L5 - Humeral responses Flashcards
What triggers the activation and proliferation (clonal expansion) of B cells?
Binding of antigen to the B cell surface.
How do B lymphocytes recognise antigen?
By expressing B cell receptors (BCRs) on their surface
When antigen binds, crosslinking Ig molecules, what happens?
The B cell is activated and secretes soluble Ig in the form of antibodies.
What types of chain make up an antibody?
2 identical light chains and 2 identical heavy chains
What do they light and heavy chains have in common?
They both have one variable region
Where do B cells arise from?
Lymphoid progenitors in the bone marrow
What are the 2 loci which can encode the light chain?
Lambda and kappa loci
How many of each region are there in the kappa chain?
40V regions and 5J regions
How many of each region are there in the lambda chain
29V regions and 7J regions
What is the first step of generating diversity in light chains and how is this controlled?
Somatic recombination of gene segments (V + J) controlled by RAG (recombination activating gene products)
Put these processes in the correct order regarding generating diversity in the light chain; Splicing, transcription, somatic recombination, translation.
Somatic recombination. transcription, splicing, translation
Which extra region is involved in somatic recombination in heavy chains?
Diversity (D). Therefore there are 2 recombination steps during the generation of diversity on heavy chains
Explain ‘combinatorial diversity’.
Any light chain can combine with any heavy chain, so in total there are around 4,000,000 different specificities/structures.
Explain ‘junctional diversity’
Imprecise joining of the V (D) J segments during somatic recombination due to deletion or addition of nucleotides between the segments.
What does TdT do?
Terminal deoxynucleotidyl transferase adds nucleotides at the junctions
Which process of diversity generation does not occur in T cells?
Somatic hypermutation
Which process(es) of diversification occur in the bone marrow?
Somatic recombination; combinatorial diversity combinatorial association and junctional diversity
Which two processes of diversity generation occur in secondary lymphoid tissues?
Somatic hypermutation and affinity maturation
Explain somatic hypermutation
Mutations in V region sequences during B cell replication causing slight changes in specificity.
Which enzyme induces hypermutation?
AID activation-induced cytidine deaminase
Explain affinity maturation
The higher the affinity of the immunoglobulins for the antigen, the stronger signals the responsible B cells receive and the more they divide. So antibody affinity increases over time.
Which 2 signals are required for B cell activation by a thymus dependent antigen?
1) Antigen binding to Ig. 2) CD40L on helper T cell binding to CD40 on B cell
Which 2 signals are required for B cell activation by a thymus independent antigen? (T cell help not required)
1) Antigen binding to Ig. 2a) Antigen binding to TLR eg. LPS, a T-independent antigen type 1 (TI-1). 2b) Extensive crosslinking by polymeric antigen, a T-independent antigen type 2 (TI-2)
Although B cells can be activated without the help of T cells, what are the implications of this which limit to effectiveness of the immune response?
Little/no isotype switching
No somatic hypermutation
No affinity maturation
No memory B cells
Where do follicular helper T cells reside?
In germinal centres of secondary lymphoid tissues
Which survival and mitogenic signals do they produce?
CXCR5 (chemokine receptor - retains T cells in B area of lymphoid tissue)
CD40L
IL-21 (important in affinity maturation)
What is BLIMP-1 and what is its function?
B lymphocyte induced maturation protein -1 is switched on by T cells and causes B cell proliferation
Memory cells produce Ig on surface and CD27. True or false
True
What are isotypes?
Different classes of immunoglobulin (IgG IgA IgM IgE IgD)
Which 2 isotypes have their own subclasses and what are there?
IgG (IgG1, IgG2, IgG3, IgG4)
IgA (IgA1, IgA2)
Following activation, which 2 isotypes are expressed on newly formed B cells?
IgD (never secreted) and IgM
Where and when does isotype switching occur?
In germinal centres of lymph nodes after B cell activation
What determines the isotype secreted by the plasma cell?
The cytokines secreted by the T cells
Which 2 processes does activation-induced cytosine deaminase (AID) induce?
Somatic hypermutation and isotype switching.
Which isotype is pentameric
IgM
Which isotype can be secreted as a monomer or a dimer?
IgA
Where is (dimeric) IgA best at working?
secreted across epithelia eg. intestinal mucosa or lung
Where is IgG best at working?
Secreted across placenta and extravascular sites
Which isotypes are found in the circulation?
IgG and IgM
Neutralisation, the prevention of the binding of viruses, toxins and bacteria is helped by which isotypes?
IgG, IgA, IgM bind to pathogen and prevent it binding to cell surface.
Which isotypes aer important in opsonisation?
IgG1, IgG3, IgG4, IgA
Antibody-dependent cellular cytotoxicity (ADCC) uses which isotypes?
IgG1, IgG3
What triggers the initiation of the complement cascade via the classical pathway?
When antibody binds to pathogen (antibody : antigen complex), the conformation changes slightly, exposing the hinge region where C1q, a key component of the complement cascade binds.
List 6 antibody functions
Neutralisation Opsonisation Antibody dependent cellular cytotoxicity Activation of the complement cascade (classical) Triggering mast cell activation Triggering eosinophil activation
Which isotype triggers mast cells and eosinophils
IgE
What is the main role of eosinophils?
To destroy multicellular parasites (by releasing Eosinophil Major Basic Protein and Cationic protein)
