Humoral Immunity 1 Flashcards
What are antibodies?
Y shaped molecules expressed by immune cells to target pathogens
How do antibodies work?
Antibodies work by preventing bacteria entering by binding to the bacteria docking site or neutralising them
Antibody structure?
2 heavy and 2 light chains
How many classes does the heavy chain have and what are they divided into?
Heavy chain has 5 classes:γ, δ, α, μ and ε.
These are further divided into 4 subclasses: Y1, Y2, Y3 & Y4.
which can be further divided into alpha-1 or alpha-2
How many domains, constant and variable regions does the heavy chain have?
Heavy chain has 4 domains, 3 constant and 1 variable
Describe the variable region and its function?
The variable region is very specific and binds to specific epitopes of specific antigens.
How many variables and constant regions does the light chain have?
1 variable and 1 constant
How many classes does the light chain have?
kappa (κ) chain or lambda (λ) chain
Describe the constant region?
The constant region is very responsible for biological activities.
How many forms do antibodies have and what are they?
B cell receptor or secreted form.
What is the final form and what is it used for?
The final form is the secreted form and is used to fight off pathogens
What is the final form of antibody anchored to?
It is anchored to the plasma membrane of B cells
What forms can the antibody be in when secreted?
When the antibody is secreted it can be in monomeric or pentameric forms.
In which form are antibodies initially secreted as?
As a monomer and then combined to produce a multimeric form
Where do B cells spend their life?
B cells spend their life in bone marrow, blood, spleen and secondary lymphoid organs.
What can the life cycle of B cells be divided into?
The life cycle can be divided into antigen-dependent and independent stages.
Describe the steps involved in the lifecycle of B cells?
8 Steps
- Starts with Stem cell which differentiates into pro B cell
- Pro B cells undergo VDJ (variable diversity joining) recombination which codes in the heavy chain- constant and variable regions and become a pre-B cell. It can only pre-b cell once it makes a functional heavy chain.
- Then it undergoes another VDJ recombination to code in the light variable and heavy chain regions.
- B cell continues to mature until it expresses IgM and IgD.
- Becomes a mature circulating B cell and then becomes activated once it encounters a pathogen.
- B cell migrates into the germinal centre (GC) and will undergo a special selection to hone its variable region to that particular pathogen.
- Undergoes affinity maturation and class switching
- Differentiates into plasma cells which secrete antibodies and memory B cells
What are somatic recombinations and an example?
Any changes at the DNA level are called somatic recombination e.g. VDJ recombination
What is differential splicing?
changes at the mRNA level are called differential splicing
What is each chain of antibody made of?
Each chain is made of one single polypeptide
What is the hinge region between in antibodies?
The hinge region is between CH1 and CH2
What makes the antibody flex and so what does this expose?
These are a stretch of polypeptides that make the antibody flex so that the active site can be exposed
What chain is the hinge region longer in?
Longer in the heavy chain
What are the Fv regions?
Variable regions of light and heavy chains working together
What are Fab regions?
Variable fragment and first constant domains
What are the Fc regions?
Heavy chain CH2 and CH3 working together
What does glycan form a part of and what does it attract?
Glycan (sugar group) forms part of the active site and forms a pocket where the receptors of the other immune cells will be attracted to.
What stabilises the antibody structure?
Disulphide bonds stabilise the structure
What are CDRs?
Protrusions that interact with the antigens
Where are CDRs located in the antibody?
They are located in the variable light and variable heavy chains
The lifecycle of B cells (Antigen independent stage)
- Stem cell differentiates into Pro-B cell
- Pro-B cell undergoes DNA recombination
(First, the V region combines with the DJ region- this is VDJ recombination) - This codes for the heavy chain variable region. the heavy chain variable region is co-expressed with μ constant region- constant region for IgM antibody class (this is the default for all B cells before they encounter pathogens)
- Pre B cell expresses valid functional chains
- This pre B cell expresses a placeholder light chain to hold it in place as light chain is not generated yet.
- Undergoes third recombination on the light chain- VJ recombination. codes in the variable and constant regions on light chain.
- There are also additional processes such as junctional flexibility and P and N nucleotide addition. This contributes to the diversity of the antibody.
- Once B cell can express IgM and IgD ( has capacity to alternatively splice mRNA), it becomes a mature/resting/naive B cell.
How many loci are there that encode Ig?
There are three genetic loci encoding Ig
- Two for the light chain: kappa and lambda locus
- One for heavy chain
What chromosome is the lambda and kappa chain found on?
In humans, the lambda chain is found on Chr22 and kappa on Chr2
What chromosome is the heavy chain found on?
The heavy chain is on Chr14
What genes regarding antibodies are inherited and not inherited?
No antibody genes are inherited and only gene segments are inherited
What does arranging gene segments in different combinations generate?
Arranging these gene segments in different combinations generate many Ig sequences causing the B cell to be unique.
What segments are there in the light chain?
In the light chain there is variable and J gene segments
What regions are there in the heavy chain?
In the heavy, there are V, D and J regions,
What do segments code for once they’ve been rearranged?
Once they are rearranged at the DNA level, they will code for the CDRs
What do the J or DJ regions code for?
The J or DJ region codes for CDR3 (3RD CDR) region
