Extravascular Space and across placenta
39
What receptor mediates IgA travel across epithelial cells?
Polymeric Immunoglobulin Receptor
40
What receptor mediates IgG travel across endothelial cell
Brambell Receptor (FcRB
41
How does IgA get across epithelial cells?
Binding to poly-Ig rec. on the basolateral face Endocytosis + Transcytosis Receptor Cleaved IgA bound to Mucus through Secretory Piece
42
Poly-Ig receptor can transfer which two antibodies
IgA and IgM (but almost always does A)
43
How big is A1 hinge region? A2?
26 aa | 13 aa
44
Role of secretory componeny in IgA dimer?
Wraps around J Chain -- May help prevent protease activity
45
IgA2 is most found...
In the digestive tract (esp. Ileum+Colon) | Shorter chain makes harder to cleave there
46
How does IgG get across endothelial cells?
Binding to FcRB, transcytosis | Mostly active transport
47
At birth, what antibodies does an infant have? | Which come along later?
Maternal IgG and Fetal IgM | Fetal IgA and IgG
48
Name three effector functions of antibodies.
Neutralization Opsonization Complement Activation
49
Who expresses Fc-gamma receptors?
Neut, Mac, B Cells, FDCs, NKs
50
Purpose of Fc-gamma receptors?
Opsonization and Antibody-dependent cell-mediated cytotoxicity
51
Purpose of Fc-epsilon receptors? Who expresses them?
Important in allergic reactions | Expressed on Mast Cells and Basophils
52
FcR1 is on _____ and has a high affinity for ___ | Describe its action.
Mac and Neut. IgG1 and IgG3 FcR1 binds the lower hinge/CH2 of Ig, Ig binds antigen More efficient phagocytosis
53
Which Fc has the strongest relative binding strength to IgG1?
Fc-gamma R1 (CD64)
54
Which Fc-gamma receptors are inhibitory
RIIIB2, RIIIB1 | CD32
55
How does antibody dependent cell mediated cytotoxicity work?
Antibody binds target Fc receptors of NK cells recognize Ab Crosslinked Fc receptors signal NK cell to kill the target Apoptosis
56
Describe the relationship of IgE and Mast Cells
IgE binds onto Fc-gammaR1 on mast cells | On second exposure, antigen binding to bound antibodies will trigger degranulation
57
IgG3 is unique for...
Long Hinge Large Heavy Chain + many disulfide bonds Very susceptible to clevage, so short half-life Great ability to activate complement
58
What is IgG4 good at?
Allergen Response
59
How long do untriggered naive B cells live?
3-8 weeks
60
Short lived plasma cells in the medulla generate....
IgM for approx. 5 days | Forms initial response to infection
61
What happens in secondary response if Naive B binds to a path coated in antibody?
Negative signal is given to naive B | Activation prevented
62
What happens in secondary response if Memory B cell binds a pathogen coated in Ab?
Memory B is activated Becomes a plasma cell Produces high-affinity IgG, A, and E