L6 Humoral Immunity Flashcards
Simplified humoral response pathway
Antigen recognition
Activation of B-lymph
Proliferation
Differentiation
Plasma cells (antibody secretion), IgG (Isotype switching), High affinity IgG (Affinity maturation, Memory b cells)
B cell receptor (BCR)
Membrane bound immunoglobulin (IgM/IgD) with a unique specificity Surface single antibody molecule associated Igα and Igβ chains (signal transduction)
Two roles in B cell activation:
- Preforms first signal of activation when it binds to cognate antigen
- Internalise antigen to be processed so peptides can be presented on MHC II molecules
Distinct feature of B-cells
- Tail and associated molecules to transduce signals
- a heavy and light chain
Same feature of B-cells and T-cells
Constant and variable regions
What happens to the constant region during class switching
It stays the same :)
Antibody (immunoglobulin) structure
- 4 polypeptide chains: : two identical heavy (H) chains and two identical light (L) chains— with each chain containing a variable region and a constant region
- Each variable region of the heavy chain (VH ) or of the light chain (VL ) contains three hypervariable regions.
Fab - fragment, antigen-binding region
Fc – fragment, crystalline
▪ There are 5 classes: IgM, IgD, IgG, IgA and IgE
Name the 5 classes of B-cell antibodies
IgM, IgD, IgG, IgA and IgE
GAMED MEGAD DEMAG
Gene rearrangement and BCR diversity
▪ A random variable region gene segments is selected and joined to a downstream DNA segment
▪ This process in the bone marrow is independent of presence of antigens
Do B-cells go through central or peripheral tolerance
Both, self-reactive cells become anergic (functionally unresponsive) or die by apoptosis
What happens to B-cells that self-recognise
Immature B lymphocytes that recognise self-antigens in the bone marrow with high affinity either change their specificity (receptor editing) or are deleted
Where does the development from immature into mature B cells occur?
within secondary lymphoid tissues
B-cell activation 2 ways
T-independent and T-dependent
T-independent antigens
Nonprotein antigens like polysaccharides and carbohydrates and lipids can activate B-cells
T-dependent antigens
Protein antigens
Antibodies that are made through protein antigens typically show what
Isotype switching and are of high affinity
What happens if activated B cells encounter specific signalling molecules through their CD40 and cytokine receptors
(both modulated by T helper cells), they undergo antibody class switching to produce IgG, IgA or IgE antibodies that have defined roles in the immune system.
isotype:
Antibodies can come in different varieties known as isotypes, which refer to the genetic variations or differences in the constant regions of the heavy and light chains of the antibody.
class switch recombination:
A biological mechanism that changes a B cell’s production of antibodies from one class to another; for example, from an isotype called IgM to an isotype called IgG.
The type of antigens that T-independent B-cells produce
- Mainly IgM
- Low affinity
- short lived plasma cells
The type of antigens that T-dependent B-cells produce
- Isotype switched
- High affinity
- Memory B cells
- Long lived plasma cells
T-independent antigens and antibodies
▪ Antigens are multivalent (e.g., bacterial polysaccharides)
▪ Responses are fast (1-2 days) and predominantly IgM, with low affinity
▪ Short-lived plasma cells
▪ Weak in infants and young children
T-dependent antigens and antibodies
▪ Antigens must contain a protein component
▪ B cell receives two signals: (i) through its antigen receptor and (ii) through interaction with T-helper cell that recognises degraded fragments of the same antigens
▪ Responses are slower (several days), and all immunoglobulin isotypes are produced and have high-affinity
▪ Memory B cells and long-lived plasma cells
B cell activation by helper T cell and germinal center reaction
▪ Activated CD4 T cells and 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
▪ The meeting of the two cells is called linked recognition
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