Transcript IMMUNISATION: HOW DOES IT WORK? File

Immunistion- How does it work?
Jacqui Boulton November 2015
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Florence Nightingale Faculty of Nursing & Midwifery
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Aims and objectives
• Appreciate the background to ,and ongoing
evolution of ,immunisation in the UK
• To understand the aims of vaccination
• To develop an understanding of the immune
system and how it may respond to vaccines
• Gain an insight into the composition of
vaccines and the implications this has
Aims of immunisation
• ‘To confer Immunity and immunologic
memory similar to natural infection but
without risk of disease’
Vaccination and immunisation
• Immunity may result from vaccination or
natural immunisation
• Vaccination may not result in immunisation
• Vaccination may be active or passive
• Vaccine failure occurs for a variety of reasons
Edward Jenner at the Smallpox Inoculation Hospital, St Pancras,
London, vaccinating the populace with cowpox, which (according
to the original caption) had ‘wonderful effects!’
)
(by james gilroy 1881
What Is the function of the immune
system?
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Recognising what is self from non-self
Recognising friend from foe
Sufficient but not excessive immunity
The right kind of response
A response in the right place at the right time
Using appropriate force, minimising collateral
damage, keeping things under control &
finding long-term solutions
• Any foreign substance recognised by the
immune system is called an antigen
Antigens • Distinguishes between self (own body) and non-self
(foreign substanes)
• Any foreign substances recognised by the immune
system are called antigens .(A molecule that is
recognised by the immune system )
• Antigens are potentially harmful
• A single bacteria will contain hundreds of
individual antigens
• Vaccines containing differing numbers depend on
their formulation
Antibodies +
• Antibodies may be produced in response to antigens
• An immunoglobulin or glycoprotein produced by B
lymphocytes that bind to an antigen to render it inactive:
• (IgM,(Largest, found in blood and lymphoid tissue first type
of antibody in response to antigen)
• IgG (73%),
• IgA,(mucosal immunity)
• IgD (enhances antibody response ),
• IgE (fight parasites… but also cause of allergic
reactions)
• Antibodies are usually beneficial/confer immunity
IgM
• Primary immune response
• First time a vaccine is encountered
• Large molecule, remains primarily in the
intravascular pool
• Does not penetrate tissue
• 5 molecules bound together (pentameric)
• Response is slow
IgG
• Secondary immune response
• Crosses placental at 32 weeks
• Penetrates serum easily, found in tissue
and serum
• Activates complement system
• Response is rapid
IgA, IgD, IgE
IgA
• Found in mucus membranes, mouth, throat
• Acts as a localised protective barrier
• Major antibody in saliva, tears, colostrum and
breast milk
IgD
• Function not fully known
• May play a role in lymphocyte differentiation
IgE
• Involved in the allergic response
Inate immunity
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This includes physical barriers of defence
plus
Macrophages (‘big eater cells’) resident in skin
Recognise antigens as non-self-engulfed/destroyed by
phagocytosis
Inflammation-release
of cytokines-additional
macrophages to site
Rapid, Non-specific
• , no memory
What else happens?
• Fever-Mobilises defenses , accelerate repairs,
inhibits pathogens
• Release of interferons- slow progress by
increasing the resistance of cells to disease
• Complement system-aids phagocytosis
• Inflamatory response- (mast cells)
Aquired immunity
• If antigen not eliminated by inate response:
• Antigens transported by macrophages in the
lymphatic system-lymphoid organs
• These organs are rich in lymphocytes (b and t
cells)
• Can you identify these organs?
AQUIRED IMMUNITY
B Cells …..and…..T Cells
• Deal with infection
• Recognise intracellular
outside of the
antigens (eg
cell(HUMORAL
meninogococcal
IMMUNITY)
-cell mediated memory
• Recognise antigens on
surface of cells(most
Secrete cytokines
bacteria)
Recruit neutrophils,
• Manufacture antibodies
basophils and
(up to 100,000 per min)
but need help of T cells
eosinophils to site to
ie T cell dependent
site of infection
The humoral response
• Surface antibodies are also known as
immunoglobulins
• Antibodies have three dimensional binding sites
specific to individual antigens
• When there is a ‘ fit’ the B cells enlarge to
become antibody manufacturing cells and
release up to 100,000 antibody molecules
per min (each with identical antigen
binding sites)
T cells
T Helper Cells
• Assist the B cells to secrete antibodies
• Essential for the differentiation of B cells to
plasma cells.
• Each T helper cell is capable of activating
hundreds of B cells.
• Required to activate macrophages to
produce cytokines
T cells
T Suppressor Cells
• Stimulated by T Helper cells
• Inhibit the development of B cells into
plasma cells
• Suppress the production of antibodies
• Suppress auto-immune responses
T cells
Natural Killer Cells
• Secrete lymphokines, which attract
phagocytes and macrophages for
phagocytosis
• Cannot attack an antigen until it has been
taken inside the cell and presented as
MHC
Memory Cells
• A few B and T cells remain as memory cells
• When these meet the antigen again either as
natural infection or booster vaccination
the response is much quicker
• IgG-persists for longer
• Each time memory cells encounter the same
antigen the immune response is boosted
Natural and specific immunity
Natural immunity (INNATE IMMUNITY)
Includes physical and chemical barriers, such
as the skin, mucous membranes, gut
secretions (acid, antibacterial).
Specific immunity (AQUIRED IMMUNITY)
Includes physical and chemical barriers,
circulating molecules (antibodies), cells
(lymphocytes) and mediators (cytokines).
MAY BE PASSIVE OR ACTIVE
Principles of immunity
Active Immunity
• Protection produced by the person's
own immune system
• Usually permanent
• How might it be achieved?
Passive Immunity
• Protection transferred from another person
or animal
• Temporary protection that wanes with time
• Examples?
Immunoglobulins and infants
• IgG transferred maternally
– The process is active, but immunity is passive
– Provides immunity to everything the mother
has immunity to
– Declines over first 6 months of life, all gone by
18 months
– No IgA which is important for mucosal
immunity
• IgA from breast milk
Active and passive immunity
Active immunity
• The body manufactures its own antibodies
• Caused by either having the infection and
producing antibodies (IgM)
• Can be through vaccination of infected
antigens
• Immunity usually lifelong
Active and passive immunity
Passive immunity
• The infusion of antibodies from another
person
• Specific antibodies injected into another
person
• Example: Mother to fetus, IgG crossing
placenta from 32 weeks onwards
• Injection of immunoglobulins
• Immunity short term only
Types of immunity
Herd immunity
• R0 basic reproductive rate
• Average number of infections caused by the
introduction of one infected person into a
susceptible population
• R0 >
1 = epidemic
• R0 1 = endemic
• R0 <
1 = no spread
• Aim is to reduce R0 < 1
• Why is Herd immunity important?
Safety -Vaccine studies
• Phase 1 Healthy volunteers
Small numbers
Main focus - safety
• Phase 2 Healthy volunteers
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larger numbers
Main focus - immunogenicity
• Phase 3 Target population
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Main focus – immunogenicity
and safety
• Phase 4 Post-licensure
Types of vaccine
General Rule
The more similar a vaccine is to
the disease-causing form of the
organism, the better the immune
response to the vaccine
Classification of Vaccines
• Live attenuated
– viral
– bacterial
Whole
Inactivated
vaccines
• Virus and
bacteria
Fractional
(protein
based)
Fractional
polysacharide
based
• toxoid
• Sub-unit
• pure
• conjugated
Live Attenuated Vaccines
• Attenuated (weakened) form of the "wild"
virus or bacterium-cannot cause disease in
HEALTHY people
• Must replicate to be effective
• Immune response similar to natural
infection
• Usually produce immunity with one dose
Live Attenuated Vaccines
• Viral
measles, mumps,
rubella, varicella, zoster,
yellow fever, rotavirus,
intranasal influenza,
rotavirus, vaccinia
• Bacterial
BCG, oral typhoid
Inactivated Vaccines
Whole-cell vaccines
• Viral
• Bacterial
polio, hepatitis A,
rabies, influenza
pertussis, typhoid
cholera,
Inactivated Vaccines
Fractional vaccines (subunit, toxoid or polysacharide)
• Subunit
• Toxoid
hepatitis B, influenza,
acellular pertussis,
human papillomavirus,
anthrax
diphtheria, tetanus
Polysaccharide Vaccines
Pure polysaccharide
• Pneumococcal 23 (pneumovax)
• meningococcal
• Salmonella Typhi (Vi)
Conjugate polysaccharide
• Haemophilus influenzae type b
• Pneumococcal 13 (prevenar)
• meningococcal
Inactivated Vaccines
• Advantages
• Stable
• Constituents clearly
defined
• Disadvantages
• Need several doses
(cannot replicate)
• Local reactions common
• Adjuvant needed
• keeps vaccine at injection
site
• activates antigen
presenting cells
• Shorter lasting immunity
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Vaccine composition
In addition to the antigen, vaccines may contain some or all of
the following components:
Component
Purpose
Example
Adjuvants
enhance the immune response to a
vaccine
aluminium salts
Preservatives
prevent bacterial or fungal contamination
of vaccine
thiomersal
Additives
stabilise vaccines from adverse
conditions such as freeze-drying or heat,
thereby maintaining a vaccine’s potency
gelatine
Residuals from
manufacturing
process
Inactivating agents
formaldehyde
Antibiotics - prevent bacterial
contamination during manufacturing
process
neomycin, streptomycin,
polymyxin B
Egg proteins- some vaccine viruses are
grown in chick embryo cells
Yeast proteins
Immunisation Department, Centre
for Infections
influenza, yellow fever
HepB vaccine
Additional resources
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Department of Health – Immunisation:
http://www.dh.gov.uk/en/Publichealth/Healthprotection/Immunisation/DH_176
DH The Green Book:
http://www.dh.gov.uk/en/Publichealth/Healthprotection/Immunisation/Greenb
ook/DH_4097254
Health Protection Agency
http://www.hpa.org.uk/EventsProfessionalTraining/InfectionsTraining/Infectio
nsTrainingResources/ImmunisationTrainingResources
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Open University OpenLearn: S320_1 Vaccination. Available at:
http://openlearn.open.ac.uk/file.php/2642/formats/print.htm
WHO – Immunization. Available at:
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http://www.who.int/topics/immunization/en
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