3: Adaptive immune system: B-cells and antibodies Flashcards
(28 cards)
Antigen
Molecular structure/foreign particle that can bind to a specific antibody or T-cell receptor (in MHC) containing a single or multiple epitopes
6-12 amino acids –> very high specificity
Cognate antigen: recognized by the BCR
Epitope
6-20 amino acids; smallest piece that a BCR/TCR can recognize as non-self
B-cell
Born in the bone marrow, 1.000.000 each day. Selects a heavy and light chain that make the BCR and the antibodies.
B-cell receptor (BCR)
Membrane-bound, almost identical to antibodies
- Made up of the heavy chain (Hc) and the light chain (Lc) encoded by gene segments
- Iga and Igß proteins that can signal; adaptive proteins that are blind to what’s going on outside the cell
What is the difference between antibodies and BCR?
Antibodies lack the transmembrane anchor and are released into the body
Antibody
Specific for one structural antigenic epitope
Explain the gene segmentation for the antibody Hc and Lc
There are multiple copies of four types of DNA (gene segments) called the Variable, Diversity, Junctional and Constant domains
Each B cell chooses one of each gene segments
Based on gene segments the repertoire contains about 12.000 BCRs/antibodies (chance on low affinity)
Constant domain
Bottom part of the heavy chain
Selection of the heavy and light chain of the BCR
Heavy chain (a): no protein –> suicide
Light chain (ß): no protein –> suicide + does not fit heavy chain –> suicide
Cross-linking
To activate B-cells, the BCRs must cluster together on the membrane; bringing together Iga and Igß sending signal (‘engaged’) –> activation
Classical complement pathway for B-cell activation
When invader is flagged through complement, the B cell needs less BCR cross-linking to become activated (co-receptors) –> sensitive to these antigens
The more opsonization, the easier the B-cell gets activated
Which 3 general signals are needed for T and B cell activation?
- Recognition via MHC
- Co-stimulation
- Cytokines (tell B and T cells what to do
Naïve/virgin B cell
Cell that has never been activated by encountering their cognate antigen
What two signal require the activation of virgin B-cells?
- Clustering of BCRs and the associated signalling molecules (cross-linking)
- Second signal
T-cell dependent activation of B cells
- Antigen attached to BCR
- Binding of MHC-II with TCR is needed when B cells hunt for matching T cell
- The second signal is the co-stimulatory signal: CD40 which binds to CD40L on Th-cells
- T-cell cytokines tell B-cell to switch class
–> B-cell and Th (CD4) cell must agree before B cell receives the second signal
T-cell independent activation
- The second signals are danger signals recognized by TLRs on B cells (or complement, or APC signalling)
- Many BCRs will be cross-linked
- Antigen specific: only the specific B-cells will be activated
- Sub-optimal antibodies: limited breath of activity and no class-switching (fast, but not very effective)
–> quicker, do not have to wait for Th cells and carbs and fats can be recognized
Polyclonal activation of B-cells
Mitogens (e.g. LPS) can bind to molecules (e.g. TLR) that are not BCRs on the cell surface and cross-link –> BCRs get cross-linked –> B-cell activation
Example of the immune system gone wrong –> multiple B-cells, recognizing different epitopes will be activated
Class switching
Upon CD40 T cell dependent activation by secreting cytokines, switching from one isotype to another (Fc region)
An activated virgin B cell first produces IgM (and IgD) and as it matures it can change class
The Fab remains the same, but the constant region (Fc) determines how and where the antibody will function
IgM
Produced rapidly when B-cells did not receive T-cell co-stimulation
- Great activating complement fixer –> classical pathway
- Goof opsonizer; brings B-cells together
- Pentameric structure (10 arms) –> high avidity (combined affinity as a whole), but low affinity
Pentamer supports multiple C1q proteins that activate each other leading to a C3 cascade
IgA
Alpha (dimeric form) that protects mucosal surfaces (e.g. lungs, intestine)
- Resistant to stomach acid (very stable)
- Secreted in milk
- No complement binding capacity
- Connected by clip that facilitates the IgA across the intestinal wall; makes sure you don’t get chronic inflammation in GI tract
- Dimeric form: allows luminal transport, stability and neutralizes pathogens
IgG
Most common antibody found in the blood; gamma
- Ok complement fixer
- Good opsonizer (coverage of pathogen by antibodies - recognize through IgG)
- ADCC: helps NK cells kill
- Can cross the placenta
IgE
Are a bit longer and protect against parasites, but also causes allergies
- Causes anaphylactic shock
- Mast cells have IgE receptors and bind –> degranulation
Degranulation: release of anti-microbial peptides, lysozyme particles, metallopeptidases - typical for histamine release
Classical pathway of complement activation
IgM and IgG bound to an antigen can bind C1 complex via c1q. C1 can get activated by clustering, like around an antibody.
- Activated C1s cleaves complement proteins C4 and C2 into C4b and C2a, respectively.
- C4b2a complex forms: C3 convertase of the classical pathway –> C3a and C3b etc.
Antibody-dependent cellular cytotoxicity (ADCC)
Fc receptor of NK cell recognizes IgG antibodies on antigen –> forms a bridge between NK and target cell, so the NK cell can kill it (without MHC I recognition)
