L6 B Cells and Antibodies Flashcards
(24 cards)
What does antigen-specific mean?
The antibody binds to a particular antigen (eg measles) with high affinity, but not to other antigens (eg pneumococcus)
Which antibody region binds the antigen?
FAB region
What antibody region interacts with other components of immunity?
Fc Region
What is the FAB region?
Antigen-binding site (FAB) is made up of light chains and heavy chains
Because this region needs to be able to bind any potential antigen, it is very VARIABLE between different antibodies; therefore also known as the variable region
What does the variable region recognise?
Epitopes of antigen
What is the relationship between B lymphocytes and antibodies?
Antibodies attached to B cells at Fc region
Each B cell produces only 1 antibody: all the antibodies on its surface are the same
Each antibody (and therefore each B cell) will be specific for particular protein antigens
In addition, antibodies are secreted into the bloodstream and circulate as free proteins
IgM [4]
First antibody produced in an immune response
Doesn’t bind antigen very well (‘low affinity’)
Makes up for it by forming pentamers, which are held together by a joining (‘j’) chain
As immune responses progress, the IgM response switches to other antibody isotypes
IgA [5]
The only antibody that can cross mucosal surfaces
Found in secretions eg gut, tears, saliva
Forms dimers (joining ‘j’ chain)
Protected from digestion by secretory component (‘s’ chain)
Colostrum (forerunner of breast milk) is rich in IgA antibody
IgD
like IgM, the first antibody produced by a B cell, but has no known function
IgG
the main mature antibody form; circulates as a monomer
IgE
circulates as a monomer; exact function not known, but believed to be important in parasitic infection. Definitely important in allergic disease
What do antibodies do?
Bind to things and directly affect them - neutralisation, receptor blocking
Bind to things and interact with another element of immune system - phagocytes, complement, mast cell activation
When bound to B cells act as a B cell receptor
What is neutralisation by antibody?
Anti-toxin antibodies bind to the toxin and neutralise it
The bacteria clostridium
Tetani releases a toxin that
causes muscle contraction
tetani
What is receptor blocking by antibody?
Viruses use receptor to attach to host cell and gain entry
Antibody blocks receptor
What is opsonisation?
Bacteria coated by circulating antibody
Phagocytic cells have receptors for the Fc portion of the antibody
This enhances phagocytosis by reducing the repulsion between two negatively charged membranes
This process of coating bacteria to enhance phagocytosis is called OPSONISATION
What is mast cell activation?
Mast cells have surface Fc receptors
Mast cells become coated wth IgE antibody from circulation
When the appropriate antigen binds to the IgE antibodies and cross-links them, the mast cell ‘degranulates’, releasing histamine
?Important in dealing with parasitic infections
Inappropriately activated in allergy
What is antibody-dependent cellular cytotoxicity?
NK cell recognises antibody-coated bacteria by Fc receptor; the target organism is then killed by non-phagocytic means.
What is antibody diversity?
Each B cell produces a single antibody
Between all these B cells, antibodies must be produced that can bind to any protein
This implies a huge number of different B cells and antibodies – we each have several million
Somatic recombination and the variable region
Total number of possible genes = number of segments in 1 x number in 2 x number in 3
What are the advantages of somatic recombination?
Huge diversity – we can recognise whatever is in our environment
A large numbers of receptors can be made from a smaller area of DNA
Everybody has a unique repertoire – resilient in different enviroments/ against emergent pathogens
Still inherit the gene segments, so get some benefit from evolutionary experience
What are the disadvantages of somatic recombination?
The receptors are generated at random - many combinations will not work out:
Some can’t fit together biochemically
Some will bind to our own proteins (self antigens)
B cells with dysfunctional receptors mostly destroyed (deleted) – process is therefore energy intensive
Deletion of B cells that can recognise self-antigens is not complete – potential for autoimmune disease
What is clonal selection?
We all start with a unique set of B cells, each producing a single antibody; small number of each B cell
During infection, those with the best response to the infection antigen are selected out
Known as ‘clonal selection’ – division and selection of the ‘fittest’ B cells
Affinity maturation
Class switch: IgM in the ‘primary response’ switches to IgG. The variable region of the antibody remains the same
Somatic hypermutation: Random mutations are introduced into the variable region of the antibody, so the daughter cells produce a slightly different antibody. Further rounds of clonal selection pick out the best receptors
Memory of the immune system
The best B cells to deal with a particular infection have now been selected
and their number increased. These mature B cells become long-lived memory cells. When stimulated again, they respond vigorously
This is the basis of the secondary immune response
