2. Immunology
• Immunology is the study of our
protection from foreign
macromolecules or invading
organisms and our responses to
them.
• Host – e.g. me!!!!
• Foreign macromolecule, antigen – e.g.
virus protein, worm, parasite (Everything
that should not be in my body)
Dr.T.V.Rao MD 2
4. Immunology
• Contains Basic science
• Clinical Application
Host defense reactions to foreign
Antigen
Substance is not self
Antigen recognizing Cell Mediated
Host defense functions
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5. 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
Dr.T.V.Rao MD 5
and molecules of the immune system
6. Role of the immune system
• Defense against microbes
• Defense against the growth of tumor
cells
– kills the growth of tumor cells
• Homeostasis
– destruction of abnormal or dead cells
(e.g. dead red or white blood cells,
antigen-antibody complex)
7. Viruses
Role of the immune systemParasites
Influenza is to protect from: Tapeworms
Polio mellitus Malaria
Helminths
Fungi Bacteria
Candida albicans Tubercule bacillus
Dr.T.V.Rao MD Staphylococci7
8. 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)
Lady Mary Wortley
Montague 1989- WHO announced
(1689-1762) smallpox was
eradicated from the world
Dr.T.V.Rao MD 8
9. 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”)
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10. First insights into mechanics of immunity…
Emil von Behring
1880’s- Metchnikoff
discovered phagocytic
cells that ingest
S. Kitasato microbes and particles
cells conferred immunity
1890- von Behring and
Kitasato discovered
blood sera could
transfer immunity
liquid of blood conferred
immunity
Q: Which confers immunity…
cells or serum?
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Elie Metchnikoff
11. Subjects In Immunology
• Cell mediated host defense functions
• Antibody related defense mechanisms
• Hypersensitivity reactions ( Including
Allergy )
• Auto Immunity
• Immunodeficiency
• Transplantation
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12. What is Response to Infection
• Immunity can
be Innate
( Nonadapative )
• Adaptive -
Acquired.
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14. 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
Dr.T.V.Rao MD 14
– one cell determines one antigenic determinant
15. 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)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
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17. The immune system
Immune system
Innate (non-specific) immunity Adaptive (specific) immunity
•Anatomic barriers (Skin, mucous •Antigen specificity
membranes) •Diversity
•Physiological barriers •Immunological memory
(temperature, pH) •Self/nonself recognition
•Phagocytic Barriers (cells that eat
invaders)
•Inflammatory barriers (redness,
swelling, heat and pain)
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19. Different types of Immunity
A - Non specific
1 Species
2 Racial
3 Individual
B Specific
1.Species
2 Racial
3 Individual
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20. Types of Immunity
Acquired Immunity
A Active
Natural
Artificial
B Passive
Natural
Artificial
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21. Resistance to Infectious Disease
• Innate immunity (nonspecific
resistance) protects us against all
pathogens: “over-the-counter
defenses”
• Adaptive immunity (specific
resistance) is defenses against
specific pathogens: “prescription
defenses”
22. Innate Immunity
Innate Immunity is resistance that is
preexisting and is not acquired
through contact with a foreign
substance known as antigen
Individual has innate Immunity by
genetic or constitutional Make Up
Non related to prior contact with
Microorganisms or Immunization
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23. Physical and Chemical Barriers
• Skin, mucus membranes
• Cilia, mucus, reflexes
• pH, lysozyme, fatty
acids, defensins
• Normal flora
• Genetic resistance
– species differences
– individual differences
24. 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
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25. Race - Immunity
• Genetic resistance
Plasmodium
falciparum malaria
resistance in Africa
• In sickle cell
anemia immune to
malaria
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26. Individual - Immunity
• Twins homozygous
twins exhibit similar
resistance
• Susceptibility similar
in Leprosy
• Tuberculosis similar
resistance
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27. 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 27
28. Hormonal Influence on Immunity
• Diabetes mellitus
• Hypothyroidism in
adults
• Adrenal
dysfunction
• Stress increases
steroids
predisposes to
Infection
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29. Mechanism's 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 29
31. Mechanism's 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
31
pyogenic infections MD
Dr.T.V.Rao
32. Respiratory tract barrier to
prevent Infections
• Cilia in
Respiratory
tract
• Propel the
foreign
particles
• Respiratory
secretion contain Dr.T
.V.Rao MD
32
33. Oral Cavity
• Saliva
• Stomach HCl
• Large
intestine large
number of
bacteria
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35. Other Mechanisms
• Flushing action of urination
drives out Microbes in the
Urethra
• Spermine in Semen
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36. Antibacterial Substances
• May be present Blood as
Complement
• Antibacterial substances in Blood
Betalysin,
Leukin
Lacto peroxidase in Milk
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37. Interferon's in Immunity
• Interferon's (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 tumor cells.
Interferon's belong to the large class of
glycoproteins known as cytokines
• Interferon's are more useful than
Antibodies
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38. Microbial Antagonists
Normal flora Help us
• Normal Microbial flora
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39. Normal flora Helps 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 Bactericides make up a
large percentage of the inhabitants. These
organisms contribute to our existence in
several ways’ Dr.T.V.Rao MD 39
40. Other Normal Flora
• Streptococcus and Bactericides make up a
large percentage of the inhabitants. These
organisms contribute to our existence in
several ways’
• Help us by competing with pathogens
such as Salmonella
• Help us by providing vitamins or eliminating toxins (e.g.
Bactericides)
• Harm us by promoting disease (e.g. dental caries)
• Cause neither help nor harm (e.g. "commensals").
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42. Cellular Factors in Innate Immunity
• Metichinkoff 1883
• Cells called as Phagocytic cells
Microphages,
Macrophages
Microphages Polymorph nuclear neutrophils
Macrophages Histiocytes wandering Amoeboid
cells
Monocytes in Blood
Cells in Reticuloendothelial System
These cells remove foreign particles
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43. Phagocytes
• Phagocytes = eating cells
–Neutrophils (PMNs) are present in
the highest numbers in blood
–Macrophages (“big eaters”) in the
tissues encounter the pathogen first
• Secrete cytokines --->
inflammation, systemic responses
44. How Phagocytes act
• Phagocytic cells
reach the site o
Inflammation
• Attracted by
Chemo tactic
substances
• Ingest particle
material
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45. Cellular and Inflammatory
Components of Innate Immunity
• Cellular
–Phagocytic
cells
• Inflammatory
–Vasodilation
–Capillary
permeability
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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
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49. Mechanism of Phagocytosis
• Bacteria are
phagocycosed into
vacuole (Phagosome)
• Forms
phagolysosome
• Lytic enzymes
destroy the Bacteria
• Brucella and Leprosy
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53. Anti-Viral Interferon's
• IFN and IFN made by virus-
infected cells
• Not virus-specific
• Bind neighboring host cells
and induce synthesis of anti-
viral proteins to block virus
replication
54. Natural Killer Cells
• All nucleated cells in body have
membrane MHC = tissue typing
antigens
• In virus-infected cells, MHC is
reduced in amount or contains virus
peptides
• NK cells recognize this ‘altered’
MHC and kill virus-infected cells
(also tumor cells)
55. 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
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56. 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
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60. Antibacterial substances in
Blood and Tissues
• The complement system possess bacterial
activity and plays role in the bactericidal
activity and destroys the pathogenic
bacteria
• Betalysin – anthrax
• Leukins and Plakins
• Lactic acid found in muscles
• Lacto peroxidase in milk
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61. Acute Phase proteins too play
a great role in Immunity
• 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.
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63. Adaptive immunity:
second line of response
• Based upon resistance acquired during life
• Relies on genetic events and cellular growth
• Responds more slowly, over few days
• Is specific
– each cell responds to a single epitope on an antigen
• Has anamnestic memory
– repeated exposure leads to faster, stronger response
• Leads to clonal expansion
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64. Adaptive immunity:
mechanisms
• Cell-mediated immune response (CMIR)
– T-lymphocytes
– eliminate intracellular microbes that survive
within phagocytes or other infected cells
• Humoral immune response (HIR)
– B-lymphocytes
– mediated by antibodies
– eliminate extra-cellular
microbes and their toxins Plasma cell
(Derived from B-lymphocyte,
Dr.T.V.Rao MD produces antibodies) 64
65. Cell-mediated immune response
1.T-cell
– recognizes peptide
antigen on macrophage
in association with
major histo-
compatibility complex
(MHC) class
– identifies molecules on
cell surfaces
– helps body distinguish
self from non-self
2. T-cell goes into effectors
cells stage that is able to
Dr.T.V.Rao MD 65
kill infected cells
66. Cell mediated immune
response
Primary response
– production of specific clones of effector T cells
and memory clones
– develops in several days
– does not limit the infection
Secondary response
– more pronounced, faster
– more effective at limiting the infection
Example - cytotoxic reactions against intracellular parasites, delayed
hypersensitivity (e.g., Tuberculin test) and allograft rejection
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67. Humoral immune response
1. B lymphocytes recognize
specific antigens
– proliferate and
differentiate into
antibody-secreting
plasma cells
2. Antibodies bind to specific
antigens on microbes;
destroy microbes via
specific mechanisms
3. Some B lymphocytes
evolve into the resting state
- memory cells
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68. Antibodies (immunoglobulin's)
•Belong to the gamma-globulin
fraction of serum proteins
•Y-shaped or T-shaped polypeptides
– 2 identical heavy chains
– 2 identical light chains
• All immunoglobulin's are not
antibodies
•Five kinds of antibodies
– IgG, IgM, IgA, IgD, IgE
69. Measurement of Immunity
• It is not possible to measure the immunity
accurately
• Detection of antibodies
• Detected by agglutination tests,
Precipitation tests, complement fixation HI
ELISA
• Skin Tests, Schick test , Dick Tests
• Tuberculin Test – Delayed Hypersentivity
tests in Tuberculosis MD
Dr.T.V.Rao 69
70. Local Immunity
• Can be produced by Oral Vaccines
• Sabin's vaccine for polio given orally X
Salk will not protect Local Immunity but
produces systemic Immunity
• Locally produced Antibodies IgA protect
the gut from entry of pathogens
• Local immunity antigen protects the
individuals
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71. Herd Immunity
• This indicates the overall level in the
community and important in control of
infections in the community (HERD )
• When Herd immunity is low epidemics
occur.
• Eradication of communicable diseases
depends on the development of high level
of herd immunity rather than high level of
Individual Immunity
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72. • Programme Created by
Dr.T.V.Rao MD for Medical and
Paramedical Students in the
Developing World
• Email
• doctortvrao@gmail.com
Dr.T.V.Rao MD 72
