S1: Adaptive Immunity I Flashcards
Name the 3 stages unseen infections progress through
- Initial infection which stimulates an immune response. This can be innate (no memory) and adaptive (acquired) which has memory
- Recovery due to immune activity
- Lasting acquired immunity is specific and often for life
What is the innate immune system?
- it is rapid and non specific
- often fails to completely eliminate the infection but is crucial in keeping an individual alive for the first few days of infection
What are the cellular and humoral components of the innate immune system?
- Cellular: phagocytes and natural killer cells (NK) cells
2. Humoral: complement, pattern receptors, enzymes and cytokines
What is the adaptive immune system?
- it has a delayed response and is highly specific
- usually eliminates the infection
- it has ‘memory’ whereby if the same antigens appears, the body with recognise it very quickly. This response the repeated infection gives long term immunity.
What are the cellular and humoral components of the adaptive immune system?
- Cellular (T cells): T helper (Th) regulation, Cytotoxic (CTL), regulatory (Treg) and cytokines
- Humoral (B cells): antibodies
Explain the difference in primary response and secondary response of the adaptive immune system
At first exposure to infection, the response to the adaptive immune system will be delayed and relatively small (little antibodies produced)
Upon the second exposure with the same microbe there is an immediate response that is much greater (large antibody concentration in less time)
What are antibodies?
Antibodies are glycoproteins that are also called immunoglobulin (Ig)
- Each antibody binds to a specific antigen (which is most often a protein, but can be glycolipids)
What happens if you take serum and do a serum electrophoresis?
The antibodies will migrate in the y-globulin fraction (band). It is a widespread band as there is a mixture of different antibodies.
Describe the structure of the basic antibody
- two identical antigen binding sites per Ig molecule
- a ‘hinge’ H region is a flexible spacer between blood bring sites
- structure is tetrameric protein: 2 identical heavy chains and 2 identical light chains.
- The 4 polypeptide chains are bound by disulphide covalent bonds between cysteine a.a. Residues into a Y shaped molecules
- folding of the antibody is the tertiary structure because it is a heavy and light chain joined
- overall structure is the antibody is quaternary
What 2 genes code for light chain?
It’s either Kappa or Lambda!
Never both
What determines the type of Ig made?
Genes determine the type of heavy chain and therefore Fc region which determine the type of Ig made
What is ‘fraction antigen binding’ (Fab)?
Each chain has a variable region (including heavy and light chain) where the sequence varies from one Ig molecule to another.
The variable sequence called Fab binds to the antigen
- Fab are crystallisable
What is the constant region (Fc)?
Fc also stands for fraction crystalline
This is responsible for the effector functions of the antibody e.g. activating complement, binding to phagocytes
-phagocytes have proteins called Fc receptors on their cell surface so they recognise the antibodies and what they are bound to —> opsonisation
Name the different classes of Ig
IgA (2 isotopes) IgD IgE IgG (4 isotopes) IgM
What is the major Ig class in circulation (75% of all Ig)?
IgG
What is the major class of Ig made by secondary responses?
IgG
Function of IgG
- It is very good at activating the complement system via classical pathway (removing the pathogen) as the complement system needs antibody to bind to antigen for it to work
- it acts as an opsonin (identify and move item) —> Ig binds to pathogen —> phagocytes recognise IgG via their Fc factors which bind to Fc receptors on phagocyte —> phagocytose the pathogen
Which is IgG essential in pregnant mothers?
It is the only class of antibody that is small enough to cross the placenta and protect the developing foetus
What can be suggested of IgG being present for long periods in serum?
IgG antibodies may indicate last exposure and no current infection
What are the two structures of antibody class IgM?
- Monomer of basic subunit B cell receptor
It has an extra heavy chain domain that is membrane bound in B cell
- Pentameter of basic sub-unit in plasma (excreted Ig)
Contains a J chain - a polypeptide involved in pentamer polymerisation
Enter blood stream
What is the first class of Ig made by B cells during the primary response?
IgM
What form is IgM first made as?
IgM is made as a basic monomer that is membrane bound on B cell surface and later made in secreted form as a pentamer
Functions of IgM
- As a membrane bound protein on the B surface it activates B cell transduction
- It is also made in secreted form the activated complement via the classical pathway (due to its pentameric structure) and also acts as an opsonin
- high valency of pentamer increases overall affinity
- binds to immune cells via Fc receptor (inducing phagocytosis)
How does IgM imply current primary infection?
IgM doesn’t last as long in serum as IgG
IgM antibodies respond to an antigen suggesting recent primary infection
What is the most abundant Ig class in external secretions (milk, sweat, tears, saliva, gut fluid etc)?
Secretory IgA
Function of secretory IgA
It is the first line of protection at external surfaces
- it initiates localised mucosal response different from more general circulating immune response
- secretory components protect IgA from degradation hence it can work in harsh environments such as the GI tract
What is the second most abundant class of Ig in circulation?
Serum IgA
Function of serum IgA
Circulatory IgA cannot activate complement (complement is in plasma while IgA is usually in secretions)
- circulatory IgA binds Fc receptor on immune cells and initiates inflammatory reactions e.g. triggers phagocytosis
Function of IgE
- it binds to Fc receptors on mast cells and basophils releasing histamine
- it is useful as a response to parasitic worms by releasing chemicals from mast cells and activating eosinophils via Fc receptor binding
- normally low concentration in circulation but raised in allergic patients—> over response can cause anaphylactic shock
Function of IgD
- role is currently unknown
- does not bind complement
What Ig class has the lowest concentration in circulation and where is it usually found?
IgD
Mainly found in the surface of B cells as antigen blood binding B cell receptor
What are the two divisions of adaptive immunity and what are they mediated and regulated by?
- Humoral Immunity
It is mediated by B-lymphocytes
Regulated by CD3+ helper T lymphocytes
- Cellular Immunity
It is mediated by CD8+ cytotoxic T-lymphocytes
Regulated by CD3+ helper T lymphocytes
Give an example of adoptive immunotherapy
Treatment of rabies by infusion of antibody
It can be demonstrated in vitro or in vivo
List steps in primary humoral response
- Clonal selection
- Antigen processing
- Generation of plasma cell (activated B cell)
- Plasma cell generates IgM and secretes it
Explain the importance of a multi-specific pool
- An individual has many B cells which increases the probability of the Ig being made being complementary to antigen
- Each B cell has a randomly assigned antigen binding specificity
- Each naiive B cell has only 1 antigen specificity
- 1 B cell activated = per antigen
- activated B cells can then differentiate and secrete many antibody molecules with same specificity for original antigen
What is clonal selection?
During an infection, a small number of B cells will by chance be making an Ig that binds one of the foreign antigens.
These B cells are activated and begin to multiply and this is called clonal selection
What is antigen processing?
Recognition of an antigen by a B cell leads to antigen processing which activate Th (T helper) cells
What does the Th cell do in primary response?
It confirms that the antigen is foreign
It also activates the B cell which generates a plasma cell (use to be B cell) that migrates to bone marrow
What does B plasma cell do in primary response?
The plasma cell begins to present IgM on the cell surface and excrete it into the blood plasma
How many days does it take for IgM to be made in primary response?
10 days
What is isotope switching?
The same B cell that produced IgM switched to produce IgG.
This occurs by the removal of some genes in the C region
IgM —> IgG3
What is the humoral secondary response?
B plasma cell is activated so it is colonially selectee and begins to proliferate.
Memory cells are created that last in the blood for long periods creating immunity
How is the secondary response different from primary response?
- secondary response is faster and stronger
- IgM conc. in both responses remain the same but IgG conc. in secondary response is much higher
Describe an antibody- antigen interaction
- non covalent interactions (electrostatic, hydrophobic van der waals forces, hydrogen bonds)
- depends on the antibody binding site being exactly complementary (sterically and chemically) with site on the surface of the antigen
- a single antigen may have many possible binding sites (epitopes)
What are epitopes?
An epitope is a piece of antigen recognised by the antibody
A single antigen can have many possible binding sites
Why is more than one Ig synthesised during a natural immune response?
- natural immune responses are polyclonal
- hence, more than one Ig is synthesised
- this is because there are multiple antigens on an microorganism and each antigen has multiple epitopes
- so different antibodies may recognised different epitopes on the same antigen or more than one antibody may recognise the same epitope
What does natural immune response being ‘polyclonal’ mean?
More than one clone of B cells are activated
How do antibodies fight infection?
NOTE: what does Ab stand for???
1) by coating and neutralising a pathogen e.g. if a virus is coated with Ab it cannot bind its receptor on the cell surface
2) by activating complement which can then blow holes in bacterial cell membrane
3) opsonisation:
Phagocytes have Fc receptors on their cell membrane
They can bind to pathogen coated with Ab and phagocytose then
