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.

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What is immunity?- Resistance to a

disease causing organism or harmful substance

- Two types- Active Immunity- Passive

Immunity

Immunology is a ComplexSubject

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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 specific 1

Species 2

Racial 3

Individual

B Specific 1.Species

2 Racial 3 Individual

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THE EVOLUTION OF IMMUNITY

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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

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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

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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 difference21Dr.T.V.Rao MD

Immune system is distributed all over the Body

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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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Immunity In Adults

• Polio infection , and Chickenpox highly severe in adults.

• Enlargement of prostate lead to UTI

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Hormonal Influces on Immunity

• Diabetes mellitus• Hypothyroidism in adults• Adrenal dysfunction• Stress increases steroids

predisposes to Infection

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Nutrition

• Immunodeficiency

• Some protection in some diseases

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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

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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

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Oral Cavity

• Saliva• Stomach Hcl• Large

intestine large number of bacteria

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Conjunctiva• Contain lachrymal

secretions• Tears contains

antibacterial substances

• Lysozyme present except in CSF, Sweat, Urine

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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 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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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 AntagonistsNormal 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").

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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, MacrtophagesMicrophages Polymorphonuclear neutrophilsMacrophages Histiocytes wandering Amoeboid

cellsMonocytes in BloodCells in Reticuloendothelial System These cells remove foreign particles

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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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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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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 barrierDesquamation

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 pHLysozyme 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 substancesCompetition for nutrients and colonization

Humoral ComponentsComponent Mechanism

Complement Lysis of bacteria and some virusesOpsoninIncrease in vascular permeabilityRecruitment and activation of phagocytic cells

Coagulation system Increase vascular permeabilityRecruitment of phagocytic cellsΒ-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 killingInflammation and tissue damage

Macrophages Phagocytosis and intracellular killingExtracellular killing of infected or altered self targetsTissue repairAntigen 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.

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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.

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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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Lymphocyte subsets

Activate B cellsand macrophagesT HELPER CELLS

Th

Kill virus-infected cellsCYTOTOXIC TLYMPHOCYTES

CTL

Produce antibodiesPLASMA CELLS

PC

T B

T CELLS B CELLS

CLP

Commonlymphoidprecursor

*DC, *NK

Natural Killer cellsNK 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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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

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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 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.

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Do not Forget to Immunise Your Child

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• 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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