B Cells and Antibody Development

Question 1

B Cells: Basics

Answer 1

Primary function: produce antibodies

Receptor: membrane bound anitbody
- high specificity, matches one epitope

Mature B cells making anitbody = plasma cell

Question 2

Humoral Immunity

Answer 2

Antibodies found in all extracellular fluid secreted from plasma cells

Primary defence against extracellular pathogens

Question 3

B Cell Receptors Recognize What?

Answer 3

Bind to 3D structures
- Usually need help from T cell
- Can be T-B direct interaction
- Can be cytokine activation

Question 4

B Cell Activation Threshold

Answer 4

Many receptors in B cell - multiple must be bound to activate

Question 5

T Cell Independent Antigens

Answer 5

Antigens that can produce small amounts of IgM production

PAMPs, toll like receptors

Question 6

T Cell Dependent Antigen

CD4 T cell with costimulatory molecules, cytokines

Answer 6

Stimulates production of all 5 classes of antibodies

Question 7

Immune Repertoire

And goals

Answer 7

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

Question 8

Chains Of A B Receptor

Answer 8

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!

Question 9

Heavy Chain Significance

Answer 9

Heavy chain segments determines consant portion and the class/isotype of the antibody

Question 10

Epitope Basics

Answer 10

Antigen that BCRs recognize
Specific molecules on epitope bind to molecules on BCR

Question 11

B Cell: Maturation Steps

Answer 11

1. Bone marrow development
2. Rearrange BCR genes (heavy, then light); is it functional? Folded correctly?
3. Immature B cell expresses IgM
4. BCR that react with self antigen - edit or delete
5. Into circulation and lymph nodes, express IgM and IgD

Question 12

B Cell: Acting As An APC

The process

Answer 12

1. Antigen binds to BCR
2. Processed internally with carrier protein
3. Carrier peptide binds to class II MHC
4. Presented on the outside for a T cell

Question 13

B Cell: Lymph Nodes Significance

Answer 13

• Activation and migration of T and B cells
• T:B interaction
• B cell differentiation: Ig, isotyope switching
• Germinal center reaction

Question 14

Full B Cell Activation

Answer 14

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

Question 15

IgM and IgD

Answer 15

• Expressed right out of the bone marrow
• Activating complement
• Link innate and adaptive immunity

Question 16

Complement

Answer 16

Effector molecule of innate immune system
- Nonspecific
- Inflammation, tissue damage

Question 17

How Do Different Isotypes Change?

Important

Answer 17

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

Question 18

B Cell: Somatic Hypermutation

Answer 18

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

Question 19

Primary to Secondary Antibody Response Process

Answer 19

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

Question 20

Antiserum

Answer 20

Serum with known antibodies against a particular antigen

Question 21

5 Types of Antibodies

Answer 21

IgG
IgE
IgD
IgM
IgA

Question 22

Antibodies: Functions in the Immune Respinse

Antibodies vs. complement activation, 3 each

Answer 22

Antibodies
- Neutralize pathogens
- Opsonization and phagocytosis of pathogens
- Antibody dependent cellular cytotoxicity

Complement Activation
- Lyse microbes
- Phagocytosis of microbes without complement fragments
- Inflammation

Question 23

Neutralizing Viruses

4 ways

Answer 23

• Blocks receptor for virus
• Prevent uncoating
• Prevents internalization
• Prevents release of virus from cell

Question 24

Opsonization and Phagocytosis

Answer 24

Something covered in antibodies - increases APC to recognize
APC have a lot of Fc receptors binding to constant portion
Recognize constant portion of antibody

Question 25

Antibody-Dependent Cellular Cytotoxicity

Answer 25

Fc receptors on NK cells recognize **constant portiont bound to antigen**, signals to kill target cell

Question 26

IgD

Answer 26

**Monomer** - Mostly on unstimulated B cells in association with IgM **Role:** play a role in B cell maturation and differentiation

Question 27

IgM

Answer 27

**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

Question 28

IgA

Answer 28

**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

Question 29

Secretory IgA Process

Answer 29

Binds to receptor on epithelial cell - Crosses through cells - Secreted

Question 30

IgG

Answer 30

**Monomer** *IgG1, 2, 3, and 4* **Role:** newborn immunity, fix complement, opsonization, neutralization, agglutination and precipitation

Question 31

IgE

Answer 31

**Monomer** Attaches to mast cell - how mast cells respond to allergens, covered in IgE, recognizes allergen **Role:** triggers acute inflammatory response