B Cells and Antibody Development Flashcards
B Cells: Basics
Primary function: produce antibodies
Receptor: membrane bound anitbody
- high specificity, matches one epitope
Mature B cells making anitbody = plasma cell
Humoral Immunity
Antibodies found in all extracellular fluid secreted from plasma cells
Primary defence against extracellular pathogens
B Cell Receptors Recognize What?
Bind to 3D structures
- Usually need help from T cell
- Can be T-B direct interaction
- Can be cytokine activation
B Cell Activation Threshold
Many receptors in B cell - multiple must be bound to activate
T Cell Independent Antigens
Antigens that can produce small amounts of IgM production
PAMPs, toll like receptors
T Cell Dependent Antigen
CD4 T cell with costimulatory molecules, cytokines
Stimulates production of all 5 classes of antibodies
Immune Repertoire
And goals
Combination of all specificities that T and B cells can bind to
Goals: large enough to recognize threats but specific so it doesn’t attack the self
Chains Of A B Receptor
Light chain: V + J + C gene segments
Heavy chain: constant portion, V + D + J + C gene segments with Ch2 and Ch3
Light: short Y, heavy: long stem of y
Important!
Heavy Chain Significance
Heavy chain segments determines consant portion and the class/isotype of the antibody
Epitope Basics
Antigen that BCRs recognize
Specific molecules on epitope bind to molecules on BCR
B Cell: Maturation Steps
- Bone marrow development
- Rearrange BCR genes (heavy, then light); is it functional? Folded correctly?
- Immature B cell expresses IgM
- BCR that react with self antigen - edit or delete
- Into circulation and lymph nodes, express IgM and IgD
B Cell: Acting As An APC
The process
- Antigen binds to BCR
- Processed internally with carrier protein
- Carrier peptide binds to class II MHC
- Presented on the outside for a T cell
B Cell: Lymph Nodes Significance
- Activation and migration of T and B cells
- T:B interaction
- B cell differentiation: Ig, isotyope switching
- Germinal center reaction
Full B Cell Activation
After expressing peptide on MHC II to T cell, fully activated by T cell dependent antigen
- Can now class switch
- Affinity maturation
- Secondary response to memory
IgM and IgD
- Expressed right out of the bone marrow
- Activating complement
- Link innate and adaptive immunity
Complement
Effector molecule of innate immune system
- Nonspecific
- Inflammation, tissue damage
How Do Different Isotypes Change?
Important
Can loop out different segments after T cell activation and change isotypes of constant portion of antibody
- Cannot switch back!
- Cytokines from T cell help decide what isotype it will make
B Cell: Somatic Hypermutation
Activated B cells in germinal center of lymph node express enzymes that randomly replace nucleotides in VJ or VDJ genes segments
Based on signal strength
- Stonger signal = more editing
- Leads to even better binding
Primary to Secondary Antibody Response Process
Primary
1. Naive B cell
2. Activated B cell
3. Antibody secreting plasma cell
4. Low level antibody production
Secondary
5. Turn into memory B cell at repeat infection
6. Antibody secreting: a lot of IgG
7. Long lived plasma cell that secrete some
8. Memory B cell needs less signal to activate
Antiserum
Serum with known antibodies against a particular antigen
5 Types of Antibodies
IgG
IgE
IgD
IgM
IgA
Antibodies: Functions in the Immune Respinse
Antibodies vs. complement activation, 3 each
Antibodies
- Neutralize pathogens
- Opsonization and phagocytosis of pathogens
- Antibody dependent cellular cytotoxicity
Complement Activation
- Lyse microbes
- Phagocytosis of microbes without complement fragments
- Inflammation
Neutralizing Viruses
4 ways
- Blocks receptor for virus
- Prevent uncoating
- Prevents internalization
- Prevents release of virus from cell
Opsonization and Phagocytosis
Something covered in antibodies - increases APC to recognize
APC have a lot of Fc receptors binding to constant portion
Recognize constant portion of antibody
Antibody-Dependent Cellular Cytotoxicity
Fc receptors on NK cells recognize constant portiont bound to antigen, signals to kill target cell
IgD
Monomer
- Mostly on unstimulated B cells in association with IgM
Role: play a role in B cell maturation and differentiation
IgM
Monomer or mainly pentamer
- Primary response to antibody
- First to appear in maturing infant
- Can bind multiple since pentamer
Roles: fix complement, opsonization, neutralization, agglutination
IgA
Dimer
Secretory IgA is main Ig in tears, saliva, milk, sweat
Two allotypes
IgA2: main form in secretions
IgA1: mostly in serum
Role: first line of defense in mucosal surface, neutralize
- Does not fix complement: cause clearing of antigen without inflammation/tissue damage
Secretory IgA Process
Binds to receptor on epithelial cell
- Crosses through cells
- Secreted
IgG
Monomer
IgG1, 2, 3, and 4
Role: newborn immunity, fix complement, opsonization, neutralization, agglutination and precipitation
IgE
Monomer
Attaches to mast cell - how mast cells respond to allergens, covered in IgE, recognizes allergen
Role: triggers acute inflammatory response
