Lecture 13: B cells and antibodies Flashcards
Tuesday 5th November 2024
Where do T cells develop and where do B cells develop?
T cells develop in the thymus, whilst B cells develop in the bone marrow
What are both B cells and T cells derived from?
Both B & T cells are derived from common lymphoid progenitor cells, which are themselves derived from haemopoietic stem cells originating in the liver (foetuses) or bone marrow (adults)
Is it true that unlike T cells, B cells recognise their antigens as soluble proteins?
Yes
How do B cells recognise their antigens as soluble proteins?
① Soluble antigens in blood or lymph.
② BCR recognises ‘self’ antigen:
no action taken
③ BCR recognises no antigen: no action taken
④ BCR recognises ‘non-self ‘ antigen: activation, mitosis and clonal expansion of SPECIFIC B cells
What do activated B cells differentiate into?
Activated B cells differentiate into Ab- secreting effectors/plasma cell
What is the difference between a Resting B cell and a plasma/effector cell?
Plasma cell is increased in volume and ER size to allow for the excretion of ~ 5000 antibodies per second
Describe 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.
If an antibody has two identical antigenic determinants, what can happen?
If an antigen has two identical antigenic determinants, antibodies can CROSS-LINK the antigens, making small cyclic complexes or linear complexes
What happens if an antibody has 3 or more identical antigenic determinants?
With more antigenic determinants expressed on antigens, antibody cross-linking can generate large 3-dimensional lattices
What happens if an antibody has 3 or more different antigenic determinants?
if multiple antigenic determinants are available, antibodies with different specificity can co-operate
what is the collective name for all the different classes of antibodies?
The collective name for antibodies is Immunoglobulin (Ig).
How many classes of antibodies do mammals usually make?
Mammals (usually) make 5 classes of Ig, distinguished by their H chains:
What is used to distinguish between the differnt classes of antibodies?
The H (heavy) chain
What are the different classes of antibodies? Describe their H chains as well
IgM – μ heavy chain
IgD – δ heavy chain
IgG – γ heavy chain
IgA – α heavy chain
IgE – ε heavy chain
Which mammals make unusual antibodies?
Camels
What is unusal about the anibodies of camels?
About 50% of their antibodies have H chains that cannot take a L chain partner.
What fish makes unusual antibodies?
Sharks
What is unusual about the antibodies of sharks?
Sharks make some H chain antibodies that cannot accept a L chain.
They also make IgM antibodies.
Do invertebrates make antibodies?
No
What is the most primitive antibody?
IgM
Describe IgM
A pentamer of the basic tetrameric unit, held together by a J (joining) chain thought to aid polymerisation of the complex.
Cross links antigens together very efficiently , as can bind 10 antigens
These are the first antibodies that a B cell makes: over time, many B cells will ‘switch’ to making other Ig molecules, but these new antibody forms will RETAIN the SAME SPECIFICITY as the original IgM.
In a pre-B cell in the bone marrow, IgM are membrane-bound and form B cell receptors
IgM and IgD are both BCRs: but IgM can be secreted
IgM and IgD are both BCRs: but IgM can be secreted
Immature naïve B cell in bone marrow expresses surface IgM as its receptor
This then migrates into the lymphoid tissue
B cell now starts to also express membrane-bound IgD. This is a developmental marker of a more mature B cell.
Once the B cell has both IgM and IgD present on its cell membranes, it can now repsond to soluble antigens. This is helped by t helper cells, which aid clonal expansion and differntiation of the b cells into plasma cells.
The plasma cells will now secrete IgM and can release the antibodies
First initial response is IgM being secreted
First initial response is IgM being secreted
When can B cell respond to soluble antigens?
When it has both IgM and IgD on its cell surface membrane
When is IgM secreted from plasma cells?
After clonal expansion
Is it true that igM can trigger the complement pathway? (C1, cleaves C2 etc)
Yes, the classical pathway though. tail regions at the bottom of IgM stimulates the complement pathway.
How efficient is IgM at activating complement?
Very efficient
Why can’t phagocytic cells recognise pathogens/antigens cross-linked or coated with IgM?
Because Phagocytic cells do not have a receptor for IgM. Thus IgM acting alone is ineffective in assisting phagocytosis.
Why is IgM considered as an opsonin?
IgM is extremely efficient at activating complement
An opsonin is any molecule that targets antigens for phagocytosis: complement is also an opsonin.
Coating of a target with IgM (or other antibodies) or complement is a process called OPSONISATION
IgM molecules of the humoural arm of the adaptive system interact with innate immune systems, directing complement for direct killing, or marking antigens with complement for phagocytosis.
IgM molecules of the humoural arm of the adaptive system interact with innate immune systems, directing complement for direct killing, or marking antigens with complement for phagocytosis.
Is it true that IgM secreting plasma cells can switch to IgG secretion?
Yes
Describe IgG
IgG has the standard tetrameric structure: 2 H chain (γ) and 2 L chains.
After switching, the IgG has the SAME binding specificity as the IgM.
It is very abundant, being 70-75% of the immunoglobulin in human serum.
There are four subclasses, 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;
- and provision of passive immunity to foetuses and newborns.
Is it true that some IgG subclasses can cross the placenta and provide passive immunity?
Yes
How do some IgG subclasses cross the placenta and provide passive immunity?
Placental cells take up maternal IgG by pinocytosis.
Placental endosomes have receptors (FcRn receptors) that recognise and bind the tail region (Fc) of IgG antibodies.
The IgG molecules are transported across the placental cells in vesicle carriers (transcytosis).
Ig is released into the foetal circulation.
Which igG subclass crosses the placenta poorly?
IgG2 crosses the placenta poorly.
How is IgG secreted into mother’s milk?
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).
Ig is released into the neonatal circulation.
How does igG act as an opsonin?
IgG can bind and coat pathogens.
Phagocytic cells have receptors (Fc receptors) that recognise and bind the tail region (Fc) of the bound IgG antibodies.
The result is stimulation of phagocytosis
Is it true that igM-secreting plasma cells can switch to IgA secretion?
Yes
Describe 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.
After switching, the IgA has the SAME binding specificity as the IgM.
IgA protects our mucosal surfaces: and provides some passive immunity to newborns via milk
Is it true that IgM-secreting plasma cells can switch to IgE secretion?
Yes
IgE..
- IgE has the standard tetrameric structure (2H, 2L chains)
After switching, the IgE has the SAME binding specificity as the IgM.
IgE binds Fc receptors on:
Mast cells (in tissues) and
Basophils (in blood)
and eosinophils
The bound IgE then act as (passively acquired) receptors for the particular antigens to which the original clonal expansion took place.
What does IgE trigger?
IgE triggers mast cell/basophil degranulation
The result is release of histamine at the site where mast cells and basophils meet pathogen/antigen.
Histamines trigger blood vessel dilation and inflammation: the vessels become leaky, allowing entry of white blood cells antibodies and complement to the site of mast cell /basophil activation.
Uncontrolled IgE reactions : hay fever, asthma
Does IgE also act as a receptor for eosinophils and how?
Yes
Eosinophils attacking a schistosome larva: it’s too big …
… but 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.
Thus the IgE-specific Fc receptors on mast cells, basophils and eosinophils allow these cells to be targeted to different antigens/pathogens.
The antibody arm of the adaptive immune system can direct parts of the innate immune system, as and when required.
