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Immunology
B Cell Immunity (T Pierce)
42
Medical
Post-Graduate
02/01/2009

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Cards

Term
Three types of B cells
Definition
  • B1 cells
  • marginal cells
  • B2/follicular/conventional cells
Term
Role of antigen strength in influencing B cell subset
Definition

difference in antigen strength will determine what B cell subset we get (if we mutate certain cascade proteins, we get more marginals and B1 cells)

Term
Role of T cells in marginal zone and B1 cell action
Definition
T cell independent antigens
Term

When do marginal zone B cells develop? What is their function

Definition
  • develop late in ontogeny (after birth)
  • function
    • early response to blood borne antigens and differentiate into plasmablasts
Term
Structure of antigens of B1 cells or marginal zone B cells
Definition
  • antigens with repetitive epitopes that heavily crosslink BCR and/or linked with pathogen motifs that activate PRR
  • marginal zone- restricted BCR repertoire
  • B1 cells- "natural Ab" of limited diversity
Term
Clinical application- affect of late appearnce of MZ B cells or not having a spleen
Definition
  • asplenic people highly susceptible to infection from encapsulated bacteria
  • if MZ B cells have delayed appearance, they correspond to inability of infants to mount a strong antibody response to bacterial polysaccharides
Term
Location, when develop, function of B1 cells
Definition
  • develop early in ontogeny (fetal life)
  • location- peritoneal and pleural cavities
  • function- produce natural AB of low affinity to bacterial cell walls and viral particles
Term

Why are conventional/follicular B cells dependent on T cell help?

Definition
  • CD40 (on B cells) needs the signal from the CD40L (on helper T cell) for isotype switching, germinal center formation, memory
  • T cell cytokines also help
Term
Results of B cell activation
Definition
  • clonal expansion (germinal center forms)
  • somatic hypermutation
  • immunoglobulin isotype switching
  • long lived memory B cells
  • plasma cell development
Term
Contents of germinal center?
Definition
  • light zone- where cells ineract with follicular dendritic cells and some T cells
  • dark zone- cells proliferate most rapidly
Term
Structure and function of follicular dendritic cells
Definition
  • structure
    • non-hematopoietic fibroblast like cells
    • contain follicular processes
  • function- "catch" antigens and display on cell surface to activated T cells
Term
Fate of cells in germinal center
Definition
  • death/apoptosis
  • antibody production factories
  • memory B cells
  • affinity maturation
  • isotype switching
Term

Define affinity maturation/somatic hypermutation. Enzyme needed for this process.

Definition
  • high rate of mutation at DNA at CDR coding regions that are passed on to daughter cells (permanent changes)
  • several rounds of mutation, antigen selection of high affinity binders, B cell proliferation
  • need activation induced cytidine deaminase (AID)
Term
When in the germinal center, what would cause the B cell to undergo apoptosis?
Definition

having a low affinity surface Ig

Term
What would cause a B cell in the germinal center to undergo differentiation into memory cells and plasma cells?
Definition
has mutation to a high affinity Ig receptor, allowing for T cell help and cross linking and sustained B cell proliferation and maturation
Term

Plasma cells "live" where? where do they come from?

Definition
  • migrate from the lymph node via efferent ductules
  • long lived in bone marrow
Term
Define isotype switching. Effect of isotype switching on function. What enzyme is needed for it? What determines isotype?
Definition
  • definition- at DNA level, alters constant region of heavy chain (variable and light chains unaltered)
  • functional effect- effector function is altered, but antigen specificity remains unchanged
  • needs activation induced cytidine deaminase (AID)
  • the isotype it chooses depends on nature of stimulus, T cell help, cytokines
Term
Process of isotype switchin
Definition
  1. loop out fragment
  2. cleave the loop
  3. rejoin the remaining segments
Term
Ig seen mainly in primary response? Ig seen mainly in secondary response?
Definition
  • primary- IgM
  • secondary- IgG
Term

Function of IgM

Definition
  • Function 
    • neutralizations
    • complement activation
    • antigen trapping

Receptors of naive B cells and some memory B cells.

 

 

Term

Function of IgG

Definition
  • neutralization
  • complement activation
  • induce phagocytosis
  • Ab directed cellular cytotoxicity (ADCC)
  • transfer adaptive immunity to offspring
  • regulate Ab production
Term
Function of IgA
Definition
  • function
    • neutralization
    • protection of mucosa
    • induction of phagocytosis
    • protect newborn mucosa via milk
Term
Function of IgE
Definition
  • activation of mast cells and basophils to promote barrier immunity
Term
Function of IgD
Definition
antigen receptor on naive follicular B cells (normally not in the serum)
Term
Function of humural (Ab) immune response
Definition
  • neutralize toxins
  • aggregation of antigens
  • ADCC
  • promote phagocytosis
  • opsonization
  • prevents binding of viruses
Term
Cytokines that cause proliferation of IgM
Definition
  • IL-2
  • IL-4
  • IL-5
Term
Cytokine that causes differentiation into IgE and IgG1
Definition
IL-4
Term
Cytokine that causes differentiation into IgA and IgG2b. Cytokine that will cause differentiation into IgG2a and IgG3
Definition

TGF-β

IFN-γ

Term
Functions of humoral immunity regulated by Fc receptor
Definition
  • mast cell activation
  • eosinophil activation
  • NK cell activation (ADCC)
Term
Structure of IgM
Definition
  • pentamer
    • multivalency enhance avidity of antigen interaction
    • has not undergone somatic hypermutation

Highest Ig in blood!!!!!!!!!!!!!!!!!!

Term
Structure of IgA
Definition
  • dimer
  • associated with secretory component to promote transport across epithelial cells
Term
Mechanism of IgA transport across epithelial surfaces at mucosal surfaces
Definition

via polymorphic Ig receptor

  1. endocytosis at basolateral end
  2. exocytosed at apical end
  3. freed from receptor by protease cleavage (secretory component stays attached)
  4. associates with mucus near membrane
Term

Role IgA in gut

Definition

neutralize bacteria and toxins (protect mucosal surface)

  • neutralize toxin by blocking its binding
  • protect against pathogen by blocking binding and preventing fusion event of virus
Term

Mechanism of action of Ab promotion of phagocytosis

Definition
  1. opsonize by coating pathogen with aggregations of Ig's
  2. this allows cross linking of Fc receptors
  3. leads to activation of macrophages, leadin to phagocytosis and destruction of bacteria
Term
Role of Fc receptor in neutrophil and eosinophil function
Definition
  • neutrophils and eosinophil recognize Fc receptor of Ab, which promotes cell targeting of pathogen
Term

Process of ADCC

Definition
  1. Ab binds Ag on surface of target cell
  2. Fc receptors on NK cells recognize bound antibody
  3. cross linking of Fc receptors signals NK cells to kill target cell
Term
What enzyme is the common meeting point for the three types of complement pathways
Definition

C3 convertase

Term

Role of C3 convertase

Definition
  • cleave C3a and C3b
    • C3a (anaphylatoxin I) has receptors for mast cells to cause histamine release, leading to degranulation of mast cells and basophils
    • C3b has receptors for neutrophils and macrophages to allow for opsonization
Term
Role of C5 convertase
Definition
  • entire complex (C1q, C2a, C4b) involved in immune complex clearance 
  • create C5a and C5b
    • C5a (anaphylatoxin II)- act on mast cells to cause histamine release
      • also chemoattractant for neutrophils
    • C5b activates C6 and C7 and acts in chemotaxis of neutrophils/ macrophages and opsonization
Term
What causes the initiation of complement cascade?
Definition
  1. IgM or IgG1-G3 binds to C1q (also has C1s and C1r subunit)
  2. cause C1q to go from a protease to an esterase
  3. it will cleave C4
    1. C4a- goes to fluid to act as anaphylatoxin
    2. C4b- attach at site of Ab fixing
  4. it will cleave C2
    1. C2a (along with C4b, become C3 convertase)
    2. C2b- goes into fluid to act as kinin
Term
Role of C8 and C9 in complement
Definition
cause permeability changes that lead to water influx (MAC forms)
Term

Original state of complement

Definition
inactive proenzymes until proteolytic cleavage exposes an active site
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