2. 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.
3. Edward Jenner, “ the founder of modern immunology”
1796- Introduction of protective vaccine against small pox:
based on cow pox (in Latin - vaccinia )
4. What is the immune system?
• The body’s defense against disease
causing organisms, malfunctioning cells,
and foreign particles
5. 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
7. Immunology
• Contains Basic science
• Clinical Application
Host defense reactions to foreign
Antigen
Substance is not self
Antigen recognizing Cell Mediated
Host defense functions
Dr.T.V.Rao MD 7
8. 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 Dönnes Andreas Hildebrandt Annette Höglund
pierre@bioinf.uni-sb.de anhi@bioinf.uni-sb.de annette@bioinf.uni-sb.de
9. Subjects In Immunology
• Cell mediated host defense functions
• Antibody related defense mechanisms
• Hypersensitivity reactions ( Including
Allergy )
• Auto Immunity
• Immunodeficiency
• Transplantation
Dr.T.V.Rao MD 9
10. What is Response to Infection
• Immunity can be
Innate
Nonadapative
• Adaptive -
Acquired.
Dr.T.V.Rao MD 10
11. What is immunity?
- Resistance to a
disease causing
organism or
harmful
substance
- Two types
- Active Immunity
- Passive
Immunity
14. The Invaders . . .
• Bacteria http://www.hhs.gov/asphep/presentation/images/bacteria.jpg
• Viruses
• parasites
such as
fungi, http://www.skidmore.edu/academics/biology/plant_bio/lab13.FUNGI.html
& worms
worm trichura.jpg
15. Different types of Immunity
A - Non specific
1
Species
2
Racial
3
Individual
B Specific
1.Species
2 Racial
3 Individual Dr.T.V.Rao MD 15
16. THE EVOLUTION OF
IMMUNITY
Immunity
Non-specific Immediate onset Specific Delay onset
Innate immunity Acquired immunity
Humoral Cellular
Immune Response Immune Response
Antibodies production T-cell activation
Dr.T.V.Rao MD 16
17. 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
Dr.T.V.Rao MD 17
18. 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, MD
Dr.T.V.Rao
Lymphocyte 18
Proliferation
19. 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
20. It is Dependent on
• Species
• Race ( Racial )
• Individual
Dr.T.V.Rao MD 20
21. 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
Dr.T.V.Rao MD 21
24. Race - Immunity
• Genetic resistance
Plasmodium
falciparum malaria
resistance in Africa
• In sickle cell
anemia immune to
malaria
Dr.T.V.Rao MD 24
25. Individual - Immunity
• Twins
homozygous twins
exhibit similar
resistance
• Susceptibility
similar in Leprosy
• Tuberculosis
similar resistance
Dr.T.V.Rao MD 25
26. Factors Influencing Innate Immunity
• Placenta prevent
infection
• But still can infected
with Toxoplasmosis,
Rubella, CMV and
Herpes infection.
• Can produce
congenital
malformations
Dr.T.V.Rao MD 26
27. Immunity In Adults
• Polio infection ,
and Chickenpox
highly severe in
adults.
• Enlargement of
prostate lead to
UTI
Dr.T.V.Rao MD 27
28. Hormonal Influces on
Immunity
• Diabetes mellitus
• Hypothyroidism in adults
• Adrenal dysfunction
• Stress increases steroids
predisposes to Infection
Dr.T.V.Rao MD 28
30. Our 1st Line of Defense...
• The Integumentary System…
–Skin
–Mucous membranes
–Mucous
• provides a physical barrier
preventing microbial access
31. 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
Dr.T.V.Rao MD 31
36. The First Line of Defense
What’s the first thing you do
when you~Saliva~ finger?
cut your
- Saliva contains many
chemicals that break down
bacteria
- Thousands of different
types of bacteria can
survive these chemicals,
however
37. Other Mechanisms
• Flushing action
of urination
drives out
Microbes in the
Urethra
• Spermine in
Semen
Dr.T.V.Rao MD 37
38. Antibacterial Substances
• May be present Blood as
Complement
• Antibacterial substances in Blood
Betalysin,
Leukin
Lacto peroxidase in Milk
Dr.T.V.Rao MD 38
39. 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
Dr.T.V.Rao MD 39
40. Microbial Antagonists
Normal flora Help us
• Normal Microbial flora
Dr.T.V.Rao MD 40
41. 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’ Dr.T.V.Rao MD 41
42. 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
44. 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
Dr.T.V.Rao MD 44
45. 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.
46. How Phagocytes act
• Phagocytic cells
reach the site o
Inflammation
• Attracted by
Chemo tactic
substances
• Ingest particle
material
Dr.T.V.Rao MD 46
48. 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
Dr.T.V.Rao MD 48
49. 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
50.
51. Anatomical Barriers - Mechanical
Factors
System or Organ Cell type Mechanism
Skin Squamous epithelium Physical barrier
Desquamation
Mucous Membranes Non-ciliated epithelium Peristalsis
(e.g. GI tract)
Ciliated epithelium (e.g. Mucociliary elevator
respiratory tract)
Epithelium (e.g. Flushing action of
nasopharynx) tears, saliva,
mucus, urine
52. Anatomical Barriers - Chemical
Factors
System or Organ Component Mechanism
Skin Sweat Anti-microbial fatty
acids
Mucous Membranes HCl (parietal cells) Low pH
Tears and saliva Lysozyme and
phospholipase A
Defensins (respiratory & GI Antimicrobial
tract)
Sufactants (lung) Opsonin
53. Anatomical Barriers - Biological Factors
System or Organ Component Mechanism
Skin and mucous Normal flora Antimicrobial
membranes substances
Competition for
nutrients and
colonization
54. 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 Compete with bacteria for iron
transferrin
Lysozyme Breaks down bacterial cell walls
Cytokines Various effects
55. 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
56. Leucocytes
Innate 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.
57. 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
58. 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
59. Mechanism of Phagocytosis
• Bacteria are
phagocycosed into
vacuole (Phagosome)
• Forms
phagolysosome
• Lytic enzymes
destroy the Bacteria
• Brucella and Leprosy
Dr.T.V.Rao MD 59
60. Lymphocyte subsets
*DC, *NK
CLP
T CELLS B CELLS
Common
lymphoid
T precursor B
Th CTL PC
Activate B cells Kill virus- Produce antibodies
and macrophages infected cells PLASMA CELLS
T HELPER CELLS CYTOTOXIC T
LYMPHOCYTES
63. 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
Dr.T.V.Rao MD 63
64. 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.
65.
66. 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 numbers
Dr.T.V.Rao MD 66