6 - Adaptive immunity (humoral immune responses) Flashcards
What is a humoral immune response mediated by
Antibodies secreted by plasma cells
Outcomes of humoral immune response
- Antibody secretion
- Isotype switching
- Affinity maturation
- Memory B cells
BCR
B cell receptor. Membrane bound immunoglobulin (IgM/IgD) with a unique specificity
What do activated B cells act as
Professional APC (present antigen and costimulatory molecules to T cells)
Two roles of BCR in B cell activation
- Performs first signal of activation (binding to
cognate antigen) - Internalise antigen (APC function) so it can be
processed, and peptides presented on MHC
class II molecules
Antibody (immunoglobulin) structure
Four polypeptide chains: two identical heavy (H) chains and two identical light (L) chains, with each chain containing a variable region and a constant region
Hypervariable regions
Each variable region of the heavy chain (VH) or of the
light chain (VL) contains three hypervariable regions
What are the 5 classes of antibodies
IgM, IgD,IgG, IgA and IgE
Fab region
Fragment, antigen binding region, variable region
What bonds hold together antibodies
Disulfide bonds
Fc region
Fragment, crystalline (tail, constant region, effector)
Gene rearrangment and BCR diversity
- A random variable region gene segments is selected and joined to a downstream DNA segment
- Process in bone marrow and is independent of presence of antigens
Where do B cells mature
Secondary lymphoid tissues
What happens to immature B lymphocytes that recognise self antigens
either change their specificity (receptor editing) or are deleted
Two types of B cell activation
T independent and T dependent
T independent B cell activation
- Antigens are multivalent (e.g., bacterial polysaccharides)
- Responses are fast (1-2 days)
- Predominantly IgM
- Low affinity
- Short-lived plasma cells
- Weak in infants and young children
T dependent B cell activation
- Antigens must contain a protein component
- B cell receives two signals
- Responses are slower (several days),
- All immunoglobulin isotypes are
produced - High-affinity
- Memory B cells and long-lived plasma cells
Two signals that B cell receives during T dependent B cell activation
- Through its antigen receptor
- Through interaction with T helper cell that recognises degraded fragments of the
same antigens
Linked recognition
- B and T cells see the same parts of the same antigen
- Requires precise regulation of the migration of activated B and T cells into specific locations
Migration of B and T cells
- Activated CD4 T cells and activated B cells migrate toward one another and interact at the edges of the follicles, where the initial antibody response develops
- Some of the cells migrate back into follicles to form germinal center, where the more specialised antibody responses are induced
B cell activation pathway
Activation of B cells and migration to germinal center –> B cell proliferation –> Somatic mutation and affinity maturation (isotype switching) –> Exit of high affinity antibody secreting cells and memory B cells
What is essential for B cell activation
- Interaction between CD40 on the B cells and CD40 ligand on the T cells
- Cytokines (e.g., IL-4, IL-21)
How is an effective vaccine against H.influenzae type b for children made
- The H. influenzae polysaccharide is linked chemically to tetanus toxoid, a protein against which infants are vaccinated (conjugate polysaccharide vaccines)
- B cells that bind the
polysaccharide component
of the vaccine are activated by helper T cells specific for tetanus toxoid antigen, generated previously
Affinity maturation
Process by which the affinity of antibodies produced in response to a protein antigen increases with prolonged or repeated exposure to that antigen
What causes affinity maturation
Caused by point mutations in the V regions of the genes
encoding the antibodies produced, particularly in the
antigen-binding hypervariable regions
Heavy chain isotype (class) switching
Helper T cells stimulate the progeny of B lymphocytes to change the heavy-chain isotypes (classes) of the antibodies they produce, without changing their antigen specificities
X-linked hyper-IgM syndrome
caused by mutations in the CD40L gene –> much of the serum antibody is IgM, because of defective heavy-chain isotype switching
Which antibodies predominate in blood
IgG and IgM
what are the major antibodies in extracellular fluid within the body
IgG and IgA
Which antibodies predominate in secretions across epithelia, including breast milk
IgA
Which antibodies for the foetus receive from mother by transplacental transport
IgG
Where is IgE found
mainly associated with mast cells just beneath epithelial
surfaces particularly in respiratory tract, gastrointestinal tract and skin
IgA function
Protect epithelial surfaces from infectious agents. Neutralises pathogens and their toxins
IgM function
Complement activation
IgE function
Binds to mast cell FcεRI triggering rapid degranulation, releasing inflammatory mediators into
surrounding tissue
IgG function
- Fc receptor dependent phagocyte responses
- Complement activation
- Neonatal immunity
Fc gamma receptors
Facilitate phagocytosis of antibody bound cells
Antibody Dependent Cellular Cytotoxicity (ADCC)
FcγRIII in NK cells binds to IgG antibodies attached to the surface of a cell, leading NK cell to discharge its granule proteins into the cell, killing it
Secondary vs primary response
Secondary response is much
more rapid, and the total antibody production is nearly 1,000 times
greater than that of the primary response
Antibody titer
measurement of serum antibody, and can be used to study antibody dynamics
