Lecture 5 - Antibody molecules Flashcards
What are they? How are they made? Structure Classes Antibody-antigen interactions Complement
What are antibody molecules?
Host proteins produced in response to the presence of foreign molecules in the body.
What cell type are antibodies primarily synthesised by?
Plasma cells (lymphoid lineage) and are components of the adaptive immune system
What do antibodies bind?
Antigens
How are antibody-antigen complexes removed from circulation?
Primarily through phagocytosis by macrophages
What did Linus Paling’s model propose?
preformed undifferentiated ‘immunoprotein’ folded over the antigen at different locations at different haptenic groups
He also proposed that a single immunoprotein reacted with all antigens but its conformation was different in each case.
What did Sir Frank MacFarlane Burnet propose in 1959?
That Pauling’s model was wrong
He proposed the ‘clonal selection theory’ of acquired immunity
He realised that during the immune response certain cells were selected for antibody production
Proposed that somatic mutation during embryonic life generates the random specificities of antibodies, that cells possess concordant antigen receptors, and that cells to self -antigens are killed
What are the 3 steps in the process of clonal selection?
1) A hematopoietic stem cell undergoes differentiation and genetic rearrangement to produce immature lymphocytes with many different antigen receptors.
2) Those that bind to antigens from the body’s own tissues are destroyed. (clonal deletion)
3) The rest are allowed to mature into inactive lymphocytes, and multiply by clonal expansion
What does clonal selection achieve?
Detection and removal of self reactive lymphocytes, which cooked lead to conditions such as autoimmunity
What are the 8 steps in the process of induction of B cell AB response by T cells?
- Germinal centres where b cells proliferate and undergo both isotype switching and somatic hypermutation, form within the B cell follicles in lymphoid organs
- This starts when DCs display antigen on their surface and activate cd4 t cells
- These proliferate and mature into effector cells capable of activating antigen specific b cells
- B Cell proliferates to form a primary focus of antigen specific b cells
- B cells migrate to follicles and proliferate
- These undergo somatic mutation, introducing new variation into the b cell receptor
- They then undergo a selection process: tested on their ability to bind antigen
- Those that don’t die undergo isotype switching – IgM-IgG…
What are the structural and functional features that are shared across families of antibodies?
Functional - able to bind both to antigens and to specialised cells or proteins of the immune system
Structural - composed of one or more copies of a characteristic unit that form a Y shape
Define antigen
Molecule or part of molecules recognised by the variable antigen receptors of lymphocytes
Define epitope
Also known as antigenic determinant, it is the specific region of the antigen bound by the variable region of an immunoglobulin
Define paratope
the antigen-binding region of an antibody
Define affinity
the measure of the strength of the binding of an antigen by an antibody.
The binding of an antibody by an antigen is non-covalent and reversible.
What is the equation that describes the relationship between the affinity of an antibody for an antigen?
Kforward
[Ab] + [Ag] [AbAg]
Kbackward
How many polypeptides does each Y shape AB contain?
4
2x identical heavy chains
2x identical light chains
What are the 4 polypeptide chains of an antibody held together by?
Disulphide bridges and non covalent bonds
What is the role of the Fc region of an antibody and where is it located within the structure?
Speaks to cells of the immune system or binds to compliment
It is located at the bottom (the ‘stem’) of the Y shape (constant region)
What is the role of the Fab region of an antibody and where is it located within the structure?
Binds to the target antigen
It is located at the top two ‘arms’ of the Y shape (variable region)
What process allows alteration of the structure of the heavy and light chains in the AB variable region?
Somatic hypermutation
What are CDRs?
Complementarity determining regions, they are able to exhibit hyper variability, giving the AB specific finite binding capability to the target antigen
What did Rodney Porter and Gerald Edelman demonstrate?
Both worked on the structure of IgGand showed that:
Porter - using proteolytic fragmentation with an enzyme, showed g-globulin consisted of 3 fractions (Fab and Fc fragments)
Edelman - Showed IgG consists of 4 chains, a pair of heavy and light coins giving a Y shape configuration