basics in immunity
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Basics in ImmunityTRANSCRIPT
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Immunology Basics Dr.T.V.Rao MD
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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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Immunology
• Contains Basic science
• Clinical Application
Host defense reactions to foreign Antigen
Substance is not self
Antigen recognizing Cell Mediated
Host defense functions 4 Dr.T.V.Rao MD
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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 5 Dr.T.V.Rao MD
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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)
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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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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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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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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 10 Dr.T.V.Rao MD
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Subjects In Immunology
• Cell mediated host defense functions
• Antibody related defense mechanisms
• Hypersensitivity reactions ( Including Allergy )
• Auto Immunity
• Immunodeficiency
• Transplantation
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What is Response to Infection
• Immunity can
be Innate ( Nonadapative )
• Adaptive -
Acquired.
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Immunology is a Complex
Subject
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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 14 Dr.T.V.Rao MD
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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) 15 Dr.T.V.Rao MD
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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
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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
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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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Types of Immunity
Acquired Immunity A Active
Natural
Artificial
B Passive
Natural
Artificial
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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”
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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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Physical and Chemical Barriers
• Skin, mucus membranes
• Cilia, mucus, reflexes
• pH, lysozyme, fatty
acids, defensins
• Normal flora
• Genetic resistance
– species differences
– individual differences
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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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Race - Immunity
• Genetic resistance
Plasmodium
falciparum malaria
resistance in Africa
• In sickle cell
anemia immune to
malaria
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Individual - Immunity
• Twins homozygous
twins exhibit similar
resistance
• Susceptibility similar
in Leprosy
• Tuberculosis similar
resistance
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Factors Influencing Innate Immunity
• Placenta prevent
infection
• But still can
infected with
Toxoplasmosis,
Rubella, CMV and
Herpes infection.
• Can produce
congenital
malformations
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Hormonal Influence on Immunity
• Diabetes mellitus
• Hypothyroidism in
adults
• Adrenal
dysfunction
• Stress increases
steroids
predisposes to
Infection
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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 29 Dr.T.V.Rao MD
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Mucous Membranes
• Respiratory
tract
Shape of
Nose,
Nasal
orifice
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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 31 Dr.T.V.Rao MD
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Respiratory tract barrier to
prevent Infections
• Cilia in
Respiratory
tract
• Propel the
foreign
particles
• Respiratory
secretion contain 32 Dr.T
.V.Rao MD
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Oral Cavity
• Saliva
• Stomach HCl
• Large
intestine large
number of
bacteria 33 Dr.T.V.Rao MD
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Conjunctiva
• Contain lachrymal
secretions
• Tears contains
antibacterial
substances
• Lysozyme present
except in CSF,
Sweat, Urine
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Other Mechanisms
• Flushing action of urination
drives out Microbes in the
Urethra
• Spermine in Semen
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Antibacterial Substances
• May be present Blood as
Complement
• Antibacterial substances in Blood
Betalysin,
Leukin
Lacto peroxidase in Milk
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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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Microbial Antagonists Normal flora Help us
• Normal Microbial flora
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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’ 39 Dr.T.V.Rao MD
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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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Normal Bacterial Flora of
Conjunctiva
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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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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
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How Phagocytes act
• Phagocytic cells
reach the site o
Inflammation
• Attracted by
Chemo tactic
substances
• Ingest particle
material
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Cellular and Inflammatory
Components of Innate Immunity
• Cellular
–Phagocytic
cells
• Inflammatory
–Vasodilation
–Capillary
permeability
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Phagocytosis
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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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Mechanism of Phagocytosis
• Bacteria are
phagocycosed into
vacuole (Phagosome)
• Forms
phagolysosome
• Lytic enzymes
destroy the Bacteria
• Brucella and Leprosy
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Natural Killer cells
NK cells
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Mediators of inflammation Vasodilation, smooth muscle contraction
Increased vascular permeability
Edema, extravasation
(histamines, prostaglandins, kinins)
Extravasation
Chemo taxis
(cytokines, chemokines, complement)
Systemic response- fever, acute-phase
proteins
C-reactive protein
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Interferon and Function
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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
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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)
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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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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 56 Dr.T.V.Rao MD
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Inflammation
• Outpour plasma,
and dilute the toxic
material
• Produce fibrin
barrier and
localized the
infection
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Fever
• Natural defense
Mechanisms
• Destroy infectious
agents
• Therapeutic –
Trepanoma palladium
• Production of
Interferon's
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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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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. 61 Dr.T.V.Rao MD
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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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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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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) 64 Dr.T.V.Rao MD
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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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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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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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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
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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 Dr.T.V.Rao MD 69
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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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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 Dr.T.V.Rao MD 71
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• Programme Created by
Dr.T.V.Rao MD for Medical and
Paramedical Students in the
Developing World
Dr.T.V.Rao MD 72