(Section B: Immunology) Lecture 16: B Cell Immunity I Flashcards
Antibodies
- 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
What are antibodies technically?
Secreted form of B Cell Receptor
How does an antibody differ from a membrane-bound version of the BCR?
Membrane-bound BCRs have a hydrophobic segment to bind to membrane
Antibodies have a hydrophilic segement so that they are soluble
BCR Structure
- 2 heavy chains
- 2 light chains
Linked together by disulfide bonds
What are the areas of the BCR receptors/antibodies?
- Variable Region
- Hinge
- Constant Region
What can BCRs/Antibodies be modified by?
By carbohydrates
What variety of the protein components can there be in BCRs/antibodies?
Light Chain:
* κ, λ
Heavy Chain:
* μ, γ, α, δ, ε
What is the antigen binding region of BCRs/antibodies?
The light and heavy chains working together
What does Fab and Fc stand for?
Fab: Fragment Antigen Binding
Fc: Fragment Crystallization
What does the hinge in the BCR/antibody structure allow for?
Allows for flexibility
How are antibody types determined?
They are determined by the heavy chains
What gene determines the antibody class?
The heavy chain constant region (C gene segments)
IgM Structure
2 binding sites as monomers
* 10 binding sites as pentamers
What is the purpose of IgM?
First class produce by B cells (primary response)
* C1q binds to IgM to start classical complement pathway
* Opsonization by IgM enhances phagocytosis
What are the two conformations of IgM?
- Planar
- Staple
True or False:
IgM cannot bind to pathogens in planar conformation
False, they can bind to pathogens in planar or staple conformation
IgD Structure
2 Binding sites
IgD Function
Main function is to bind antigen as BCR
* Only 0.2% of circulating antibodies
* Function is not well understood
What antibodies do Immature B cells express?
IgM and IgD BCR at the same time
IgG Structure
2 binding sites
Subclasses:
1. IgG1
2. IgG2
3. IgG3
4. IgG4
IgG Function
- Most abundant antibody type in serum (plasma)
- Long-lived
- Efficient at activation of phagocytosis
- Efficient at activation of complement
IgA Structure
Exists in monomer form (2 binding sites)
* Exists predominantly in dimeric form in secretions (4 binding sites)
Subclasses:
* IgA1
* IgA2
IgA Function
- 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
How does IgA work in the gut?
IgA is transported into the gut through the epithelial cells
IgE Structure
2 binding sites
IgE Function
- 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
What are the 6 effector mechanisms of antibodies?
- Neutralization of pathogens and toxins
- Agglutination of particulate antigens
- Opsonization
- Complement activation
- ADCC
- Degranulation
What does neutralization of pathogens and toxins do?
Inactivates, prevents binding to cells
What does agglutination of particulate antigens do?
Prevents binding to cells, enhances clearance
What does opsonization do?
Enhances phagocytosis
What does complement activation do?
Causes cell lysis
What does ADCC do?
NK cell-induced apoptosis
What does degranulation do?
Release chemicals that can kill parasite
What can BCRs/Antibodies recognize?
Any type of antigen
1. Extracellular pathogen
2. Toxins or allergens
3. Sugars
4. Peptidoglycans
5. Organic chemicals (e.x. phenols)
6. Lipids
What does B cell development in the bone marrow result in?
Generation of a diverse range of BCR specificities
What are the stages in B Cell Development?
- Heavy chain recombination (Early+Late Pro B)
- Light chain recombination (Pre B)
- Immature B Cells
Where do Immature B Cells go?
Spleen
* Negative selection occurs through deletion and receptor editing
What gene segments code for BCRs/antibodies?
V, D, J segments code for the variable region
C segment code for the constant region
What cells are eliminated in the Bone Marrow and Spleen?
Self-Reactive B cells
Natural passive immunity
- 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)
Artificial passive immunity
E.x. Intravenous Immunoglobulin (IVIG)
What are the 4 antibody drugs we talked about?
- Keytruda
- Humira
- Dupixent
- Stelera
What are the 4 antibody drugs we talked about?
- Keytruda
- Humira
- Dupixent
- Stelera
