13 - B Cell Effector Functions Flashcards
Humoral immune response
Mediated by antibodies secreted by plasma cells
Signals that induce B cells to proliferate and differentiate into plasma cells
Signals from the bound antigen and from helper T cell in the form of CD40L and cytokines
Three main ways antibodies protect the host from infection
- Neutralisation
- Opsonisation
- COmplement activation
Signals required for B cell activation
- First signal is delivered through the B cell antigen receptor
- Second signal is either thymus dependent (TD) or thymus independent (TI)
Thymus dependent antigen second signal
Delivered by helper T cells that recognise antigen bound to MHC-2 molecules. (CD40, CD40L is essential part of second signal)
Thymus independent antigen second signal
Delivered with antigen, through TLR that recognise antigen associated TLR ligands (e.g. bacterial LPS)
Helper T cells
Stimulate proliferation and then differentiation of antigen binding B cells in lymph nodes
Cytokines secreted by T cells in B cell activation
- IL-4, 5 and 6
- Drive proliferation and differentiation of B cell into antibody secreting plasma cells
Linked recognition
B cells and helper T cells must recognised epitopes of the same molecular complex in order to interact
Process of linked recognition
- B cell binds virus through viral coat protein
- Virus particle is internalised and degraded
- Peptides from internal proteins of the virus are presented to the T cell, which activated the B cell
- Activated B cell produces antibody against viral coat protein
Structure of a germinal centre
- A specialised microenvironment in which B cell proliferation and somatic hypermutation occur
- Composed mainly of proliferating B cells
- Antigen specific T cells make up ~10% of germinal center lymphocytes
- Grows in size as immune response proceeds
Germinal center after clearance of infection
- Shrinks and disappears
- Present for about 3-4 weeks after intial antigen exposure
Centroblasts
Rapidly proliferating B cells in dark zone
Centrocytes
B cells dividing less frequently in light zone
IL-4
- Produced by CD4+ helper T cells and upregulate CD40L (on T cells)
- Confined to space between B and T cell after secretion
Helper T cell cytoskeleton and secondary apparatus during B cell activation
Reoriented towards the B cells
T cell and B cell migration to border between T cell area and B cell follicle in lymphoid tissue
Naive CCR7+ T cells and CXCR5+ B cells home to distinct regions where the chemokines CCL21 and CXCR13, respectively,
are produced
Subcapsular macrophages
The low endocytic and degradative activity of subcapsular macrophages preserves the antigens trapped on their surface, allowing B cells to encounter them
Iccosomes
immune complexes bound to FDCs form iccosomes which are released and taken up by B cells in germinal centres
Activated B cells form germinal centres in lymphoid tissues
- Naive B cells enter the lymph node via HEV and leave via efferent lymphatics
- B cells that encounter antigen in the follicle form a primary focus, some form a germinal center
- Plasma cells migrate to the medullary cords or leave via efferent lymphatics
- Plasma cells migrate to bone marrow
Rounds of mutation and selection of activated B cells
Mutation and selection for higher affinity mutants in the germinal centre, resulting in high affinity antibody secreting plasma cells and high affinity memory B cells
Somatic hypermutation and affinity maturation
- In the germinal centres of a lymph node, the variable regions of BCRs are constantly acquiring mutations
- Mutations that negatively affect the BCR’s affinity for its antigen will be selected against, while mutations in that positively affect affinity will cause proliferation
Processes that germinal center B cells undergo
- Somatic hypermutation
- Affinity maturation
- Class switching
What antibody isotype do all naive B cells initially express
IgM and IgD
Which part of antibody is specific for antigen
Variable region (must be maintained during recombination events in isotype switching)
Recombination events in isotype switching
- Genes encoding the constant region corresponding to each isotype are arranged in a linear fashion
- During isotype switching, a portion of the DNA is looped out as switch regions recombine
- After recombination, the constant region directly downstream of the VDJ region will encode the isotype produced on the surface of the B cell and secreted
What is class switching controlled by
Cytokines
Polyclonal activation
- At high concentration, the signal delivered by the TI-1 antigen is sufficient to induce proliferation and antibody secretion by B cells in the absence of specific antigen binding to the surface Ig.
- Therefore all B cells respond.
Another name for TI-1 antigens
Mitogens (substance that induces cells to undergo mitosis)
Disadvantages of polyclonal antibody responses
Pathogens have evolved to induce polyclonal antibody responses so that specific antibody is diluted
Multiple cross linking of BCR by TI-2 antigens
- Can lead to IgM production
- Cytokines (e.g. BAFF secreted by DCs) increase these responses and lead to class switching
Infant immunity
Capable of mounting adaptive immune responses, but their ability to develop long lasting immunity is limited
Hib vaccine
- Against Haemophilus influenzae type b
- Conjugate of bacterial polysaccharide and the tetanus toxoid protein
How does Hib vaccine work
- The B cell recognises and binds the polysaccharide, internalises and degrades the whole conjugate and then displays toxoid-derived peptides on surface MHC Class II molecules
- Helper T cells generated in response to earlier vaccination against tetanus toxoid recognize the complex on the B cell surface and activate the B cell to produce anti polysaccharide antibody
The immune system antibodies against blood types
Forms antibodies against whichever ABO blood group antigens are not found on the individual’s RBC’s (e.g. Blood group A have antibodies againts blood group B)
