Dr. Alok Tripathi studies immunology at the Department of Biotechnology. The document discusses the history and key concepts of immunology, including: 1. The dual immune system of vertebrates, consisting of cell-mediated and humoral immunity. 2. Early theories on immunity proposed by scientists like Metchnikoff, von Behring, and Paul Ehrlich to explain concepts like phagocytosis, humoral immunity, and the generation of antibody diversity. 3. The development of the clonal selection theory by Burnet, Jerne, and others to explain how the immune system achieves antigen specificity through clonal expansion and memory cells.

1. Dr Alok Tripathi
Department of Biotechnology
09795894495
aquaimmuno@yahoo.co.in

2.  Phylogeny of vertebrate and invertebrate
immunity
 (see Fig. JL-1 and Fig. JL-2)
• Self vs not-self:
• Graft rejection:
• CMI - humoral immunity:
• Bi-functional system
• Epithelium from gills of fish-Lymphoid Organ

5. • immunis
• variolation
• vaccine
• 2. Vaccination
• 1718 - Lady Mary Wortley
Montagu
• 1789 - Edward Jenner
• >100 years later - Louis
Pasteur
1. Concepts
of immunity
Exp. I. Vaccine vs fowl cholera
“Serendipity”
Attentuation of virulent cultures
Exp. II. Vaccine vs Bacillus anthracis (1881
Attenuated bacillus cultures
immunized sheep
Exp. III. Immunizing human against rabies
Joseph Meister
Ethics?

6. 3. Discovery of humoral immunity and Cellular
immunity
• cellular immunity
• phagocytosis
• concept of cell-
mediated
• immunity (CMI)
• *Nobel Prize for
Metchnifoff in 1908
1883 -
Metchnikoff
1890 -
• von Behring* &
Kitasato
• in serum - humors
• humors = antibodies
• humoral immunity
• *Nobel Prize for
von Behring in
1901

7. • 1900 - Paul Ehrlich
• Side chain receptors
• Ag binding
• Cells induced
• more side chains
produced
Selective
Theory
• 1930-1940 - Breinl &
Haurowitz
• popularized by Linus Pauling
• Ag as template
• Ab would fold, assumes
• configurations
complementary
• to that Ag
• more Ab made
Instructional
theory
1950 - Clonal Selectional theory (Fig. 1-11)
Burnet, Nils Jerne, Talmadge & Macfarlane
4. Early theories of Immunity How is specificity achieved?
AntigenAntibody

8. The immunology may be define as the
branch of Animal Science which deals with
the defense mechanism adopted by the
host body against any invading pathogens
Resistance against infectious disease agents was the
principal concern of bacteriologists and pathologists,
establishing the basis of classical immunology in the
latter half of the 19th and early 20th centuries.

9. What immune System does?
Specifically
recognizes
selectively
eliminates
displays a
long-term
memory
Immu
ne
System
Effectively
Attack

10. Pathogens are always every where
Environ
ment
Pathog
ens
Host
Metab
olism

11. It is Environment which decides weather
disease will occur or not…………………
Host
Pathogen
s
Environm
ent
Interaction
Disease
s
metabolism

13. Vertebrates are protected by a dual immune system
known as cell-mediated immunity and humoral immunity
Immune System
Cellular
Specific
Nonspecific
Humoral
Specific
Nonspecific

14. Nonspecific
Cellular
Response
Specific
Cellular
Nonspecifi
c Humoral
Specific
Humoral
Who
do it?
Cells:
Macrophages,
Monocytes,
Polymarphonuc
leocyts
T-
Lymphocytes
Acute phage
proteins, like
CRP,
Ceruloplasmin
, Transferrine
Lysozymes etc
Antibodies
(Immunoglob
uline) i.e. IgA,
IgD, IgE, IgG,
IgM
What
they
do?
Phagocytosis, Apoptosis,
Kiiling by
Cytotoxic
Lymphocytes
The whole
components
cause
hindrence in
establishment
of pathogenic
gr
Form Ag-Ab
complex to
neutralized the
harmful
components
Components of immune system

15. Location of
Lymphoid
Organs in
human Body

16. Lymphoid organs
peripheral or secondary
central or primary
Lymphocytes, monocytes and
granulocytes derive from precursor
stem cells in the bone marrow.
bone
marrow and
thymus.

17. Lymphocytes,
Natural killer cells
Mononuclear
phagocytes,
Dendratic Cells,
Eosinophils,
Basophils, and Neutrophils.

18. Granulocytes
Cells with various types of granules
Agranulocytes
Cells without granules
Eosinophils
Stain with acidic dyes
Lymphocytes
Basophils
Satin with basic dyes
Monocytes
Neutrophils
Stain with neutral dyes

19. Immune System
Nonspecific
immunity
includes mechanisms
that resist a variety of
threatening agents or
conditions.
Specific immunity
involves mechanisms
that recognize specific
threatening agents and
respond by targeting
their activity against
these agents--and these
agents only.

20. Nonspecific Immunity :
It do not act
on one or
two specific
invaders, but
rather
provide a
more general
defense by
simply acting
against any
thing
recognized as
not self
Specific resistance
Refers to a phenomenon in which
genetic characteristics common
to a particular kind of organism,
or species, provide defense
against certain pathogens.
For example, humans do not
have to worry about getting
Dutch Elm Disease or canine
viral distemper.
Usually, species
resistance in
humans results
from the fact that
our internal
environment is not
suitable for certain
pathogens.

21. Mechanical and Chemical Barriers
OH- T-136 Nonspecific Defenses
• Often called the first line
of defense
Internal environment of the
human body is protected by a
continuous mechanical barrier
formed by the cutaneous
membrane (skin) and mucous
membranes.
• Sebum--contains pathogen-
inhibiting agents.
• Mucus--pathogens may
stick and be swept away.
• Enzymes--may hydrolyze
pathogens.
• Hydrochloric acid--may
destroy pathogens.
Besides forming a protective
wall, the skin and mucous
membranes operate various
additional immune
mechanisms.

22. An inflammation is a more or less coordinated series
of responses by the body to injuries and infections.
The characteristics of the inflammatory response
are
swelling, redness, heat, and pain

23. When tissue is injured or
invaded by microbes, a
series of more or less
predictable events ensues.
A series of reactions in the
tissue itself which induces
the activation of a number
of proteolytic enzymes
including plamin, fibrin,
kallikrein, and
complement.
localized increases in
vascular permeability,
• smooth muscle contraction
• and production of chemotactic
molecules like some fragments of
the complement proteins (C3a,
C5a)

24. Pathogensdamages of tissue triggers the release of mediators from cells
such as mast cells found in connective tissue.
These
inflammation
mediators include:
Histamine, Kinins,
Prostaglandins,
Many of these mediators are substances that
attract white blood cells to the area by a process
called chemotaxis.

26. …various cell types out of the blood stream, by
binding to specific receptors on their cell surface
and inducing a migratory behavior out of the
blood stream into the tissues.
• The first cells to extravasate are neutrophils
• followed subsequently by monocytes (macrophages that haven't
yet made a commitment)
• and lymphocytes.

28. Phagocytosis is the ingestion and destruction of microorganisms or other small particles by
phagocytes.
 The most numerous types of phagocytes are the neutrophils and the macrophages.
 Macrophages are phagocytocytic monocytes that have grown to several times their normal
size after migrating out of the blood stream.
 Natural Killer Cells Derivation and Distribution of Lymphocytes
▪ Are a group of lymphocytes that kill many types of tumor cells and cells infected by
different kinds of viruses.
▪ Generally kill cells by releasing enzymes that lyses the pathogen's cell membrane or protein
coat.
 Interferon
▪ Several types of cells, if invaded by viruses, respond rapidly by synthesizing the protein
interferon and releasing some of it into circulation.
▪ Interferon proteins interfere with the ability of viruses to cause disease by preventing the
viruses from multiplying in the cell.
▪ Three (3) major types of interferon:
▪ Leukocytes interferon
▪ Fibroblast interferon
▪ Immune interferon
 Complement
▪ Is the name given to each of a group of about twenty (20) inactive enzymes in the plasma.
▪ Are activated in a cascade of chemical reactions triggered by either specific or nonspecific
mechanisms.
▪ The complement cascade causes lysis of the foreign cell that triggered it.

30. IV. ACQUIRED IMMUNITY
4
characteristics:
Antigenic
specificity Diversity Memory
Self / non-self
recognition
Adaptive Heightened response

31. 1. Cells of the immune system
- developed from
hematopoietic
stem cells
Pluripotent
a) B lymphocytes -
mature in bone marrow
unique Ag-
binding surface
receptors - Abs
encounter Ag
Memory cells
Plasma cells Secret Ab

32. b) T lymphocytes - mature in
thymus
have unique
CD surface
Ags
once mature,
express TCRs
-
heterodimers
of a & b
polypeptides
bind
processed Ag-
MHC complex
Memory cells
Effector T
cells
c) Antigen presenting
cells (APC’s)
Macrophages Dendritic cells B-Cells
Secrete
cytokines
or exert killing
function

33. 2-Functions of humoral and cell-mediated
immune response
antigen recognition
antigen processing and presentation (Fig. JL-
3)
role of MHC
B cell specificity
T cell specificity
Generation of diversity

34. 3. Clonal selection & expansion (Fig. 1-
11)
stimulation due to
interaction with antigens
proliferation of
particular clones
provides diversity &
specificity

35. 4. Primary (1°) &
secondary (2°)
immune response
(Fig. 1-12)
1° response - long lag
phase,
modest level
2° response - shorter
lag phase,
higher (heightened)
level

36. B cells - produce Abs
Tc cells (CTLs)
- lyse virus infected cells
TH cellsAPCs

37. Antigen processing and presentation by MHC molecules

39. Overview of Specific Immunity
Specific immunity involves mechanisms that recognize
specific threatening agents and respond by targeting their
activity against these agents; and these agents only.
These
mechanisms
often take
some time to
recognize
their targets
and react
with
sufficient
force to
overcome
the threat.
As in any body system, the work of the immune
system is done by cells or substances made by
cells.
Primary types of cells involved in nonspecific
immunity.
Neutrophils Monocytes Macrophages
Natural-Killer
(NK) cells

40. The primary types of cells involved in
specific immunity are: T-cells B-cells
• Specific immunity is
orchestrated by two
different classes of
lymphocytes.
The various types of
specific immune
mechanisms attack specific
agents that the body
recognizes as "not self".
• Lymphocytes are
formed in red bone
marrow and are derived
from primitive cells
called stem cells. OH
T-135 Derivation
and Distribution of
Lymphocytes

41. Production of Lymphocytes
Stem cells destined to become
lymphocytes follow two
developmental paths and
differentiate into two major classes of
lymphocytes.
•B-lymphocytes or B-cells
•T-lymphocytes or T-cells
B-cells do not attack pathogens
themselves but, instead produce
antibodies that attack the pathogens
or direct other cells, such as
phagocytes, to attack them.
•B-cell mechanisms are often classified as
antibody-mediated-immunity.

43. B-CELLS AND ANTIBODY-MEDIATED IMMUNITY
First Stages in the Development and Activation of B-Cells: B-cells
start their development in the embryonic yolk sac, then the red marrow or
fetal liver.
By the time a human infant is a few months
old, its pre-B-cells have completed the first
stage of development.
Are then known as
inactive B-cells.
Inactive B-cells synthesize antibody
molecules but secrete few if any of them.
Instead, they insert on
the surface of their
plasma membranes
perhaps 100,000
antibody molecules.
The combining sites of these surface antibody molecules are
now ready to serve as receptors for a specific antigen if it
comes by.
After being released from the
bone marrow, inactive B-cells
circulate to the lymph nodes,
spleen, and other lymphoid
structures.

44. Second Stage of B-Cell Development :Occurs
when the inactive B-cells become activated.
Activation of a B-cell must be
initiated by an encounter
between an inactive B-cell and
its specific antigen.
The antigen binds
to these antibodies
on the B-cell's
surface.
Antigen-antibody binding
activates the B-cell triggering a
rapid series of mitotic divisions.
By dividing rapidly,
a single B-cell
produces a clone.
Some of them
become
differentiated to
form plasma cells.
Others do not differentiate
completely and remain in
lymphatic tissue as memory
B-cells.

45. Plasma cells synthesize and
secrete large amounts of
antibody.
Memory B-cells do not themselves secrete
antibodies, but if they are later exposed to the
antigen that triggered their formation,
memory B-cells become plasma cells and the
plasma cells secrete antibodies that can
combine with the initiating antigen.
The ultimate function of B-cells is to serve as ancestors
of antibody-secreting plasma cells.

46. Antibodies are proteins of the family
called immunoglobulins.
Each immunoglobulin molecule consists of four (4) polypeptide
chains joined together by disulfide bonds (S-S)
Two (2)
heavy
chains.
Two (2)
light
chains.
Each
polypeptid
e chain is
folded to
form
globular
regions
that are
joined
together in
such a way
that the
whole
molecule is
Y-shaped.
Each chain
has a V
(variable)
region,
which has
a markedly
different
amino acid
sequence
in different
antibodies,
and a C
(constant)
region,
which is
essentially
identical in
different
antibodies
of the same
class.
The variable
regions are the
antigen-binding
sites of the
antibody; hence
each antibody
monomer has two
binding sites.
OH (b)
Enlargeme
nt of an
antigenic
determina
nt bound
to an
antigen-
binding
site.
OH (c)
Computer
generated
image of
antibody
structure.
Each tiny
colored dot
(sphere)
represents an
individual
amino acid of
the polypeptide
chain.
Each of us
is thought
normally to
have
millions of
different
kinds of
antibody
molecules
in our
bodies.
Each of these has its own
uniquely shaped combining
sites.
It is this structural
feature that enables
antibodies to
recognize and
combine with
specific antigens,
both of which are
crucial first steps in
the body's defense
against microbes
and other foreign
cells.

47.  There are five (5) classes of antibodies
identified by letter names as immunoglobulins
M, G, A, E, and D.
 Ig M (Immunoglobulin M)
 Is the antibody that immature B cells synthesize
and insert into their plasma membranes.
 Is the predominate class of antibody produced
after initial contact with an antigen in the blood.
 Ig G (Immunoglobulin G)
 Most abundant circulating antibody.
 Normally makes up about 75% of the antibodies in
the blood.
 Ig A (Immunoglobulin A)
 Major class of antibody present in the mucous
membranes of the body, in saliva, and in tears.
 Ig E (Immunoglobulin E)
 Minor in amount.
 Can produce harmful effects such as those
associated with allergies.
 Ig D (Immunoglobulin D)
 Present in the blood in very small amounts and its
precise function is unknown.

48.  The function of antibody molecules is to produce antibody-mediated immunity.
 This type of immunity is also called humoral immunity because it occurs within the plasma. OH T-140 Humoral
Immunity
 Antigen-Antibody Reactions
 Antibodies fight disease by distinguishing non-self antigens from self antigens.
 Recognition occurs when an antigen's epitopes fit into and bind to an antibody molecule's antigen-binding sites.
 The binding forms an antibody-antigen complex that may produce one or more effects.
▪ It transforms antigens that are toxins into harmless substances.
▪ It agglutinates antigens that are molecules on the surface of microorganisms which makes them stick together so phagocytes can
engulf them.
 Complement OH-T-137 Complement Activation
 Is a component of blood plasma that consists of about twenty (20) protein compounds.
 Are inactive enzymes that become activated by the binding of an antibody to an antigen located on the surface of
a cell.
 By binding to these sites, complement protein becomes activated and touches off a cascade reaction that causes
cytolysis of the cell.
 Clonal Selection Theory
 Proposed in 1959 by Sir Macfarlane Burnet
 Has two (2) basic tenets.
▪ The body contains an enormous number of diverse clones of cells, each committed by certain of its genes to synthesize a different
antibody.
▪ When an antigen enters the body, it selects the clone whose cells are committed to synthesizing its specific antibody and stimulated
these cells to proliferate and to produce more antibody.
 We now know that the clones selected by the antigens consist of lymphocytes.
 We also know how antigens select lymphocytes--by the shape of the antigen receptors on the lymphocyte's
plasma membrane.
 By selecting the precise clone committed to making its specific antibody, each antigen provides its
own destruction.

49.  Development of T-Cells: Stimulation and Effects of T Cells
 By definition, T-cells are lymphocytes that have made a detour through the thymus gland before
migrating to the lymph nodes and spleen.
 During their residence in the thymus, pre-T-cells develop into thymocytes.
 Thymocytes divide up to three (3) times/day and their numbers increase enormously in a relatively short period
of time.
 They leave the thymus and move into the blood and take up residence in areas of the lymph nodes and spleen
called t-dependent zones.
▪ From this time on they are known as T-cells.
 Activation and Function of T-Cells
 Each T-cell, like each B-cell, displays antigen receptors in its surface membrane.
 When an antigen (preprocessed and presented by macrophages) encounters a T-cell whose surface
receptors fit the antigen's epitopes, the antigen binds to the T-cell's receptors.
 This activated or sensitizes the T-cell, causing it to divide repeatedly to form a clone of sensitized T-cells.
 The sensitized T-cells then travel to the site where the antigen originally entered the body.
 There in inflamed tissue, the sensitized T-cells bind to antigens of the same kind that led to their formation.
▪ T-cells will bind to their specific antigen only if the antigen is presented by a macrophage.
 The antigen-bound sensitized T-cells then release chemical messengers into the inflamed tissues
called cytokines.
 Names of some cytokines and their function.
▪ Chemotactic factors--attracts macrophages causing hundreds of then to migrate into the vicinity of the antigen bound, sensitized
T-cells.
▪ Macrophage activating factor--causes the macrophages to destroy antigens by phagocytosing them at a rapid rate.
▪ Lymphotoxin--powerful poison that acts more directly, quickly killing any cell it attacks.
 Sensitized T-cells that release lymphotoxin are called killer T-cells or cytotoxic T-cells.
 Types of Specific Immunity
 Inherited immunity--immunity to certain diseases develops before birth--also called inborn
immunity.
 Example--inborn resistance to diseases that affect animals--viral canine distemper.

50.  Acquired immunity
 Natural immunity--Exposure to the causative agent
is not deliberate.
▪ Active (exposure)--A child develops measles and acquires
an immunity to subsequent infection.
▪ Passive (exposure)--A fetus receives protection from the
mother through the placenta, or an infant receives protection
by way of the mother's milk.
 Artificial immunity--exposure is deliberate.
▪ Active--injection of the causative agent, such as vaccination
against polio, confers immunity.
▪ Passive--injection of protective material (antibodies) that was
developed by another individual's immune system.

51. Non specific Specific
Humoral Cellular Humoral Cellular
Bacterium Acute phage
proteins cause
hindrance/ or
even kill the
pathogens
By the
phagocytes the
host cell engulf
& Destroy the
pathogens
Antibodies so
produced by the
B- cells, form a
Ag-Ab complex
& deteriorate the
efficiency of
pathogens
Finally T-Cells
proliferate into
Th & CTL, and
cause the
elimination of
pathogens
Virus
Fungus

52. You receive a cut
 Bacteria enter the wound.
 Many are destroyed rapidly by complement and the phagocytes recruited
through acute inflammation (innate immunity).
 Some of the dead bacteria or their breakdown products are taken up by the tissue
resident dendritic cells.
 The combined action of bacterial products and cytokines (from acute
inflammation etc.) activate the tissue dendritic cells.
 This causes them to migrate to the local lymph node via afferent lymphatic.
 Dendritic cells enter the node in the T cell areas. They become resident there
displaying their 'wares'
 T cells enter the node from the blood, trafficking through the T cell area to the
efferent lymph. Those which recognize the bacterial antigenic peptides displayed
on the dendritic cells stop, activate, divide and differentiate; some later become
memory T cells.
 B cells entering nodes from the blood must cross the T rich area in transit to the B
cell rich areas. The antigen-specific ones must acquire antigen too, presumably via
the lymph. Then they can have their MHC-peptide complexes recognized by
activated T cells and receive help.
 Some become IgM secreting plasma cells. Some migrate to the B cell rich areas
and form germinal centers. Here B cells proliferate and give rise to progeny with
high affinity for antigen through a process called affinity maturation. The products
of germinal centers become IgG,A etc plasma cells and memory B cells.