Adaptive Immune System (B Cells) Flashcards
As a recap, what is the first response to infection?
The first response to an infection would be the innate immune system. It has a rapid response and is non-specific (working with generic anti-bacterial or anti-viral mechanisms).
Most of the time, it fails to completely eliminate the infection.
When the first line of defence fails, what is there as the ‘back-up’?
As a back-up in case the innate immune system fails, the adaptive immune system is present.
It has a delayed response, but is highly specific in targeting an infection. It usually eliminates the infection, and in the process, creates a ‘memory’, providing the body with long-term immunity from that specific pathogen.
Some pathogens can evade this system by mutating rapidly.
List the two branches of adaptive immunity, and what mediates them.
The two branches are:
- HUMOURAL IMMUNITY: mediated by B-lymphocytes, the plasma will contain antibodies
- CELLULAR IMMUNITY: mediated by CD8 and cytotoxic T-lymphocytes
Both of these branches are regulated by CD4 and helped T-lymphocytes (T-helped cells).
Describe the structure of antibodies.
It is an immunoglobulin glycoprotein released by plasma cells (differentiated B-cells). It is Y shaped and tetrameric, made up of 2 identical light chains and 2 identical heavy chains. These are held together by non-covalent interactions and S-S crosslinks between cysteine residues.
Each antibody has a variable region, which is where the amino acid sequence varies from one Ig molecule to the other. It is the part of the antibody that binds the antigen.
Each antibody also has a constant region, which is responsible for the effector functions of the antibody (ie. what the Ig will do after binding, for example, activating complement, binding to phagocytes)
Each Ig molecule has two antigen binding sites and a flexible hinge region. If you were to cut the antibody at the hinge region, you would end up with two fragments. The two fragments are:
- Fab-fraction: antigen binding
- Fc-fraction: crystallisable because it’s not variable
What are the three ways in which antibodies fight infection?
1) BY COATING AND NEUTRALISING A PATHOGEN:
eg. if a virus is coated with antibodies, it cannot bind to its receptors on the cell surface
2) BY ACTIVATING COMPLEMENT:
- these can then blow holes in a bacterial cell membrane
- these can also act as chemoattractants for opsonisation and phagocytes
3) BY OPSONISATION
- phagocytes have Fc (for the antibody Fc-fraction) receptors on their cell membrane
- they bind to pathogens coated with antibodies, and phagocytose them
How does an antibody bind to an antigen?
It does so through non-covalent interactions: electrostatic, hydrophobic, van der Waals forces, hydrogen bonds.
This depends on the antibody binding site being exactly complementary, sterically (shape-wise) and chemically, with a site on the surface of the antigen.
The binding site on the antigen for one specific antibody is called an EPITOPE.
Does the body design specific antibodies to bind to specific antigens?
No, it doesn’t; instead, the body generates over 100,000,000 different B-cells, each making a ‘random’ immunoglobulin. These naive B-cells wait around in the lymph nodes.
During an infection, a small number of B-cells will, by chance, be making an immunoglobulin that binds to one of the foreign antigens. These B-cells are then activated and begin to multiply to make more of that specific immunoglobulin. This is known as ‘clonal selection’.
Describe lymphocyte development in the bone marrow.
First, we have a haematopoietic stem cell. This can differentiate to either a common myeloid progenitor or a common lymphoid progenitor. The common myeloid progenitor goes on to differentiate into red blood cells, platelets, etc.
The common lymphoid progenitor differentiates into either a pre-T-cell or a pre-B-cell. The pre-T-cell is sent for further development to the thymus. The pre-B-cell rearranges its Ig genes, to make a possible combination for a certain Ig. It then becomes an immature B-cell, awaiting activation.
These immature B-cells are sent to secondary lymphoid organs, such as the lymph nodes, spleen, gut, etc. They sit in follicles on the organs.
Describe the role of immunoglobulin in B-cell activation.
Functional Ig is first expressed as IgM on the cell surface (mIgM). This acts as a ‘B-Cell receptor’ in a similar way to a growth factor receptor. The IgM doesn’t have intrinsic tyrosine kinase activity (as it’s not joined to the protein on the inside), but it associates with other tyrosine kinases (in the cytosol).
The binding of an antigen to IgM activates the tyrosine kinases and their signal transduction pathways. In essence, the IgM is acting as a cell signalling receptor. If an antigen doesn’t bind to this B-cell, it will sit in the lymph node and eventually die by apoptosis.
What does the activation of B-cells require?
Follow up with explaining the end results of activation of B-cells.
It requires:
- an antigen binding to the B-cell receptor (mIgM), resulting in stimulation of signal transduction pathways
- the co-stimulation by T-cells (this is becuase the immune system is very tightly regulated)
The activated B-cell then begins to secrete soluble IgM (sIgM). The activated B-cells multiply rapidly and differentiate into either Ig-secreting cells or memory B-cells.
Ig-secreting cells first make IgM, but then undergo class switching to make IgG, IgA, etc. Memory B-cells survive for a long time after infection. They allow the very rapid response spoken about earlier to second exposure. It results in the immediate production of IgG, rather than IgM.
Describe class (or isotype) switching.
Once a B-cell starts making an immunoglobulin which binds a specific antigen, it can switch to making immunoglobulins with the same antigen-binding site, but different constant regions.
This is so that they can carry out different functions in different parts of the body.
What are the different classes of immunoglobulins?
- IgA
- IgM
- IgG
- IgD
- IgE
Note that there are actually four subclasses of IgG (IgG1 - IgG4) and two subclasses of IgA (IgA1 and IgA2)
Describe IgM.
Membrane-bound IgM (mIgM) is formed of a single Ig tetramer, while in the secreted IgM (sIgM), five moecules of the basic Ig tetramer polymerise to form a pentamer.
It is always the first class of immunoglobulin made by B-cells during the primary response. It is first made a membrane-bound protein (mIgM) in the B-cell surface, which activates the B-cell by signal transduction. Later, it is made in a secreted form (sIgM), which activates complement and acts as an opsonin.
Thus, it can be used as an indicator of a primary response.
Describe IgA.
It is the most abundant class in external secretions (eg. milk, sweat, tears, gut secretions). It protects mucosal surfaces. It doesn't activate complement (makes sense becuase complement are found in the plasma while IgA is found mainly in secretions). It does, however, bind to Fc receptors, triggering phagocytosis and inflammatory reactions.
Describe IgG.
It is a major class on Ig in the circulation. It is very good at activating the complement system, and it’s also good as an opsonin.
It is formed from a single Ig tetramer.
