INTRODUCTION TO IMMUNOLOGY

1. INTRODUCTION TO
IMMUNOLOGY
Dr.T.V.Rao MD
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Dr.T.V.Rao MD

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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Dr.T.V.Rao MD

3. Immunity
The Latin term “IMMUNIS” means EXEMPT,
referring to protection against foreign agents.
• DEFINITION: - The integrated body system of
organs, tissues, cells & cell products that
differentiates self from non – self &
neutralizes potentially pathogenic organisms.
• (The American Heritage Stedman's Medical
Dictionary)
Designed by Dr.T.V.Rao MD 3

4. • Protect against pathogens
• Eliminate damaged or malignant cells
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Dr.T.V.Rao MD

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
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Dr.T.V.Rao MD

6. 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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Dr.T.V.Rao MD

7. Immunology is a Complex
Subject
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Dr.T.V.Rao MD

8. Bacteria
Tubercule bacillus
Staphylococci
Fungi
Candida albicans
Viruses
Influenza
Polio mellitus
Parasites
Tapeworms
Malaria
Helminths
Role of the immune
system is to protect from:
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9. PRINCIPAL FUNCTION OF THE IMMUNE SYSTEM
• To protect humans from pathogenic
microorganisms
• 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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Dr.T.V.Rao MD

10. General Immunology
Immunology stems from L.- immunis = “exempt;”
Eng. = protection from disease
*Protective adaptations in higher organisms to rid the body of
foreign particles (microbial and otherwise) and
abnormal cells
Our Immune system involves the interplay between our
Non-specific and our 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
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Dr.T.V.Rao MD

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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Dr.T.V.Rao MD

12. Divisions of Immunology
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Dr.T.V.Rao MD

13. 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 13
Dr.T.V.Rao MD

14. March towards modern times…
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
eradicated from the world
Lady Mary Wortley
Montague
(1689-1762)
War on smallpox…
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Dr.T.V.Rao MD

15. 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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Dr.T.V.Rao MD

16. Pasteur inoculating sheep at Msr.
Rossignol’s farm – May, 1881
1879- discovered that
aged bacterial cultures
of Pasteurella lost
virulence. Referred to
injection of weakened
culture a “vaccine” in
honor of Jenner
1881- He applied the
same technique vs.
anthrax
….and then rabies
Louis Pasteur
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Dr.T.V.Rao MD

17. Louis
Pasteur
watching as
Joseph
Meister
receives
attenuated
rabies
vaccine
(1885)
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Dr.T.V.Rao MD

18. First insights into mechanics of immunity…
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?
Emil von Behring
S. Kitasato
Elie Metchnikoff 18
Dr.T.V.Rao MD

19. Types Of Immunity
• Inborn or innate immunity: 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
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Dr.T.V.Rao MD

20. 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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Dr.T.V.Rao MD

21. Basic classification of Immunity
Designed by Dr.T.V.Rao MD 21

22. 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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Dr.T.V.Rao MD

23. 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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24. 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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Dr.T.V.Rao MD

25. THE EVOLUTION OF IMMUNITY
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Immunity
Innate immunity Acquired immunity
Non-specific Specific
Immediate onset Delay onset
Humoral
Immune Response
Cellular
Immune Response
Antibodies production T-cell activation
Dr.T.V.Rao MD

26. 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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Dr.T.V.Rao MD

27. 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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Dr.T.V.Rao MD

28. 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, PMN’s, mast
cells
–Lymphoid lineage
• Small and large lymphocytes 28
Dr.T.V.Rao MD

29. HUMAN Lymphoid Organs
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Dr.T.V.Rao MD

30. The immune system
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Immune system
•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
Innate (non-specific) immunity Adaptive (specific) immunity
Dr.T.V.Rao MD

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Dr.T.V.Rao MD

32. Central Immune organs
Central Immune Organs
are the sites of
generation,
differentiation and
maturation of
immunocytes.
 Bone marrow
 Thymus
 Bursa of Fabricius
(the site of B cells
maturation in birds)
But absent in Humans
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Dr.T.V.Rao MD

33. Innate Immunity
• Nonspecific host defenses that exist prior
to exposure to an antigen. Involves the
following components:
–Anatomic
–Physiologic
–Phagocytic
–Inflammatory
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Dr.T.V.Rao MD

34. Barriers to Antigenic Insult
• Anatomic
–Skin
–Mucous membranes
• Physiologic
–Temperature
–pH
–Chemical mediators
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Dr.T.V.Rao MD

35. THE INNATE IMMUNE RESPONSE
• Mediated (initiated) by phagocytes, NK cells and
soluble proteins
• Phagocytes
– Cells specialized in the process of phagocytosis
• Macrophages
– Reside in tissues and recruit neutrophils
• Neutrophils
– Enter infected tissues in large numbers
– Recognize common molecules of bacterial cell surface
using a few surface receptors
• Phagocytosis
– Capture, engulfment and breakdown of bacterial pathogen
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Dr.T.V.Rao MD

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Important components of innate immunity
Factors that limit growth of microorganisms within the body
• Natural killer cells
• Neutrophils
• Macrophages and dendritic
cells
• Interferons
• Complement
• Transferrin and Lactoferrin
• Fever
• Inflammatory response
• APOBEC3G (apolypoprotein is RNA
editing enzyme)
• Kill virus infected cells
• Ingest and destroy microbes
• Ingest and destroy microbes, and present
antigen to helper T-cells
• Inhibit viral replication
• C3b is an opsonin, membrane attack
complex creates holes in bacterial
membranes
• Sequester iron required for bacterial
growth
• Elevated temperature retards bacterial
growth
• Limits spread of microbes
• Causes hyper mutation in retroviral DNA
and mRNA
Dr.T.V.Rao MD

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Main Components of Innate and acquired Immunity that
contribute to humoral ( antibody-mediated ) immunity and
cell mediated immunity
Humoral
Immunity
Cell mediated
Immunity
Innate Complement
Neutrophil
Macrophages
Natural killer
cells
Acquired B cells
Antibodies
Helper Tcells
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) eg,
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 )eg
poison oak
3) Graft and tumor rejection
4) Regulation of antibody response
(help and suppression)
Dr.T.V.Rao MD

39. Cellular and Inflammatory Components of
Innate Immunity
• Cellular
–Phagocytic cells
• Inflammatory
–Vasodilation
–Capillary
permeability
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Dr.T.V.Rao MD

40. 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 40
Dr.T.V.Rao MD

41. 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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Dr.T.V.Rao MD

42. 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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Dr.T.V.Rao MD

43. 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 43
Dr.T.V.Rao MD

44. 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
(HLDA) 44
Dr.T.V.Rao MD

45. THE CLUSTER OF DIFFERENTIATION
(CD)
• CD markers on leukocytes
Granulocyte CD45+, CD15+
Monocyte CD45+, CD14+
T lymphocyte CD45+, CD3+
T helper lymphocyte CD45+, CD3+, CD4+
T cytotoxic lymphocyte CD45+, CD3+, CD8+
B lymphocyte CD45+, CD19+
Natural killer cell CD45+, CD16+, CD56+, CD3-
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Dr.T.V.Rao MD

46. Physiologic Mediators
of Innate Immunity
• Chemical
mediators
–Enzymes
–Interferon
–Complement
• Three pathways
– Classical
– MB Lectin
– Alternative
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Dr.T.V.Rao MD

47. Physiologic Mediators
of Innate Immunity(cont’d)
• Chemical
mediators
–Collections
–Toll-like
receptors
–Acute phase
proteins
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Dr.T.V.Rao MD

48. 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 48
Dr.T.V.Rao MD

49. Dynamics of Phagocytosis
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White Blood Cell Development
Dr.T.V.Rao MD

52. LYMPHOCYTES, LYMPHOID
TISSUES AND ORGANS
• Lymphocytes originate in bone marrow
• Lymphoid tissues and organs
– Primary
• Development and maturation of lymphocytes
• Bone Marrow (B cells) and thymus gland (T cells)
– Secondary
• Mature lymphocytes meet pathogens
• Spleen, adenoids, tonsils, appendix, lymph nodes,
Peyer’s patches, mucosa-associated lymphoid tissue
(MALT)
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Dr.T.V.Rao MD

53. THE LYMPHATIC SYSTEM
• Lymph
– Fluid and cells in lymphatic vessels
• Lymphatic vessels
– Collect and return interstitial fluid to blood
– Transport immune cells throughout body
– Transport lipid from intestine to blood
• Lymph nodes
– Kidney shaped organs at intervals along lymphatic
vessels
• Other secondary lymphatic tissues and organs
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Dr.T.V.Rao MD

55. SECONDARY LYMPHOID TISSUES
ASSOCIATED WITH MUCOUS MEMBRANES
• Primary portals of entry for pathogens
– Respiratory tract
– Gastrointestinal tract
• Secondary lymphoid tissues
– Bronchial-associated lymphoid tissue (BALT)
– Gut-associated lymphoid tissues (GALT)
• Tonsils, adenoids, appendix, Peyer’s patches
• Pathogens are directly transferred across
mucosa by “M” cells
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Dr.T.V.Rao MD

56. Innate immunity: mechanisms
• Mechanical barriers / surface secretion
– skin, acidic pH in stomach, cilia
• Humoral mechanisms
– lysozymes, basic proteins, complement, interferons
• Cellular defense mechanisms
– natural killer cells neutrophils, macrophages,, mast
cells, basophils, Eosinophils
Neutrophil
NK Cell Monocyte
Macrophage
Basophils & Mast
cells
Eosinophils
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Dr.T.V.Rao MD

57. 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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Dr.T.V.Rao MD

58. 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,
produces antibodies)
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Dr.T.V.Rao MD

59. 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 kill
infected cells
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Dr.T.V.Rao MD

60. 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
Dr.T.V.Rao MD 60

61. 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
Dr.T.V.Rao MD 61

62. 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

63. 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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Dr.T.V.Rao MD

64. Natural Killer cells
NK cells
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Dr.T.V.Rao MD

65. 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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66. • 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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