PMI02-2005 Adaptive immunity: B cell response Flashcards
Where do B lymphocytes originate?
Stem cells in the bone marrow
What are the functions of antibodies?
Attach to host tissues
Activate complement
Enhance phagocytosis
Induce degranulation of mast cells, eosinophils and neutrophils
What is the structure of an antibody?
It has 2 identical pairs of light chains and 2 identical pairs of heavy chains that are bound by disulphide bonds
Both heavy and light chains are divided into variable and constant regions
What does the variable region of the antibody contain?
The antigen-binding site
what is an antigen?
any molecule that binds specifically to an antibody
What is an epitope?
Specific site on the antigen that binds to the antibody
What is an immune complex?
Antibody bound to antigen
How many antibody classes are there?
5
What are the differences between the different antibody classes?
They differ in the number of immunoglobulin regions in the Fc region
What is class switching?
As the antibody response continues, B cells change the class of antibody so they produce antibody at a more suitable rate for elimination
What happens to the structure of antibodies during class switching?
The constant region of the heavy chain changes but not the variable region, therefore antigen specificity stays the same
What is the effector function of IgM?
IgM is a strong activator of complement binding with a high affinity for C1q because it has 5 times as many C1q binding sites
What is the effector function of IgG?
It is the only antibody to cross the placenta and provide protection for the infant
It has 4 sub classes: IgG1, IgG2, IgG3 and IgG4
IgG1 and IgG3 bind with higher affinities for Fcy receptors
What is the effector function of IgA?
IgA binds to Fca receptors on macrophages and neutrophils, which promotes phagocytosis and destruction
This results in degranulation and release of compounds that are highly toxic to pathogens
What is the effector function of IgE?
Largely bound to high affinity Fcy receptors on mast cells
Cross linking of IgE/ Fc receptor causes degranulation- release of histamine, serotonin, proteases, cytokines and leukotrienes
What are the 2 ways complement activation can kill pathogens?
Lysis by C9 formation
Phagocytosis of the pathogen mediated by C3b receptors
What antibodies produce a Th1 response? what does this result in?
IgG1 and IgG3
Results in phagocytosis and destruction of pathogen
What antibody mediates Th2 response?
IgE
What does the Th2 response result in?
Degranulation- release of histamine, serotonin, proteases, cytokines and leukotrienes
This attracts lymphocytes, eosinophils, neutrophils and macrophages
What is receptor editing?
Each B cell that expresses sIgM and sIgD that recognise self antigens undergo apoptosis or undergo further DNA rearrangement of light chain of the surface Ig
What occurs to B cells that do not recognise self antigens or bind weakly?
Migrate to the spleen and lymph nodes
How are B cells activated?
There is binding of sIgM and sIgD on the B cell to antigens that deliver signal 1
The B cell acts as an antigen presenting cell
Antigen is internalised by the B cell, then undergoes proteolytic antigen processing with peptide products presented in association with MHC II, which are exported to the surface of the B cell
Th cell recognises MHC complex and delivers further activating signals to the B cell via CD40
Th cell secretes cytokines that induce B cell proliferation, and production of antibodies
What does rapid proliferation and differentiation of B cells give rise to?
Plasma cells that migrate to the bone barrow
How long do plasma cells live?
2-3 days
What do naive B cells produce when activated initially?
IgM and IgG
What interleukins induce switching to IgE and IgG1?
IL-4
What interleukins induce switching to IgA and IgG3?
IL-21
What occurs if IL-4 is secreted as well as IL-21?
IgA switching does not occur
What is somatic hypermutation of B cells and class switching initiated by?
Activation Induced Cytidine Deaminase (AICD)
What is the function of AICD?
Converts cytosine to uracil and therefore breaks correct base pairing
Repairing this lesion introduces random DNA mutations
What is somatic hypermutations?
Mechanism that introduces point mutations in V region axons during RNA transcription that exposed single stranded DNA
Mutated forms of antigen receptors that have higher affinity for antigens will be selected
