| what are the steps for the activation of proliferation and differentiation of B cells? | 1. two or more Ig molecules need to cross-link together by the binding of two or more antigens
2. the signals that arise are transduced by receptor-associated proteins
3. the tyrosines of ITAM are phosphorylated by kinases
4. Syk tyrosine kinase is recruited and phosphorylates tyrosine residues on adapter proteins
5. the adaptor proteins recruit and activate many molecules
6. the result is proliferation and differentiation of B cells |
| how is the innate immune response involved in the B cell activation? | - complement system: the B cells express CR2, which is a receptor for proteolytic fragment C3d of the complement system. CR2-C3d binding enhances responses of the B cell
-binding of microbes to the TLRs of the B cells directly. this stimulates B cell proliferation, differentiation and Ig secretion |
| what is T-independent B cell activation and when does it occur? | it is the activation of the B cells without the involvement of the T cells. it happens when the antigen that binds is a non-protein, such as a polysaccharide or lipid.
they cause such a strong activation that no T cells are needed. |
| what happens in T-dependent B cell activation? | 1. the naive CD4 T cells are activated in the T cell zones and the naive B cells are activated in follicles, both by the same antigens
2. they migrate towards each other to the paracortical areas, because B cells express CCR7 and T cells express CXCR5
3. the B cells then present their antigens on the MHC-II molecules so that the T cells can recognize them
4. the T cells then express the CD40L and the B cells express CD40, they bind to each other and proliferation of the B cells occurs |
| what happens to the B cells in the germinal centers? | 1. B cell proliferation
2. somatic mutation, affinity maturation and isotype switching with the help of follicular helper cells
3. high affinity B cells become plasma cells or memory B cells |
| what are the different parts of an immunoglobulin molecules? | they have two heavy and two light chains, each chain containing a variable and a constant region. this is all connected by disulfide bonds
there are three functional parts;
- fab (fragment antigen binding) -> the entire light chain attached to the V and part of the C domain of the heavy chain (recognition of antigens)
- fc (fragment crystalline) -> remaining part of the heavy chain (effector function of the antibody)
-hinge region -> flexible region |
| what are the functions of the different immunoglobulin classes? | IgM: providing immunity against extracellular polysaccharides on microbes, promoting phagocytosis and bacteriolysis, activating the complement system
IgG: activates complement system, stimulating chemotaxis, facilitating phagocytosis, neonatal immunity (crossing the placenta)
IgA: mucosal immunity
IgE: fighting allergens and parasites
IgD: initiating antibody responses |
| how can IgM be present in the body? | in monomeric form and as a pentamer, in which five monomers are held together with a J chain |
| what is the structure of IgA? | it can occur as a monomer, but also as a dimer, trimer and multimer held together by a J chain.
it has two isotypes; IgA1 (mostly in serums, linked with disulfide bonds) and IgA2 (mostly in secretions, linked with non-covalent bonds) |
| how is the chromosome with the immunoglobulin genes organized? | it starts with a heavy chain variable region (VDJ) and then the heavy chain constant region. in between the constant regions, switch regions are present |
| what is the process of isotype switching? | 1. the CD40L-CD40 interaction of the T and B cells and the cytokines that are produced induce activation-induced deaminase (AID)
2. AID converts cytosines into uracils in the switch regions
3. this causes double-stranded DNA breaks, which causes deletion of the DNA
4. RNA splicing causes the VDJ region to be spliced right next to the exon that is needed for the immunoglobulin, e.g. IgG |
| how does the B cell know which immunoglobulin is needed? | the CD40L-CD40 interaction produces NFkappaB and the cytokines produce a certain transcription factor. these molecules bind to the chromosome at the location where the cut needs to happen |
| which cytokines produce which type of immunoglobulin? | IgG -> by various cytokines, such as Il-10
IgE -> Il-4
IgA -> cytokines produced in mucosal tissues, such as TGF-beta and BAFF |
| how does affinity maturation occur? | 1. AID produces uracils in the Ig V region of the DNA
2. these uracils are often converted to thymidines or are removed. these mutations are called somatic hypermutations
3. the result is different B cell clones that have varying affinities to the antigen
4. the B cells with the highest affinity are selected by follicular dendritic cells (FDCs) |
| what is the difference between the primary and secondary antibody response? | primary response: the entire differentiation needs to happen starting with the naive B cells, the response takes 5 to 10 days, not many antibodies are produced, antibody affinity is low, mostly IgM and IgG
secondary response: memory B cells are already present, the response takes 1 to 3 days, much more antibodies are made, antibody affinity is quite high, the antibodies are more specific |
| what does SSC and FSC mean in a FASC analysis? | SSC: side scatter, shows the granularity of the cells
FSC: forward scatter, shows the size of the cells |
