Introduction to Immunity

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Introduction to Immunity

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Introduction to Immunology:

Introduction to Immunology Science of Immunity Dr.T.V.Rao MD 1 Dr.T.V.Rao MD

Immunology:

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.

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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?:

What is the immune system? The body’s defense against disease causing organisms, malfunctioning cells, and foreign particles

A Short History of Immunology:

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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6 Dr.T.V.Rao MD

Immunology:

Immunology Contains Basic science Clinical Application Host defense reactions to foreign Antigen Substance is not self Antigen recognizing Cell Mediated Host defense functions 7 Dr.T.V.Rao MD

Jenner - Smallpox vaccine:

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 Dönnes pierre@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de

Subjects In Immunology:

Subjects In Immunology Cell mediated host defense functions Antibody related defense mechanisms Hypersensitivity reactions ( Including Allergy ) Auto Immunity Immunodeficiency Transplantation 9 Dr.T.V.Rao MD

What is Response to Infection:

What is Response to Infection Immunity can be Innate Nonadapative Adaptive - Acquired. Dr.T.V.Rao MD 10

What is immunity?:

What is immunity? Resistance to a disease causing organism or harmful substance Two types Active Immunity Passive Immunity

Immunology is a Complex Subject:

Immunology is a Complex Subject 12 Dr.T.V.Rao MD

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The Invaders . . . :

The Invaders . . . Bacteria Viruses parasites such as fungi, & worms

Different types of Immunity:

Different types of Immunity A - Non specific 1 Species 2 Racial 3 Individual B Specific 1.Species 2 Racial 3 Individual Dr.T.V.Rao MD 15

THE EVOLUTION OF IMMUNITY:

THE EVOLUTION OF IMMUNITY Dr.T.V.Rao MD 16 Immunity Innate immunity Acquired immunity Non-specific Specific Immediate onset Delay onset Humoral Immune Response Cellular Immune Response Antibodies production T-cell activation

Innate Immunity:

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 17 Dr.T.V.Rao MD

Organs Of Immune System:

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:

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:

It is Dependent on Species Race ( Racial ) Individual Dr.T.V.Rao MD 20

Species and Immunity:

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 21 Dr.T.V.Rao MD

Immune system is distributed all over the Body:

Immune system is distributed all over the Body Dr.T.V.Rao MD 22

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Race - Immunity:

Race - Immunity Genetic resistance Plasmodium falciparum malaria resistance in Africa In sickle cell anemia immune to malaria 24 Dr.T.V.Rao MD

Individual - Immunity:

Individual - Immunity Twins homozygous twins exhibit similar resistance Susceptibility similar in Leprosy Tuberculosis similar resistance 25 Dr.T.V.Rao MD

Factors Influencing Innate Immunity:

Factors Influencing Innate Immunity Placenta prevent infection But still can infected with Toxoplasmosis, Rubella, CMV and Herpes infection. Can produce congenital malformations 26 Dr.T.V.Rao MD

Immunity In Adults:

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:

Hormonal Influces on Immunit y Diabetes mellitus Hypothyroidism in adults Adrenal dysfunction Stress increases steroids predisposes to Infection 28 Dr.T.V.Rao MD

Nutrition:

Nutrition Immunodeficiency Some protection in some diseases Dr.T.V.Rao MD 29

Our 1st Line of Defense...:

Our 1 st Line of Defense... The Integumentary System… Skin Mucous membranes Mucous provides a physical barrier preventing microbial access

Mechanisms of Immunity:

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 31 Dr.T.V.Rao MD

Mucous Membranes:

Mucous Membranes Respiratory tract Shape of Nose, Nasal orifice 32 Dr.T.V.Rao MD

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Cilia in Respiratory tract Propel the foreign particles Respiratory secretion contain 33 Dr.T.V.Rao MD

Oral Cavity:

Oral Cavity Saliva Stomach Hcl Large intestine large number of bacteria 34 Dr.T.V.Rao MD

Conjunctiva:

Conjunctiva Contain lachrymal secretions Tears contains antibacterial substances Lysozyme present except in CSF, Sweat, Urine 35 Dr.T.V.Rao MD

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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:

Other Mechanisms Flushing action of urination drives out Microbes in the Urethra Spermine in Semen Dr.T.V.Rao MD 37

Antibacterial Substances:

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 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 39 Dr.T.V.Rao MD

Microbial Antagonists Normal flora Help us:

Microbial Antagonists Normal flora Help us Normal Microbial flora 40 Dr.T.V.Rao MD

Normal Flora Help Us:

Normal Flora Help Us We harbour near 10 14 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’ 41 Dr.T.V.Rao MD

Normal Flora Help Us:

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 :

Normal Bacterial Flora of Conjunctiva 43 Dr.T.V.Rao MD

Cellular Factors in Innate Immunity:

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 44 Dr.T.V.Rao MD

Role of phagocytes:

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:

How Phagocytes act Phagocytic cells reach the site o Inflammation Attracted by Chemo tactic substances Ingest particle material 46 Dr.T.V.Rao MD

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Capsule In Innate immunity:

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 48 Dr.T.V.Rao MD

Innate Host Defenses Against Infection:

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:

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:

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:

Anatomical Barriers - Biological Factors System or Organ Component Mechanism Skin and mucous membranes Normal flora Antimicrobial substances Competition for nutrients and colonization

Humoral Components:

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:

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

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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:

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:

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:

Mechanism of Phagocytosis Bacteria are phagocycosed into vacuole (Phagosome) Forms phagolysosome Lytic enzymes destroy the Bacteria Brucella and Leprosy 59 Dr.T.V.Rao MD

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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:

Natural Killer cells NK cells 61 Dr.T.V.Rao MD

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Role of Natural killer Cells:

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 63 Dr.T.V.Rao MD

Role of inflammation:

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:

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 66 Dr.T.V.Rao MD

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Inflammation:

Inflammation Outpour plasma, and dilute the toxic material Produce fibrin barrier and localized the infection 68 Dr.T.V.Rao MD

Fever:

Fever Natural defense Mechanisms Destroy infectious agents Therapeutic – Trepanoma pallidum Production of Interferons 69 Dr.T.V.Rao MD

Acute Phase proteins:

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. 70 Dr.T.V.Rao MD

Do not Forget to Immunise Your Child:

Do not Forget to Immunise Your Child 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 Email doctortvrao@gmail.com Dr.T.V.Rao MD 72

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