Module 6 Flashcards
(27 cards)
What inititiates the b-cell response in Thymus independent (TI) antigens?
Usually non-microbial constituents, can trigger antibody productions by B cells in the absence of T cell help. This includes LPS and other repetitive bacterial structures.
Difference between TI-1 and TI-2 antigens?
TI-1 (eg., LPS) activate B cells via innate receptors (eg TLRs) regardless of BCR specificity
TI-2 (eg bacterial capsule) are highly repetitive, cross-link BCRs extensively and require mature B-cells
How do TI-1 antigens differ in B cell activation at high vs low concentrations?
High concentration: Polyclonal B cell activation (non-specific). Bacterial mitogens are a stimuli to induce.
Low concentration: Specific BCR engagement leads to monoclonal antibody production
What kind of help may be involved in B cell activation by TI-2 antigens?
TI-2 antigen activation does not require T cells but may be enhanced by immune cells like DC’s and NK cells. Induces mainly IgM
Fates when B-cell activated?
- IgM bodies specific for LPS
- IgM bodies specific for other components of the bacterial surface
- IgM bodies specific for bacterial surface antigen
What happens when helper T cell interact with APC?
T helper cells recognise the MHC class II complex and provide signals via CD40L and CD40 binding. Cytoskeleton merges towards end pole in which B cell is interacting with the APC. Cytokines like IL-4 are released and induce activation of B-cells which lead to plasma pathway generation.
Helper T-cells can only recognize peptides and the protein antigen presented in MHC class II context.
What are the outcomes of B-cell activation?
B-cell proliferation by IL-4
Differentiation into resting memory cells IL-4, IL-5, IL-6
or antibody-secreting cells byIL-5, IL-6, IL-10
Where do activated B-cells migrate and what happens in germinal centres?
Cognate pair goes to germinal centre and differentiates here to produce large amount of antibody
What are the two main zones in a germinal centre and what happens in each?
Dark zone: contains rapidly dividing B cells (centroblasts) with reduced expression of surface Ig.
Light zone: centrocytes are small non-dividng B-cells with high levels of surface Ig and going to be selected for capacity to bind to antigen more effectively often.
fDCs: are going to present antigen to select for these cells that have higher affinity.
What is affinity maturation & how is it achieved?
For centroblasts: point mutations into the V regions (VH and VL) at a very high rate giving rise to mutant B cell receptors. Result is that they differ subtly in antigen affinity.
For centrocytes they will express Ig’s with a range of affinities. These antigens are presented by fDC’s and Ig’s compete for binding. But only high affinity Igs will get survival signal.
Importance of high affinity in centrocytes
A centrocyte whos membrane Ig binds and undergoes cross-linking by FDC’s-bound antigen receives a survival signal. Those who fail to receive signal die. Centrocytes with high-affinity receptors are more likely to be successful in binding antigen than those of lower affinity.
Which cytokines form memory cells and plasma cells?
IL-4 and IL-10, respectively
Where does affinity maturation occur?
germinal centres
Mini process B cell activation with T cell.
Activated B-cell by cognate pair of signal 1 and signal 2 + cytokines. Germinal centre B cell with mutated high-affinity surface ig survives and sustain B-cell proliferation and maturation into memory B cell or plasma cell.
The influence of cytokines drives the selection of isotype switching in different ways. Dependent on CD4 (CD40L) via cytokines
Fate of centrocytes?
- Make antibodies that fight and terminate the current infection.
- The investment of memory B-cells that prevents future infections from causing disease.
Features of memory B-cells
Long-lived (light zone)
Low replication
Express Ig but doesnt secrete antibodies
Increased affinity
What can plasma cells do?
After B-cell activated by antigen and helper T-cells they make the plasma cell and that will release antibodies which can further go and neutralise, opsonise and start complement.
What is neutralisation of a toxin and virus
Toxins bind to receptors. Endocytosis of toxin:receptor and dissociation of toxin which poisons cell. But then antibody protects cell by blocking binding of toxin.
Endocytosis of bacteria is by acidification of endosome after endocytosis triggers fusion of virus with cell and entry of viral DNA.
Neutralisation (complement mediated)
Pentameric IgM molecules bind to antigens on bacterial surface and adopt the staple form. C1q comes over and binds to IgM and this induces activation of C1r, which cleaves and activates serine protease C1.
Macrophage activation?
Cross link Fc receptors bind to Fc component of the antibody. Macrophage is activated and leads to phagocytosis and destcruction of the bacterium.
Opsonisation mini process and two molecules to do this?
- coat complement molecule like C3b all over bacterium and igG antibody.
- C3b binds to Cr1 of macrophage. Phagocytosed by macrophage and makes membrane-bound vesicle (phagosome).
- Lysosomes fuse with the vesicle and delivers enzymes that degrade the bacterium.
Which Ig isotype is crucial for its function and binding to pathogens and effector molecules?
IgG and has major flexibility to bind.
