2. Phylogeny of vertebrate and invertebrate
(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
• 2. Vaccination
• 1718 - Lady Mary Wortley
• 1789 - Edward Jenner
• >100 years later - Louis
Exp. I. Vaccine vs fowl cholera
Attentuation of virulent cultures
Exp. II. Vaccine vs Bacillus anthracis (1881
Attenuated bacillus cultures
Exp. III. Immunizing human against rabies
6. 3. Discovery of humoral immunity and Cellular
• cellular immunity
• concept of cell-
• immunity (CMI)
• *Nobel Prize for
Metchnifoff in 1908
• von Behring* &
• in serum - humors
• humors = antibodies
• humoral immunity
• *Nobel Prize for
von Behring in
7. • 1900 - Paul Ehrlich
• Side chain receptors
• Ag binding
• Cells induced
• more side chains
• 1930-1940 - Breinl &
• popularized by Linus Pauling
• Ag as template
• Ab would fold, assumes
• to that Ag
• more Ab made
1950 - Clonal Selectional theory (Fig. 1-11)
Burnet, Nils Jerne, Talmadge & Macfarlane
4. Early theories of Immunity How is specificity achieved?
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?
Cells with various types of granules
Cells without granules
Stain with acidic dyes
Satin with basic dyes
Stain with neutral dyes
20. Nonspecific Immunity :
It do not act
on one or
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
from the fact that
environment is not
suitable for certain
21. Mechanical and Chemical Barriers
OH- T-136 Nonspecific Defenses
• Often called the first line
Internal environment of the
human body is protected by a
continuous mechanical barrier
formed by the cutaneous
membrane (skin) and mucous
• Sebum--contains pathogen-
• Mucus--pathogens may
stick and be swept away.
• Enzymes--may hydrolyze
• Hydrochloric acid--may
Besides forming a protective
wall, the skin and mucous
membranes operate various
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
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,
localized increases in
• smooth muscle contraction
• and production of chemotactic
molecules like some fragments of
the complement proteins (C3a,
24. Pathogensdamages of tissue triggers the release of mediators from cells
such as mast cells found in connective tissue.
Many of these mediators are substances that
attract white blood cells to the area by a process
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
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
▪ 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
▪ 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
▪ The complement cascade causes lysis of the foreign cell that triggered it.
31. 1. Cells of the immune system
- developed from
a) B lymphocytes -
mature in bone marrow
receptors - Abs
Plasma cells Secret Ab
32. b) T lymphocytes - mature in
of a & b
c) Antigen presenting
Macrophages Dendritic cells B-Cells
or exert killing
33. 2-Functions of humoral and cell-mediated
antigen processing and presentation (Fig. JL-
role of MHC
B cell specificity
T cell specificity
Generation of diversity
34. 3. Clonal selection & expansion (Fig. 1-
stimulation due to
interaction with antigens
provides diversity &
35. 4. Primary (1°) &
1° response - long lag
2° response - shorter
36. B cells - produce Abs
Tc cells (CTLs)
- lyse virus infected cells
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.
some time to
As in any body system, the work of the immune
system is done by cells or substances made by
Primary types of cells involved in nonspecific
Neutrophils Monocytes Macrophages
40. The primary types of cells involved in
specific immunity are: T-cells B-cells
• Specific immunity is
orchestrated by two
different classes of
The various types of
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
and Distribution of
41. Production of Lymphocytes
Stem cells destined to become
lymphocytes follow two
developmental paths and
differentiate into two major classes of
•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
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
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 synthesize antibody
molecules but secrete few if any of them.
Instead, they insert on
the surface of their
The combining sites of these surface antibody molecules are
now ready to serve as receptors for a specific antigen if it
After being released from the
bone marrow, inactive B-cells
circulate to the lymph nodes,
spleen, and other lymphoid
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
activates the B-cell triggering a
rapid series of mitotic divisions.
By dividing rapidly,
a single B-cell
produces a clone.
Some of them
form plasma cells.
Others do not differentiate
completely and remain in
lymphatic tissue as memory
45. Plasma cells synthesize and
secrete large amounts of
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
Each immunoglobulin molecule consists of four (4) polypeptide
chains joined together by disulfide bonds (S-S)
e chain is
such a way
has a V
and a C
of the same
regions are the
sites of the
monomer has two
nt of an
amino acid of
Each of us
Each of these has its own
uniquely shaped combining
It is this structural
feature that enables
both of which are
crucial first steps in
the body's defense
and other foreign
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
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
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
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
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
▪ 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
By selecting the precise clone committed to making its specific antibody, each antigen provides its
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
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
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
▪ 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
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
even kill the
host cell engulf
& Destroy the
produced by the
B- cells, form a
& deteriorate the
Th & CTL, and
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.