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Immunology - CORE > B Cell Activation and Antibody Isotypes > Flashcards

B Cell Activation and Antibody Isotypes Flashcards

1
Q

Describe antibodies

A
  • random arrangement of Ig genes allows response to any protein/glycan
  • battle pathogens that evolve very quickly
  • create a stronger immune response the second time
  • however includes food, gut bacteria, organs, unborn child
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2
Q

Describe Tolerance

A

Prevents adaptive immune system from incorrect response:
- central tolerance - primary lymphoid organs
- peripheral tolerance - secondary lymphoid organs

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3
Q

Describe B cell development

A
  • primary lymphoid organ is bone marrow
  • stromal cells provide appropriate factors (soluble) and cell-cell interactions for B cell development
  • multipotent progenitor cell -> common lymphoid progenitor -> early pro-B cell -> late pro-B cell -> pre-B cell -> immature B cell
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4
Q

Describe central tolerance in B cells

A
  • stromal cells aid
  • where BCR genomic rearrangement and negative selection for B cell occurs
  • negative selection - removal of lymphocytes encoding self-reactive antigen receptors
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5
Q

Describe the 4 outcomes of immature B cells in bone marrow

A
  • no self reaction -> migrates to periphery -> mature B cell
  • multivalent self molecules -> clonal deletion or receptor editing -> apoptosis or generation of non-subreactive mature B cell
  • soluble self molecule -> migrates to periphery -> anergic B cell
  • low affinity non-cross-linking self molecule -> migrates to periphery -> mature B cell (clonally ignorant)
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6
Q

Describe B cell activation from Signal 1

A
  • BCR interaction with specific antigen
  • BCR binds epitopes on pathogen antigen
  • mediates endocytosis of antigen
  • follicular DC assist and maintain intact antigens on surface
  • present on lymph nodes
  • can also involve interactions with antigen
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7
Q

Describe antigen interactions from Signal 1 B cell activation

A
  • CD35 (CR1) and CD21 (CR2)
  • these can bind antigens opsonised with complement
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8
Q

Describe activation of B cells via Signal 2

A
  • interaction with specific antigen T-cell
  • B cell processes antigen
  • presents on surface MHC II molecule
  • interaction with TCR on activated specific T cell
  • not necessarily same epitope or antigen the B and T cell are responding to
  • linked recognition
  • T cell produces cell-bound co-stimulatory signals and cytokines
  • activation of B cell
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9
Q

Describe co-stimulation

A
  • CD40 receptor on B cell
  • CD154 receptor (CD40L) on T cell
  • cytokines such as IL-4
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10
Q

What are the key cells involved in B cell activation

A
  • B cells
  • follicular dendritic cells - signal 1 for B cells
  • T cells - signal 2 for B cell activation
  • dendritic cells - activate T cells
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11
Q

Where do B and T cells reside before activation and what do they express?

A
  • resting B cells express CXCR5 in follicles
  • resting T cells express CCR7 in T cell zones
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12
Q

Describe naive B cells expression of CXCR5

A
  • chemokine receptor
  • binds CXCL13
  • released by FCDs
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13
Q

Describe naive T cell expression of CCR7

A
  • chemokine receptor
  • binds CCL21
  • released by DCs
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14
Q

What do activated B and T cells induce?

A
  • activated B cells induce CCR7 and EB12
  • activated T cells induce CXCR5
    both cells migrate to follicular and interfollicular regions
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15
Q

What does interactions with T cells sustain on B cells?

A
  • EB12 expression on b cells
  • which move to outer follicular and interfollicular regions
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16
Q

What happens to some T and B cells after Signal 2 is recieved?

A
  • some B cells migrate to form a primary focus and differentiate into plasmablasts
  • some T cells induce Bcl-6 and become TFH cells
17
Q

What are the 3 outcomes of activated B cells?

A
  • rapid proliferation and differentiation into plasmablasts or plasma cells - short lived
  • migration to germinal centre before differentiation into plasma cells - long lived
  • development into a memory B cell
18
Q

What are the response characteristics of secondary response?

A
  • faster response
  • more antibodies produced
  • isotype switching occurs: IgM -> IgG, IgA, IgE
19
Q

What are the main 5 antibody types and what are their constant regions on heavy chains?

A

IgM - µ
IgD - δ
IgG - ү
IgA - α
IgE - ϵ

20
Q

Describe antibody isotypes

A
  • class-switching leads to removal of DNA encoding constant regions 5’ of selected
  • can’t go back to IgM/D after switching to IgG/A/E
  • heavy chains determine distinct properties of isotopes
  • antibodies interact with host cell receptors via Fc region
  • range of Fc receptors (FcR) found on immune system cells
  • different isotypes activate different effector immune responses
21
Q

What occurs before any class switching?

A
  • BCRs present on B cell surface are IgD and IgM
  • can express both due to alt. splicing mechanism
  • both IgM and IgD can be secreted after activation
22
Q

Describe IgM

A
  • most commonly first Ab detected in a primary immune response
  • can form pentamers but not always - sometimes monomers, hexamers
  • low affinity before affinity maturation occurs
  • efficient in stimulating complement system
  • occurs in blood and lymph - pentamers too big to cross easily into tissues
23
Q

Describe IgD

A
  • fails to activate classical complement pathway
  • no link to phagocytosis or helminth responses
  • very limited levels in blood
  • evolutionarily highly conserved
  • can bind FcR to mast cell/basophils
  • present in mucosa, especially nasopharyngeal cavities
24
Q

What does evidence suggest about IgD?

A
  • associated with regulatory responses
  • peripheral tolerance against commensals, food antigens etc
25
Q

Describe IgG

A
  • class-switching to IgG common in most primary responses
  • dominant in most memory responses
  • multiple subclasses - different constant region
26
Q

Where is IgG located?

A
  • most common Ab in blood
  • present in mucosal surfaces - esp reproductive and lower respiratory tracts
27
Q

What is the function of IgG?

A
  • effective as neutralizing antibody in blood & extracellular spaces
  • opsonizes pathogens
  • some subclasses activates complement
28
Q

Describe IgA

A
  • opsonizes pathogens less well and weakly activates complement
  • dimeric IgA occurs in secretions on epithelia
  • dimeric IgA secreted by plasma cells in lamina propria of gut
29
Q

Describe IgE

A
  • acts in conjunction with eosinophils, mast cells and basophils
  • very little free IgE in blood
  • bound to resting & activated mast cells by high affinity receptors - FcR (FcϵR1)
  • key in response to larger organisms - too large to phagocytoze
  • attacked by eosinophils which bind to surface antibody via FcRs
30
Q

What is high IgE / mastocytosis associated with?

A

resistance to intestinal helminths

Immunology - CORE (18 decks)

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