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Biotechnology and Pharmacology Course

PRINCIPLES OF IMMUNOLOGY
Le Van Dong MD., PhD
Deputy Head, Department of Immunology
Vietnam Military Medical University
levandong@vmmu.edu.vn;
g@
levandong@yahoo.com
g@y

EDUCATION
RESEARCH
INDUSTRY/ TREATMENT

Text books

2011

2011

Syllabus
y
[1] Topic 1: Introduction to Immunity and Immune Systems
[2] Topic 2: Cells and Organs of the Immune System
[3] Topic 3: Innate Immunity
[4] Topic 4: Antigen
[5] Topic 5: Antibody
[6] Topic 6: Humoral Immune Responses
[7] Topic 7: Cell-Mediated Immune Responses
[8] Topic 8: Immune Responses Against Tumors and Transplants
[9] Tutorial/ Practice
[10] Topic 9: Hypersensitivity Diseases, Immunodeficiencies and Autoimmunity
[11] Topic 10: Immunotherapy
[12] Topic 11: Common immunological techniques
[13] Tutorial/ Practice
[14] Lab work

Biotechnology and Pharmacology Course Topic 01

INTRODUCTION TO IMMUNITY
AND IMMUNE SYSTEMS
Le Van Dong MD., PhD
Deputy Head, Department of Immunology
Vietnam Military Medical University
levandong@vmmu.edu.vn;
g@
levandong@yahoo.com
g@y

EDUCATION
RESEARCH
INDUSTRY/ TREATMENT

Contents

Immunological terms and definition

Brief
e history
sto y o
of Immunology
u o ogy

Classification of immunity

Classification of immune responses

Other roles of the immune system


y

Causes of infectious diseases


Human and
H
d pathogen
th
are separated:

No infectious diseases

Human iis liliving


H
i with
ih
pathogen

Infectious diseases

How to avoid infectious diseases?


No contact with microbe

How to avoid infectious diseases?


No contact with microbe
Fiction

How to avoid infectious diseases?


No contact with microbe
Real life

David Phillip Vetter 1971 1984:


Born without the immune system, lived inside the plastic chamber

Totally separated with environtment......., died from cancer.

How to avoid infectious diseases?


No contact with microbe
Real life: clean room for maintaining of patient who has immune
system
t
d t
destroyed
d by
b radiation
di ti or chemotherapy
h
th

Real living environment


Pathogen
g is circulating
g in a population: epidemic of
infectious disease.
In one epidemic, some people got the disease (nonimmune) some do not got the disease (immune)
immune),
(immune).

Immunity: the status/


ability to resist to
diseases,
d
seases, espec
especially
a y
infection and cancer.

Why we can have immune?


Because of the immune system
The immune system comprise of cells, tissues, molecules
participate in the body defence.

Immune system:
y
Bodys
y arm forces
Immune system = Ministry of Defence + Ministry of Public Security

What does the immune system do to protect


our bodies?
Immune system produces immune response
Immune response is the coordinated reactions of the
immune system to infections and foreign substances.

Principal functions of the immune system

Prevent new infections


and remove established
infections (against
outside enemies).

Surveillance and
destroy cancer (fight
against internal crimes).

Notes

Immunity is stage/ability to resist to diseases,


diseases
especially infections and cancers. This ability
is performed by the immune system.

Immune system comprises of tissues, cells,


molecules participating in defending the body.

The immune system produces


response to protect body.

Immunology studies components of the


immune system and their reactions to
pathogens which enter the body and strange
cells and substance appear in the body.

immune

Milestones in Immunology
Before 1900

Edward Jenner (1796) - an English physician discovered that


g
smallpox
cowpox vaccination protected against

Vacca,, vaccine,, vaccination


Vaccine: A preparation of microbial antigen,
Vaccine
antigen often
combined with adjuvant, that is administered to
individuals to induce protective immunity against
microbial infections.
Vaccination:
A general term for immunization
against infectious diseases, originally derived
from immunization against smallpox which uses
the Vaccinia virus.

Edward Jenner and patients waiting for cowpox vaccination to


protect against smallpox

Louis
L
i P
Pasteur
t
(1885) used
d rabies
bi
vaccine for the first time on human

Eli M
Metchnikoff.
t h ik ff Phagocyte
Ph
t is
i
important to kill bacteria

1900-1959

1960-1979

1980-1990

1990-2000

Active immunity, passive immunity


and adoptive immunity

Active immunity: immunity induced in an individual by


infection or vaccination.

Passive immunity:
y immunityy conferred on an individual
by transfer of antibodies from an actively immunized
individual (i.e., protection of newborns from infection by
acquiring antibodies from their mothers through the
placenta and in milk).

Adoptive immunity: immunity conferred on an


individual by transfer of primed lymphocytes from an
actively immunized individual.

Acquired immunity (actively)


Systemic TB; died
(No immunity)

BK

Mouse does not


expose to BK

No systemic TB;
surmised (Has
immunity after BK
i f ti )
infection)
Mouse survived
after infected with BK

Acquired immunity (passively)

Passive immunity and adoptive immunity


Serum
Transfer
serum
(antibodies)

Mouse has
passive
immunity

Transfer
Immune cells

Mouse has
adoptive
immunity

Mouse surmised
after infected with BK
(Has active immunity)

Primed
immune cells

Classification of immune responses


Innate immune response
(None-specific )

First line of defense


Non-specific

><

Adaptive
Ad
ti iimmune response
(Specific)

Second line of defense


Highly specific with
memory

Innate immunity (non-specific)


and adaptive immunity (specific)

Abbas A. K and Lichtman A. H


Basic Immunology 3rd Ed Saunders 2011

Phagocytosis
g y

Innate immune response

><

Epithelial
p
barriers ((and the
specialized cells and natural
antibiotics present in epithelia)
Phagocytes
g y

Adaptive immune response


Humoral immune response: B

lymphocytes; Antibodies
(eliminate microbes in
extracellular fluids)
Cell-mediated immune

Dendritic cells
Natural killer cells
Complement
C
l
t ((and
d other
th plasma
l
proteins)

response: T lymphocytes;
Effector T cells ((eliminate
microbes living inside cells)

Adaptive immune responses often use the cells and


molecules of the innate immune system to eliminate
microbes, and adaptive immunity functions to greatly
enhance these antimicrobial mechanisms of innate
immunity.

Properties of Innate Immunity


The innate immune
imm ne system
s stem usually
s all responds in
the same way to repeat encounters with a
microbe (non
(non-specific)
specific).

Unlike the adaptive immune system, it doesnt


have immunologic memory.
memory

Adaptive
p
((specific)
p
) immunity
y

Abbas A. K and Lichtman A. H


Basic Immunology 3rd Ed Saunders 2011

General overview and main functions of


humoral immunity
1. Extracellular microbes present
2. B lymphocytes respond by secreting antibodies.
Main functions: block infections and eliminate
extracellular microbes.
microbes

B cell and antibodyy secreting


g

General overview and main


functions of cell
cell-mediated
mediated immunity
- Phagocytosed microbes present in macrophage
- Helper T lymphocytes respond by binding to macrophage
Main functions: activate macrophages
p g to kill p
phagocytosed
g y
microbes
AND
- Intracellular microbes (i.e., viruses) replicated within cell
- Cytotoxic T lymphocytes respond by binding to the infected
cell
Main functions: kill infected cells and eliminate reservoirs of
infection

T cell kills viral infected cell


NK cell kills cancer cell

Properties of Adaptive Immunity

Specificity: ensures
Specificit
ens res that distinct antigens elicit
specific responses

Diversity:
Di
it enables
bl immune
i
system
t
t respond
to
d to
t
a large variety of antigens

Memory: leads
M
l d to
t enhanced
h
d responses to
t
repeated exposures to the same antigens

Primary and secondary immune responses:


specificity and memory

Abbas A. K and Lichtman A. H


Basic Immunology 3rd Ed Saunders 2011

Properties of Adaptive Immunity

Clonal expansion: increases number of antigenspecific lymphocytes to keep pace with


microbes

The process of
clonal selection

Abbas A. K and Lichtman A. H


Basic Immunology 3rd Ed Saunders 2011

Burnets Clonal selection theory (1957)


(Nobel Prize 1960)

Properties of Adaptive Immunity

Clonal expansion: increases number of antigenspecific lymphocytes to keep pace with


microbes
S
Specialization:
generates responses that are
optimal for defense against different types of
microbes
Contraction and homeostasis: allows immune
system to respond to newly encountered
antigens
Nonreactivity to self: prevents injury to the host
during responses to foreign antigens

Controling: lymphocytes only fight to


the real bad guy
Antigen

(often referred to as
signal
1)
and
molecules
produced during the innate
immune response (signal 2)
function cooperatively to activate
antigen-specific
antigen
specific lymphocytes.
The

requirement for microbetriggered


gg
signal
g
2 ensures that
the adaptive immune response is
induced by microbes and not by
harmless substances.
substances

Phases of an adaptive immune response

Abbas A. K and Lichtman A. H


Basic Immunology 3rd Ed Saunders 2011

Capture (at epithelia, dendritic cells)


and display (at lymph node or splenic
follicle,, byy dendritic cell;; naive T cells
recognize peptide-MHC complex on
APCs; naive B cells recognize
antigens (including non-protein
substances) directly via antibodies on
the cell surface) of microbial antigens.

Abbas A. K and Lichtman A. H


Basic Immunology 3rd Ed Saunders 2011

Activation of lymphocytes (clonal


expansion and differentiation; T cell
expansion
p
and differentiation
stimulated by the expression of
costimulators on the surface of and
secretion of cytokines by activated
dendritic cells; B cell expansion and
differentiation stimulated by the
activation of complement)

Antigen elimination
(i) via humoral immunity; B cells proliferate and
diff
differentiate
ti t iinto
t plasma
l
cells
ll th
thatt secrete
t antibodies;
tib di
antibodies then bind to microbes and prevent them
from infecting cells and eliminate them
(ii) via
i cell-mediated
ll
di t d immunity;
i
it h
helper
l
T cells
ll (CD4
(CD4+))
produce cytokines promoting macrophage killing of
microbes; CTLs (CD8+) directly kill cells harbouring
y p
]
microbes in the cytoplasm]

Abbas A. K and Lichtman A. H


Basic Immunology 3rd Ed Saunders 2011

Homeostasis
H
t i iis
achieved by
apoptosis

Memory
(surviving
from the
initial
activation)

Other roles of the immune system


y

Over
O
er response cell and tiss
tissue
e inj
injuries
ries
(hypersensitivity).

Other roles of the immune system


y

Over
O
er response cell and tiss
tissue
e inj
injuries
ries
(hypersensitivity).
Under response Immunodeficiency.
Immunodeficiency
Congenital:

no antibody, no thymus
Acquired: malnutrition,
malnutrition pregnancy
pregnancy, infection
infection,
HIV/AIDS

Immunodeficiency

Other roles of the immune system


y

Over
O
er response cell and tiss
tissue
e inj
injuries
ries
(hypersensitivity).
Under response Immunodeficiency.
Immunodeficiency
Congenital:

no antibody, no thymus
Acquired: malnutrition,
malnutrition pregnancy
pregnancy, infection
infection,
HIV/AIDS

Disorders of immune responses


p
autoimmune
diseases.

Autoimmune diseases

Other roles of the immune system


y

Over
O
er response cell and tiss
tissue
e inj
injuries
ries
(hypersensitivity).
Under response Immunodeficiency.
Immunodeficiency
Congenital:

no antibody, no thymus
Acquired: malnutrition,
malnutrition pregnancy
pregnancy, infection
infection,
HIV/AIDS

Disorders of immune responses


p
autoimmune
diseases.
Graft rejections.

SUMMARY
The Immune system comprises of tissues, cells,
molecules participating in defending the body.
The physiologic function of the immune system
is to prevent infections and to eradicate
established infections. The major
j roles of the
immune system include:
1) Defense against infections.
2) Recognition and response to newly introduced
proteins and cells such as tumours and tissue grafts.

Summary (cont.)
Clinical implications of these roles include:
1) Deficient immunity results in increased susceptibility to
infection ((exemplified
p
byy AIDS)) .
2) Vaccination boosts immune defenses and protects
against infections.
3) Immune responses are barriers to transplantation and
gene therapy.
4) Potential for immunotherapy of cancer.

Summary (cont.)
Innate immunity:
y mediates the initial p
protection against
g
infections; is always present in healthy individuals and
prepared to block the entry of microbes and to rapidly
eliminate microbes that do succeed in entering host tissues.
tissues
Adaptive
Adapti
e immunity:
imm nit develops
de elops more slowly
slo l and mediates
the later, even more effective, defense against infections; is
the type of host defense that is stimulated by microbes that
invade tissues (in other words, it adapts to the presence of
microbial invaders)

Summary (cont.)
Active immunity: immunity induced in an individual by
infection or vaccination.
Passive immunity: immunity conferred on an individual by
transfer of antibodies from an actively immunized
individual.
Adoptive immunity: immunity conferred on an individual
by transfer of primed lymphocytes from an actively
immunized individual.

Review questions
q
1.

What are three major roles of the immune system? What


are some clinical implications of these roles?

2.

What are mechanisms of innate immunity?

3.

What are mechanisms of adaptive immunity?

4.

Why is adaptive immunity needed in a person with a


functioning innate immune system?

5.

Provide a general overview (consider: the microbe,


responding lymphocyte(s) and effector mechanism) of
humoral immunity. What are the main functions of
humoral immunity?

Review questions
q
6.

Provide a general overview (consider: the microbe,


responding lymphocyte(s) and effector mechanism) of
cell-mediated immunity. What are the main functions of
cell-mediated
cell
mediated immunity?

7.

What is the difference between active immunity and


passive immunity? Provide an example of passive
immunity.

8.

What are the seven properties or features of adaptive


immune responses?

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