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Introduction to ImmunologyScience of Immunity
Dr.T.V.Rao MD
1Dr.T.V.Rao MD
Immunology• Immunology:
– Study of the molecules, cells, organs, and systems responsible for the recognition and disposal of foreign (nonself) material
– Study of the MECHANISMS that protect an individual from injury from:
• Exogenous microorganisms – bacteria, fungi, viruses
• Exogenous chemicals – pollen, poison ivy, etc.
• Endogenous cells – malignant or senescent cells
– IMMUNE RESPONSE: Broad range of defense mechanisms including inflammation, phagocytosis, antibody synthesis, etc.
Edward Jenner, “ the founder of modern immunology”
1796- Introduction of protective vaccine against small pox:
based on cow pox (in Latin - vaccinia )
What is the immune system?
• The body’s defense against disease
causing organisms, malfunctioning cells,
and foreign particles
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
• 15th centurry: Chinese and Turks use dried crusts of smallpox as ”vaccine”
• 1798: Edward Jenner – smallpox vaccine
6Dr.T.V.Rao MD
Immunology
• Contains Basic science
• Clinical Application
Host defense reactions to foreign Antigen
Substance is not self
Antigen recognizing Cell Mediated
Host defense functions
7Dr.T.V.Rao MD
Jenner - Smallpox vaccine
• Noticed that milkmades that had contracted cowpox did NOT get smallpox
• Test on an 8 year old boy, injected cowpox into him (NOT very nice……)
• Follwed by exposure to smallpox
• Vaccine was invented (latin vacca means ”cow”)
Pierre Dö[email protected]
Annette Hö[email protected]
Andreas [email protected]
Subjects In Immunology
• Cell mediated host defense functions
• Antibody related defense mechanisms
• Hypersensitivity reactions ( Including Allergy )
• Auto Immunity
• Immunodeficiency
• Transplantation
9Dr.T.V.Rao MD
What is Response to Infection
• Immunity can be
Innate
Nonadapative
• Adaptive -
Acquired.
Dr.T.V.Rao MD 10
What is immunity?
- Resistance to a
disease causing
organism or
harmful
substance
- Two types- Active Immunity
- Passive
Immunity
Immunology is a Complex
Subject
12Dr.T.V.Rao MD
13Dr.T.V.Rao MD
The Invaders . . .
• Bacteria
• Viruses
• parasites
such as
fungi,
& worms
worm trichura.jpg
http://www.hhs.gov/asphep/presentation/images/bacteria.jpg
http://www.skidmore.edu/academics/biology/plant_bio/lab13.FUNGI.html
Different types of Immunity
A - Non specific1
Species
2 Racial
3 Individual
B Specific 1.Species
2 Racial
3 IndividualDr.T.V.Rao MD 15
THE EVOLUTION OF
IMMUNITY
Dr.T.V.Rao MD 16
Immunity
Innate immunity Acquired immunity
Non-specific SpecificImmediate onset Delay onset
Humoral
Immune Response
Cellular
Immune Response
Antibodies production T-cell activation
Innate Immunity
Innate Immunity is resistance that is preexisting and is not acquired through contact with a nonself ( Foreign known as antigen
Individual has innate Immunity by genetic or constitutional Make Up
Non related to prior contact with Microorganisms or Immunization
17Dr.T.V.Rao MD
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
Dr.T.V.Rao MD 18
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
Dr.T.V.Rao MD 19
It is Dependent on
• Species
• Race ( Racial )
• Individual
Dr.T.V.Rao MD 20
Species and Immunity
• Immunity refers to total resistance to a Pathogen by all members of the species
• Eg Human do not get plant diseases
• Humans do not get some animal diseases
• Dependent on Human configuration physiology ? Biochemical difference
21Dr.T.V.Rao MD
Immune system is distributed all over
the Body
Dr.T.V.Rao MD
22
Dr.T.V.Rao MD 23
Race - Immunity
• Genetic resistance
Plasmodium
falciparum malaria
resistance in Africa
• In sickle cell
anemia immune to
malaria
24Dr.T.V.Rao MD
Individual - Immunity
• Twins
homozygous twins
exhibit similar
resistance
• Susceptibility
similar in Leprosy
• Tuberculosis
similar resistance25Dr.T.V.Rao MD
Factors Influencing Innate Immunity
• Placenta prevent
infection
• But still can infected
with Toxoplasmosis,
Rubella, CMV and
Herpes infection.
• Can produce
congenital
malformations
26Dr.T.V.Rao MD
Immunity In Adults
• Polio infection ,
and Chickenpox
highly severe in
adults.
• Enlargement of
prostate lead to
UTI
Dr.T.V.Rao MD 27
Hormonal Influces on
Immunity• Diabetes mellitus
• Hypothyroidism in adults
• Adrenal dysfunction
• Stress increases steroids
predisposes to Infection
28Dr.T.V.Rao MD
Nutrition
• Immunodefic
iency
• Some
protection in
some
diseasesDr.T.V.Rao MD 29
Our 1st Line of Defense...
• The Integumentary System…
–Skin
–Mucous membranes
–Mucous
• provides a physical barrier
preventing microbial access
Mechanisms of Immunity
• Epithelial surfaces
Skin and Epithelial surfaces cover the
body and protects the individuals
Healthy skin poses bactericidal influence,
salt, drying sweat , Long fatty acids
Wet hand predisposes to Mycotic and
pyogenic infections
31Dr.T.V.Rao MD
Mucous Membranes
• Respiratory
tract
Shape of
Nose,
Nasal
orifice 32Dr.T.V.Rao MD
• Cilia in
Respiratory tract
• Propel the
foreign particles
• Respiratory
secretion contain
33Dr.T.V.Rao MD
Oral Cavity
• Saliva
• Stomach Hcl
• Large
intestine large
number of
bacteria34Dr.T.V.Rao MD
Conjunctiva
• Contain lachrymal
secretions
• Tears contains
antibacterial
substances
• Lysozyme present
except in CSF,
Sweat, Urine
35Dr.T.V.Rao MD
The First Line of Defense~Saliva~
What’s the first thing you do
when you cut your finger?
- Saliva contains many
chemicals that break down
bacteria
- Thousands of different
types of bacteria can
survive these chemicals,
however
Other Mechanisms
• Flushing action
of urination
drives out
Microbes in the
Urethra
• Spermine in
SemenDr.T.V.Rao MD 37
Antibacterial Substances
• May be present Blood as
Complement
• Antibacterial substances in Blood
Betalysin,
Leukin
Lacto peroxidase in Milk
Dr.T.V.Rao MD 38
Interferons in Immunity
• Interferons (IFNs) are natural proteins produced by the cells of the immune system of most vertebrates in response to challenges by foreign agents such as viruses, parasites and tumour cells. Interferons belong to the large class of glycoproteins known as cytokines
• Interferons are more useful than Antibodies
39Dr.T.V.Rao MD
Microbial Antagonists
Normal flora Help us
• Normal Microbial flora
40Dr.T.V.Rao MD
Normal Flora Help Us• We harbour near 1014 bacteria. This group
of organisms, traditionally referred to as
"normal flora" (although they are not
plants) is composed of a fairly stable set of
genera, mostly anaerobes. While each
person has a relatively unique set of
normal flora, members of the
Streptococcus and Bacteroides make up a
large percentage of the inhabitants. These
organisms contribute to our existence in
several ways’41Dr.T.V.Rao MD
Normal Flora Help Us
• Help us by competing with pathogens
such as Salmonella
• Help us by providing vitamins or
eliminating toxins (e.g. Bacteroides)
• Harm us by promoting disease (e.g. dental
caries)
• Cause neither help nor harm (e.g.
"commensals").
Dr.T.V.Rao MD 42
Normal Bacterial Flora of
Conjunctiva
43Dr.T.V.Rao MD
Cellular Factors in Innate
Immunity• Metichinkoff 1883
• Cells called as Phagocytic cells
Microphages,
Macrtophages
Microphages Polymorphonuclear neutrophils
Macrophages Histiocytes wandering Amoeboid cells
Monocytes in Blood
Cells in Reticuloendothelial System
These cells remove foreign particles
44Dr.T.V.Rao MD
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.
How Phagocytes act
• Phagocytic cells
reach the site o
Inflammation
• Attracted by
Chemo tactic
substances
• Ingest particle
material
46Dr.T.V.Rao MD
47Dr.T.V.Rao MD
Capsule In Innate immunity
• Some bacteria have capsules
• Streptococcus pneumonia
• Klebsiella pneumonia
• Bacteria with capsules are not ingested by Phagocytes unless in the presence of opsonins
• Bacteria are fixed against fixed surface such as alveoli
48Dr.T.V.Rao MD
Innate Host Defenses Against Infection
• Anatomical barriers– Mechanical factors
– Chemical factors
– Biological factors
• Humoral components– Complement
– Coagulation system
– Cytokines
• Cellular components– Neutrophils
– Monocytes and macrophages
– NK cells
– Eosinophils
Anatomical Barriers - Mechanical
Factors
System or Organ Cell type Mechanism
Skin Squamous epithelium Physical barrier
Desquamation
Mucous Membranes Non-ciliated epithelium
(e.g. GI tract)
Peristalsis
Ciliated epithelium (e.g.
respiratory tract)
Mucociliary elevator
Epithelium (e.g.
nasopharynx)
Flushing action of
tears, saliva,
mucus, urine
Anatomical Barriers - Chemical
Factors
System or Organ Component Mechanism
Skin Sweat Anti-microbial fatty
acids
Mucous Membranes HCl (parietal cells)
Tears and saliva
Low pH
Lysozyme and
phospholipase A
Defensins (respiratory & GI
tract)
Antimicrobial
Sufactants (lung) Opsonin
Anatomical Barriers - Biological Factors
System or Organ Component Mechanism
Skin and mucous
membranes
Normal flora Antimicrobial
substances
Competition for
nutrients and
colonization
Humoral Components
Component Mechanism
Complement Lysis of bacteria and some viruses
Opsonin
Increase in vascular permeability
Recruitment and activation of phagocytic cells
Coagulation system Increase vascular permeability
Recruitment of phagocytic cells
Β-lysin from platelets – a cationic detergent
Lactoferrin and
transferrin
Compete with bacteria for iron
Lysozyme Breaks down bacterial cell walls
Cytokines Various effects
Cellular Components
Cell Functions
Neutrophils Phagocytosis and intracellular killing
Inflammation and tissue damage
Macrophages Phagocytosis and intracellular killing
Extracellular killing of infected or altered self
targets
Tissue repair
Antigen presentation for specific immune
response
NK and LAK cells Killing of virus-infected and altered self targets
Eosinophils Killing of certain parasites
LeucocytesInnate immunity is mediated largely by GRANULOCYTES
Adaptive immunity mediated by LYMPHOCYTES
The growth, development and activities of granulocytes and
lymphocytes are interconnected and often co-operative.
Neutrophils
• 60% of WBCs
• ‘Patrol tissues’ as they squeeze out of the
capillaries.
• Large numbers are released during
infections
• Short lived – die after digesting bacteria
• Dead neutrophils make up a large
proportion of puss.
Dr.T.V.Rao MD 57
Macrophages
• Larger than neutrophils.
• Found in the organs, not the blood.
• Made in bone marrow as monocytes,
called macrophages once they reach
organs.
• Long lived
• Initiate immune responses as they display
antigens from the pathogens to the
lymphocytes.Dr.T.V.Rao MD 58
Mechanism of Phagocytosis
• Bacteria are
phagocycosed into
vacuole (Phagosome)
• Forms
phagolysosome
• Lytic enzymes
destroy the Bacteria
• Brucella and Leprosy
59Dr.T.V.Rao MD
Lymphocyte subsets
Activate B cells
and macrophages
T HELPER CELLS
Th
Kill virus-
infected cells
CYTOTOXIC T
LYMPHOCYTES
CTL
Produce antibodies
PLASMA CELLS
PC
T B
T CELLS B CELLS
CLP
Common
lymphoid
precursor
*DC, *NK
Natural Killer cells
NK cells
61Dr.T.V.Rao MD
62Dr.T.V.Rao MD
Role of Natural killer Cells
• Natural killer cells (or NK cells) are
a type of cytotoxic lymphocyte that
constitute a major component of the Innate
immune system. NK cells play a major role
in the rejection of tumours and cells
infected by viruses. The cells kill by
releasing small cytoplasmic granules of
proteins called perforin and granzyme that
cause the target cell to die by apoptosis 63Dr.T.V.Rao MD
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.
Inflammation
• Tissue Injury
• Irritation
• Arterioles constrict initially and then
dilate
• Slow the Blood flow and Margi nation
of Leucocytes
• Escape into tissues by diapedesis
and accumulate in large numbers66Dr.T.V.Rao MD
67Dr.T.V.Rao MD
Inflammation
• Outpour plasma,
and dilute the
toxic material
• Produce fibrin
barrier and
localized the
infection68Dr.T.V.Rao MD
Fever
• Natural defense
Mechanisms
• Destroy infectious
agents
• Therapeutic –
Trepanoma pallidum
• Production of
Interferons
69Dr.T.V.Rao MD
Acute Phase proteins
• Infection and Injury produces Acute phase proteins
• C- Reactive proteins CRP
• Mann in binding proteins
• CRP activates alternative pathway
• Increases host defenses
• Prevents issue injury
• Repair inflamed lesions.70Dr.T.V.Rao MD
Do not Forget to Immunise
Your Child
Dr.T.V.Rao MD 71
• Programme Created by Dr.T.V.Rao
MD for Medical and Paramedical
Students in the Developing World
Dr.T.V.Rao MD 72