The humoral response Flashcards
What does humoral immunity refer to?
The part of the immunity which exists in the cell-free part of the blood, plasma or serum
What is humoral immunity predominantly mediated by?
Antibody
Complement
What are the two functions of the humoral immunity?
Can directly inactivate a pathogen
Can act indirectly by promoting phagocytosis and cellular recruitment
What is the Fc portion of the antibody?
Long part of the heavy chain which is anchored to the cell membrane
What is the function of the Fc portion?
Gives the antibody most of the functional capability
What differentiates a mature B cell from a naive B cell?
The production and secretion of antibodies
What happens when a B cell is activated?
Differentiates into a plasma cell
Settles in the bone marrow
Produces antibodies that mop up the target in the blood
Switches off all genes but those essential for cell survival
How are cell membrane-bound antibodies converted to secreted antigens?
The transcription of genes is changed
The constant region has two start sites for transcription:
- one that codes for the transmembrane form of the antibody
- one that codes for the secreted form of the antibody
Initially, antibodies will start transcription at the position which includes the exon coding for transmembrane formation
Once the B cell is activated, it starts transcription at a site further along the sequence and forgets the exons that code for the transmembrane part
How are the transmembrane and secreted forms of the antibody different?
They are essentially the same molecule
The secreted form is a little shorter since the same molecule is formed lacking the longer sequence making it a transmembrane protein
What is the primary response?
The first time a cell is exposed to an antigen
Characteristics of the primary response
Slow
Takes between 1 week - 10 days
What is the secondary response?
When the same host is exposed with the same antigen
A secondary immune response is formed which is stronger and faster
What is the difference between subunit and live attenuated vaccines?
Subunit vaccines need multiple boosts to provide high numbers of circulating antibodies
Infection with the live organism provides the host with long-term immunity
The primary and secondary responses merge into one
What is another name for antibodies?
Immunoglobulins
What is the main difference between an immunoglobulin and an antibody?
Antibodies do not have transmembrane domains
Immunoglobulins have transmembrane domains
What are the different immunoglobulin isotypes?
IgG
IgA
IgM
IgD
IgE
What differentiates the different antibody isotypes?
The heavy chains making them up
IgG - gamma heavy chain
IgA - alpha heavy chain
Ect.
What determines the class of antibodies required?
The signals the B cell receives
What is the difference between VDJ variations and constant variations?
VDJ variations form before B cells become mature
Constant variations form when they are needed
What immunoglobulin is most common in blood?
IgG
What immunoglobulin is secreted into the gut, milk or lung spaces?
IgA
What immunoglobulin is present on naive B cells?
IgM
What is the importance of IgA?
Provides protection before the antigen gets into the body
However, deficiency is common and sufferers present with little immunodeficiency
Controversy about its importance
What is the function of IgD?
Present on naive B cells only
Function is unknown
What is the funciton of IgE?
Main type mediating common allergies
Which immunoglobulins form polymers when secreted?
IgA
IgM
What type of polymer does IgA make?
Dimer
What type of polymer foes IgM make?
Pentamer
Which immunoglobulin is released in high concentration in the primary immune response?
IgM
Why is IgM released in high concentration in the immune response?
It is the immunoglobulin with the highest avidity, since it forms a pentamer structure
So the cumulative strength of bond of the antigen to the whole structure is bigger than in a monomer or dimer
What is the difference between affinity and avidity?
Affinity explains how tightly a ligand binds to one receptor
Avidity describes the cumulative bonds between the ligand and its receptors on a structure
Why does the immune system prioritise on making an immunoglobulin with high avidity instead of high affinity?
In the primary immune response, you don’t want to find the antibody which binds most strongly to the antigen, since this takes a long time
Instead, you want to find and make antibodies with relatively low affinity and multiple binding sites to increase the avidity
Which antibody is release following secondary exposure to an antigen?
IgG
Why is IgG released on secondary exposure to an antigen?
They expand wuicker
Multivalent antibodies are dangerous since they can lead to blood clots
Describe a condition involving the switch between multivalent to single valent antibodies
Some rare individuals can’t switch between IgM and IgG
Present with overactive immune systems
What 3 ways does an antibody work through?
Neutralisation
Direct opsonisation and phagocytosis
Complement activation
Which processes do IgG carry out?
Neutralisation
Direct opsonisation and phagocytosis
Which processes do IgM carry out?
Complement activation
How do antibodies neutralise toxins?
Toxins work through binding to receptors on cells
Antibodies can prevent this from happening by binding to the toxin
A lot of the antibody has to be produced in order to favour the equilibrium where more toxin binds to the antibody than to the receptor
What is a disadvantage in the way antibodies neutralise toxins?
In order for antibodies to neutralise toxins, there must be antibody present within the time of infection
Therefore, the subject has to have already built immunity to the toxin in order to work
Examples of toxins
Diphtheria toxin
Tetanus
How do antibodies fight viral infection?
In order for viruses to work, they bind to cell receptors
Antibodies can block this and stop the virus from infecting the cell
What is a disadvantage of how antibodies prevent viral infection?
The mechanism won’t work if the subject has not been exposed to the virus, or the virus is already in the cell
How do neutrophils and macrophages kill bacteria?
Production of toxic agents
What is problematic with killing encapsulated bacteria?
They can prevent phagocytosis through preventing the phagocyte from fixing onto them
How has the body adapted to the resistance of encapsulated bacteria to phagosomes?
Antibodies have been developed against the cell wall through adaptive immunity
The antibodies recognise the proteins of the cell wall and coats the bacteria
The phagosome recognises the antibodies
How do phagosomes recognise antibodies?
Through the Fc portion on antibodies
Fc receptors on macrophages and neutrphils bind to the Fc portion on antibodies
What does the Fc and FcR interaction represent?
An important example of interaction between the innate and adaptive immunity
Describe the function of the different FcR on phagocytes
FcRy facilitates uptake and activates phagocytic killing mechanisms
FcRg binds to IgG
FcRe binds to IgE
What is the complement system an example of?
Part of the innate immunity enhanced by the help of the adaptive immunity
Classical pathway is activated by IgG and IgM
Which two Immunoglobulins trigger the classical complement pathway?
IgG
IgM
Which complement protein do IgG and IgM bind to?
C1q
Why is serum not a useful tool in conferring passive immunisatio?
Contains a lot of different antibodies
Difficult to control
What technology allows the formation of monoclonal antibodies?
Hybridoma technology
What are monoclonal antibodies?
Population of one specific antibody specific for an antigen
Describe the formation of monoclonal antibodies
Mice are injected with antigen you want an antibody against
Spleen is removed
Fuse spleen cells with tumour cells to multiply them
Produce different antibodies
Put one of each B cell extracted in wells to see if you obtained the antibody you want
Harvest the B cell producing the antibody you want, leading to a high concentration of monoclonal antibody production
