CMB2004/L06 Lymphocyte Activation Flashcards
Explain lymphocyte maturation simply. (4)
Progenitor cell gives rise to many LYMPHOCYTES with DIFFERENT specificity
REMOVAL of potentially self-reactive immature LYMPHOCYTES
Pool of mature NAIVE lymphocytes
PROLIFERATION and DIFFERENTIATION of activated SPECIFIC lymphocytes to form a clone of effector cells
Give 3 functions of antibodies.
Neutralisation
Opsonisation
Complement activation
Describe B cell activation. (2 signals)
Binding of Ag to BCR provides signal 1
Signal 2 provided by antigen or extensive cross-linking of BCR
Describe the molecular basis of Ag/BCR signal 1. (2)
BCR-associated polypeptides involved in signalling
Crosslinking BCR activates intracellular kinases
How can signal to B cells be increased/enhanced? (2)
If antigen has activated complement cascade
Lots of C3b
Complement receptor 2 (CR2) on B cell surface (CD21)
CR2/CD19/CD81 form the BCR co-receptor complex
If an Ag that binds BCR is coated with C, then it can bind what?
CR2 on B cells to give an increased signal 1
By which mechanisms can B cells receive signal 2?
Dependent on type of Ag they bind
From Ag itself OR
Extensive cross-linking of BCR
How do thymus-dependent antigens work? (4)
Require T cell help for B cell activation and antibody production
B cells recognise antigen through BCR
Once activated, B cells present processed antigen to helper T cells (CD4+)
Helper T cells provide signals for B cell proliferation and differentiation into plasma cells
What is the difference between TI-1 Ag and TI-2 Ag?
TI-1 Ag
Bind to other receptors on B cells providing signal 2
Act as polyclonal activators in high concentrations
TI-2 Ag
Cross-link many BCR molecules on B cell surface
Take longer to induce B cell activation
Don’t develop response until >5 years
Describe the effect that TI-2 antigens elicit on dendritic cells.
TI-2 antigens signal B cells to produce IgM
Activated dendritic cells release cytokine, BAFF, that augments production of antibody against TI-2 antigens and induces class switching
Describe how thymus-dependent antibodies work.
T cells activated by MHC/peptide on APC
BCR binds antigen - signal 1
B cell internalises Ag, processes and presents Ag to CD4+ T cells - signal 2
Cytokines secreted by T cell (class switching)
All classes of antibodies can be produced to TD Ag
Describe how binding of a viral epitope leads to antibody production. (4)
B cell binds virus through viral coat protein
Virus particle internalised and degraded
Peptides from internal proteins of virus presented to T cell, activating B cell
Activated B cell produces antibody against viral coat protein
How would B cells be described in terms of their relationship to TD Ag?
Antigen-presenting cells
How must epitopes recognised by the antibody and T cell be physically linked? (2)
Either from different parts of the same molecule
Or from different molecules of complex (e.g., viral proteins)
How do B cells convert TI Ag to TD Ag to improve efficiency of a vaccine against pathogens that have T1 antigens? (4)
B cell binds bacterial polysaccharide epitope linked to tetanus toxoid protein
Antigen internalised and processed
Peptides from protein component presented to T cell
Activated B cell produces antibody against polysaccharide antigen on surface of bacterium
Give an example of a conjugate vaccine.
Haemophilus influenzae type B
MenC
Pneumococcal conjugate vaccine
How are B/T cell conjugates formed?
If Ag is TD, B cell presents peptide from Ag to CD4+ T(H) cells at boundary of T/B areas wihtin lymph node
Where to B cells migrate after surviving the bone marrow selection process?
Into blood and lymphatics
How are CD40 ligands expressed?
B cell binds BCR and presents peptide (on MHC class II) from Ag to activated T(H) cell
T cell expresses CD40L
What is the role of CD40L?
Ligand provides signal 2 to B cells
Signal also induces activation induced deaminase (AID) for class-switching and somatic hypermutation
Where do B cells receive the signals to proliferate?
B cell follicles
What are germinal centres (GC)?
Conjugates of B lymphoblasts and T cells moved to primary follicles (B cell areas)
Within a B cell follicle in secondary lymphoid tissues
Once B cells divide rapidly and form centroblasts, what else can occur? (2)
Somatic hypermutation of Ig genes
Isotype switching
What is a centrocyte?
B cell with a cleaved nucleus
Non-dividing cell formed after activation with TD Ag
