B cell development and the functions of antibodies

Question 1

What are antibodies?

Answer 1

Glycoproteins that specifically target antigens
Secreted B cell receptors and are also known as immunoglobulins
Present in body fluids and external secretions but can also be found on specialised cells (e.g. IgE bound to mast cells)

Question 2

What is an antigen?

Answer 2

Molecules that induce an immune response through the activation of antigen specific lymphocytes and/or T lymphocytes
Virtually all molecular structures (carbohydrates, proteins, DNA) may provoke an immune response

Question 3

What is an antigenic determinant?

Answer 3

Molecular structure recognised by the binding site of an antibody molecule or a T cell receptor.
Antibodies bind to structures presented on the surface of native bio-molecules
T cell receptors recognise fragments of bio-molecules in association with MHC molecules

Question 4

What are the 5 classes of human immunoglobulins?

Answer 4

IgM, D, G, A, E - defined by structure of the constant region of their heavy chains = determines function

Question 5

What are the two types of light chain constant regions?

Answer 5

Kappa and lambda

- individual antibody molecule will have either 2 kappa or 2 lambda

Question 6

What is the structure of IgM?

Answer 6

Heavy chain = 4 constant domains
Expressed as a monomeric transmembrane molecule on B cells
Secreted by plasma cells as a pentamer - this conformation forms due to the inclusion of a J chain produced within the plasma cells

Question 7

What is the structure of IgG?

Answer 7

4 subclasses
Heavy chains demonstrate 95% homology in constant domains to one another
Differ in their hinge regions

Question 8

What is the structure of IgA?

Answer 8

2 subclasses
Heavy chains comprised of 3 constant domains
A1: extends, highly gbycoslyated hinge region
Predominantly monomeric
When present in external secretions, it is a product of local immune system - produced by plasma cells as a dimer

Question 9

What do dimer IgA antibodies bind to and what happens?

Answer 9

Bind to poly Ig receipts on basal surface of epithelial cells
This complex is then transported to the apical surface, and the receptor is cleaved, releasing IgA (Secretory piece) = transcytosis

Question 10

What is the structure of IgE?

Answer 10

comprised of 4 constant domains

Question 11

What is the structure of IgD?

Answer 11

heavy chain is composed of 3 constant domains + extended gbycoslyated region
Expressed on the surface of mature B cells

Question 12

What is the difference between the Fab site and Fc region of antibodies?

Answer 12

Fab antigen binding site binds to the antigen, while th Fc region acts as a target for the Fc receptors of phagocytes (neutrophils, macrophages)

Question 13

What is opsonisation?

Answer 13

Pathogen marked for ingestion and removal by phagocyte
Binding of an opsonin (antibody) to an antigen or pathogen
Antbibody/Fc recepto binding on the phagocytes facilitates phagocytosis and also activates important components of complement system (C3b and C4b)

Question 14

What is neutralisation?

Answer 14

Binding of antibodies to the antigen/pathogen blocks it binding and infecting host cells

Also able to neutralise viruses by binding to the envelope proteins, preventing docking and entry

Question 15

What are immune complexes?

Answer 15

Interaction of antigen molecule with several immunoglobulin complexes = can limit diffusion of the antigen molecules so they are removed and destroyed by phagocytosis (complement activation with further opsonisation)

Question 16

What happens in complement activation?

Answer 16

Single IgM pentamer or at least 2 IgG molecules bind to the microbial surface causing the complement system to be activated releasing c3b opsonin, anaphylatoxins (C3a and C5a) and triggering lytic C5-9

Question 17

What is direct cellular activation?

Answer 17

Fc receptors trigger specific unctions

e.g. IgE - triggers mast cell activation through high affinity Fc epsilon receptor 1 in allergic reactions

Question 18

What is antibody dependent cell mediate cytotoxicity?

Answer 18

Cell mediated innate mechanism 
Effector cell (NK cell, monocyte, macrophage, eosinophil) lyses an opsonised target by specific antibodies

Question 19

What happens with IgG?

Answer 19

Specifically binds to the target cell
Fc portion of the antibody recognises the Fc receptor on an effector cells (e.g. NK cell)
NK cell releases cytokines such as interferon which attracts phagocytes and cytotoxic granules (perforin and granzymes) - they enter the cell and trigger apoptosis

Question 20

What is anti-helminth immunity?

Answer 20

Example of ADCC: Large parasites called helminths are too big to be engulfed and killed by phagocytosis
Antigens on their surface are recognised by IgE - Fc receptor of an eosinophil binds the IgE= interaction signals the effector cell to degranulate releasing substances toxic to the helminth