EXAM 3 B Cell Mediated Immunity Flashcards

1
Q

maturation into immature committed B cells occurs in the ___, and antigen-dependent proliferation and differentiation into plasma and memory cells occurs in the ___

A
  • bone marrow
  • peripheral lymphoid tissue
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2
Q

describe how B cells mature within and migrate through secondary lymphoid tissues

A

*the “mature B cell” in the yellow box is naive

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3
Q

B cell activation drives what 3 things?

A

clonal expansion, class switching, and somatic hypermutation

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4
Q

___ are stromal cells involved in B cell development and activation

A

follicular dendritic cells

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5
Q

follicular dendritic cells accumulate antigens via ___

A

complement receptors

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6
Q

do follicular dendritic cells have phagocytic activity?

A

no

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7
Q

___ and ___ display antigen to B cells

A

macrophages and follicular dendritic cells

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8
Q

___ is expressed on FDCs and subcapsular sinus macrophages, and its function is to capture and display ___

A
  • CR2
  • intact antigens
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9
Q

B cell activation involves what 3 signals?

A
  1. antibody crosslinking (via IgD) - activation
  2. co-receptor signaling - survival and proliferation
  3. cytokines - differentiation; class switching, SHM

1st and 2nd signals are requisite

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10
Q

what are the 2 antigen types involved in B cell activation?

A
  • thymus-dependent antigen
  • thymus-independent antigen
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11
Q

describe thymus-dependent antigen

A
  • protein
  • protein-associated antigen
  • Th cell interaction required
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12
Q

describe thymus-independent antigen

A
  • PRR-detected antigen
  • complement-bound antigen
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13
Q

describe antibody cross-linking involved in B cell activation

A
  • signal 1
  • antibody is bound to antigen
  • clustering and aggregation
  • Ig-alpha and Ig-beta signaling
  • ITAM phosphorylation and signal recruitment
  • *don’t need to know the specific molecules in the diagram
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14
Q

describe B cell co-receptor signaling in B cell activation

A
  • signal 2
  • ensures target is pathogenic
  • prevents anergy
  • foreign or self antigen
  • initiates clonal expansion
  • co-receptor signals are diverse
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15
Q

describe how co-receptor signals are diverse in B cell co-receptor signaling

A
  • B cell co-receptor complex
    • CR2, CD19, CD81 complex
    • binds to complement (C3b)
  • pattern recognition receptors
    • TLRs
  • CD40
    • CD4 T cells
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16
Q

describe cytokine signaling of B cell activation

A
  • signal 3
  • Tfh cells are the most common source of cytokines during B cell activation
  • local cytokines can provide signals in the absence of T cell-mediated activation (TI activation)
  • 4 roles of cytokine signaling (different card)
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17
Q

what are the 4 roles of cytokine signaling in B cell activation?

A
  1. survival and proliferation
  2. class switching - same epitope binding, different heavy chain
  3. somatic hypermutation - increases antibody specificity
  4. differentiation - produces plasma cells and memory B cells
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18
Q

Tfh cells drive what 4 things in B cells?

A
  • activation
  • proliferation
  • enhanced specificity
  • differentiation into plasma and memory cells
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19
Q

what is the most common pathway of B cell activation?

A

Tfh cell activation is the most common

thymus-independent activation can also happen, but it is much less common

Tfh cell activation typically yields a larger population of plasma cells and memory cells

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20
Q

describe how B and T cells form cognate pairs at the follicle boundary

A
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21
Q

describe the process of Tfh cells aiding in B cell activation

A
  • B cell is first activated by antigen binding
  • B cell presents antigen to Tfh cells
  • CD40 induces survival and proliferation (secondary activating signal - co-receptor signal)
  • cytokines
    • differentiate (plasma vs memory)
    • isotype switch (in germinal centers)
  • most common B cell activation pathway
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22
Q

B cells form plasma cells in which two stages and locations?

A
  1. cognate pairs first move to the primary focus
    1. produce IgM expressing plasma cells for several days (allows B cells to prevent systemic infection)
    2. no class-switching or somatic hypermutation
  2. cognate pairs then move to the secondary focus and form germinal centers
    1. enormous proliferation (every 6H) and plasma/memory cell production
    2. class switching and somatic hypermutation
    3. selection of most specific plasma cells
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23
Q

where do B cells hypermutate and class switch?

A

germinal centers

24
Q

cognate pairs form germinal centers in ___

A

the follicular zone

25
Q

cognate pairs first form centroblasts. what are they?

A
  • form the germinal center dark zone
  • proliferating source of new B cells
  • do not express surface immunoglobulins
  • somatic hypermutation
  • class switching
  • create centrocytes
26
Q

centrocytes form plasma cells and memory B cells. describe centrocytes.

A
  • form the light zone
  • divide slowly
  • express surface immunoglobulin
  • cannot class switch or hypermutate
  • interact with and selected by follicular dendritic cells
  • programmed to die
27
Q

___ and ___ improve antibody specificity

A

class switching and somatic hypermutation

28
Q

describe class switching

A
  • RAG proteins reactivated
  • change heavy chain Fc region
  • cytokine induced
  • classes dictate effector functions
29
Q

describe somatic hypermutation

A
  • directed hypervariable region mutation
  • singla nucleotide insertions and substitutions
  • produces new epitope binding region
  • as centroblasts divide, more mutations are produced
  • increases antibody affinity
  • paired with selection process
30
Q

follicular dendritic cells select ___ centrocytes

A

high-affinity

31
Q

after centrocytes have undergone the first round of somatic hypermutation, what is the result?

A
  • the new antibody is different than cognate B cell antibody
  • activating antigen presented on FDCs
32
Q

how do follicular dendritic cells select high-affinity centrocytes?

A
  • at this point, centrocytes have undergone the first round of somatic hypermutation
  • competition for FDC-presented antigen
    • only centrocytes that bind FDCs can bind Tfh cells
  • FDC-bound centrocytes are bound by Tfh cells - survival signal
33
Q

what happens when FDC-bound centrocytes are bound to Tfh cells?

A
  • limited Tfh cell population in the germinal center
  • survival signals
  • selection of centrocytes with the highest antibody affinity
  • further proliferation; several rounds of affinity maturation
  • differentiation into plasma cells or memory B cells
34
Q

plasma cells secrete large quanitites of ___

A

antibody

high-rate Ig secretion (intrinsic)

35
Q

give an overview of B cell activation

A
36
Q

describe the 4 broad effector functions of antibodies

A
  1. virus and toxin neutralization - prevents pathogen-host binding
  2. opsonization - phagocytosis
  3. complement fixation, formation of MAC - phagocytosis and lysis
  4. antibody-dependent cell-mediated cytotoxicity - NK induced apoptosis
37
Q

what are the basic functions of the different antibody isotypes?

A
  • IgM, IgG, IgA: internal tissues
  • IgA: mucosal surfaces
  • IgE: parasite immunity; receptor
  • IgD: B cell receptor
38
Q

___ receptors bind antibodies and provide adaptive specificity to innate cells

A

Fc

Fc receptors allow adaptive immunity to enhance innate immunte cells specificity and function

39
Q

describe how Fc receptors are widespread and diverse

A
  • monomeric and dimeric
  • often require dimerization
  • expressed on most leukocytes
  • IgG, IgE, IgA
  • enhance innate immunity
  • stimulate and inhibit effector functions
  • involved in Ig transport
40
Q

in what ways do Fc receptors stimulate and inhibit effector functions?

A
  • cytokine production/release
  • phagocytosis
  • degranulation
  • targeted killing
41
Q

describe how Fc receptors facilitate IgG transport into tissues

A
42
Q

transcytosis of IgA protects ___

A

mucosal surfaces

43
Q

describe how transcytosis of IgA protects mucosal surfaces

A
44
Q

___ prevent pathogen establishment

A

neutralizing antibodies

IgA and IgG

45
Q

describe how neutralizing antibodies prevent pathogen establishment during exposure to influenza virus

A
46
Q

describe how neutralizing antibodies prevent pathogen establishment of strep pyogenes in the pharynx

A
47
Q

___ clear agglutinized antigens

A

erythrocytes

48
Q

how do erythrocytes clear agglutinized antigens?

A
49
Q

how does opsonization lead to phagocytosis?

A
50
Q

which cells does IgE make competent?

A

mast cells, basophils, and eosinophils

targeted degranulation, important in allergies

51
Q

how does IgE make mast cells competent?

A
52
Q

how does IgE make eosinophils competent?

A
53
Q

___ and ___ initiate the complement classical pathway

A

IgM and IgG

54
Q

describe antibody-dependent cellular cytotoxicity

A
55
Q

antibodies provide ___ immunity during development

A

passive

56
Q

in what ways do antibodies provide passive immunity during development?

A
  • IgG during gestation
  • IgA from breastfeeding protects infant mucosal surfaces
  • mother’s immunity is passed to the infant