Describe how co-stimulation is used
When TCRs bind to their specific MHC (usually class 2), a signal is produced which causes CD28 (found on T cells) to bind to B7-2 (found on APCs)
This upregulates CTLA-4 and B7-1, which downregulates any further immune response
Explain Fc mediated effects
The Fc region is the bottom part of the antibody
Its effects will change dependent on what type of receptor/cell it binds to, as well as the type of immunuglobulin that is present (eg, A,D,G....)
Eg, when bound to a mast cell, degranulation occurs....releasing histamine
Whilst binding to a neutrophil will cause phagocytosis of the attatched microbe/pathogen
What are inactivated vaccines?
These are not alive and cannot replicate, so cannot form a disease state....even in the immunocompromised
Produced by culturing the virus/bacteria in a media, and then inactivation by heat/chemicals
This can be expensive, and people can have hypersensitivities to them
What are the 4 types of hypersensitivity reactions?
I - Immediate Hypersensitivity (allergy)
II - Autoantibodies
III - Deposition of immune complexes
IV - T cell mediated tissue injury
How are B cells and T cells activated?
The B cell presents the T cell with an antigen (which it has taken from a chopped up pathogen)
CD40, from the B cell, then binds to its receptor on the T cell, activating the T cell
T cell activation causes cytokines to be released, which bind to the original B cell --> causing them to proliferate
Why does our immune response struggle with tumours?
As they are mainly 'self' cells, and so are seen as weakly immunogenic
There are also few specific oncoproteins or self-antigens that are easy to target (normally hidden)
These are normally targeted by Cytotoxic T cells and NK cells
What are Somatic Hypermutations?
These are beneficial mutations that occur in amino acid chains, making antibodies more specific, and so better
Explain how blood grouping works
Everybody has a basic glycolipid antigen (O)
Some people have attatched carbohydrate groups (A or B)
These groups produce antibodies against the other types of blood (eg, A produces anti B antibodies)
How are Conjugate Polysaccharide vaccines made?
The surface polysaccharide from the pathogen is grown (via fermentation) and isolated
The carrier protein is also grown and purified seperately
Toxins are then removed from the polysaccharide, before being covalently bonded to the carrier protein
Purification and formulation then occurs
Describe Type 1 hypersensitivity reactions
This is the stimulation of mast cells via the binding of FcR to IgE specifically
This causes increased vascular permeability, vasodialation, smooth muscle contraction and local inflammation
This occurs rapidly after antigen exposure
What are the first type of cells that respond to an infection?
Describe Type II hypersensitivties
Autoantibodies --> Occurs by 3 possible mechanisms
Activates complement and stimulate phagocytosis (eg, haemolytic anaemia)
Recruit neutrophiles, which can cause cell damage (eg, glomerular nephritis)
Can bind to receptors, which can stimulate or inhibit certain functions (eg, graves disease or myasthenia gravis)
What are live (attenuated) vaccines?
These are a weakend version of the real virus/bacteria
These must grow to a sufficient level inside the body to trigger the immune response
These are cheap and dont need adjuvants
But it can sometimes cause a disease to occur!!
How are live (attenuated) vaccines made?
The pathogen is passaged many times (eg, in chick embryo eggs) under stress conditions which causes the pathogen to have slower replication, and to lose its virulence factors
Purification and formulation then occurs
How can B cell activation be downregulated?
By the engagement of an Fc co-receptor
This occurs by antibodies returning to its parent B cell, binding to its Fc receptor
This switches off the B cell proliferation
What is the concept of vaccinology?
Being exposed to a pathogen that does not lead to a disease state
But memory cells still being produced
What are the 2 forms of T cells?
Helper T Cells (CD4+) - Recongnise fragments on class 2 MHC
Th1 - Activate macrophages and cytotoxic T cells (IFN/TNF)
Th2 - Provides co-stimulatory help to B cells, helping activating them (eg, IL-4/5/10)
Cytotoxic T Cells (CD8+) - Recognise fragments on class 1 MHC --> This kills the infected cells, and so is best for viral infections
What is a recombinant sub-unit vaccine?
Recombinantly (using other microbes) made vaccines that are made up of one antigenic part of the pathogen, such as proteins or surface polysaccharides
Explain how Antigen Recognition occurs?
T Cell recognise small fragments of antigens that are presented by APCs
Peptide fragments bind to the grooves of the MHC
The TCR binds to the MHC and peptide residues
CD4/8 (dependent on the class of MHC can also bind the MHC, preventing the death of the TCR
What is a vaccine adjuvant?
And what are the 4 reasons for having them?
They enhance the protection provided by vaccines by promoting rapid, long lasting and broad immunity
Stronger and longer immunity
Antigen-Sparing --> as less antigens are needed to form an immune response
Cross-reactive immunity --> induces a broader immune response
To overcome weakened immunity --> eg immunocompromised
What are the physical barriers of the innate immune system?
Can secrete defensins, which act as broad-spectrum antibiotics
The secretion of these is increased by the secretion/presence of cytokines
What are the 2 types of thymic selection?
Positive Selection - When the T cell doesnt recognise/bind to our test MHCs, so it signalled to die (via apoptosis)
Negative Selection - The T cell binds too strongly to the test MHC (activating it) and so is signalled to die (via apoptosis)
Explain the differences between the 2 classes of Major Histamine Complexes (MHC)?
Class 1 - These are recognised by CD8+ cells (cytotoxic T cells)
Present on all cells, so define what our 'self is' --> important for transplant patients
Class 2 - Recognised by CD4+ cells (helper T cells)
Only found on antigen presenting cells, like macrophages
When does Autoimmunity occur?
When there is a faliure/breakdown in mechanisms that are normally responsible for maintaining self tolerance
What are the 5 classes of antibody/immunoglobulin?
A --> Airborne
E --> Allergy
G --> General
M --> Immature
Describe Type III hypersensitivities
Deposition of immune complexes
This is the cross-linking of antibodies, which can cause several responses --> Can block blood vessels as they're so large
Normally causes complement activation and FcR -- neutrophil reponses
When systemic = Systemic Lupus Erythematosus (SLE)
What are Conjugate Polysaccharide vaccines?
Polysaccharides from the bacteria are attatched to a carrier protein (which are often toxoids)
This is because the polysaccharide itself will not illict a T-cell immune reponse
They have high efficacy and safety
What are the 5 different types of vaccine?
Can T cell receptors undergo somatic hypermutation?
So their affinity remains at a constant low level
What are the 3 vital functions that a good immune system has?
It has quick recognition
Pathogens can be neutralised quickly
A good memory can be produced