Lecture 6: B cells and antibodies Flashcards
What are antibodies?
Antibodies are Y-shaped antigen-specific proteins produced by B lymphocytes
Describe the structure of antibodies
Antibodies are comprised of 2 identical heavy chains and 2 identical light chains.
What leads to variation in antibodies?
Different heavy chain constant regions produce antibodies with different properties
What do antibodies recognise?
Antibodies recognise ‘epitopes’ of an antigen through there variable antigen-binding site (FAB) on the heavy chain
What is the role of the Fc region of antibodies?
The Fc region at the ‘stem’ of the antibody interacts with other cells and molecules of the immune system.
Where are antibodies found?
Antibodies are attached to B cells at Fc region and are also secreted into the bloodstream and circulate as free proteins
How many types of antibodies does each B cell produce?
Each B cell produces only 1 antibody; each antibody (and therefore each B cell) will be specific for particular protein antigens.
What are the 5 antibody isotypes?
IgM, IgA, IgD, IgE, IgG
MADEG
What is the role of IgM antibodies?
First antibody produced in an immune. Low affinity for antigen but produces pentamer to increase affinity.
What is the role of IgA antibodies?
Only antibody that can cross mucosal surfaces and found in secretion. Protected from digestion by secretory component.
What is the role of IgD antibodies?
Like IgM, the first antibody produced by a B cell, but has no known function.
What is the role of IgE antibodies?
Circulates as a monomer; exact function not known, but believed to be important in parasitic infection and allergic disease.
What is the role of IgG antibodies?
Main mature antibody form; circulates as a monomer.
How does IgM differ as infection progresses?
As immune responses progress, the IgM response switches to other antibody isotypes.
What are the 6 actions of antibodies?
- Neutralisation
- Receptor blocking
- Opsonisation
- Mast cell activation
- Antibody-dependent cellular cytotoxicity (ADCC)
- Complement activation
How do antibodies trigger neutralisation?
Anti-toxin antibodies bind to the toxin and neutralise it.
How do antibodies trigger receptor blocking?
Antibody blocks receptor used by organism to gain entry to host cell.
How do antibodies trigger opsonisation?
Coat bacteria to allow for phagocytic cells to identify it and reduce repulsion between two negatively charged membranes. Phagocytic cells have receptors for the Fc portion of antibodies.
How do antibodies trigger mast cell activation?
Mast cells have surface Fc receptors and become coated with IgE antibody from circulation. When antigen binds to the IgE antibodies and cross-links them, the mast cell ‘degranulates’, releasing histamine.
How do antibodies trigger antigen-dependent cellular cytotoxicity (ADCC)?
NK cell recognises antibody-coated bacteria by Fc receptor; the target organism is then killed by non-phagocytic means.
How do antibodies trigger complement activation?
Activates sequential proteolysis of proteins to generate enzyme complexes with proteolytic activity that trigger opsonisation, phagocytosis, inflammation and terminal attack pathway.
How is IgE involved in allergy?
Inappropriate cross linking of normal proteins with IgE on mast cells causes unnecessary release of histamine.
How is the variation in antibodies generated?
Somatic recombination of variable regions
What are the advantages of somatic recombination of antibodies?
- Huge diversity
- large number of receptors from small area of DNA
- Everybody has a unique repertoire
What are the disadvantages of somatic recombination of antibodies?
- Many combinations will not work out
- B cells with dysfunctional receptors are destroyed and this is energy intensive
- Deletion of B cells that can recognise self-antigens is not always efficient and so potential for autoimmune disease
What is ‘clonal selection’ in B cells?
Clonal selection is the division and selection of the ‘fittest’ B cells. B cells receptors (antibodies) are generated at random, so presumably some will react to self-antigens, but they undergo selection to try and remove these.
What is ‘affinity maturation’ in antibodies?
Affinity maturation is the strength of bonding between antibody and antigen
What affects affinity maturation of antibodies?
- Class switch
2. Somatic hypermutation
What happens during class switching of antibodies?
IgM in the ‘primary response’ switches to IgG. The variable region of the antibody remains the same
What happens during somatic hypermutation of antibodies?
Random mutations are introduced into the variable region of the antibody so produce a slightly different antibody. Clonal selection will determine the most beneficial mutations.
How does subsequent exposure improve affinity maturation and the adaptive immune response?
Antibody response improves by affinity maturation so subsequent exposures to the same pathogen are characterised by high-affinity IgG antibodies in the secondary immune response.
