• B1 cells
• marginal cells
• B2/follicular/conventional cells

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)

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

• develop late in ontogeny (after birth)
• function
  • early response to blood borne antigens and differentiate into plasmablasts

• 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

• 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

• 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

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

• 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

• clonal expansion (germinal center forms)
• somatic hypermutation
• immunoglobulin isotype switching
• long lived memory B cells
• plasma cell development

• light zone- where cells ineract with follicular dendritic cells and some T cells
• dark zone- cells proliferate most rapidly

• structure
  • non-hematopoietic fibroblast like cells
  • contain follicular processes
• function- "catch" antigens and display on cell surface to activated T cells

• death/apoptosis
• antibody production factories
• memory B cells
• affinity maturation
• isotype switching

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

• 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)

having a low affinity surface Ig

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

• migrate from the lymph node via efferent ductules
• long lived in bone marrow

• 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

1. loop out fragment
2. cleave the loop
3. rejoin the remaining segments

• primary- IgM
• secondary- IgG

Function of IgM

• Function 
  • neutralizations
  • complement activation
  • antigen trapping

Receptors of naive B cells and some memory B cells.

Function of IgG

• neutralization
• complement activation
• induce phagocytosis
• Ab directed cellular cytotoxicity (ADCC)
• transfer adaptive immunity to offspring
• regulate Ab production

• function
  • neutralization
  • protection of mucosa
  • induction of phagocytosis
  • protect newborn mucosa via milk

• activation of mast cells and basophils to promote barrier immunity

• neutralize toxins
• aggregation of antigens
• ADCC
• promote phagocytosis
• opsonization
• prevents binding of viruses

• IL-2
• IL-4
• IL-5

TGF-β

IFN-γ

• mast cell activation
• eosinophil activation
• NK cell activation (ADCC)

• pentamer
  • multivalency enhance avidity of antigen interaction
  • has not undergone somatic hypermutation

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

• dimer
• associated with secretory component to promote transport across epithelial cells

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

Role IgA in gut

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

Mechanism of action of Ab promotion of phagocytosis

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

• neutrophils and eosinophil recognize Fc receptor of Ab, which promotes cell targeting of pathogen

Process of ADCC

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

C3 convertase

Role of C3 convertase

• 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

• 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

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

Original state of complement