Adaptive immunity 2 (B cells) Flashcards
Which subset of T cells drive antibody production by B cells?
TH2 CD4+ T cells
Where do B cells originate and mature?
Bone marrow (from haemopoetic stem cells)
Where are B cells found in large populations?
lymph, lymph nodes, spleen, specialised lymphoid tissues (secondary lymphoid organs)
Which branch of the adaptive immune system is driven by B cells?
Humoral immunity (produce antibodies)
Function of B cells
produce antibodies, and are capable of antigen presentation for T cell activation
What are the 2 main subsets of B cells?
plasma cells and memory B cells
How many types of antibodies exist?
5
Which professional immune cells are capable of antigen presentation?
dendritic cells, macrophages, B cells
How do B cells recognise antigens?
via the B cell receptor (BCR) which has extreme diversity
What is the B cell receptor essentially?
an antibody (2 of the 5 antibody types are BCRs)
Which of the 2 antibody types form BCRs?
IgM or IgD
When does BCR diversity arise?
during B cell education in the bone marrow
Where are B cells activated?
In the periphery in secondary lymphoid organs (lymph nodes, spleen, specialised lymphoid tissues)
What happens once B cells are activated?
differentiate into plasma cells and memory B cells
Function of plasma cells
produce antibodies
function of memory B cells
produce a faster antibody response during a reinfection
Where does B cell education occur?
In the bone marrow
What happens during B cell education?
VDJ recombination and negative selection
What process creates diversity in the BCR?
VDJ recombination
Which region of the BCR is affected by VDJ recombination?
variable region (antigen binding site) - constant region remains the same.
Why do B cells not need to undergo positive selection?
B cells do not need to interact with MHC receptors on host cells (unlike T cells)
Which gene segments code for the light chain of BCRs?
V (variable) and J (joining)
Which gene segments code for the heavy chain of BCRs?
V (variable), D (diversity), J (joining) - all 3
How is the variable region of BCRs unique?
VDJ recombination means that multiple options can be selected for each gene segment leading to a huge number of possible gene combinations.
Function of B cell negative selection
ensures there are no self reacting B cells circulating that will recognise and target self antigens
Where does negative selection occur?
bone marrow
How does negative selection occur?
specialised bone marrow cells present self antigens to B cells which are expressing antibodies/BCR (IgM, IgD)
What happens if B cells do not bind to self antigens during negative selection?
B cells are released from the bone marrow and migrate to secondary lymphoid tissues
What happens if BCR binds to the self antigen during negative selection?
the self-reacting B cell is engulfed and removed by macrophages
How can autoimmune disease arise?
if there is a breakdown in negative selection (and self-reactive B cells are released)
What are B cells called when they leave the bone marrow?
naive B cells (not yet encountered antigens)
Examples of specialised lymphoid tissues
(found in barrier and mucosal sites) tonsils, adenoids, Peyer’s patches
What are the 2 types of B cell activation?
Thymus-dependent (requires help of T cells) and thymus-independent (without help from T cells)
Which T cells enable thymus-dependent activation of B cells?
CD4+ TH2 cells and TFH (T follicular helper cells)
How can B cells be activated without T cell involvement?
Thymus-independent activation - involves the BCR recognising an antigen, and the PRRs (e.g. TLR) on the B cell recognising a PAMP (component of microorganism e.g. LPS) at the same time
What happens when naive B cells are activated?
They differentiate into plasma cells which initially releases IgM. Naive B cells also differentiate into memory B cells but only in thymus-dependent activation.
How are B cells activated by thymus-dependent activation?
- B cells present antigen to T cells (CD4+ TH2 and TFH cells)
- Costimulatory molecules of B cell (CD40) and T cell (CD40L) interact
- T cell releases cytokines which leads to B cell differentiation
Which cells do B cells differentiate into during thymus-dependent activation?
plasma cells and memory B cells
What cells do B cell differentiate into during thymus-independent activation?
plasma cells only
Which type of B cell activation does not provide long-term immunity?
thymus-independent B cell activation because memory B cells are not produced
What does B cells activation lead to?
class switching
What is the first type of antibody produced by plasma cells following B cell activation?
IgM
What is class switching?
When B cells change the production of antibodies from one type to another (IgM -> IgG)
Why does class switching occur?
to produce a more effective immune response (IgM has a weak response, other antibodies have different functions too)
How does class switching occur?
by gene rearrangement to alter the constant region which allows the production of antibodies with different structures but with the same antigen binding site
What features determine the effectiveness of antibodies?
affinity and avidity
What is the affinity of an antibody?
strength of binding to antigen
What is the avidity of an antibody?
the number of binding sites the antibody has
Which antibodies have low avidity?
IgD, IgM, IgE, IgG (only 2 antigen binding sites)
Which antibodies have high avidity?
IgA (4 antigen binding sites) and secreted IgM (10 binding sites)
What is the structure of secreted IgM?
pentametric complex - made of 5 antibodies so a total of 10 antigen binding sites
Which antibodies have low affinity?
IgM, IgD, IgA
Which antibodies have high affinity?
IgG and IgE (therefore are most effective and so are produced the most)
What are the 5 types of antibodies / immunoglobulins?
IgM and IgD (BCRs), IgG, IgE, IgA
Example of where secretory IgA is found
saliva
What are the functions of B cell antibodies?
Neutralisation, opsonisation (tag microorganisms/allergens for removal), activate the complement cascade
Which antibody has the function of neutralisation?
secretory IgA - binds to 4 antigens simultaneously and prevents microorganisms attaching to host cells.
Function of opsonisation
antibodies (opsonins) tag microorganisms and allergens for removal which initiates phagocytosis (e.g. by macrophages) or degranulation (of NK, mast cells, eosinophils, basophils)
Which pathway of the complement cascade can be activated by antibodies?
classical pathway
What does the complement cascade produce?
Anaphylatoxins
Functions of anaphylatoxins
recruit immune cells to the site of infection, form membrane attack complexes, drive opsonisation for phagocytosis
Which cells play a role in vaccinations?
B and T cells (adaptive immune system)
Which antibodies are produced in a primary response (e.g. vaccination)?
initially IgM which is then switched to IgG
Which antibodies are produced in a secondary response?
Mainly IgG (and some IgM)
Why is a much larger concentration of IgG released more rapidly in a secondary response?
memory B cells are primed to produce IgG upon re-exposure to a specific antigen
