AB and B cells Flashcards
What is an AB? What is its basic structure? Talk about light, heavy, constant and variable regions, flexible linker
An AB is a protein that can specifically bind an epitope. They belong to the immunoglobulin family, and are produced by B cells
An AB is made of 2 Light chains and L heavy chains.
Each light chain has a variable region (VL) with 3 CDR loops at the end, and a constant region which links to the heavy chains with SS bonds
The heavy chains have a variable region (Vh) with 3 CDR loops, then long constant region-the Fc end interact with Ig receptors on cells, and is what determines class)
Overall 2 Fab arms that each bind the same AG-can bind at the same time-flexible SS bonds/H chain allow head movement
Discuss CDR regions and explain how AB bind AG. List the forces involved, and talk about affinity vs avidity
CDR are 3 loop at the end of each variable region with conserved structure but different sequence-random mutations allow binding different AG. Forces invloved are Hydrogen bind, Ionic bind, Hydrophobic, VDW.
affinity is defined at strength of non covalent interactions of one AB to one AG
Avidity is strength of multiple AB to multiple AG - polymers with low affinity can have v high affinity
Describe the 5 different classes of AB. What are the roles these AB can take?
All light chains are either Kappa/lamda for each class
In order of abundance:
IgG-gamma chain-Occurs as monomer but 4 subclasses (variable at hinge and amount of CH)-present in blood and ECF-major activator of complement-usually secondary response to pathogen (after IgM)-can transport across placenta
IgA-Alpha chain-Occurs as monomer (blood) or dimer (secretion)-main secreted Ig, aggregates pathogen and neutralises them-protects surfaces. Secretes from B cells inside-bind receptor, uptaken by epithelia then cleaved (into dimer) and released
IgM-mu chain-large pentameric (joined by J)-mostly in blood as initial defence-and first synthesised. Low afinity but high avidity, agglutinate pathogen and activates complement
IgD-Delta chain-low cons-surface Ig expressed early in B cells development (involved in that and activation)
IgE-Epsilon chain-low blood conc-High affinity to receptors-mostly found bound to them-cause degranulation (allergy or parasite) when bind AG
Overall AB can: Neutralise, Agglutinate, Opsionise, Activate complement, bind Fc receptor and activate the cells
What are B cells? Where do they come from? How are they selected? is there a failsafe? What do they use to recognise AG?
White blood cells-adaptive immune leukocytes-from hematopeotic cells=>mostly produce AB, form memory and APC
Derived from BMSC, and mature there. Migrate to blood and secondary lymhpoid tissue until find AG-always specific for 1 AG
Selected upon activation-once receptor binds AG, clonal expansion-fast replication-all daughters cells have the same AB. Before cells circulate, any AB reacting to self antigens are elimitaned
Uses the BCR-surface bound AB-same FAB and similar Fc (just can be TM). Always attachted to Igalpha and IgBeta (signalling chains)-thousands present on each B cell. Structure is literally same as AB-and 2 IgAlphaBeta with long cytoplasmic tails for signals
How do BCR recognise to many AG? What is VDJ recombination? Explain the many levels at which diversity is assured
BCR have to recognise/encode a massive repertoire-impossible with the genes we have. Instead, each chain (kappa/lamgda/heavy) are encoded by gene multifamilies, with many variations for each possible part. Kappa light chain has 40 V, 0D and 5J-all different, and randomly chosen by recombination (splicing). Heavy chain is similar with a V, D and J region
On top of that, Light chains and heavy chains put together (can be either), and VDJ recombinase is unprecise->creates even more diveristy
What are the 3 fates of activated B cells?
Antibody production, affinity maturation and Memory B cells
Explain B cell AB production and class switch
General rule is that AG alone cannot activate a cell alone-need extra signals from 1) microbial constituant or 2) Th cell Thymus independent-bacterial polyscharrides around the cell or LPS bind toll like receptors and give co-stimulation ontop of AG binding=> activates cell Th dependent-B cells can be APC-uptake AG and go to nodes, where they look for T cell with same AG. Present it, and t cell becomes a T helper cell, activating the B cell into a plasma cell (CD40L on T cell to CD40 on B cell) Different cytokines help decide on the produced AB-and class switches of the AB-INFgamma-Ig2A,3, or IL4-IgE Class switch is part of a gene which possess all 5 classes-the first one available is always chosen (IgM)-Th cells can tell the B cell to cleave certain chains (always in order) to switch to the next class-impossible to switch back after but can continue forward (IgM->igG yes, IgE->IgM NO)
Explain B cell affinity maturation
Some B cells are selected for somatic hypermutation-maturation of their AB by random mutation. AID protein deaminated G to T and forces point mutations-> chance to improve AB as it happens. Interestingly, AID mutatues the whole genome-not just the AB gene-> longer an infection goes, the more mutated some B cells will be.
Once a better AB is found-clonal expansion and repeat process
Explain B cell memory selection
Cells selected for memory have a longer lifespan-and contrary to T cell memory, B memory cells dont activate-just made from clonal expansion and stored in lymph node
These help mount 2ary response-Faster and much larger, but also immediate class switch to IgG (more effective)
memory B cells activate with less cytokine, (faster) and replicate much faster (amount)
This is exploited to make vaccines (mostly humoral), and AB are exploited to target cancers
What happens when B cells go bad?
ABs Can cause many autoimmune disease
IgE-allergy, or farmers lung
B cells can become cancer-Lymphomas and myelomas-sometimes because of viruses
