Memory and Vaccination Flashcards
1
Q
what is immunological memory?
A
- when infected for a second time get a much better response
- B cells more specific
- get lifelong immunity
- vaccines stop the pathogen from being hyper aggressive
2
Q
what is the response to the same pathogen?
A
- secondary immune response
3
Q
what is the secondary immune response governed by?
A
memory cells
4
Q
what are the key features of memory cells?
A
- faster
- more powerful
- more specific
5
Q
what are the properties of memory T cells?
A
- long lived small resting cells
- numbers are consistent throughout our lives
- express survival genes
- requires the cytokine IL-7
- high levels integrins
- cytokine response faster and more powerful
6
Q
what does the consistent numbers throughout life suggest about memory T cells?
A
- a balance between proliferation and death
- need a constant number
- think they are stem cell like
- memory cells spontaneously proliferating
7
Q
what survival genes are expressed by memory T cells?
A
- eg Bcl-2
- over expressing survival genes means a reduced ability to die off
8
Q
why does the memory T cell require IL-7?
A
- for survival
- to memory cell for CD4 and CD8
- memory cell CD8 also requires IL-15
9
Q
what integrins are found on the surface of memory T cells?
A
- LDA1 and CD2
- helps them to respond/migrate quickly
- makes a really strong immunological synapse
10
Q
what are the properties of effector memory T cells?
A
- CCR7 negative
- rapidly matures into an effector cell
- secrete large quantities of cytokines early after stimulation
- express receptors for pro-inflammatory chemokines and integrins
- specialised for rapidly entering inflammed tissue
11
Q
what are effector memory T cells CCR7 negative?
A
- secretes more cytokines than central memory T cell
- put sentinels where the pathogen first came in
- needs to make sure it resides in that one tissue
- no CCR7 means its not responsive to CCL21/19 which draws T cells to lymph nodes
12
Q
what are the properties of central memory T cells?
A
- CCR7 positive
- sentinels that circulate lymph node and spleen
- take longer to be reactivated
- do not secrete large amounts of cytokines
- upon re-stimulation differentiate into effector memory T cells
13
Q
what are the secondary response dominated by?
A
- class switched B cells
- in secondary exposure they have class switched IgG (compared to IgM)
- more in tune and have a higher affinity
14
Q
how long does it take to make B cell memory?
A
- lag in making memory
- slower to develop than memory T cells
- at least * days to develop
15
Q
why does it take B cells longer to make memory cells?
A
require CD4 helpter T cells and undergo somatic hyper mutation in the germinal centre
16
Q
what is the role of FCyRIIB at the end of an immune response?
A
- shits down signalling through BcR once pathogen is eradicated
- signals to make sure only memory cells are triggered to respond during re-infection
17
Q
how does FCyRIIB ensure only memory cells are active during re-infection?
A
- expressed on B memory cells
- antibodies that already exist can bind
- bind pathogen molecule to naive B cell and signal through FCyRIIB to shut down B cells
- only class switched antibodies produced
18
Q
how does the CD4 T helper cell help the memory B cell?
A
- BcR binds pathogne
- higher levels of MHC II-peptide complexes and co-stimulatory molecules of memory B cells bind to CD4 T helper cells
- CD4 T helper cell gives cytokine and co-stimulatory signals to the memory B cell to proliferate
- move to the germincal centre and undergo somatic hyper mutation
19
Q
what happens once the memory B cell is activated?
A
- moves to germinal centre
- somatic hyper mutation
- leaves the lymph node
- exists as long lived plasma cell in bone marrow or continues to recirculate
- will still go through negative selection
20
Q
what were the risks of virioliation?
A
- viral load, aggressive infection leading to death
21
Q
what was virioliation?
A
transmission of a small amount of the dangerous pathogen to induce a robust immune response upon secondary encounter
22
Q
how did edward jenner develop vaccination to small pox?
A
- use cowpox pus to infect someone which would protect them against smallpox
- essentially took an attenuated version to elicit protective immunity
23
Q
what is a vaccine?
A
a biologically prepared weakened version of a disease causing micro-organism that induces a robust immune response to the aggressive form of the microorganism upon secondary encounter
24
Q
what is immunisation?
A
strategy to protect the host from disease
25
how can vaccination manipulate the immune system?
- protect against disease causing pathogens
- protect against or treat cancer
- desensitise the immune system to allergens
- desensitize auto-aggressive immune cells, or elecit regulatory T cell response, to control autoimmunity
26
what is the goal of vaccination?
to induce herd immunity
- around 80% of the population needs to be immune for herd immunity to occur
- takes away the reservoir for the pathogen to replication
27
why is people not having vaccinations dangerous?
- need to vaccinate a large number of the population in order to protect the population
- vaccinated person could protect an unvaccinated person
28
why does age predetermine a vaccine programme?
- immune systems change over time
- babies are susceptible as they do not have a fully formed immune system
- as you get older the thymus shrinks
29
what are the consequences of your thymus shrinking as you age?
- make fewer new T cells
- repertoire of T cells is reduced
- when you're older most circulating B and T are memory cells
- may not have the T cells for a new pathogen
- B cells need T cell help
30
what can inducing neutralizing antibodies achieve?
blocks the pathogen from entering the cells and decreases damage to cells
31
what do you need to consider when developing a vaccine?
- how will you store it
- how much will it cost
- will you need boosters
32
what two groups can immunisation be divided into?
- passive
| - active
33
what is passive immunisation?
- got a memory response, isolate the antibodies and give them to somebody who doesnt have protective immunity
- can have natural or artificial passive immunity
34
what is active immunisation?
- give them a vaccine to make the immune system think its infected
- can have natural or artificial active immunity
35
what are some examples of natural passive immunisation?
- natural via the placenta
| - natural via colostrum (breast milk)
36
what is the process of natural passive immunisation via the placenta?
- foetus recieves maternal IgG
- IgG is transported through endocytosis, can be very acific so binds to the molecule FcRn
- when the pH rises IgG is released
- transfer of IgG antibodies against toxins, viruses and bacteria
- lasts around 3 months after birth
37
what is the process of natural passive immunisation via the colostrum?
- contains lysozyme, interferons and some leukocytes
- high concentration of IgA
- IgA results from stimulation of B cells in mothers intestine and migration to the breast
38
what are some examples of artificial passive immunisation?
- artificial and heterologous (different host), eg during WWI used anti-tetanus serum from horses
- artificial and homologous (eg man to man), antibodies used for passive immunisation can be polyclonal or monoclonal
39
how was using anti-tetanus serum from horses an example of artificial and heterologous passive immunisation?
- protection was brief but powerful
- horses have a good antibody response to tetanus toxin
- take the serum and inject into the soldiers
40
what were the main problems with using anti-tetanus serum from horses?
1. catabolised and removed by the recipients immune mechanisms
2. 'serum sickness'; immune response to foreign antibody results in immune complex formation and depletion of complement
41
what is polyclonal artificial passive immunisation?
- taking plasma, get lots of antibodies and recognises lots of epitopes
- multiple isotypes
- multiple antigenic targets leads to diversity
42
what is monoconal artificial passive immunisation?
- single antibody isotype
- single antigenic target
- one BcR that is closed
43
what is the process of artificial and homologous passive immunisation?
- take serum from plasma from people who have protective immunity
- can take the B cells that make the antibody
- clone them and immortalise them
- use in a vaccine
44
what is active immunisation?
- aims to achieve immunological
| - give weakened versions of the pathogen to fool the immune system
45
what was louis pasteurs discover?
- found a weakened version of chicken cholera
| - artifically induced damage to natural pathogen weakens the virulence of the pathogen yet induces excellent immunity
46
what are the 3 I's in active immunisation?
- isolate
- inactivate
- inject
47
what are live attenuated vaccines?
- one dose to achieve a substantial immune response: body thinks its the real deal
- get a B and T cell response
- similar to natural infection
- antigen processed and presented to CD4 and CD8 cells
- will also lead to antibdoy production
48
what is meant by attenuated?
altered pathogen does not cause disease but grows in host transiently
49
how do you attenuate a pathogen?
- grow in abnormal conditions
- culture in an inappropriate host cell to induce mutations
- put back into the human
- wont infect but get an immune response
50
what are the problems with a live attenuated vaccine?
- can mutate back to wild-type pathogen in vaccinated host
| - if its in the body for a long time - can't give to immunocompromised people
51
how do you genetically engineer an attenuated vaccine?
- isolate and in vitro mutate the virulent gene
- can generate mutants incapable of reversion to wild-type
- idenfitiy parts that are receptor binding and core proteins
- genetically manipulate the virus to reomve virulence
- resulting virus is viable but avurilent
52
what are the problems with killed/dead vaccines?
- need several boosters to achieve a substantial immune response
- good at producing an antibody response but not good for T cell response
- inactivation must preserve the structure of immunogenic epitope
53
what are the advantages of taking a reductionist approach to vaccination?
- elicits an immune response only to desired antigens
- less side effects
- industrial production
54
what are the disadvantages of taking a reductionist approach to vaccination?
- requires detailed knowledge of the pathogen
| - rarely immunogenic on their own - require adjuvants or viral vectors`
55
what is the reductionist approach to vaccines?
too genetically synthesise the key components of the pathogen that induces a protective immune response
56
why are polysaccharides poor at eliciting the correct type of B cell response which may be T cell dependent?
- induce IgM antibodies but no memory
57
how do we solve the problem of polysaccharides being poor at eliciting the correct type of B cell response which may be T cell dependent?
- conjugate vaccines are constructed
- bacterial polysaccharide chemically linked to T-dependent antigen tetanus toxoid protein
- conjugate is internalised
- tetanus toxin peptides induce T helper cells that secrete cytokines
- cytokines act on the polysaccharide specfic B cells to class switch to an appropriate class of antibdoy
58
how are polysaccharides used in the reductionist approach?
targets to make an immune response to as they will prevent the virus/bacteria entering the cell
59
what are adjuvants?
- components of killed or dead vaccines
- materials used to boost the adaptive immune response
- act on the innate immune response
- complex that absorbs the vaccine, holds and stabilises it in your body
- can tak multiple boosters
60
what are the main types of action of adjuvants?
1. act as a depot enhancing the time for APCs to find them
2. stimulate innate immune cells to make the cells think they have seen a pathogen resulting in the release of cytokines
3. transport the antigen to the lymph node
61
why are viral vectors proving an effective way to carry pathogenic molecules into the immune system?
- viral vector is relatively harmless, eliciting only mild-discomfort
- boost a response to subunit vaccines
- taking genes into adenovirus vector
62
how are dendritic cell based vaccines gaining strength in cancer biology?
- Tumour RNA is inserted into a dendritic cell slight different from human cells
- Transported into DC’s (modified)
- The dendritic cell matures produces tumour antigens and is injected into patient and the dendritic cell displays tumour antigen and activates T cells
Present tumour antigen to T cells
- Activated T cells attack the cancer cell
Try and destroy the tumour
63
what are the key considerations when designing an effective vaccine?
- balancing efficacy and safety
- safety is always more important
- cost stability and geography
