Introduction to ImmunologyScience of Immunity

Dr.T.V.Rao MD

1Dr.T.V.Rao MD

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.

Edward Jenner, “ the founder of modern immunology”

1796- Introduction of protective vaccine against small pox:

based on cow pox (in Latin - vaccinia )

What is the immune system?

• The body’s defense against disease

causing organisms, malfunctioning cells,

and foreign particles

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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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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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 Dönnespierre@bioinf.uni-sb.de

Annette Höglundannette@bioinf.uni-sb.de

Andreas Hildebrandtanhi@bioinf.uni-sb.de

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.

Dr.T.V.Rao MD 10

What is immunity?

- Resistance to a

disease causing

organism or

harmful

substance

- Two types- Active Immunity

- Passive

Immunity

Immunology is a Complex

Subject

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The Invaders . . .

• Bacteria

• Viruses

• parasites

such as

fungi,

& worms

worm trichura.jpg

http://www.hhs.gov/asphep/presentation/images/bacteria.jpg

http://www.skidmore.edu/academics/biology/plant_bio/lab13.FUNGI.html

Different types of Immunity

A - Non specific1

Species

2 Racial

3 Individual

B Specific 1.Species

2 Racial

3 IndividualDr.T.V.Rao MD 15

THE EVOLUTION OF

IMMUNITY

Dr.T.V.Rao MD 16

Immunity

Innate immunity Acquired immunity

Non-specific SpecificImmediate onset Delay onset

Humoral

Immune Response

Cellular

Immune Response

Antibodies production T-cell activation

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

17Dr.T.V.Rao MD

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

Dr.T.V.Rao MD 18

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

It is Dependent on

• Species

• Race ( Racial )

• Individual

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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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Immune system is distributed all over

the Body

Dr.T.V.Rao MD

22

Dr.T.V.Rao MD 23

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 resistance25Dr.T.V.Rao MD

Factors Influencing Innate Immunity

• Placenta prevent

infection

• But still can infected

with Toxoplasmosis,

Rubella, CMV and

Herpes infection.

• Can produce

congenital

malformations

26Dr.T.V.Rao MD

Immunity In Adults

• Polio infection ,

and Chickenpox

highly severe in

adults.

• Enlargement of

prostate lead to

UTI

Dr.T.V.Rao MD 27

Hormonal Influces on

Immunity• Diabetes mellitus

• Hypothyroidism in adults

• Adrenal dysfunction

• Stress increases steroids

predisposes to Infection

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Nutrition

• Immunodefic

iency

• Some

protection in

some

diseasesDr.T.V.Rao MD 29

Our 1st Line of Defense...

• The Integumentary System…

–Skin

–Mucous membranes

–Mucous

• provides a physical barrier

preventing microbial access

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

31Dr.T.V.Rao MD

Mucous Membranes

• Respiratory

tract

Shape of

Nose,

Nasal

orifice 32Dr.T.V.Rao MD

• Cilia in

Respiratory tract

• Propel the

foreign particles

• Respiratory

secretion contain

33Dr.T.V.Rao MD

Oral Cavity

• Saliva

• Stomach Hcl

• Large

intestine large

number of

bacteria34Dr.T.V.Rao MD

Conjunctiva

• Contain lachrymal

secretions

• Tears contains

antibacterial

substances

• Lysozyme present

except in CSF,

Sweat, Urine

35Dr.T.V.Rao MD

The First Line of Defense~Saliva~

What’s the first thing you do

when you cut your finger?

- Saliva contains many

chemicals that break down

bacteria

- Thousands of different

types of bacteria can

survive these chemicals,

however

Other Mechanisms

• Flushing action

of urination

drives out

Microbes in the

Urethra

• Spermine in

SemenDr.T.V.Rao MD 37

Antibacterial Substances

• May be present Blood as

Complement

• Antibacterial substances in Blood

Betalysin,

Leukin

Lacto peroxidase in Milk

Dr.T.V.Rao MD 38

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

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Microbial Antagonists

Normal flora Help us

• Normal Microbial flora

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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’41Dr.T.V.Rao MD

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

Normal Bacterial Flora of

Conjunctiva

43Dr.T.V.Rao MD

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

44Dr.T.V.Rao MD

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.

How Phagocytes act

• Phagocytic cells

reach the site o

Inflammation

• Attracted by

Chemo tactic

substances

• Ingest particle

material

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47Dr.T.V.Rao MD

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

48Dr.T.V.Rao MD

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

Anatomical Barriers - Mechanical

Factors

System or Organ Cell type Mechanism

Skin Squamous epithelium Physical barrier

Desquamation

Mucous Membranes Non-ciliated epithelium

(e.g. GI tract)

Peristalsis

Ciliated epithelium (e.g.

respiratory tract)

Mucociliary elevator

Epithelium (e.g.

nasopharynx)

Flushing action of

tears, saliva,

mucus, urine

Anatomical Barriers - Chemical

Factors

System or Organ Component Mechanism

Skin Sweat Anti-microbial fatty

acids

Mucous Membranes HCl (parietal cells)

Tears and saliva

Low pH

Lysozyme and

phospholipase A

Defensins (respiratory & GI

tract)

Antimicrobial

Sufactants (lung) Opsonin

Anatomical Barriers - Biological Factors

System or Organ Component Mechanism

Skin and mucous

membranes

Normal flora Antimicrobial

substances

Competition for

nutrients and

colonization

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

transferrin

Compete with bacteria for iron

Lysozyme Breaks down bacterial cell walls

Cytokines Various effects

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

LeucocytesInnate 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.

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

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

Mechanism of Phagocytosis

• Bacteria are

phagocycosed into

vacuole (Phagosome)

• Forms

phagolysosome

• Lytic enzymes

destroy the Bacteria

• Brucella and Leprosy

59Dr.T.V.Rao MD

Lymphocyte subsets

Activate B cells

and macrophages

T HELPER CELLS

Th

Kill virus-

infected cells

CYTOTOXIC T

LYMPHOCYTES

CTL

Produce antibodies

PLASMA CELLS

PC

T B

T CELLS B CELLS

CLP

Common

lymphoid

precursor

*DC, *NK

Natural Killer cells

NK 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 63Dr.T.V.Rao MD

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.

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 numbers66Dr.T.V.Rao MD

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Inflammation

• Outpour plasma,

and dilute the

toxic material

• Produce fibrin

barrier and

localized the

infection68Dr.T.V.Rao MD

Fever

• Natural defense

Mechanisms

• Destroy infectious

agents

• Therapeutic –

Trepanoma pallidum

• Production of

Interferons

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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.70Dr.T.V.Rao MD

Do not Forget to Immunise

Your Child

Dr.T.V.Rao MD 71

• 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