T4 L6: B-cells and antibodies

Define antigen-specific

The antibody binds to a particular antigen (eg measles) with high affinity, but not to other antigens (eg pneumococcus)

Label an antibody-antigen interactions

Label an antibody

How many heavy and light chains are there?

2 identical heavy chains

2 identical light chains

What is the FAB and what is it made up from/

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 is an epitope

Antigenic determinant

What is the Fc region?

Constant region is made up only by heavy chains

The Fc region at the ‘stem’ of the antibody interacts with other cells and molecules of the immune system

How do antibodies and B lymphocytes interact?

• Antibodies attached to B cells

• 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

What do B cells do?

• B cells each produce a unique antibody

• The antibody comprises two heavy and two light chains, which combine to form a variable region that binds to a particular antigen

• The basis of this binding is physio-chemical affinity for antigen epitopes

• The antibody is expressed on the B cell surface as a receptor and is also secreted into the bloodstream

Another name for antibody

immunoglobulin

How many types of antibody isotypes are there?

IgM, IgD, IgA, IgG, IgE

Does the antibody isotype affect what ot binds to

Note that the antibody isotype

doesn’t affect what it binds to;

This is a function of the variable region

Summarise IgM

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

Summarise IgA

• 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

Summarise IgD, IgG, IgE

• 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

How can antibodies help us?

By binding to things and directly affecting them

• eg toxin neutralisation, receptor blocking

By binding to things then interacting with another element of the immune system

• eg phagocytes (opsonisation), complement, mast cell activation, antibody-dependent cellular cytotoxicity

When bound to B cells: by acting as the B cell receptor (see slides 29 onwards)

Neutralisation by an antibody: clostridium Tetani

The bacteria clostridium Tetani releases a toxin that causes muscle contraction (tetanus). Tetanus immunoglobulin is effective for prevention after high-risk injuries and for treatment.  The antibodies are taken from plasma donors

What is opsonisation?

• This process of coating bacteria to enhance phagocytosis is called 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

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.

Advantages of somatic recombnation

• 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 environments/ against emergent pathogens

• Still inherit the gene segments, so get some benefit from evolutionary experience

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

What is the maturation of an immune response?

When the B cells divide in the antigen-driven process, they do two things:

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