(Section B: Immunology) Lecture 16: B Cell Immunity I

Question 1

Antibodies

Answer 1

• Soluble polypeptide molecules manufactured and secreted by B cells
• Have neutralizing or cytotoxic activities (cell or complement-mediated)
• Can recognize any substance
• Enormous medical and commercial importance

Question 2

What are antibodies technically?

Answer 2

Secreted form of B Cell Receptor

Question 3

How does an antibody differ from a membrane-bound version of the BCR?

Answer 3

Membrane-bound BCRs have a hydrophobic segment to bind to membrane

Antibodies have a hydrophilic segement so that they are soluble

Question 4

BCR Structure

Answer 4

• 2 heavy chains
• 2 light chains

Linked together by disulfide bonds

Question 5

What are the areas of the BCR receptors/antibodies?

Answer 5

• Variable Region
• Hinge
• Constant Region

Question 6

What can BCRs/Antibodies be modified by?

Answer 6

By carbohydrates

Question 7

What variety of the protein components can there be in BCRs/antibodies?

Answer 7

Light Chain:
* κ, λ

Heavy Chain:
* μ, γ, α, δ, ε

Question 8

What is the antigen binding region of BCRs/antibodies?

Answer 8

The light and heavy chains working together

Question 9

What does Fab and Fc stand for?

Answer 9

Fab: Fragment Antigen Binding
Fc: Fragment Crystallization

Question 10

What does the hinge in the BCR/antibody structure allow for?

Answer 10

Allows for flexibility

Question 11

How are antibody types determined?

Answer 11

They are determined by the heavy chains

Question 12

What gene determines the antibody class?

Answer 12

The heavy chain constant region (C gene segments)

Question 13

IgM Structure

Answer 13

2 binding sites as monomers
* 10 binding sites as pentamers

Question 14

What is the purpose of IgM?

Answer 14

First class produce by B cells (primary response)
* C1q binds to IgM to start classical complement pathway
* Opsonization by IgM enhances phagocytosis

Question 15

What are the two conformations of IgM?

Answer 15

• Planar
• Staple

Question 16

True or False:

IgM cannot bind to pathogens in planar conformation

Answer 16

False, they can bind to pathogens in planar or staple conformation

Question 17

IgD Structure

Answer 17

2 Binding sites

Question 18

IgD Function

Answer 18

Main function is to bind antigen as BCR
* Only 0.2% of circulating antibodies
* Function is not well understood

Question 19

What antibodies do Immature B cells express?

Answer 19

IgM and IgD BCR at the same time

Question 20

IgG Structure

Answer 20

2 binding sites

Subclasses:
1. IgG1
2. IgG2
3. IgG3
4. IgG4

Question 21

IgG Function

Answer 21

• Most abundant antibody type in serum (plasma)
• Long-lived
• Efficient at activation of phagocytosis
• Efficient at activation of complement

Question 22

IgA Structure

Answer 22

Exists in monomer form (2 binding sites)
* Exists predominantly in dimeric form in secretions (4 binding sites)

Subclasses:
* IgA1
* IgA2

Question 23

IgA Function

Answer 23

• Mainly present in secretions (saliva, mucus of the gut, tears and breast milk etc.)
• Can be found in low lwevels in circulation
• Does not opsonize cells or activate complement
• Neutralizes pathogens and toxins

Question 24

How does IgA work in the gut?

Answer 24

IgA is transported into the gut through the epithelial cells

Question 25

IgE Structure

Answer 25

2 binding sites

Question 26

IgE Function

Answer 26

• Mainly known for roles in allergy and asthma (and parasitic response)
• Made in very small quantities (but with potent effects)
• Activates mast cells, basophils and eosinophils

Question 27

What are the 6 effector mechanisms of antibodies?

Answer 27

1. Neutralization of pathogens and toxins
2. Agglutination of particulate antigens
3. Opsonization
4. Complement activation
5. ADCC
6. Degranulation

Question 28

What does neutralization of pathogens and toxins do?

Answer 28

Inactivates, prevents binding to cells

Question 29

What does agglutination of particulate antigens do?

Answer 29

Prevents binding to cells, enhances clearance

Question 30

What does opsonization do?

Answer 30

Enhances phagocytosis

Question 31

What does complement activation do?

Answer 31

Causes cell lysis

Question 32

What does ADCC do?

Answer 32

NK cell-induced apoptosis

Question 33

What does degranulation do?

Answer 33

Release chemicals that can kill parasite

Question 34

What can BCRs/Antibodies recognize?

Answer 34

Any type of antigen
1. Extracellular pathogen
2. Toxins or allergens
3. Sugars
4. Peptidoglycans
5. Organic chemicals (e.x. phenols)
6. Lipids

Question 35

What does B cell development in the bone marrow result in?

Answer 35

Generation of a diverse range of BCR specificities

Question 36

What are the stages in B Cell Development?

Answer 36

1. Heavy chain recombination (Early+Late Pro B)
2. Light chain recombination (Pre B)
3. Immature B Cells

Question 37

Where do Immature B Cells go?

Answer 37

Spleen
* Negative selection occurs through deletion and receptor editing

Question 38

What gene segments code for BCRs/antibodies?

Answer 38

V, D, J segments code for the variable region

C segment code for the constant region

Question 39

What cells are eliminated in the Bone Marrow and Spleen?

Answer 39

Self-Reactive B cells

Question 40

Natural passive immunity

Answer 40

• During pregnancy, antibodies are transferred from other to fetus (IgG)
• Vaccination during pregnancy also transfers protection to baby (e.g. vaccine for tetanus, diphtheria, pertusis)
• After birth, antibodies are transferred from mother to baby via breastmilk (IgA)

Question 41

Artificial passive immunity

Answer 41

E.x. Intravenous Immunoglobulin (IVIG)

Question 42

What are the 4 antibody drugs we talked about?

Answer 42

1. Keytruda
2. Humira
3. Dupixent
4. Stelera

Question 43

What are the 4 antibody drugs we talked about?

Answer 43

1. Keytruda
2. Humira
3. Dupixent
4. Stelera