Download An Introduction to Vaccine Science and Basic Immunology

An Introduction to Vaccine Science and
Basic Immunology
Franco Pissani, Ph.D.
Scientist
Immunomic Therapeutics, Inc.
[email protected]
@FPissani
Understanding Vaccines:
What are vaccines- how do they work?
(or don’t)
Understanding Vaccines:
The beginning: Smallpox
Understanding Vaccines:
The beginning: Smallpox
Understanding Vaccines:
The beginning: Smallpox
Understanding Vaccines:
The greatest success story of modern medicine
Understanding Vaccines:
The greatest success story of modern medicine
smallpox
mumps
measles
So how do vaccines work?
Understanding the immune response & immunological memory
The Immune Response:
How your body fights off disease
Immunology: The study of the body’s defense against disease
The Immune Response:
How your body fights off disease
Your immune system is AWESOME
•
•
•
Exposed to
literally MILLIONS
of microbes each
day
>2,000 different
kinds of microbes
present in the air
you breathe
More bacteria
found on cell
phones than on
toilets
Q: Then why do I still get sick?
A: (1) Because it takes time for the immune system to “ramp up”; (b) Some
microbes “hide” and “outrun” the body’s defenses.
Malaise and Fatigue are byproducts of the immune system fighting the infection.
Your immune system is INTRICATE
Your immune system is elegantly ELABORATE
The Immune System consists of many different cell types and
structures that interact with each other and the pathogens to
mediate the immune response
Overview of the Immune System
Physical
Barriers
Immunological
Barriers
Overview of the Immune System: Innate Immunity
Physical
Barriers
Immunological
Barriers
Peeling back the layers: First Line of Defense
Innate Immunity: Physical Barriers
Goal: to stop pathogens from entering the body
→ Skin – acts as a barrier to invasion
→ Sweat – has chemicals which can kill different
pathogens.
→ Tears - have lysozyme which has powerful
digestive abilities that render antigens harmless.
→ Saliva – also has lysozyme.
→ Mucus - can trap pathogens, which are then
sneezed, coughed, washed away, or destroyed by
chemicals.
→ Stomach Acid – destroys pathogens
Peeling back the layers: First Line of Defense
Innate Immunity: Immunological Barriers
Peeling back the layers: First Line of Defense
Innate Immunity: Immunological Barriers
Recon
Peeling back the layers: First Line of Defense
Innate Immunity: Immunological barriers
Toll-like Receptors (TLR)
• Barriers are not 100%
effective, all the time
• A series of detectors and
traps that recognize
foreign material
• “Innate” immune system
recognizes when
something doesn’t
belong
• Present on innate
various types of cells
Peeling back the layers: First Line of Defense
Innate Immunity: Immunological barriers
Toll-like Receptors (TLR)
• Originally discovered in fruit flies
(Drosophila)
• Shared by fish, insects, birds, and
mammals (that’s YOU)
• Recognize parts of microbes that
are not present in that particular
organism
Peeling back the layers: First Line of Defense
Innate Immunity: Immunological barriers
Peeling back the layers: First Line of Defense
Innate Immunity: Immunological barriers
•
Triggering of TLRs initiate signaling cascade that “sounds the
alarm” to other cells of the immune system
• Induce inflammation, fever, and host defense peptides
• Recruit and Activate lymphocytes
Interplay between Innate & Adaptive Immunity
Help!!!
Physical
Barriers
Immunological
Barriers
Interplay between Innate & Adaptive Immunity
•
Triggering of TLRs initiate signaling cascade that “sounds the
alarm” to other cells of the immune system
• Induce inflammation, fever, and host defense peptides
• Recruit and Activate lymphocytes
Interplay between Innate & Adaptive Immunity
•
Triggering of TLRs initiate signaling cascade that “sounds the
alarm” to other cells of the immune system
• Induce inflammation, fever, and host defense peptides
• Recruit and Activate lymphocytes
Interplay between Innate & Adaptive Immunity
Recon
Infantry
Peeling back the layers: Second Line of Defense
Engaging the intruders: Adaptive Immunity I
Cellular Immunity: T cells
•
Helpers and Killers
•
Recognize internalized antigen
that is presented on the surface
of infected cells (and recon unit)
•
Helpers activate other arm of
the adaptive immune system
•
Killers identify and destroy
infected cells
Peeling back the layers: Second Line of Defense
Engaging the intruders: Adaptive Immunity II
Humoral Immunity: B cells
•
Recognize external antigen,
become activated, and turn
into antibody-producing
•
plasma cells
There are several different
types of antibodies
(immunoglobulins, Ig), each
with different functions
Putting It All Together:
The Immune Response – your immune repertoire
With millions of different germs, all expressing different antigens, how
do the right cells meet each other in high-enough frequency to fight…
Putting It All Together:
The Immune Response – your immune repertoire
Clonal Selection Theory: Process that ensures an organism’s immune
cell can recognize a wide range of pathogens and respond to each one
individually
Putting It All Together:
The Immune Response – the Lymph Node
The Lymph Nodes – specialized structures that houses your immune
repertoire and site of antigen presentation and lymphocyte
activation/proliferation.
Putting It All Together:
The Immune Response – effector mechanisms
Putting It All Together:
The Immune Response – effector mechanisms
Humoral Immunity: Antibodies
•
Mark pathogen to signal
other cells and molecules
to clear or destroy it
•
Block pathogen from
infecting the cell
Vaccine Immunology:
So how do vaccines work?
Understanding the immune response &
immunological memory
Vaccine Immunology:
Understanding vaccines: Immunological memory
Immunological memory protects an organism from disease by a
previously encountered pathogen by establishing antigen-specific
lymphocytes ready to act at the time of exposure
Vaccine Immunology:
Understanding vaccines: Immunological memory
Immunological memory protects an organism from disease by a
previously encountered pathogen by establishing antigen-specific
lymphocytes ready to act at the time of exposure
Primary
Response to infection
(become sick)
Memory
Formation
Secondary
Response
Vaccine Immunology:
How vaccines work? Artificial induction of immunological memory
Vaccines expose your immune system to recognizable components of pathogens –
without the risk of disease – inducing immunological memory that results in a
faster, stronger response during the initial encounter with the actual pathogen,
avoiding/ minimizing sickness and disease
Primary
Response to VACCINE
(no/mild sickness)
Memory
Formation
Secondary
Response
to INFECTION
(faster/stronger)
Vaccine Immunology:
How to induce immunological memory: What is in the vial?
Vaccine Immunology:
All vaccines are NOT created equal – Safety vs. Efficacy
The other face of the immune system
When the immune system misbehaves
When the immune system misbehaves
Allergies and autoimmune diseases
Autoimmune Disorders occurs when the immune system
attacks an antigen that is native to that organism
When the immune system misbehaves
Allergies and autoimmune diseases
Autoimmune Disorders occurs when the immune system
attacks an antigen that is native to that organism
Allergies occur when the immune
system recognizes a harmless
environmental antigen (allergen)
and responds as if it were a
pathogen
Immunomic Therapeutics, Inc. (ITI)
Making vaccines to prevent/treat allergies by rectifying immune
response to allergens
Normal Response
IgE
IgG
Immunomic Therapeutics, Inc. (ITI)
Making vaccines to prevent/treat allergies by rectifying immune
response to allergens
Normal Response
IgE
IgG
I want to be a scientist, now what?
Lots of different types of Scientist, but…
… PhD training in biomedical science is one of the most intensive and prolonged...
Undergrad
•
•
•
•
•
•
•
Molecular
Biology
Biochemistry
Organic
Chemistry
Microbiology &
Immunology
Calculus
Physics
Genetics
Life in Graduate School…
Comprehensive Qualifying
Exam
Exam
Classes
Write Thesis
&
Thesis Defense
6
Lab rotations
Select Thesis
Topic
Lab research/
seminars/
journal clubs/
write & publish research articles
7
Being a scientist…
Being a scientist…
Science – So Easy, A Caveman Could Do It
Disclosure: Slides were unashamedly borrowed from SlideShare
(www.slideshare.com), Wikipedia, general google searches, or generously
provided by Jeff Teigler, Ph.D. (USMHRP) and Bill Hearl, Ph.D. (ITI) and modified for
the purposes of this talk.
Vaccines and Autism – study linking MMR
and autism-associated characteristics
Vaccines and Autism – study linking MMR
and autism-associated characteristics
Deer B. How the case against the MMR vaccine was fixed. BMJ 2011.
So why is it still an issue?
So why is it still an issue?
www.geneticsliteracyproject.com
So why is it still an issue?
So why is it still an issue? – IT’S NOT