B cells, B- cell receptors and Antibodies Flashcards
What is an antigen and immunogens
Antigens- Molecular determinants that can be recognised by antibodies, B- and T-cell receptors and can induce immune responses.
Most antigens are proteins but some are carbohydrates, lipids or nucleic acids.
Immunogens- molecular determinants that induce or elicit an immune response (could be adaptive or innate) e.g antigens are immunogens but not all immunogens are antigens
Which cells are part of adaptive immune system?
B-Lymphocytes
T-Lymphocytes — Cytotoxic T cells (CD8+) and T helper Cells (CD4+).
CD4+ is further divided into major classes: TH1, TH2 and THREG
What are molecules of adaptive immune system?
Molecules can be soluble e.g. cytokines/chemokines and antibodies
They can be cell-associated e.g B and T cell receptors
What’s the difference in structure between BCR and antibodies?
Both are made up of 2 light and 2 heavy chains.
Both contain variable and constant regions.
BCR has a small transmembrane region whereas an antibody does not
What is the structure of antibodies?
Made up of :
~ 2 identical light chains. Light chains can either be made up of kappa (k) or lambda λ).
~ 2 identical Heavy Chains- (heavy chains determine the class of antibodies). There are 5 heavy chains.
1) alpha chains (a1-a-2) - IgA
2) gamma chain (1-4) - IgG
3) mu - IgM
4) delta- IgD
5) epsilon -IgE
Constant region of heavy chains determine the class of antibodies
What is papain and what does it do to antibodies?
Papain is a proteolytic enzyme that cleaves antibodies into 3 fragments:
~ Two Fab fragment (Fragment antigen binding)
1- Contains variable regions of both heavy and light chains
2- Responsible for recognising and binding to antigens
3- Varies in structure to recognise the vast range of antibodies
~ Fc fragment (fragment, crystallisable)
1) no antigen binding activity
2) can bind to Fc- binding receptors on :
❖ phagocytic cells (macrophages, neutrophils and monocytes) (→ phagocytosis)
❖ NK cells and eosinophils (→ ADCC)
❖ mast cells (→ degranulation)
~can activate the complement (the humoural part of the innate system)
~ In order for cells to bind to Fc fragment, it must be bound to an antigen
What are 5 antibodies and their structure? Which antibodies can be transported across epithelial cells?
IgA- monomer or dimer (2 monomers joined together by J chain)
IgM- pentamer (5 monomers joined together by J chain)
IgD, E, G - monomers
Both IgA (in dimeric form) and IgM contain J chains, which are recognised by polymeric immunoglobulin receptors and bind to them (J chain) and allow them to be transported across epithelial cells.
How does the J-chain interact with pIgR (polymeric immunoglobin receptor)?
1- The polymeric immunoglobulin receptor (pIgR) is the receptor on the epithelial cells that binds to the J-chain of dimeric IgA or pentameric IgM.
2- pIgR recognizes and binds to the J-chain of these antibodies, facilitating their transcytosis (transport) across the epithelial layer.
3- Once the antibody reaches the mucosal surface, the pIgR is cleaved, and the antibody is secreted into the mucosal area, where it can provide immune defense
What is the structure and function of BCR?
BCR are membrane forms of antibodies.
As well as containing light and heavy chains, they also contain heavy chain transmembrane domains and short cytoplasmic tail (3 aa).
Cytoplasmic tail does not send signals directly as it is too short but it interacts with signalling proteins IgA and IgB, which relay signals from B cell receptors to inside of the B cell, helping activate it.
The transmembrane domain anchors the BCR to the cell membrane, ensuring the receptor stays in place and facilitates the transmission of signals across the membrane.
What happens once antigen binds to the BCR?
There’s a signalling cascade, activating the B cells.
Signalling is mediated by Iga and IgB as cytoplasmic tails are too short.
1- This leads to enhanced B- cell survival.
2- Increased proliferation- The B cell proliferates, producing many clones of itself that recognize the same antigen.
3- Differentiation into plasma and memory B cells
Plasma cells secrete antibodies
What are the functions of antibodies?
1- neutralisation
2-opsonisation
3-classical complement activation
4-antibody-dependent cell mediated cytotoxicity (ADCC)
5- Degranulation
How do antibodies carry out neutralisation?
Many viruses and some bacteria bind to specific receptors on host cell surfaces.
This binding triggers endocytosis, allowing pathogens to enter and replicate.
E.g. Influenza virus expresses hemagglutin, which binds to sugar modified proteins on epithelial cells.
Antibodies bind to these viral/bacterial surface proteins, blocking them from attaching to host cells which prevents the pathogen from entering the cell and causing infection
How do antibodies carry out opsonisation?
Antibodies bind to pathogens such as bacteria, viruses, fungi and parasites via their Fab region.
The Fc region of the antibody interacts with FcY or Fca receptors expressed by the phagocytic cells (macrophages, dendritic and B cells)
This triggers phagocytosis, where pathogens are digested and destroyed.
Which antibody is the biggest activator of complement activation?
IgM due to its pentameric structure followed by IgG
How do antibodies cause antibody dependent cell mediated cytotoxicity? and which antibody strongly induces ADCC?
IgG antibody strongly induces ADCC.
Specific antibodies bind to antigens expressed on cells infected with viruses or bacteria.
FcyRIII, the only Fc receptor expressed on NK cells binds to the Fc fragments of the bound antibody.
Cross-linking of Fc receptors signals the NK to kill the target cell
Target cell dies via apoptosis (fas-dependent or fas independent mechanism)
Apart from NK cells, which other cells can perform ADCC?
Macrophages, neutrophils and eosinophils-
as they all express FCRyIII receptor (Fc receptor)
How do antibodies cause degranulation?
IgE antibodies bind to antigen on a pathogen. It interacts with the FceR receptor expressed by granulocytes. (e.g. eosinophils)
This leads to granulocyte degranulation which causes:
~ Local inflammatory responses e.g. release of TNFa, leukotrienes
~ release of histamine which causes vasodilation (leading to increased blood flow to affected area) and increased permeability (which causes immune cells and fluid to move from bloodstream into the tissue, leading to oedema and redness)
~ recruitment of innate and adaptive immune cells
~ defence against helminths by secretion of proteases and reactive oxygen species. The proteases can break down the worms’ outer protective layers, while ROS can damage the worms directly.
~ expulsion of worms from the gut by stimulating gut musculature
~allergic responses
Role of IgA?
Exists as monomers or dimers (2 monomers linked together by J chains)
It is found in breast milk, saliva etc.
Secreted through epithelial cells which line the gut, respiratory tract etc.
Protects mucosal surfaces (e.g. the gut, respiratory tract and urogenital tract) from pathogens and acts as a 1st line of defense against infections at mucosal surfaces.
It is resistant to proteases which helps maintain its stability in harsh environments like digestive tract where acidic conditions can kill it.
Function of IgD?
IgD is expressed as a B-cell receptor (BCR) (alongside IgM) on mature B cells where it controls B-cell activation and suppression.
When a B cell encounters an antigen, the BCR, which is often an IgD molecule (along with IgM), binds to the antigen, triggering a signaling cascade that leads to B-cell activation. This activation results in the differentiation of B cells into plasma cells, which then secrete antibodies specific to that antigen.
Role of IgM?
IgM is the first antibody produced by plasma B cells in response to an antigen.
It is a potent activator of classical complement pathways.
It is a good opsoniser due to its pentamer structure.
Role of IgG?
- an activator of the classical complement pathway (not as strong as IgM)
- good opsoniser
- its ability to be transferred across the placenta from the mother to the fetus provides passive immunity to the newborn, offering protection against infections during the first few months of life (3-6 months) while their immune system is still developing.
-neutralises viruses, bacteria and toxins - mediates antibody dependent cell-mediated cytotoxicity by natural killer cells
Role of IgE?
IgE plays a crucial role in defending against parasitic infections. When IgE binds to the parasite, it triggers degranulation of eosinophils, releasing toxic proteins and enzymes that help destroy the parasites.
It also causes degranulation of mast cells and basophils, leading to allergic reactions.
