Immunology 1 Flashcards
Why should we vaccinate individuals?
Vaccination is effective at reducing or preventing disease
Certain pathogens cause life-threatening or life-altering disease
After clean water, vaccination is the most effective public health intervention in the world
In basic terms what is vaccination?
Deliberate exposure to an antigen
In basic terms why do we vaccinate people?
To induce immunologically-mediated resistance to a disease
In basic terms how does vaccination work?
Through the induction of memory
What does immunological memory require?
The stimulation and maturation of the immune response after exposure to an antigen such that it is able to respond immediately and robustly upon re-exposrure to that antigen.
What cells are involved in immunological memory?
Memory CD4+ T cells
Memory B cells
Memory CTLs
Long lived plasma cells
When are the long lived memory T and B cells generated?
During primary adaptive immune responses
How long can memory T and B cells survive?
They can survive in a dormant state for many years after the antigen had been eliminated
What do memory T and B cells do rapidly in response to a second encounter with a specific antigen?
They re-activate, go into colonial proliferation and expansion, differentiation and into effector cells.
Describe the IgM and IgG antibodies etc on primary infection?
IgM peaks early and is down by 14 days
IgG raises over months and years and peaks after 14 days, leading to clinical disease
Describe the IgM and IgG antibodies etc on secondary infection?
IgM - peaks early and is down by 14 days
IgG - peaks very early, very high levels and the clinical features are aborted
What does pre existing IgG antibody result in, in terms of the secondary antibody response?
Results in ability to clear infection during incubation periods
More specifically what does the pre existing IgG antibody result in, in terms of the secondary antibody response?
Direct ability to neutralise bacteria and bacterial products
Rapid mobilisation of phagocytes and complement
Preformed IgA blocks bacterial attachment to mucous membranes
Diphtheria: an individual may clear the toxin through anti-toxin antibodies, but remain a carrier of microorganism
What is the secondary antibody response mediated by?
Long lived plasma cells
- Reside in the bone-marrow where they continually secrete antigen specific antibodies of the IgG type (and other Ig classes)
- They have already undergone an Ig class switching reaction during the Germinal centre reactions of the primary immune response
Where do the long lived plasma cells reside?
In the bone marrow
How can vaccination also generate memory T and B cells?
Vaccination simulates rare naive T and B cells
Induces a strong T cell and B cell response in 14–21 days
Some become effector cells, which:
- Mostly die by apoptosis in the absence of persisting antigen
Smaller number become memory cells and are maintained at low frequency
What happens after the removal and destruction of the initiating pathogen or antigen? (in terms of effector and memory cells)
The effector cells die (via apoptosis)
The memory T and B cells persist in the body for a long period of time
What does the increase in cell number due to the increase of memory T and B cells mean?
This increase in cell number means that the system is primed to respond better and faster upon a second exposure to the initial antigen.
Describe some characteristics of memory T and B cells?
Make a more effective immune response:
- Memory cells are present in greater numbers than the original parent lymphocyte
- Memory CD8+ T cells are able to kill immediately upon antigen stimulation - No requirement for help from Th cells
- Memory CD4+ T cells are able to produce cytokines immediately upon antigen stimulation - No requirement for co-stimulation
- Memory B cells have already undergone Ig class switching and hypermutation - Produce IgG and other Ig classes, Produce high affinity antibodies
- Memory cells have enhanced properties of cell adhesion and chemotaxis - they can access non-lymphoid tissues effectively (i.e. where the bugs actually are)
Longevity
- Memory Cells are long-lived, persisting in the absence of antigen
What are CD8+ T cells able to do?
Kill immediately upon antigen stimulation - No requirement for help from Th cells
What are CD4+ T cells able to do?
Produce cytokines immediately upon antigen stimulation - no requirement for co-stimulation
Memory cells have enhanced properties of cell adhesion and chemotaxis, which means they can?
they can access non-lymphoid tissues effectively (i.e. where the bugs actually are)
What is immunisation?
Immunisation is the process through which an individual develops immunity/memory to a disease
Includes both deliberate and natural infection
What is vaccination?
Vaccination is the deliberate administration of antigenic material to produce immunity to a disease
What is active immunity?
Protection produced by the person’s own immune system
Can be stimulated by vaccine or naturally acquired infection
Usually permanent
what is passive immunity?
Protection transferred from another person or animal
Temporary protection that wanes with time
How does active vaccination work?
It stimulates an immune response to antigen through the same pathways as natural infection.
Generates immunity and immunologic memory similar to natural infection
In general, the more similar a vaccine is to the disease-causing form of the organism, the better the immune response to the disease
What are some methods for generating immunological memory?
Exposure of an individual to the infectious organism
Exposure to a similar but less virulent pathogen (cowpox protects from smallpox)
Exposure to the inactivated pathogen
What are the key features of inactivated vaccines? (Killed/attenuated vaccines)
Cannot replicate
Generally not as effective as live vaccines
Immune response primarily antibody based (not T cells)
Antibody titer may diminish with time
Require multiple doses to stimulate immune response
What are the problems from making an inactivate vaccine from a live pathogen?
Under-inactivation
- Leaves viable pathogens or toxins within organism
Over-inactivation
- Loss of tertiary structure and conformational antibody binding sites loss of antigenicity
What are the pros of inactivated vaccines?
Advantages
- Can be made quickly (prevent epidemics)
- May elicit good antibody responses
- Easy to store - no refrigeration required
- Usually safe
- Can be given to immunocompromised individuals
What are the cons of inactivated vaccines?
Disadvantages
- May be very difficult to stimulate an immune response to many killed organisms
- Doesn’t replicate or disseminate
- Often require adjuvants to improve immunogenicity
- Poor at eliciting T cell responses
- Memory variable
- Require multiple injections
- Booster immunisation required
What are adjuvants?
Mixture of inflammatory substances required to stimulate immune responses to coadministered peptides, proteins or carbohydrates
- Aluminium hydroxide
- Toxins eg tetanus toxoid
- Other pathogens
- Bordetella pertussis
Why do adjuvants work?
Create inflammatory environment
Bind to macrophages and signal the unequivocal presence of a microbial invader
Activate the innate immune system to stimulate development of antibody and T cell responses
What are the problems of adjuvants?
- Toxic
- Alter the immune response
- Immune response is generated to vaccine:protein conjugates rather than vaccine itself
- CD4+ T cells may recognise the carrier only
- Therefore infection challenge will not necessarily elicit a secondary response
What are fractional vaccines, like subunit vaccines used in Hep B?
Only part of the organism used in the vaccine
Describe the Hep B vaccine?
Its a subunit vaccine
Consists of Hepatitis B surface antigen only
Produced by recombinant DNA technology
Stimulates protection in 85% of individuals
No risk of infection
First of the anti-cancer vaccines
Protects against Hepatitis B associated hepatocellular cancer
Describe polysaccharide vaccines?
- Polysaccharide sugars from the outer capsule of some bacteria determines pathogenicity and antigenicity
- However polysaccharides are not good at stimulating response,
- Generates antibody with less functional activity
especially in immature immune system - Immunogenicity can be improved by conjugating to an adjuvant (“conjugate vaccines”)
Describe live attenuated vaccines?
Attenuated (weakened) form of the “wild” virus or bacterium
Immune response similar to natural infection
Organism must replicate to be effective
Usually generate immunity with single dose
Examples - BCG (bacterial) Measles, mumps (viruses)
What are the pros to live attenuated vaccines?
Very similar to natural infection, so relevant effector mechanisms elicited (antibody + activated T cells)
Localised, strong response
Memory good, therefore boosting not usually required
What are the cons to live attenuated vaccines?
Immune response can be interfered with by circulating antibody
Safety
- May acquire new mutations and revert to virulence (eg vaccine associated poliomyelitis)
- May cause infection in immunocompromised host
Fragile – must be stored and handled carefully i.e. depends on cold chain
In passive immunity describe transfer of material antibody?
Maternal antibody
- Crucial to protection of infant in first 6 months of life
- Active transport of maternal IgG in third trimester
- Breast milk, especially colostrum, contains IgA: important for colonisation of infant GI tract
Maternal antibody also important in enabling subsequent memory
- Exposure to an antigen while under cover of maternal antibody may result in an less severe illness, but nonetheless memory to the antigen is generated
What are some sources of passive immunity?
Naturally acquired passive immunity - Transplacental transfer of antibody (IgG) - Breast milk (sIgA) Therapeutic passive immunisation - Pooled normal human immunoglobulin - Hyperimmune globulin - Heterologous hyperimmune serum - Monoclonal antibody against specific pathogen
Describe pooled immunoglobulin?
Transfer of antibody from an unrelated individual
Pooled normal immunoglobulin from immune humans
- Previously used for protection against hepatitis A (now superceded by inactivated Hep A vaccine)
Hyperimmune globulin
- Administered after specific exposure
- Immunoglobulin from an individual known to have high antibody levels against a specific pathogen
- Rabies (post exposure)
- Snake venom anti-toxin
Why is it so difficult to develop vaccines for some organisms?
Chronic or latent infections
- Immune system doesn’t normally generate a response that clears organism
- Tuberculosis
- Hepatitis C
- HIV
- Herpes viruses: CMV, HSV, EBV
Rapidly evolving infections
- Pathogens highly adept at immune evasion
- HIV
- Influenza
