Transcript Applied Immunology - European Centre for Disease Prevention and

Applied Immunology
Aftab Jasir: European Centre for Disease Prevention and Control (ECDC)
European Public Health Microbiology training program (EUPHEM)
Introductory course, Menorca,2012
Objectives
• Define basic components of immunology
• Describe important terms in immunology
• Explain major applications of immunology
What is immunology?
 Immunology is a broad branch of biomedical
science that covers the study of all aspects of the
immune system in all living organisms.
 It deals with the physiological functioning of the
immune system in states of both health and
disease
What is the immune system?
The immune system is the ministry of defence of the human/animal
body
Immunodeficiency and Immunosuppression
Immunodeficiencyis a state in which the immune
system's ability to fight infectious disease is low or
entirely absent.
Immunosuppression involves an act that reduces the
activation or efficacy of the immune system.
immunosuppression may occur as an adverse
reaction to treatment of other conditions.
Major defence components of the human
immune system
Cells
Immunoglobulins
Overview of the immune system
Immune
system
Innate
(nonspecific)
1st line of defense
Cellular
components
Humoral
components
Adaptive
(specific)
2nd line of
defense
Cellular
components
Humoral
components
Definitions/terminology
Antigens (Ag)
Large molecules, is anything that obtain the formation of a
specific immune response (Anomy)
Ag determinants (epitopes) are the particular chemical
groups on a molecule that are antigenic
Antibody(Ab)/immunoglobulin (Ig).
A special group of soluble proteins that are produced in
response to foreign antigens (substances)
Antigen and antibody
5 classes of IGs
1. IgM (first exposure, large, not
passing placenta, huge amont)
2. IgG (secondary exposure, small,
passing placenta)
1. IgD (proteins in the plasma
membranes of mature Blymphocytes, same time as IgM)
1. IgA (mucosal immunity, respiratory
tract)
1. IgE (Allergy and parasites)
Haptens
Vaccine conjugate
Ministry of defence of the human body
Antibody Protection of the Host
Primary and secondary antibodies
P: antibodies raised against an antigenic target of
interest and are typically unconjugated.
S: antibody that binds to primary antibodies or antibody
fragments. They are typically labeled with probes that
make them useful for detection,
Immune Precipitation
Antigen
Antibody
Agglutination
RBC
IgM Antibody
RBC
RBC
RBC
RBC
RBC
RBC
RBC
IgG Antibody
RBC
RBC
RBC
Factors influencing immunogenicity
Factors
Contribution
of immunogen
Contribution
of biological
system
Method of
administration
Class Switching
Biological mechanism that changes a B cell's production of
antibody from one class to another, for example, from IgM to
IgG.
antibody
titer
IgM
IgG
time
Four phases of the primary response
• lag phase where no antibody is detected
• log phase in which the antibody titer rises
logarithmically
• plateau phase during which the antibody titer
stabilizes
• phase (decline) during which the antibody is
cleared or catabilized
Kinetics of the Ab Response
T-dependent Ag; 1o Response
LOG
PLATEAU
DECLINE
Ab Titer
• Lag
• Log
LAG
• Plateau
• Decline
Ag
Days After Immunization
Kinetics of the Ab Response
• Lag
• Log
• Plateau
• Decline
Ab Titer
T-dependent Ag; 2o Response
1o Ag
2o Ag
Days After Immunization
Major practical applications of immunology
– Use of antiserum and vaccination to provide
protection against disease.
– Diagnostic tool to detect disease.
– Epidemiological investigation of vaccine preventable
diseases
My face is my fortune
Where are you going, my pretty maid?
I’m going a-milking, sir, she said
May I go with you, my pretty maid?
You’re kindly welcome, sir, she said
What is your father, my pretty maid?
My father is a farmer, sir, she said
What is your fortune, my pretty maid?
My face is my fortune, sir, she said
Variolation
The word ‘variolation’ comes from the Latin word ‘variola’ for
human smallpox.
Discovery of small pox vaccine
Edward Jenner 1780AD
Blossom
Types of acquired immunity
Passive – receive Abs made by another
1. natural
2. artificial - γ globulin, hyperimmune serum
Natural
Artificial
Mode of delivery
Advantages and Disadvantages
of Active Immunization
Advantages
Disadvantages
Not immediate
Long term immunity
Herd immunity
Immune
suppressed/deficiency
Risk of infection
Risk of contamination
Animal ???
Attenuated can revert to
their pathogenic form
Advantages and Disadvantages
of Passive Immunization
Advantages
Disadvantages
no long term
protection
immediate
protection
serum sickness
risk of
hepatitis and HIV
graft vs. host
disease
Serology
 A science that attempts to detect signs of
infection in a patient’s serum such as Ab for a
specific microbe
 Serological tests based on Abs specifically
binding to Ag
– Ag of known identity will react with Ab in an
unknown serum sample.
– Known Ab can be used to detect Ag in serum
 Ag-Ab reactions are visible by clumps,
precipitates, color changes or release of
radioactivity.
 The most effective tests have high specificity
and sensitivity.
Enzyme (ELISA) Immunoassay
Enzyme conjugated
to anti-Ig antibody
(“second
antibody”)
anti-antigen
antibody
Antigen
Add
substrate
for enzyme
a) The presence of a specific Ab
b) Identification of microbes
Specificity, sensitivity, and cross reactivity
a) Specificity
– Ab attaches with great
exact-ness to only one type
of Ag.
b) Sensitivity
– Ab can locate Ag, even
when it is greatly diluted.
c) Cross reactivity
– the ability of an individual
antibody combining site to
react with more than one
antigenic determinant or
the ability of a population
of antibody molecules to
react with more than one
antigen.
Examples of serological tests
1.
2.
3.
4.
5.
6.
7.
Agglutination tests
Precipitation tests
Immunoelectrophoresis
Western blot tests
Complement fixation tests
Immunofluorescence testing
Immunoassays
Acute infection
Onset of
symptoms
Incubation
Primary
infection
Days
Weeks
Months
Years
Acute infection
Onset of
symptoms
IgM
Incubation
Primary
infection
Days
Weeks
Months
Years
Acute virus infection
Onset of
symptoms
IgG
IgM
Incubati
on
Primary
infection
Days
Weeks
Months
Years
Acute virus infection
Avidity = the sum of affinities
between:
antibody
Onset of
symptom
s
and
antigen
IgG avidity
IgG
IgM
Incubation
Primary
infection
Days
Weeks
Months
Years
Onset of
symptom
s
IgG avidity
IgM
IgG
Incubation
Persistence
Primary
infection
Days
Weeks
Months
Secondary
infection or
Years
reactivation
Onset of
symptoms
IgG avidity
IgM
IgG
Viremia
Primary
infection
Days
Weeks
Months
Secondary
infection or
Years
reactivation
Q fever
IgM2
IgM1
IgG2
1/800
IgG1
IG
titter
1/64
1/40
1
2
1
1
2
Time
What should you have in mind!!!
Tack home massage
 Some times Ag x Ab based tests can results in wrong
alarm of outbreak ( Salmonella)
 Antigen variation is always a problem (Chlamydia,
grouping of streptococci)
 Cross-reactivity can give wrong information of an
outbreak
 Any unusual or unexpected results should be
confirmed by genetic test
 If possible use other methods than serology in an
outbreak situation or combine with other methods