‫بسم اللة الرحمن الرحيم‬

‟IMMUNOLOGY”
‟Introduction”
 How Important is the Immune System?
 The skeletal system includes the bones of the body and
serves as a support system for the rest of the body
systems.
 The muscular system allows the body to move, and the
digestive system allows us to take in food and convert it
to forms needed to build and maintain the body.
 The immune system is extremely important to us. It is
the most important system in the body for voiding and
fighting infections. It also prevents the development of
certain types of cancer.
 Immune system under functions AIDS
 Immune system over functions Allergic reactions
and autoimmunity
 Introduction
The immune system is:
a system of biological structures and processes within an organism
that protects against disease by identifying and killing pathogens
and tumor cells.
It detects a wide variety of agents, from viruses to parasitic worms,
and needs to distinguish them from the organism's own healthy
cells and tissues in order to function properly.

Defense body mechanism

an interacting set of specialized cells and
proteins designed to identify and destroy
 HISTORY OF IMMUNOLOGY
• 1798 Edward Jenner, Smallpox vaccination
• 1862 Ernst Haeckel, Recognition of phagocytosis
• hypothesis
1877 Paul Erlich, recognition of mast cells
• 1879 Louis Pasteur, Attenuated chicken cholera vaccine
development
• 1883 Elie Metchnikoff Cellular theory of vaccination
• 1885 Louis Pasteur, Rabies vaccination development
•
•
1888 Pierre Roux & Alexandre Yersin, Bacterial toxins
1888 George Nuttall, Bactericidal action of blood
• 1891 Robert Koch, Delayed type hypersensitivity
• 1894 Richard Pfeiffer, Bacteriolysis
• 1895 Jules Bordet, Complement and antibody activity in
bacteriolysis
• 1900 Paul Erlich, Antibody formation theory
• 1901 Karl Landsteiner, A, B and O blood groupings
• 1901-8 Carl Jensen & Leo Loeb, Transplantable tumors
• 1902 Paul Portier & Charles Richet, Anaphylaxis • •1975
1950 Richard Gershon and K Kondo, Discovery of
suppressor T cells
• •
reactions Monoclonal antibodies
1903 Almroth Wright & Stewart Douglas, Opsonization
1952 Ogden and Bruton, discovery of
agammagobulinemia (antibody
• 1906 Clemens von Pirquet, coined the word allergy
• histamine in mast cells
1907 Svante Arrhenius, coined the term immunochemistry
• 1910 Emil von Dungern, & Ludwik Hirszfeld, Inheritance of
ABO blood groups
• 1910 Peyton Rous, Viral immunology theory
• 1914 Clarence Little, Genetics theory of tumor
transplantation
• 1915-20 Leonell Strong & Clarence Little, Inbred mouse
strains
• 1917 Karl Landsteiner, Haptens
• 1921 Carl Prausnitz & Heinz Kustner, Cutaneous reactions
• 1924 L Aschoff, Reticuloendothelial system
• 1926 Lloyd Felton & GH Bailey, Isolation of pure
antibody preparation
• 1934-8 John Marrack, Antigen-antibody binding
• 1936 Peter Gorer, Identification of the H-2 antigen in
mice
• 1940 Karl Lansteiner & Alexander Weiner, Identification
• 1941
• 1798 Edward Jenner,
of the Rh antigens
Albert Coons, Immunofluorescence technique
•
•
Smallpox vaccination
1942 Jules Freund & Katherine McDermott, Adjuvants
1942 Karl Landsteiner & Merill Chase, Cellular transfer
of sensitivity in guinea pigs (anaphylaxis)
• 1944 Peter Medwar, Immunological hypothesis of
allograft rejection
• 1948 Astrid Fagraeus, Demonstration of antibody
production in plasma B cells
• 1948 George Snell, Congenic mouse lines
• 1949 Macfarlane Burnet & Frank Fenner,
Immunological tolerance hypothesis
Kohler
and Milstein,
used
in genetic• analysis
immunodeficiency)
1984 Robert Good, Failed treatment of severe combined
immunodeficiency (SCID, David the bubble boy) by bone
• 1953 Morton Simonsen and WJ Dempster, Graft-
versus-host reaction
• 1953 James Riley & Geoffrey West, Discovery of
• 1953 Rupert Billingham, Leslie Brent, Peter Medwar, &
Milan Hasek, Immunological tolerance hypothesis
• 1955-1959 Niels Jerne, David Talmage, Macfarlane
Burnet, Clonal selection theory
• 1957 Ernest Witebsky et al., Induction of autoimmunity
in animals
• 1957 Alick Isaacs & Jean Lindemann, Discovery of
interferon (cytokine)
• 1958-62 Jean Dausset et al., Human leukocyte antigens
• 1959-62 Rodney Porter et al., Discovery of antibody
structure
•
1959 James Gowans, Lymphocyte circulation
• 1961-62 Jaques Miller et al., Discovery of thymus
involvement in cellular immunity
• 1961-62 Noel Warner et al., Distinction of cellular and
humoral immune responses
• 1963 Jaques Oudin et al., antibody idiotypes
• 1964-8 Anthony Davis et al., T and B cell cooperation in
immune response
• 1965 Thomas Tomasi et al., Secretory immunoglobulin
antibodies
• 1967 Kimishige Ishizaka et al., Identification of IgE as
the reaginic antibody
• 1971 Donald Bailey, Recombinent inbred mouse strains
• 1974 Rolf Zinkernagel & Peter Doherty, MHC restriction
• 1975 Kohler and Milstein,
Monoclonal antibodies used in
genetic analysis
marrow grafting. 1985 Tonegawa, Hood et al.,
Identification of immunoglobulin genes
• 1985-7 Leroy Hood et al., Identification of genes for the
T cell receptor
• 1990 Yamamoto et al., Molecular differences between
the genes for blood groups O and A and between those
for A and B
• 1990 NIH team, Gene therapy for SCID using cultured T
cells.
• 1993 NIH team, Treatment of SCID using genetically
altered umbilical cord cells.
• 1985-onwards Rapid identification of genes for immune
cells, antibodies, cytokines and other immunological
structures.
 Introduction
The immune system must be able to:
differentiate between material that is
a normal component of the body
(“self”) and material that is not
native to the body “nonself”

A highly specialized receptors present

for discriminating between ”self” and
“nonself” body components
 Immunity
Innate immunity Adaptive immunity

Humeral Cell-mediated

Components Components
Macrophages antigen presenting cells
Granulocytes T-cells
Natural killer cells B-cells
Complement Antibodies
Other chemicals: HCL, lysozyme Complement

Characteristics
* Action is immediate
* Response is non-specific
* Response is not enhanced on
repeated exposure to pathogen
Characteristics
* Action requires days to develop
* Response is specific
* Response is enhanced on
repeated exposure to pathogen
 Innate Immunity
 The Immune System Includes (Defensive mechanisms):
 1) Innate immunity (Natural or Non specific)
 innate immunity, provides the first line of defense against
infection.
 Most components of innate immunity are present before
the beginning of infection and constitute a set of disease-
resistance mechanisms that are not specific to a particular
pathogen
 2) Acquired immunity (Adaptive or Specific)

Cell-mediated immunity Humoral immunity

adaptive immunity, does not come into play until
there is an antigenic challenge to the organism.
Adaptive immunity responds to the challenge with a
high degree of specificity as well as the remarkable
property of “memory.”
 Typically, there is an adaptive immune response
against an antigen within five or six days after the
initial exposure to that antigen.
Exposure to the same antigen some time in the future
results in a memory response occurs more quickly
than the first, is stronger, and is often more effective in
neutralizing and clearing the pathogen.
 The major agents of adaptive immunity are
lymphocytes and the antibodies and other molecules
they produce.
 Component of Innate Immunity
 Innate immunity can be seen to comprise four types
of defensive barriers: anatomic, physiologic,
phagocytic, and inflammatory (Table 1-1).
Innate Immune system

First line Second line

1) Mechanical barriers A- cells
2) Chemical & biochemical inhibitors 1- Natural killer
3) Normal flora 2- Phagocytes

B- Soluble factors
C- Inflammatory barriers
 First line
 Physical and anatomic barriers that tend to prevent
the entry of pathogens are an organism’s first line
of defense against infection.
 The skin and the surface of mucous membranes are
included in this category because they are effective
barriers to the entry of most microorganisms.
 1) Mechanical barriers include:-
- Intact skin, Mucous coat, Mucous, secretion,
Blinking reflex and tears, The hair at the nares,
Coughing and sneezing reflex.
 The skin consists of two distinct layers: a thinner
outer layer—the epidermis—and a thicker layer—
the dermis. The epidermis contains several layers of
tightly packed epithelial cells.
 The outer epidermal layer consists of dead cells and
is filled with a waterproofing protein called keratin.
 The dermis, which is composed of connective tissue,
contains blood vessels, hair follicles, sebaceous
glands, and sweat glands.
 The sebaceous glands are associated with the hair
follicles and produce an oily secretion called sebum.
 Sebum consists of lactic acid and fatty acids,which
maintain the pH of the skin between 3 and 5; this pH
inhibits the growth of most microorganisms.
 The conjunctiva and the alimentary, respiratory, and
urogenital tracts are lined by mucous membranes,
not by the dry, protective skin that covers the
exterior of the body.
 These membranes consist of an outer epithelial layer
and an underlying layer of connective tissue.
 Although many pathogens enter the body by binding
to and penetrating mucous membranes, a number of
nonspecific defense mechanisms tend to prevent this
entry. For example, saliva, tears, and mucous
secretions act to wash away potential invaders and
also contain antibacterial or antiviral substances.

 First line
2) Chemical & biochemical inhibitors
- Sweet and sebaceous secretion
- Hydrolytic enzymes in saliva
- HCl of the stomach
- Proteolytic enzyme in small intestine
- Lysozyme, a hydrolytic enzyme found in mucous
secretions and in tears, is able to cleave the
peptidoglycan layer of the bacterial cell wall.
- Acidic pH in the adult vagina
3) Normal bacterial flora
- Competition for essential nutrients
- Production of inhibitory substances
 Second line
A) cells
1- Natural killer (NK)
Definition: Large granular cytotoxic lymphocyte
that constitute a major component of the innate
immune system.
Source : Bon marrow precursors

Location : 10% or 15% of lymphocytes in peripheral blood

1% or 2% of lymphocytes in spleen

Tumor cells
Function : Cytotoxic for Viral infected cells
Bacterial, fungal, parasitic
infection

Responsible for antibody–dependent cell

They kill cells by releasing small cytoplasmic
granules of proteins called perforin and granzyme
that cause the target cell to die by apoptosis.

Activation
• Cytokines
Cytokines involved in NK activation include IL-12,
IL-15, IL-18, and IL-2
• Fc receptor
That binds the Fc portion of antibodies. This allows
NK cells to target cells against which a humoral
response has been mobilized and to lyse cells through
• Activating and inhibitory receptors
• NK cells have two types of surface receptors:
activating receptors and inhibitory receptors .
• These receptors bind to various ligands on target
cells, both endogenous and exogenous, and have an
important role in regulating the NK cell response.
 Second line
2- Phagocytes
Specialized cells for capture, Ingestion and destruction
of invading microorganisms and which include;-

* Polymorphonuclear leucocytes, mainly neutrophils:

granulocytes circulate in blood

* Mononuclear cells (macrophages)

- Monocytes in blood
- Histocytes in connective tissues
- Fixed reticuloendothelial cells in liver, spleen,
lymph, nods, and bon marrow
 Phagocytosis
 The engulfment, digestion, and subsequent processing
of microorganisms by macrophages and neutrophils
 1) Chemotaxis & attachment:
 During an infection, chemical signals attract
phagocytes to places where the pathogen has invaded
the body. These chemicals may come from bacteria or
from other phagocytes already present. The phagocytes
move by a method called chemotaxis.
 a- Attraction by chemotactic substances (microbes,
damaged tissues)
 b- Attachment by receptors on surfaces of
 Phagocytosis
2) Ingestion:
* Phagocyte pseudopodia surround organism
forming phagosom
* Opsonins and co-factors enhance phagocytosis
* Fusion with phagocyte granules and release
digestive, toxic contents
 Phagocytosis
3- Killing (two microbicidal routes)
a- Oxygen depended system (powerful microbicidal

agents)
Oxygen converted to superoxide, anion,
hydrogen peroxide, activated oxygen and
hydroxyl radicals.

b- Oxygen-independent system (anaerobic

conditions)
Digestion and killing by lysozyme. Lactoferrin,
low pH, cationic proteins and hydrolytic and
proteolytic enzymes
 Second line
B- Soluble factors
1- Acute phase protein (Plasma protein, CRP=C reactive
protein, Fibrin.)
C-reactive protein (CRP) is a protein found in the blood,
the levels of which rise in response to inflammation
2- Complement (proteins in serum, body fluids)
2- Interferons (Proteins against viral infections)
3- Properdin (Complement activation)
4- Beta lysine (Antibacterial protein from Platelets)
5- Lactoferrrin,Transferrin (Iron binding protein)
6- Lactoperoxidase (Saliva & Milk)
7- Lysozyme (Hydrolyze cell wall)
 Complement
 Definition : series of heat-labile serum proteins
 Site : serum and all tissue fluids except urine and CSF
 Synthesis : in liver – appear in fetal circulation
during 1st 13 W
 Function : Responsible for certain aspects of
immune response and inflammatory response
 Activation : antigen-antibody complex or endotoxin,
capsule series of proteins activated sequentially
 Inactivation: inhibitors in plasma (short lived)
 Biological effects: either beneficial or harmful to host
 Complement pathway
 A) Classical pathway:
 - Complement is activated by antigen –antibody
complex (IgM or IgG)

 - Fc portion of the antibody form a binding site for

C1q

 - The numerical sequence of the complement

factors in the classic pathway is: C1q,r,s , C4, C2,
C3, C5, C6, C7, C8, C9
 A) Classical Pathway
The reaction sequence divided into three stages:
1) Recognition stage:
- C1q act as the recognition element
- It binds to Fc portion of IgM or IgG
- The activated C1 molecule can cleave many C4 molec.

2) Activation stage:
The complement components C4, C2, C3, C5, C6, C7,
C8, C9 participate in that order

3) Membrane attack stage:

Complement components C5, C6, C7, C8, C9 participate
where cell membrane damage and cell lysis occur
 B) Alternative pathway
This pathway is initiated by:
* Bacterial endotoxin, polysaccharide capsule,
aggregates of IgE and properdin

* It starts at C3 then C5, C6, C7, C8, C9

* The complement compon. C1, C4, C2 are by-passed

* Antibodies are not required to initiate activation of

this pathway

* This pathway provides a means of non-specific

resistance
 Classic And Alterenative pathways

Classic Pathway Alternative pathway

* Specific acquired immunity * Non-specific innate immunity

* Initiated by antibody * Bacterial endotoxin, capsule

* Interaction of all components * C1, C4, C2 are by-passed

* Properdin system not involved * Properdin system is involved

 Biological Effects of Complement
Beneficial effects:
1) Cytolysis:C56789
- activated complement proteins polymerize on cell
surfaces of bacteria or erythrocyte to form pores
in its membrane (killing by osmotic lysis).
 Biological Effects of Complement
2) Opsonization:
- binding of complement proteins opsonin (C3b)
to surfaces of foreign organisms or particles
- Phagocytic cells express specific receptors for
opsonins, so promote phagocytosis.
3) Immune complex clearance:
- C3b facilitate binding of immune complex to
several surfaces (erythrocytes) and enhance removal
by liver and spleen
- C3 deficiency associated with Immunocomplex
disease and susceptibility to recurrent infections
 Biological Effects of Complement
4) Inflammatory response :
Small fragments released during complement
activation have several inflammatory actions:
a) C5a is chemotactic and attract neutrophiles and
macrophages

b) C5a activate phagocytes and neutrophils

C) C3,C4 and C5 are anaphylatoxins

Cause degranulation of mast cells and release of
histamine and other inflammatory mediators
 Biological Effects of Complement

5-Enhancement of antibody production:

- Binding of C3b to its receptors on activated B cells

greatly enhances antibody production

- Patient who are deficient in C3b produce

much less antibody than normal individuals and
more susceptible to pyogenic infection
 Interferons
 Proteins usually produced by virally infected cells
 Interferons (IFNs) are proteins or glycoprotein made and
released by lymphocytes in response to the presence of
pathogens—such as viruses, bacteria, or parasites—or
tumor cells.
 They allow communication between cells to trigger the
protective defenses of the immune system that destroy
pathogens or tumors.
* Types of interferons:

1- Alpha interferon Secreted by Macrophages and NKs

Induced by Viruses or Polynucleotide
2- Beta interferon Secreted by Fibroblasts, Viruses
3- Gamma interferon T- lymphocytes, Specific antigens
 Interferons
Protective action of interferons:

1) Activate T-cells

2) Activate macrophages

3) Activate NK
4) induce IgG produce from B-cells
 C) Inflammatory Barriers
* Tissue damage by a wound or by invading pathogen

* Inflammatory response:
Tissue damage
Release of chemical mediators from Leukocytes
(Histamine, fibrin, kinins, cytokines) Invading microbe

Vasodilatation of capillaries
Redness of tissue
Tissue temperature
Capillary permeability
Influx of fluids
Influx of phagocytes
into tissues
Thanks