IMMUNOLOGY

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 IMMUNOLOGY
Bashir Ahmed Shaheen
Assistant Professor (Biochemistry)

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 Immunology
• Immunology is the study of protection of
living organisms from foreign
macromolecules or invading organisms
and our responses to them.
• Foreign macromolecule, antigen– e.g.
virus protein, worm, parasite
(Everything that should not be in our
body)

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 What is Immune System

• Protect against pathogens

• Eliminate damaged or malignant cells

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March towards modern times…

War on smallpox…
❖ 1718- Lady Montague became aware
of a practice, called variolation or
inoculation, and introduced it to
Britain after first having her own
children treated.
❖ 1774 – Benjamin Justy
❖ 1776- Geo. Washington
❖ 1798 –Edward Jenner noticed
immunity bestowed to milkmaids –
injected fluid from cowpox blister
into skin of patient (orphan or
prisoner)
❖ 1989- WHO announced smallpox was
Lady Mary Wortley Montague eradicated from the world
(1689-1762)
 A Short History of Immunology

• 430 B.C: Peloponesian War, Thucydides describes

plague – the ones who had recovered from the
disease could nurse the sick without getting the
disease a second time In
• 15th century: Chinese and Turks use dried crusts of
smallpox as ”vaccine”
• In 1718, Lady Mary Wortley Montagu, the wife of the
British ambassador to Constantinople, observed
• The positive effects of variolation on the native
population and had the technique performed on her
own children
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 Jenner Smallpox vaccine

• 1798 Edward Jenner Noticed the fact that milkmaids

who had contracted the mild disease cowpox were
subsequently immune to smallpox,
• To test this idea, he inoculated an eight-year-old boy with fluid
from a cowpox pustule and later intentionally infected the
child with smallpox. As predicted, the child did not develop
smallpox.
• Vaccine was invented (latin vacca means ”cow”)

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 Louis Pasteur

• Louis Pasteur had succeeded in growing the bacterium

thought to cause fowl cholera in culture and then had
shown that chickens injected with the cultured
bacterium developed cholera.
• After returning from a summer vacation, he injected
some chickens with an old culture. The chickens became
ill, but, to Pasteur’s surprise, they recovered.
• Pasteur then grew a fresh culture of the bacterium with the
intention of injecting it into some fresh chickens.
• But, as the story goes, his supply of chickens was limited, and
therefore he used the previously injected chickens. Again to
his surprise, the chickens were completely protected from the
disease.
 Louis Pasteur Contd…

• Pasteur hypothesized and proved that aging had weakened the virulence
of the pathogen and that such an attenuated strain might be
administered to protect against the disease
• He called this attenuated strain a vaccine (from the Latin vacca,
meaning “cow”), in honor of Jenner’s work with cowpox
inoculation.
• Pasteur extended these findings to other diseases,
demonstrating that it was possible to attenuate, or weaken, a
pathogen and administer the attenuated strain as a vaccine
• At Pouilly-le-Fort in 1881, Pasteur first vaccinated one group of
sheep with heat-attenuated anthrax bacillus (Bacillus anthracis);
• He then challenged the vaccinated sheep and some unvaccinated
sheep with a virulent (Infectious) culture of the bacillus.
• All the vaccinated sheep lived, and all the unvaccinated animals
died.
• These experiments marked the beginnings of the discipline of
immunology
 First insights into mechanics of immunity…
Emil von Behring • 1880’s-Metchnikoff
discovered phagocytic cells
that ingest microbes and
particles cells conferred
immunity

• 1890- von Behring and

Kitasato discovered blood
sera could transfer
immunity liquid of blood
conferred immunity

Elie Metchnikoff S. Kitasato 17

 Emil von Behring and Shibasaburo Kitasato
• Although Pasteur proved that vaccination worked,
he did not understand how
• In 1890 Emil von Behring and Shibasaburo Kitasato
gave the first insights into the mechanism of
immunity, earning von Behring the Nobel prize in
medicine in 1901.
• They demonstrated that serum(the liquid, noncellular
component of coagulated blood) from animals
previously immunized to diphtheria could transfer
the immune state to unimmunized animals.
• Various researchers during the next decade
demonstrated that an active component from
immune serum could neutralize toxins, precipitate
toxins, and agglutinate (clump) bacteria.
• In each case, the active agent was named for the
activity it exhibited: antitoxin, precipitin, and
agglutinin, respectively
 Elvin Kabat and Antibodies

• Initially, a different serum component was thought to

be responsible for each activity,
• But during the 1930s, mainly 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.
• Because immunity was mediated by antibodies
contained in body fluids (known at the time as
humors), it was called humoral immunity.
 Elie Metchnikoff and blood Cells
• In 1883, even before the discovery that a serum
component could transfer immunity,
• Elie Metchnikoff demonstrated that cells also contribute
to the immune state of an animal (phagocytes) can
ingest microorganisms and other foreign material
• Metchnikoff hypothesized that cells, rather than serum
components, were the major effector of immunity
(blood monocytes and neutrophils)
• In the 1940s,Merrill Chase succeeded in transferring
immunity against the tuberculosis organism by
transferring white blood cells between guinea pigs.
• With the emergence of improved cell culture techniques
• In the 1950s, the lymphocyte was identified as the cell
responsible for both cellular and humoral immunity.
• 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
• The work of Karl Landsteiner and those who
followed him showed that injecting an animal with
almost any organic chemical could induce
production of antibodies that would bind
specifically to the chemical.
• These studies demonstrated that antibodies have a
capacity for an almost unlimited range of
reactivity
Immunology is a Complex
Subject

Dr.T.V.Rao MD 6
 Role of the immune
system is to protect from
Viruses Parasites
e.g. Influenza
Polio mellitus, Hep, Tape worms e.g. Malaria
Corona Helminths

Toxins and chemicals

Bacteria
Fungi e.g. M.Tuberculosis bacillus
e.g. Candida Foreign Materials
Staphylococci etc.
albicans
 Principal Function of the
Immune System

• To protect humans from pathogenic microorganisms

(Pathogens) Microorganisms capable of causing
infection and/or disease
Infection
• Ability of pathogen to enter host, multiply and
stimulate an immune response
Disease
• Clinical manifestations associated with infection

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 General Immunology
• The discipline of immunology grew out of the
observation that individuals who had recovered from
certain infectious diseases were thereafter protected
from the disease.
• The Latin term immunis, meaning “exempt,” is the
source of the English word immunity, Protective
adaptations in higher organisms to rid the body of
foreign particles (microbial and otherwise) and
abnormal cells
• Immune system involves the interplay between Non-
specific and Specific Immune responses
• Non-specific immunities collectively referred to as our
Innate immunity
• Specific immunities are referred to as our Adaptive
immunity for which there are 2 branches:
• Humoral immunity & Cell-mediated immunity 19
 Subjects In Immunology

• Cell mediated host defense functions

• Antibody related defense mechanisms
• Hypersensitivity reactions ( Including Allergy )
• Auto Immunity
• Immunodeficiency
• Transplantation

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Divisions of Immunology

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 Definitions
Immune system
Cells, tissues, and molecules that mediate resistance to
infections
Immunology
Study of structure and function of the immune system
Immunity
Resistance of a host to pathogens and their toxic effects
Immune response
Collective and coordinated response to the introduction of
foreign substances in an individual mediated by the cells
and molecules of the immune system
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Ag Ag
 Types of Immunity

• The Immune System Includes Innate and Adaptive

Components
• Immunity—the state of protection from infectious disease
has both a less specific and more specific component.
• The less specific component, innate immunity, provides the
first line of defense against infection
• That are not specific to a particular pathogen but that
include cellular and molecular components that recognize
classes of molecules peculiar to frequently encountered
pathogens.

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 Types of Immunity
• Phagocytic cells, such as macrophages and neutrophils,
barriers such as
• Skin, and a variety of antimicrobial compounds
synthesized by the host all play important roles in innate
immunity
• In contrast to the broad reactivity of the innate immune
system, which is uniform in all members of a species, the
specific component, adaptive immunity, does not come
into play until there is an antigenic challenge to the
organism.
 Types of Immunity

• Innate immunity (Inborn): it is present at birth; this

is our first line of defense.
• Acquired or specific: It is not present at birth but
becomes part of our immune system as the lymphoid
system develops.
• 1970: WHO defined immunity as immune response
to antigen ( Foreign body) in form of
• Humoral ( activation of B-lymphocytes)
• Cellular (by activation of T-lymphocytes
 Two types of immunity
1. Innate (non-adaptive)
• First line of immune response
• Relies on mechanisms that exist before infection

2. Acquired (adaptive)
• Second line of response (if innate fails)
• Relies on mechanisms that adapt after infection
• Handled by T- and B- lymphocytes
• One cell determines one antigenic determinant

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 Innate Immunity
• Physical and anatomic barriers that tend to prevent the
entry of pathogens are an organism’s first line of
defense against infection Innate immunity can be seen
to comprise four types of defensive barriers:
• Anatomic Skin and mucus membranes
• Physiologic Temperature, pH, chemical mediators
Lysozymes cytokines and Interferon
• Phagocytic blood monocytes, neutrophils, tissue
macrophages
• Inflammatory vascular fluid, containing serum proteins
with antibacterial activity, and influx of phagocytic
cells into the affected area.
 Distinction Between Innate and Adaptive
Immune Responses

• Innate immunity is non adaptive and helps to initiate

adaptive immune responses (first line of defense but
limited)
• Immediate (0-4 hours)
• Adaptive immunity provides a more universal line of
defense and has long-lived memory to provide
protection upon re-infection
➢ Second line of defense
➢ Generation of Ag-specific effector cells
➢ Early (4-96 hours)
➢ Late (>96 hours)

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 Immunology Overview

• Lymphocytes
• Antigen-presenting cells
• Effector cells
Responses
• The innate immune response
• Capturing and displaying antigens
• Cell-mediated immunity
• Humoral immunity
• Immunologic memory
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 Defense Mechanisms of The
Human Host

• Innate Mechanisms (Innate immunity)

First line of defense
Non-specific
• Adaptive Mechanisms (Adaptive immunity)
Second line of defense
Highly specific with memory
• Cooperation between mechanisms

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 Adaptive Immunity

• Adaptive immunity is capable of recognizing and

selectively eliminating specific foreign microorganisms
and molecules (i.e., foreign antigens).
• Unlike innate immune responses, adaptive immune
responses are not the same in all members of a species
but are reactions to specific antigenic challenges.
• Adaptive immunity displays four characteristic
attributes:
• Antigenic specificity
• Diversity
• Immunologic memory
• Self/Nonself recognition
 Characteristic/attributes

The antigenic specificity

• The antigenic specificity of the immune system permits it to
distinguish subtle differences among antigens.
• Antibodies can distinguish between two protein molecules that
differ in only a single amino acid.
Diversity
• The immune system is capable of generating tremendous diversity
in its recognition molecules, allowing it to recognize billions of
unique structures on foreign antigens.
• Once the immune system has recognized and responded to an
antigen,
3. immunologic memory
• It exhibits immunologic memory; that is, a second encounter
with the same antigen induces a heightened state of immune
reactivity.
• Because of this attribute, the immune system can confer life-
long immunity to many infectious agents after an initial
encounter.
4. self/nonself recognition
• The immune system normally responds only to foreign
antigens, indicating that it is capable of self/nonself
recognition.
• The ability of the immune system to distinguish self from
nonself and respond only to nonself molecules is essential
the outcome of an inappropriate response to self molecules
can be fatal.
 Organs of Immune System

Primary Lymphoid Organs

• Bone Marrow and Thymus
• Maturation Site
Secondary Lymphoid Organs
• Spleen, lymph nodes,
• MALT (mucosal associated lymph tissue)
• GALT (gut associated lymph tissue)
• Trap antigen, APC, Lymphocyte Proliferation

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ORIGIN OF CELLS OF THE IMMUNE SYSTEM

• Derived from common progenitor cell in bone

marrow
Pluripotent hematopoietic stem cell
• Progenitor Stem Cells
Erythroid lineage
Erythrocytes and Megakaryocytes
Myeloid lineage
Monocyte/macrophage, dendritic cells, polymorph
nuclear neutrophils (PMN’s), mast cells
Lymphoid lineage
Small and large lymphocytes
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Origin of Cells of The Immune System
White Blood Cell
Development
HUMAN Lymphoid Organs

Dr.T.V.Rao MD 27
 Important components of innate immunity
Factors that limit growth of microorganisms within the body

• Natural killer cells • Kill virus infected cells

• Neutrophils • Ingest and destroy microbes
• Macrophages and • Ingest and destroy microbes, and
dendritic present
cells antigen to helper T-cells
• Interferons • Inhibit viral replication
• Complement • C3b is an opsonin, membrane
attack complex creates holes in
bacterial membranes
• Transferrin and • Sequester iron required for
Lactoferrin bacterial growth
• Fever • Elevated temperature retards
bacterial growth
• Inflammatory response • Limits spread of microbes
• APOBEC3G (apolypoprotein is • Causes hyper mutation in retroviral
RNA editing enzyme) DNA and mRNA
 Main Components of Innate and acquired Immunity that
contribute to humoral ( antibody-mediated ) immunity and
cell mediated immunity

Humoral Cell mediated

Immunity Immunity

Innate Complement Macrophages

Neutrophil Natural killer
cells

Acquired B cells Helper Tcells

Antibodies Cytotoxic T cells

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Major Functions of T Cells and B cells
Antibody-Mediated Immunity
(B Cells)
1) Host defense
against infection
2) (Opsonize bacteria,
neutralize toxins and
viruses)
3) Allergy (hypersensitivity)
e.g. hay fever
anaphylactic shock
4) Autoimmunity
Cell Mediated Immunity
1. Host defense against
infection (especially M.
tuberculosis, fungi and
virus infected cells)
2. Allergy (hypersensitivity)
e.g. poison of oak tree
3. Graft and tumor
rejection
4. Regulation of antibody
response (help and
suppression)
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 Cells of Innate And Adaptive Immunity

• Myeloid Lineage
– Neutrophil
• Principal phagocytic cell of innate
immunity
– Eosinophil
• Principal defender against parasites
– Basophil
• Functions similar to Eosinophils and mast
cells
– Referred to as
• Polymorph nuclear leukocytes (PMN’s)
– Nuclei are multilobed (2 to 5)
• Granulocytes
– Cytoplasmic granules
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 CELLS OF INNATE AND ADAPTIVE IMMUNITY

• Myeloid lineage
Monocytes
• Leukocytes with bean shaped or
brain-like convoluted nuclei
• Circulate in blood with half life of 8
hours
• Precursors of tissue macrophages
Macrophages
• Mononuclear phagocytic cells in tissue
• Derive from blood monocytes
• Participate in innate and adaptive
immunity
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 CELLS OF INNATE AND ADAPTIVE
IMMUNITY
• Myeloid lineage
– Dendritic cells
• Cells with dendriform (star shaped)
morphology
• Interdigitating reticular cells (synonym)
• Capture and present antigens to T lymphocytes
– Mast cells
• Located in mucous membrane and connective
tissue throughout body
• Major effector cell in allergy
• Modulation of initial immune response
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 CELLS OF INNATE AND ADAPTIVE
IMMUNITY

• Lymphoid Lineage
– Large lymphocytes (large granular lymphocytes)
• Natural killer (NK) cells (CD16, CD56)
• Innate immunity to viruses and other intracellular
pathogens
• Participate in antibody-dependent cell-mediated
cytotoxicity (ADCC)
– Small lymphocytes
• B cells (CD19)
• T cells (CD3, CD4 or CD8)
• Adaptive immunity
– Lymphocytes refers to small lymphocytes

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 The Cluster of Differentiation (CD)

• A protocol for identification and investigation of cell surface

molecules
• CD number assigned on basis of 1 cell surface molecule
recognized by 2 specific monoclonal antibodies
• CD nomenclature established in 1982
• 1st International Workshop and Conference on Human Leukocyte
Differentiation Antigens

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Dynamics of Phagocytosis

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