Lecture 8 - Humoral Immunity Flashcards
Define the Two roles of BCRs in B-cell Activation
- Transmit Signals directly into cell interior following antigen binding
- Delivers Antigen to Intracellular Sites, where it can be degraded and loaded onto MHC Class II
Define the Two Types of Antigens which can Activate B-cells
- TD Antigens - must be presented to an antigen-specific helper T-cell to induce antibody responses
- TI Antigens - microbial constituents that can induce antibody production in absence of Helper T-cell
How to TD Antigens induce Antibody Production?
- Recognition of MHC:Peptide Complexes triggers Helper T-cell to synthesise effector molecules
(e.g., CD40L, IL-4, IL-5, IL-6) - Effector Molecules drive clonal expansion of B-cell, and following several rounds of proliferation the B-cells further differentiate into plasma cells
Compare the Activation Signals required for TD/TI Antigens
|3 Points)
- TD Antigens:
- Signal 1 - Antigen-bound BCR
- Signal 2 - provided by Helper-T cell recruited by MHC:Peptide Complex (e.g., CD40L, IL-4)
- TI Antigens:
- Antigen provides both signals via crosslinking of BCRs, or via recognition of common microbial constituent e.g., PAMP
What is Linked Recognition?
(3 Points)
- B-cells are bound and thus activated by Helper-T cells which recognise the same antigen
- Although they must recognise the same antigen, they do not need to recognise the same epitope
- They may recognise the same pathogen, but different antigens (i.e. BCR recognises coat protein, whilst TCR recognises an internal protein antigen that is exposed following peptide processing and presentation)
Why is Linked Recognition Important?
(2 Points)
- Self-Tolerance - autoimmune response requires simultaneous presence of self-reactive T-cell and self reactive B-cell
- Vaccine Design
How can Linked Recognition be utilised for Vaccine Design
(Give Example)
- E.g., Haemophilius Influenzae B:
- Children are unable to mount efficient response to polysaccharide antigens (Adults can)
- H. Influenzae Polysaccharide can be chemically linked to tetanus toxiod, which children are routinely vaccinated with, hence they have tt-specific TH2 cells
- Leads to Efficient Humoral Response against bacteria
Describe Antigen-Specific Trapping
(2 Points)
- Antigen specific T/B Lymphocytes are trapped within specific regions of the secondary lymphoid organs via interactions with APCs
- This increases the likelihood of two lymphocytes that recognise the same antigen interacting, and therefore increases the rate of B-cell activation
Define Primary Focus
- B-cell interaction with an Armed Helper T-cell activates both cells to undergo clonal expansion, forming a primary focus at boundary between T-cell zone and medullary cords/red pulp of spleen
What are the fates of Plasmoblasts in the Primary Focus?
- After Several Days the Plasmablasts Stop Dividing and either:
- Die
- Differentiate into Plasma cells (dont respond to antigen/T-helper cells)
- Some proliferating B/T cells migrate into the primary lymphoid follicle, where they continue to proliferate and form a Germinal Centre (GC)
Define the Term Germinal Centre in terms of:
(i) What it is
(ii) Difference between GC and Primary Focus
(i) Site of Intense B-cell Proliferation
(ii) B-cells in GCs do not produce antibodies, but allow a more effective immune response in case of chronic infection or re-infection
What Modifications do B-cells undergo in Germinal Centres?
(3 Points)
- Somatic Mutations
- Affinity Maturation
- Isotype Switching
What is the Fate of GC B-cells?
(2 Points0
- GC Plasma cells migrate to bone marrow, where a subset survive for years and are a source of long-lasting high affinity antibodies
- Other GC B-cells become memory cells, which divide very slowly and continue to circulate until re-exposure occurs, resuming proliferation and antibody secretion
