Lecture 13. B Cells and Antibodies Flashcards
Where do B cells develop?
Bone marrow
How do B cells recognise their antigens?
As soluble proteins
Process of B cells binding to antigens
- Soluble antigens in blood or lymph
- BCR (B cell receptor) recognises ‘self’ antigen: no action taken
- BCR recognises no antigen: no action taken
- BCR recognises ‘non-self’ antigen: activation, mitosis and clonal expansion of specific B cells
What is the structure of a resting B cell?
Has membrane-bound antibodies that constitute the B cell receptor
What is the structure of an effector B cell?
Massive increase in ER allows secretion of ~5000 antibodies per second
What is the basic structure of an antibody?
Tetrameric, with four polypeptide chains – 2 identical heavy chains (H) and two identical light chains (L), held together by covalent disulfide bonds at the hinge and between H and L chains
What can one antibody tetramer bind to?
Two identical antigens
What can antibodies do if an antigen has two identical antigenic determinants?
Can cross-link the antigens, making small cyclic complexes or linear complexes
What can antibodies do if an antigen has three identical antigenic determinants?
Antibody cross-linking can generate large 3-dimensional lattices
What can antibodies do if an antigen has three or more different antigenic determinants?
If multiple antigenic determinants are available, antibodies with different specificity can co-operate
Why is cross-linkage important for phagocytes?
These large networks make it easier for phagocytes to engulf pathogens or soluble antigens, which can then be degraded and re-presented to T cells, amplifying the immune response
What is the collective name for antibodies?
Immunoglobulin (Ig)
What are the 5 classes of immunoglobulin?
IgM - μ heavy chain
IgD - δ heavy chain
IgG - γ heavy chain
IgA - α heavy chain
IgE - ε heavy chain
What distinguishes the 5 classes of immunoglobulin?
H chains
What is unusual about antibodies produced by camels?
About 50% of their antibodies have H chains that cannot take a L chain partner
What is unusual about antibodies produced by sharks?
Sharks make some H chain antibodies that cannot accept a L chain
They also make IgM antibodies
Do invertebrates make antibodies?
No
Which Ig is the most primitive?
IgM
What is the structure of IgM?
A pentamer of the basic tetrameric unit, held together by a J (joining) chain thought to aid polymerisation of the complex
What are the first antibodies B cells make?
IgM
What does bound IgM trigger?
‘Classical‘ pathway via their tail regions
Can activate complement proteins
Why is IgM considered an opsonin?
IgM is extremely efficient at activating complement
What is an opsonin?
Any molecule that targets antigens for phagocytosis
What is the structure of IgG?
IgG has the standard tetrameric structure: 2 H chains (γ) and 2 L chains
How abundant is IgG?
Very abundant, being 70-75% of the immunoglobulin in human serum
How many subclasses of IgG are there?
4: IgG1-4
What are the functions of IgG?
Toxin neutralisation
Binding to micro-organisms and opsonisation by coating a pathogen and by activating complement, thus leading to phagocytosis
Provision of passive immunity to foetuses and newborns
How do placental cells take up maternal IgG?
By pinocytosis
Placental endosomes have receptors (FcRn receptors) that recognise and bind the tail region (Fc) of IgG endosome antibodies
The IgG molecules are transported FcRn across the placental cells in vesicle Fc carriers (transcytosis)
Which subclass of IgG crosses the placenta poorly?
IgG2
How does IgG secreted in maternal milk provide passive immunity?
FcRn receptors on neonatal gut cells (enterocytes) recognise and bind the tail region (Fc) of IgG antibodies
The IgG molecules are transported across the enterocytes in vesicle carriers (transcytosis)
What is the structure of IgA?
IgA is a dimer of two tetrameric structures held together by a J chain, and also an S chain (secretory component), which allows secretion into saliva, tears, milk and mucus
What does IgM share with IgG, IgA and IgE?
The same binding specificity
What is the function of IgA?
IgA protects our mucosal surfaces: and provides some passive immunity to newborns via milk
What is the structure of IgE?
IgE has the standard tetrameric structure (2H, 2L chains)
What does IgE bind to?
Fc receptors on mast cells (in tissues), basophils (in blood) and eosinophils
What does IgE trigger?
Cell/basophil degranulation resulting in the release of histamines where the mast cells and basophils meet the pathogen/antigen
What does uncontrolled IgE reactions lead to?
Hay fever and asthma
How can eosinophils kill schistosome larva?
If the larva is opsonised (coated) with complement or if the eosinophils use IgE as a passively required receptor, eosinophils can recognise and collectively kill it
