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
What is ITAM?
Immunoreceptor tyrosine-based activation motif
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
How do thymus-independent antigens work? (3)
Activate B cells directly without T cell help
B cells recognise antigen through BCR
Activation produces IgM without additional signals by B cells - less sophisticated
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
What is signal 3 delivered by antigen-presenting cells?
IL-6 acting on T(FH) cells
What can occur with B ells once they are in a germinal centre (GC)? (3)
Differentiate into plasma cells
Form long-lived memory cells
Die within lymphoid tissue
Describe somatic hypermutation.
Introduces point mutations into V regions of Ig
Approx. 1 mutation per V region per cell division
Enzymes involved are AID (activation induced deaminase) and DNA repair genes
What is the role of follicular dendritic cells?
Cells in primary follicle that capture intact Ag for centrocytes to bind via BCR
Present antigen for B cells
What happens to an activated B cell with mutated BCR with lower affinity for Ag?
BCR not cross-linked
Cannot present antigen to cell
Death by apoptosis
What is the role of CD40 expressed by B cells? (2)
Protects centrocytes from apoptosis
Induces isotype switching
Describe the action of activation-induced deaminase (AID).
Induces DNA breakage new constant region of antibody joined without affecting existing VDJ region
Which types of Ag induce:
a) IgM
b) IgG1, IgG3 or IgG4?
a) Polysaccharides
b) Proteins
Which kind of antibody do antigens at mucosal surface induce?
IgA
Which antibody is induced by IL-4?
IgE
