Introduction to immunology, Science of Immunity

1. Introduction to Immunology
Science of Immunity
How we are Protected
Dr.T.V.Rao MD
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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)
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5. 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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6. 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
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and molecules of the immune system

7. 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)

8. Jenner - Smallpox vaccine
• Noticed that milkmaids 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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9. First insights into mechanics of immunity…
Emil von Behring
S. Kitasato
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
Q: Which confers immunity…
cells or serum?
Elie Metchnikoff
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10. Dr.T.V.Rao MD
Louis
Pasteur
watching as
Joseph
Meister
receives
attenuated
rabies
vaccine
(1885)
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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. •
Protect against pathogens
•
Eliminate damaged or malignant
cells
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13. What is Response to Infection
• Immunity can
be Innate
( Nonadapative )
• Adaptive Acquired.
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14. Immunology is a Complex
Subject
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15. 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
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– one cell determines one antigenic determinant

16. 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 longlived 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
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17. THE EVOLUTION OF
IMMUNITY
Immunity
Non-specific Immediate onset
Specific Delay onset
Innate immunity
Acquired immunity
Humoral
Immune Response
Cellular
Immune Response
Antibodies production
T-cell activation
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18. Basic classification of
Immunity
Designed by Dr.T.V.Rao MD
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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. The immune system
Immune system
Innate (non-specific) immunity
Adaptive (specific) immunity
•Anatomic barriers (Skin, mucous
membranes)
•Physiological barriers
(temperature, pH)
•Phagocytic Barriers (cells that eat
invaders)
•Inflammatory barriers
(redness, swelling, heat and pain)
•Antigen specificity
•Diversity
•Immunological memory
•Self/nonself recognition
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21. Innate, Surface Defenses
• Skin
– physical barrier to microbes
– Keratin resistant to most bacterial enzymes & toxins
– secretions are acidic pH 3-5
• Mucosa
– physical barrier & produces a variety of protective
chemicals
• Gastric mucosa
– very acidic & produces proteolytic enzymes
• Saliva & lacrimal fluid contain lysozyme
• Mucous
– traps bacteria & moves them away from epithelial
surface

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23. 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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24. Types of Immunity
Acquired Immunity
A Active
Natural
Artificial
B Passive
Natural
Artificial
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25. 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”

26. 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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27. Physical and Chemical Barriers
• Skin, mucus membranes
• Cilia, mucus, reflexes
• pH, lysozyme, fatty
acids, defensins
• Normal flora
• Genetic resistance
– species differences
– individual differences

28. It is Dependent on
Species
• Race
( Racial )
• Individual
•
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29. 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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30. Race - Immunity
• Genetic resistance
Plasmodium
falciparum malaria
resistance in Africa
• In sickle cell
anemia immune to
malaria
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31. Individual - Immunity
• Twins homozygous
twins exhibit similar
resistance
• Susceptibility similar
in Leprosy
• Tuberculosis similar
resistance
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32. Factors Influencing Innate Immunity
• Placenta prevent
infection
• But still can
infected with
Toxoplasmosis, Ru
bella, CMV and
Herpes infection.
• Can produce
congenital
malformations Dr.T.V.Rao MD
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33. Immunity In Adults
• Polio infection ,
and Chickenpox
highly severe in
adults.
• Enlargement of
prostate lead to
UTI
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34. Hormonal Influence on Immunity
• Diabetes mellitus
• Hypothyroidism in
adults
• Adrenal
dysfunction
• Stress increases
steroids
predisposes to
Infection
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35. Nutrition
• Some
protection
in some
diseases
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36. 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
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37. Mucous Membranes
• Respiratory
tract
Shape of
Nose, Nas
al orifice
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38. 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
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pyogenic infections MD
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39. • Cilia in
Respiratory
tract
• Propel the
foreign
particles
• Respiratory
secretion contain
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.V.Rao MD
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40. Oral Cavity
• Saliva
• Stomach HCl
• Large
intestine large
number of
bacteria
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41. Conjunctiva
• Contain lachrymal
secretions
• Tears contains
antibacterial
substances
• Lysozyme present
except in
CSF, Sweat, Urine
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42. Other Mechanisms
• Flushing action
of urination
drives out
Microbes in the
Urethra
• Spermine in
Semen
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43. Innate, Internal Defenses
• Phagocytes
– Macrophages: derived from monocytes
• Free Macrophages: roam through tissues
• Fixed Macrophages: Kupffer cells (liver) &
microglia (brain)
• Ingest cellular debris, foreign
material, bacteria, fungi
– Neutrophils: ingest pathogens
– Eosinophils: weakly phagocytic of pathogens.
Attack parasites (degranulation)
– Mast Cells: phagocytic of various bacteria

44. Antibacterial Substances
• May be present Blood as
Complement
• Antibacterial substances in Blood
Betalysin,
Leukin
Lactoperoxidase in Milk
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45. 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 tumour cells.
Interferon's belong to the large class of
glycoproteins known as cytokines
• Interferon's are more useful than
Antibodies
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46. Microbial Antagonists
Normal flora Help us
• Normal Microbial flora
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47. 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 Bacteroides make up a
large percentage of the inhabitants. These
organisms contribute to our existence in
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several ways‟

48. Other Normal Flora
• Streptococcus and Bacteroides 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.
Bacteroides)
• Harm us by promoting disease (e.g. dental caries)
• Cause neither help nor harm (e.g. "commensals").
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49. Normal Bacterial Flora of
Conjunctiva
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50. Cellular Factors in Innate Immunity
• Metchnikoff 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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51. 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

52. How Phagocytes act
• Phagocytic cells
reach the site o
Inflammation
• Attracted by
Chemo tactic
substances
• Ingest particle
material
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53. Cellular and Inflammatory
Components of Innate Immunity
• Cellular
–Phagocytic
cells
• Inflammatory
–Vasodilation
–Capillary
permeability
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55. Phagocytosis

56. 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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57. Mechanism of Phagocytosis
• Bacteria are
phagocycosed into
vacuole (Phagosome)
• Forms
phagolysosome
• Lytic enzymes
destroy the Bacteria
• Brucella and Leprosy
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58. Natural Killer cells
NK cells
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59. Mediators of inflammation
Vasodilation, smooth muscle
contraction
Increased vascular permeability
Edema, extravasation
(histamines, prostaglandins,
kinins)
Extravasation
Chemo taxis
(cytokines, chemokine's,
complement)

60. Interferon  and  Function

61. Anti-Viral Interferons
• IFN and IFN made by virusinfected cells
• Not virus-specific
• Bind neighboring host cells and
induce synthesis of anti-viral
proteins to block virus replication

62. 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)

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
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64. 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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66. Inflammation
• Outpour plasma,
and dilute the toxic
material
• Produce fibrin
barrier and
localized the
infection
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67. Fever
• Natural defense
Mechanisms
• Destroy infectious
agents
• Therapeutic –
Trepanoma palladium
• Production of
Interferon's
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68. 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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69. 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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70. 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.
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71. 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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72. 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
Dr.T.V.Rao MD
Plasma cell
(Derived from B-lymphocyte,
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produces antibodies)

73. Cell-mediated immune response
1.T-cell
– recognizes peptide
antigen on macrophage
in association with
major histocompatibility 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
kill infected cells

74. 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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75. 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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76. 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

77. 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
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78. 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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79. 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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80. • Programme Created by Dr.T.V.Rao MD
for Medical and Paramedical Students
in the Developing World
• Email
• doctortvrao@gmail.com
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