B Cell Development and the Functions of Antibodies Flashcards
What are antibodies?
- glycoproteins that specifically bind target antigens
- secreted by B cell receptors
- also called immunoglobulins
- present in body fluids and external secretions but can also be found on specialised cells e.g. IgE bound to mast cells
What is an antigen?
- molecules that can induce an immune response through the activation of antigen specific B and/or T cells
- virtually any molecular structure may provoke an immune response e.g. proteins, carbohydrates, DNA, lipids etc
What is antigenic determinant?
- epitope
- the molecular structure recognised by the binding site on an antibody molecule or a TCR
- BCRs bind to structures presented on the surface of native bio-molecules
- TCR recognises fragments of bio-molecules presented in associated with MHC molecules
How many classes of immunoglobulin are there?
What defines them?
5 = IgM, IgG, IgA, IgE, IgD (MGADE)
They are defined by the structure of the constant region of their heavy chains which in turn determines their function.
The heavy chains of each of the classes and subclasses of immunoglobulin is encoded by a separate gene.
Where are these genes located?
on chromosome 14
What are the two variants of light chain?
kappa and lambda
an individual antibody molecule bears either two kappa or two lambda chains, never one of each. This reflects the fact that B cells and their progeny and plasma cell clones synthesise only one light cain type and one heavy chain type
Which immunoglobulin is a:
- dimer
- pentamer
What are they linked by?
dimer = IgA
pentamer = IgM
linked by inclusion of J chain
What are fc receptors?
- mediates effector functions of antibody
What are the 6 functions of antibodies?
- opsonisation
- neutralisation
- precipitation (immune complex formation)
- complement activation (classical pathway)
- direct cell activation by Fc receptors - phagocytes, mast cells
- antibody dependent cell mediated cytotoxicity (NK cell activation)
What is antibody opsonisation?
- process by which a pathogen is marked or highlighted for ingestion ad removal by a phagocyte
- involves the binding of an opsonin (in this case the antibody) to pathogen which then attracts phagocytes
- antibody/Fc receptor being on phagocytes facilitates phagocytosis and activates components of complement system (C3b and C4b)
- these components are deposited on the cell surface on the pathogen, providing further opsonisation and aiding in its destruction
What is antibody neutralisation?
- blocks molecular docking mechanism that allows toxins, viruses and some bacteria to gain access to cells
- e.g. tetanus neurotoxin has a carbohydrate side chain that binds to a molecule on the surface of nerve cells
- docking of toxin is essential to subsequent internalisation by pinocytosis and neurotoxic activity
- antibody specific for this carbohydrate prevents the toxin entering the nerve cells and is protective
- can also neutralise viruses by biding to envelope proteins that allow docking
- can also inhibit bacterial adhesion
What is an immune complex?
- antigen molecules interact with several immunoglobulin molecules to form a complex lattice work of antigen and immunoglobulin molecules
- provide a degree of protection by limiting diffusion, complexes are removed and destroyed
- achieved through phagocytosis directed by Fc receptors and complement activation with further opsonisation
Complement activation:
When a single IgM ………. or at least to IgG molecules bind a microbial surface the ……… pathway of complement is activated, releasing C….. opsonin, …………… (C3a, C5a) and triggering lytic …… complex
pentamer classical 3b anaphylatoxins C5-9
How do antibodies do direct cellular activation?
- Fc receptors on cells can trigger specific functions
- e.g. IgE triggering mast cell activation through the high affinity Fc epsilon receptor 1 in allergic reactions
What is antibody dependent cell mediated cytotoxicity?
- ADCC is a cell-mediated innate immunity mechanism
- effector cell (NK, monocyte, macrophage, eosinophil) lyses a target cell that has been opsonised by specific antibodies.
- importnat in containing infected cells or mutated cells
- antibody specifically binds to target cell
- Fc portion of antibody is recognised by FcR on effector cell
- NK cells releases cytokines such as intereferon
- this attracts and activates phagocytes, and cytotoxic granules containing perforin and granzymes
