Introduction to Immunology Science of Immunity

Dr.T.V.Rao MD

Dr.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 bodys 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 Dnnes pierre@bioinf.uni-sb.de

Andreas Hildebrandt anhi@bioinf.uni-sb.de

Annette Hglund annette@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 Complex Subject

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The Invaders . . .

Bacteria Viruses parasites such as fungi, & worms

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

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

worm trichura.jpg

Different types of Immunity

A

- Non specific
1 2

Species
Racial 3 Individual B Specific 1.Species 2 Racial 3 Individual

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THE EVOLUTION OF IMMUNITY

Immunity
Non-specific Immediate onset Specific Delay onset

Innate immunity

Acquired immunity

Humoral Immune Response

Antibodies production

Cellular Immune Response

T-cell activation
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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, MD Lymphocyte Dr.T.V.Rao Proliferation

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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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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

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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
Immunodefic iency Some protection in some diseases
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Our

st 1

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

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 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 Whats the first thing you do when you~Saliva~ finger? cut your

- 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 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 Dr.T.V.Rao MD 41 several ways

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, Macrtophages Microphages Polymorphonuclear neutrophils Macrophages Histiocytes wandering Amoeboid cells Monocytes in Blood Cells 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
Skin

Cell type
Squamous epithelium

Mechanism
Physical barrier Desquamation Peristalsis

Mucous Membranes Non-ciliated epithelium (e.g. GI tract)

Ciliated epithelium (e.g. respiratory tract)

Epithelium (e.g. nasopharynx)

Mucociliary elevator
Flushing action of tears, saliva, mucus, urine

Anatomical Barriers - Chemical Factors

System or Organ Component Mechanism

Skin

Sweat

Anti-microbial fatty acids

Low pH Lysozyme and phospholipase A

Mucous Membranes HCl (parietal cells) Tears and saliva

Defensins (respiratory & GI Antimicrobial tract)

Sufactants (lung) Opsonin

Anatomical Barriers - Biological Factors

System or Organ Skin and mucous membranes Component Normal flora Mechanism Antimicrobial substances Competition for nutrients and colonization

Humoral Components
Component Complement Mechanism Lysis of bacteria and some viruses Opsonin Increase in vascular permeability Recruitment and activation of phagocytic cells Increase vascular permeability Recruitment of phagocytic cells -lysin from platelets a cationic detergent Compete with bacteria for iron

Coagulation system

Lactoferrin and transferrin

Lysozyme
Cytokines

Breaks down bacterial cell walls

Various effects

Cellular Components
Cell Neutrophils Functions 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
Killing of virus-infected and altered self targets Killing of certain parasites

NK and LAK cells Eosinophils

Leucocytes
Innate 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. 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
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Lymphocyte subsets
*DC, *NK

CLP
T CELLS

B CELLS

T Th
Activate B cells and macrophages T HELPER CELLS

Common lymphoid precursor

B PC
Produce antibodies PLASMA CELLS

CTL
Kill virusinfected cells CYTOTOXIC T LYMPHOCYTES

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
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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 and accumulate in large numbers
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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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