1.
Overview of the Immune System
Prepared by:
Dr. Ami B. Naik
Assistant Professor
CGBIBT,
Uka Tarsadia University

2.
Immunity
 Immunity is body's ability to resist or
eliminate potentially harmful foreign
materials or abnormal cells.

3.
Immunity
1.Immunity: : Meaning the state of protection from
infectious disease.
2. Agents: microorganisms (viruses, bacteria etc) and
their products, foods, chemicals, pollen, tumor cells, etc.
3.Immune system: immune tissues and organs, immune
cells, immune molecules
4.Immune response: collective and coordinated response
to the introduction of foreign substances.
5.Immunology: study the structure of immune system and
its functions.

4.
Consists of following activities
◦ Defense against invading pathogens (viruses &
bacteria)
◦ Removal of 'worn-out' cells (e.g., old RBCs) & tissue
debris (e.g., from injury or disease)
◦ Identification & destruction of abnormal or mutant
cells (primary defense against cancer)
◦ Rejection of 'foreign' cells (e.g., organ transplant)
◦ Inappropriate responses:
 Allergies - response to normally harmless substances
 Autoimmune diseases

5.
Brief History of Immunology
 1. Empirical Immunology (AD1700-1900)
 2. Scientific Immunology (1900-1950s)
 3. Modern Immunology (1960s-Present)

6.
History
 Discipline of immunology grew out of observation that
individuals who recovered from infectious diseases and
protected from disease.
 430 BC
 phenomenon of immunity can be traced back to Thucydides,
the great historian of the Peloponnesian War.- plague in
Athens.
 Recovered from plague and nurse others.
 After 2000 years concept recognized.
 15th Century
 Chinese and Turks tried to prevent smallpox
 Dried crust from pustules were inhaled or inserted into small cuts
 Variolation
 1718
 Lady Montagu had that technique done in her children

7.
Documents show that as
early as AD 1000,
the ancient Chinese
custom existed of having
children inhale powders
made from the
crusty skin lesions of
patients recovering
from smallpox

8.
History
 1798
◦ Edward Jenner
 Noticed that milkmaids that contracted cowpox were
immune to smallpox
 Innoculated small boy with fluid from cowpox pustule
 He then intentionally infected the boy with smallpox –
the child did not develop smallpox
 Lack of disease target and knowledge of their cause.
 Technique applied to other disease after ~100 years.
 1881
◦ Louis Pasteur
 Cholera and chicken--- Vaccine
 Vaccinated sheep with heat-attenuated anthrax
 Then infected sheep with virulent strain of anthrax – they
did not develop anthrax and non vaccinated, died.

9.
Edward Jenner (1749-1823) Jenner vaccination

10.
 Lious Pasteur
(1822~1895).
 The genius of Pasteur
carried him to the
solution of many
problems: the spoilage of
beers and wines, with
the accompanying
pasteurization process;
the discovery of
anaerobic bacteria, virus
vaccines, and
attenuation of virulence;
and studies of
spontaneous generation.
 His studies in
immunology have rightly
earned him the position

11.
History
 1883
 Metchnikoff demonstrated that certain white
blood cells were able to phagocytes
microorganisms

12.
 Elie Metchnikoff
(1845~1916)
 He shared the Nobel
Prize with Ehrlich in
1908.

13.
 Paul Ehrlich
(1854~1915).
 He shared the Nobel
Prize with Metchnikoff in
1908.
 Selective theories(Paul
Ehrlich,1900）
 The binding like the fitting of
a lock with key, the side-
chain specificity was
determined before its
exposure to Ag, and the Ag
selected the appropriate
side-chain receptor.

14.
 Around 1900,
 Jules Bordet at the Pasteur Institute expanded
the concept of immunity by demonstrating
specific immune reactivity to nonpathogenic
substances, such as red blood cells from other
species.
 Serum from an animal inoculated previously
with material that did not cause infection would
react with this material in a specific manner,
and this reactivity could be passed to other
animals by transferring serum from the first.

15.
 1901
◦ Von Behring and Kitasato
 Demonstrated that serum (noncellular
component of blood) from animals, immunized
to diptheria could transfer that immunity to non-
immunized animals.

16.
 1930s,
 Through the efforts of Elvin Kabat, a fraction of serum first
called gamma-globulin (now immunoglobulin) was
shown to be responsible for all these activities.
 The active molecules in the immunoglobulin fraction are
called antibodies.
 In due course, a controversy developed between
those who held to the concept of humoral
immunity and those who agreed with Metchnikoff ’s
concept of cell-mediated immunity.
 Immunity requires both cellular and humoral
responses.

17.
 1940s,
 Merrill Chase succeeded in transferring
immunity against the tuberculosis organism
by transferring white blood cells between
guinea pigs. This demonstration helped to
rekindle interest in cellular immunity.
 With the emergence of improved cell culture
techniques in the 1950s, lymphocyte was
identified as the cell responsible for both
cellular and humoral immunity

18.
1930s and 1940s
 Instructional Theory, challenged selective
theory.
 Antigen would be served as template where, antibody would fold.
 Antibody is a configuration complementary to antigen.
 Postulated by Friedrich Breinl and Felix Haurowitz
in 1930 and redefined by Linus Pauling in 1940 in
terms of protien folding.

19.
Clonal selection theory and
immune tolerance

20.
The clonal selection hypothesis

21.
MHC

22.
Monoclonal Ab and Immune
regulatory theories

23.
Susumu Tonegawa is
a Japanese
Scientist who won the
Nobel Prize for
physiology or medicine in
1987 "for his discovery of
the genetic principle for
generation of antibody
diversity"
Antibody Diversity

24.
Peter C. Doherty Rolf M. Zinkernagel
”for their discoveries concerning the
specificity of the cell mediated immune
defence”

25.
The Nobel Prize in Physiology or Medicine 2011 was
divided, one half jointly to Bruce A. Beutler and Jules
A. Hoffmann "for their discoveries concerning the
activation of innate immunity" and the other half to
Ralph M. Steinman "for his discovery of the dendritic
cell and its role in adaptive immunity".

26.
Overview of the Immune
System
Immune System
Innate
(Nonspecific)
1o line of defense
Adaptive
(Specific)
2o line of defense

27.
Innate Immunity Adaptive Immunity

28.
29
 The innate immune response is
essential for elimination of a
pathogen but not sufficient.
 The adaptive immune response
requires certain key players of the
innate immune response to become
activated.

29.
Herd immunity
 Herd immunity (or community immunity) occurs
when a high percentage of the community is
immune to a disease (through vaccination and/or
prior illness), making the spread of this disease
from person to person unlikely.
 Even individuals not vaccinated (such as newborns
and the immunocompromised) are offered some
protection because the disease has little
opportunity to spread within the community.

30.
Innate immune system:
components of Blood
Complement
proteinsCoagulation
proteins
Cyto
kines
WBCs
Extracellular

31.
White blood cells (WBCs)
Macrophages
B-lymphocytes
T-lymphocytes
Natural killer(NK)
cells
Mast cells

32.
Neutrophils in innate immune
response
 Most abundant WBCs (~50-60%)
 Efficient phagocytes
 Most important cells of the innate immune
system

33.
Phagocytosis
 Phago = to eat
 Cyte = cell
 WBCs (eg. Neutrophils) – find, eat and
digest microbes !

34.
How do neutrophils eat and digest
microbes ?
Granule
s

35.
What’s in the granules ?
Lysozyme – digests bacterial cell
wall; other antimicrobial proteins

36.
Additional role of neutrophils
Triggers inflammatory response

37.
Monocytes
 Monocytes (~5% of
WBCs)
 Migrate into the tissues
and become
Macrophages
Lung Bone
Liver Brain
intestine

38.
Macrophages
 “Big eaters”
 Phagocytosis of microbes in tissue
(Neutrophils are present only in blood)
 Antigen presentation

39.
Natural killer cells
 Not B-lymphocytes / T-
lymphocytes
 Important part of the
innate immune system
 Kill virus /bacteria
infected cells
(Intracellular pathogens)
 Kills cancer cells

40.
NK cells differentiate choose
cells to kill ?
Uninfected cell / Normal cell
Microbe infected cell / cancer
cell
Some cell surface proteins are miss

41.
How does the killer kill ?
Kills both host cells and microbe
Release of granules with perforins and proteases

42.
Defense Against Disease
If these barriers are penetrated,
the body responds with
If the innate immune response is insufficient,
the body responds with
Adaptive Immune Response
cell-mediated immunity, humoral immunity
Nonspecific External Barriers
skin, mucous membranes
Innate Immune Response
phagocytic and natural killer cells,
inflammation, fever

43.
First line of defense
 Non-specific defenses are designed
to prevent infections by viruses and
bacteria. These include:
◦ Intact skin
◦ Mucus and Cilia
◦ Phagocytes

44.
Role of skin
 Dead skin cells are
constantly sloughed off,
making it hard for
invading bacteria to
colonize.
 Sweat and oils contain
anti-microbial
chemicals, including
some antibiotics.

45.
Role of mucus and cilia
 Mucus contains lysozymes,
enzymes that destroy
bacterial cell walls.
 The normal flow of mucus
washes bacteria and viruses
off of mucus membranes.
 Cilia in the respiratory tract
move mucus out of the lungs
to keep bacteria and viruses
out.

46.
Role of phagocytes
 Phagocytes are several types
of white blood cells (including
macrophages and neutrophils)
that seek and destroy
invaders.
 Some also destroy damaged
body cells.
 Phagocytes are attracted by
an inflammatory response of
damaged cells.

47.
Role of inflammation
 Inflammation is signaled by mast cells,
which release histamine.
 Histamine causes fluids to collect around an
injury to dilute toxins. This causes swelling.
 The temperature of the tissues may rise,
which can kill temperature-sensitive
microbes.

48.
Role of fever
 Fever is a defense mechanism that can
destroy many types of microbes.
 Fever also helps fight viral infections by
increasing interferon production.
 While high fevers can be dangerous,
some doctors recommend letting low
fevers run their course without taking
aspirin or ibuprofen.

49.
Specific defenses
 Specific defenses are those that give us
immunity to certain diseases.
 In specific defenses, the immune system
forms a chemical “memory” of the
invading microbe.
 If the microbe is encountered again, the
body reacts so quickly that few or no
symptoms are felt.

50.
Major players
 The major players in the immune
system include:
◦ Macrophage
◦ T cells (helper, cytotoxic, memory)
◦ B cells (plasma, memory)
◦ Antibodies

51.
Some vocabulary:
 Antibody: a protein produced by the human
immune system to tag and destroy invasive
microbes.
 Antibiotic: various chemicals produced by
certain soil microbes that are toxic to many
bacteria. Some we use as medicines.
 Antigen: any protein that our immune
system uses to recognize “self” vs. “not
self.”

52.
Antibodies
 Antibodies are
assembled out of
protein chains.
 There are many
different chains that
the immune system
assembles in
different ways to
make different
antibodies.

53.
Antibodies as Receptors
 Antibodies can
attach to B cells,
and serve to
recognize foreign
antigens.

54.
Antigens as Effectors
 Free
antibodies
can bind to
antigens,
which “tags”
the antigen
for the
immune
system to
attack and
destroy.

55.
Antigen recognition
 Cells of the immune system are “trained” to
recognize “self” proteins vs. “not self”
proteins.
 If an antigen (“not self”) protein is
encountered by a macrophage, it will bring
the protein to a helper T-cell for
identification.
 If the helper T-cell recognizes the protein as
“not self,” it will launch an immune

56.
T cells
◦ Arise in bone marrow but mature in thymus
◦ 2 well define subpopulations of T cells
 T helper cells
 T cytotoxic cells

57.
 T cells
 Cytokines secreted by TH cells can
activate phagocytic cells
 TC cells can kill altered self-cells
 Cells infected by viruses
 Tumor cells

58.
B cells
 B-cells in general produce antibodies.
 Those with antibodies that bind with the
invader’s antigen are stimulated to
reproduce rapidly.
 B-cells differentiate into either plasma cells
or memory B-cells.
 Plasma cells rapidly produce antibodies.
 Memory cells retain the “memory” of the
invader and remain ready to divide rapidly if
an invasion occurs again.

59.
Clonal Selection

60.
Role of antibodies
 Antibodies released into the blood stream
will bind to the antigens that they are
specific for.
 Antibodies may disable some microbes, or
cause them to stick together (agglutinate).
They “tag” microbes so that the microbes
are quickly recognized by various white
blood cells.

61.
“Killer” T cells
 While B-cells divide and differentiate, so
do T-cells.
 Some T-cells become cytotoxic, or “killer”
T-cells. These T-cells seek out and
destroy any antigens in the system, and
destroy microbes “tagged” by antibodies.
 Some cytotoxic T-cells can recognize and
destroy cancer cells.

62.
Adaptive Immunity
 Antigenic specificity
 Diversity
 Immunologic memory
 Self/nonself recognition

63.
B Lymphocyte

64.
T Lymphocyte