Flashcards in IMI3: Why is the adaptive immune response so specific? Deck (124)
What line of defence is the adaptive immune system?
What are the 2 key cells involved in adaptive immunity?
1) B cells – humoral immunity
2) T cells – cell-mediated immunity
What is the B cell receptor (BCR) made up of?
Transmembrane proteins known as immunoglobulins
How do BCRs act?
They directly bind to antigens, causing the B-cell to mature into plasma cells (effector B cells)
What do plasma cells (effector B cells) produce?
Antibodies (soluble Ig molecules).
Where does the BCR antibody vary?
Only by their C-terminus
What are the distinctive features of the adaptive arm of the immune system?
1) Specificity in recognising antigens
2) Memory to recognise the same antigen in later infections
What's the difference between a PAMP and an antigen?
Antigen: part of a molecule recognised by an adaptive immune protein.
PAMP: a broad characteristic of a pathogen class that is recognised by an innate immune protein
What is the BCR made up of?
4 polypeptide chains: 2 identical heavy chains and 2 identical light chains. The light chains can be either kappa or lambda.
Completely describe the the structure of BCR
Y-shaped molecule. The top contains the antigen binding site (made up of 2 variable regions on each Ig molecule; VL and VH).
There are also 2 constant regions in each Ig molecule: CL and CH.
The constant region on the heavy chain can contain 1-4 CH domains depending on the Ig molecule
The chains are held together by intra and inter chain disulphide covalent bonds
Which region of the BCR has the broadest diversity in amino acid sequence?
Antigen binding site (variable regions - VL and VH)
Which type of Ig molecules have CH1-CH3?
Which type of Ig molecules have CH1-CH4?
What mechanism determines whether the Ig molecules will be an antibody or a BCR?
Alternative polyadenylation and splicing
What does alternative splicing lead to for antibodies and BCRs?
The primary transcript is the same, but:
- antibodies are coded to be soluble Ig
- BCRs are translated with a C-terminus containing a transmembrane segment and a short, cytoplasmic tail
What can Papain do?
Digest Ig molecules to produce 3 fragments
What are the three fragments Papain digests Ig molecules into?
- 2 fragments (from 2 x Y arms) corresponding to the antigen binding region, called 'Fab'
- 1 fragment (from Y stem) called 'fragment crystallisable (Fc)'
What do the Fab regions do?
Its the part of the antibody that binds to the antigen
What do the Fc regions do?
Crucial for the effector function by binding to various antibody receptors (Fc receptors)
What are the Fc region effector functions?
- Opsonisation that results in an immune cells' phagocytosis or degranulation
- Complement fixation via C1q
- On the placenta: allows antibodies to transfer from the mother’s blood to the foetal blood.
- On the baby’s gut epithelium: allows the transfer of antibodies from mother’s milk to the baby’s blood
How do IgG, IgA, IgM, IgD and IgE vary?
Amino acid composition
Method of assembly
What are the two arms of adaptive immunity and the key players?
1) Antibodies - humoral response
2) T cells - cell-mediated immunity
Which cells from the adaptive immune system directly act against pathogens?
Cytotoxic T cells (TC, CTLs, CD8+)
Which cells from the adaptive immune system have a modulator role?
Helper T cells (CD4+)
Regulator T cells
What's the difference between B cells and B plasma cells?
- B cells can phagocytose but do so mainly to present antigens, not to kill
- Plasma cells are the effector cell version of B cells - they act more indirectly by producing many antibodies
What are the two types of immunoglobulin?
- A transmembrane form that studs, or dots, the surface of the B cell. This is called the B cell receptor (BCR) - membrane bound
- A version missing the transmembrane domain which has a signal peptide instead - soluble
Why does the bonding between the chains in an Ig have to be highly complex?
To survive in the circulation for months
What does the constant domain of the heavy chain determines what?
The effector function, once an antigen is bound: (eg)
- activation of a B cell
- neutralisation of a viral pathogen before it can affect a cell
The V or C regions are encoded by?