INTRODUCTION TO IMMUNOLOGYDr.swaathy.R 1st yr PG Dept. of microbiology CMC

Branch of MICROBIOLOGY study of bodys responses to infectious pathogens Immune- derived from immunis (latin) meaning exemption from taxes

HISTORY

ORIGIN OF IMMUNOLOGY 430 BC- Thucydides- a great historianobserved during an epidemic of plague that those who recovered from plague would nurse the sick because they wouldnt contract the disease a second time 15th century- chinese and turks- variolation dried crusts of small pox pustules either inhaled or inserted into skin cuts, to develop immunity to small pox

EDWARD JENNER father of vaccine Improved variolation technique Observed that milkmaids whod contracted cowpox were subsequently immune to small pox Inoculated fluid of cowpox pustule in a small boy and he became immune to small pox in 1978

LOUIS PATEUR Coined the name VACCINE for attenuated strain of pathogen, derived from latin word vacca meaning cow in honour of JENNERs work in cowpox vaccine 1879-1881 Developed 3 attenuated vaccineschicken cholera, anthrax and rabies 1885- 1st vaccine to HUMAN (rabies)

ROBERT KOCH Discovered cause and nature of TB, by doing its culture out of body and injecting it to an animal in 1880s Nobel prize in 1905 for cellular immunity and other discoveries in TB

CELLULAR IMMUNITY ELIE METCHINKOFF 1883 Introduced rose thorn into starfish larva, observed that in few hrs it was surrounded by motile cells starting point of cellular immunology Coined the term phagocytosis Nobel prize in 1908 with PAUL EHRLICH FATHER OF CELLULAR IMMUNOLOGY

HUMORAL IMMUNITY VON BEHRING- nobel prize in 1901- work on serum therapy against diphteria VON BEHRING and KITASATA demonstrated neutralising antitoxic activity of animal sera immunised with diphteria or tetanus toxin 1st proof of humoral immunity CALMETTE 1894demonstrated neutralising activity of snake venom antiserum

Continued.. PFEIFFER PHENOMENON: Cholera vibrios injected into previously immunised guinea pig peritonium - lost mobility, clumped together and become unstainable phagocytosed by leukocytes, also lysed in absence of cells demonstrated by PFEIFFER AND ISAEFF in 1894

PAUL EHRLICHS SIDE CHAIN THEORYKEY AND LOCK HYPOTHESIS cells possessed side chains on their surface( Ag receptor) When toxic substance combine with one of side chains thro accidental affinity Cell respond by making large no. of side chains

Spill out into blood Function as circulating Ab

ANAPHYLAXIS- coined by CHARLES RICHETS and PORTIER, while studying toxic effects of actinaria tentacles by injecting glycerine extract to dogs,1st doseno response,2nd doselethal. Nobel prize in 1913

ALLERGY- coined by VON PIRQUET, for modified immune response

PERIOD OF SEROLOGYKARL LANDSTEINER 1900 Demonstrated several antigenic specificities of same species- ABO blood groups in humans Also Rh specificity in rhesus monkey Nobel prize in 1930 for blood groups

Continued.. JULES BORDET Nobel prize in 1919, complement related discoveries Bacteriolysis or RBC lysis require 2 factors: sensitiser: thermostable and specific alexine: thermolabile, it is called as cytase by Metchinkoff and complement by Ehrlich Discovered CFT in 1901 with Octave Gengue

IMMUNOFLUORESCENCE: ALBERT COONS, demonstrated the presence of Ag and Ab inside cells by this new technique

ASTRID FAGRAEUS,1948- Ab made in plasma cells NIELS JERNE, 1955- natural selection theory of Ab formation. Explained imm. Memory, log. rate of rise of Ab. Nobel prize in 1984 with KOHLER and MILSTEIN MACFARLANE BURNET- clonal selection theory- each of the cells that makes antibodies, make only Abs of a single specificity , and Ag selectively induces those cells. Received nobel prize in 1960 for acquired immunological tolerance

BESREDKA- 1902- antileukocyte antisera possess cytotoxic activity against WBCs FELTON PHENOMENON- FELTON in 1942 immunological tolerance. 1st to obtain purified preparation of Abs.

NOBEL LAURETES IN IMMUNOLOGY GERALD MAURICE EDELMAN and RODNEY ROBERT PORTER- 1972- chemical structure of antibodies ROSALYN YALOW-1977- radioimmunoassay of peptide hormones BARUJ BENACERRAF, JEAN DAUSSET, GEORGE DAVID SNELL- 1980- genetically determined structures on cell surface that regulate immunological reactions

continued.. SUSUMU TONEGAWA-1987- genetic principle for generation of Ab diversity JOSEPH E. MURRAY, E.DONNALL THOMAS1990- human organ and cell transplantation PETER C.DOHERTY, ROLF M.ZINKERNAGEL1996- role of MHC in Ag recognition of cells SYDNEY BRENNER, H.ROBERT HORNTZ, J.E.SULSTON- 2002- genetic regulation of organ development and cell death

IMMUNITY

DEFINITION IMMUNITY- resistance exhibited by the host towards injury caused by micro organisms and their products In entirety, concerned with reaction of body against any foreign antigen

Protection by immune system : by, Recognition- distinguishes foreign from self distinguishes one pathogen from other by subtle chemical differences Response- recognition triggers response eliminates invader memory response (educating immune system to prepare itself for later attacks)

CLASSIFICATION

INNATE IMMUNITY Resistance to infection, by virtue of genetic and constitutional make up Not affected by prior contact with microbes or immunisation

TYPES OF INNATE IMMUNITY Species immunity: total or relative refractoriness to a pathogen by all members of a species. Eg.humans totally unsusceptible to plant pathogens. May be due to physiological or biochemical differences between tissues of different hosts Racial immunity: within a species, different races show difference in susceptibility to infections eg.high resistance of algerian sheep to anthrax people of negroid origin of USA are more susceptible to TB than caucasians genetic resistance to malaria in some african parts and mediterranean coast

Continued.. Individual immunity: differences in innate immunity exhibited by different individuals in a race homozygous twins exhibit similar levels of susceptibility and resistance to infections like TB leprosy but not so in heterozygous

FACTORS INFLUENCING INNATE IMMUNITYAGE: Very young and very old highly susceptible. Eg. 1.TORCH infections more common in fetus owing to immaturity of immune system inspite of maternal antibodies 2. tinea capitis of microsporum audouinii, gonococcus in girls undergoes spontaneous cure at puberty 3. poliomyelitis and chicken pox are severe in adults, due to hypersensitivity causing greater tissue damage

HORMONAL INFLUENCES: some endocrine disorders are with enhanced susceptibility corticosteroids depress hosts resistance by its anti inflammatory and antiphagocytic actions. But beneficial effect on endotoxins(neutralisation) staphylococcal infection common in DM, because of excess carbohydrates in tissues effects of stress to infections also due to release of steroids

NUTRITION: both cell mediated and humoral are reduced in malnutrition Eg. Mantoux test is negative in kwashiorkar Paradoxically, certain infections not clinically apparent in malnutrition. Eg. malarial infection may not induce fever in famine striken area

PHYSIOLOGICAL BARRIERS

MECHANISMS OF INNATE IMMUNITY EPITHELIAL SURFACES: Intact skin and mucous membrane of body. Skin possess bactericidal activity. Illustrated by frequent mycotic and pyogenic infections of persons who immerse their hand sin soap water for prologed periods Mucosa of respiratory tract. Cough reflex cilia of respiratory tract secretions phagocytic cells of pulmonary alveoli

Continued.. Mucosa of GIT: Mouth has saliva with inhibitroy effects on microbes. acidity of stomach rich and varied intestinal flora of ileum and colon Conjuctiva: flushing action of lacrimal secretions tears contain lysozyme ( thermolabile, lmw susbstance, contain muraminidase) genitourinary: flushing action of urine spermine and zinc in semen. acidity of vagina

Continued.. ANTIBACTERIAL SUBSTANCES IN BLOOD AND TISSUES: Complement system possess bactericidalproperty and plays important role Betalysin: active against anthrax and related bacilli Leukins and plakins: basic polypeptides Lactic acid in muscle and inflammatory zone Lactoperoxidase in milk Interferons protects from viral infections, produced by cells stimulated by live or killed virus

MICROBIAL ANTAGONISM: Resident skin flora of skin and mucous membranes prevent colonisation by pathogens CELLULAR FACTORS: Phagocytic cells classified into microphages and macrophages. Microphages: PMNs Macrophages: histiocytes, wandering ameboid cells of tissues, RE system and monocytes in blood They reach inflammatiory site by chemotactic substances and ingest the foreign particle like bacteria

INFLAMMATION: nonspecific defence mechanism Arterioles constrict then dilate increased blood flow Margination of leukocytes Diapedesis at site of injury Phagocytosis Outporing of plasma neutralise toxic products

FEVER: natural defence following infection Accelerate physiological process and also destroy infecting organism Therapeutic fever induction in syphylis patients before advent of penicillin

ACUTE PHASE REACTANTS: infection or injury cause rise of these plasma proteins CRP, mannose binding protein, alpha-1 acid glycoprotein, serum amyloid P component

ACQUIRED IMMUNITY Resistance that an individual acquires during life TYPES: Active passive

TYPES Resistance developed as a result of antigenic stimulus Durable, effective protection Immunity effective only after a lag period Immunological memory present Booster effect on subsequent dose Negative phase Not applicable in immunodeficient Resistance transmitted passively to recipient in readymade form Transient, less effective Immediate immunity No memory Subsequent dose less effective No negative phase Applicable in immunodeficient

ACTIVE IMMUNITY-NATURALresults from clinical or inapparent infection. Duration varies with type of pathogen Chicken pox and measles-lifelong Influenza- antigenic variation Common cold- infection by large no. of viruses syphylis- premunition Chancroid- may recur during active disease!

ACTIVE IMMUNITY-ARTIFICIAL Resistance induced by vaccines Live vaccines- immunity lasts for several years, booster may be necessary Killed vaccines- less immunogenic. Effective for short period only. require atleast 2 doses

PASSIVE IMMUNITYNATURAL: Resistance transferred passively from mother to baby Human colustrum rich in IgA, gives protection upto 3 months

PASSIVE IMMUNITY-ARTIFICIAL Passively transferred by administering antibodies. Used for prophylaxis and therapy Hyperimmune sera of human or animal origin -demerits of hypersensitivity and immune elimination convalescent sera- of patients recovering from infectious diseases pooled human gammaglobulin- of healthy persons

COMBINED IMMUNISATION: Whenever passive immunisation needed for immediate protection, ideal to put combined immunisation. Eg. tetanus prone wound, bite rabid animal

ADOPTIVE IMMUNITY: Injection of immunologically competent lymphocytes An extract of immunocompetent lymphocytes called transfer factor Used in diseases like lepromatous leprosy

MEASUREMENT OF IMMUNITY Testing resistance of individual to a challenge by the pathogen Convenient indicator- demonstration of specific antibodies Using techniques: agglutination,precipitation, complement fixation,hemagglutination,ELISA. In diphtheria- immunity to well defined Ag(toxin)- assessed by in vivo schick test

LOCAL IMMUNITY Concept proposed by BESREDKA in 1919. Of importance in treating infections that are either localised or where it is operative in combating infection at the site of primary entry of pathogen IgA- secreted locally, by plasma cells of mucosal surfaces, following intestinal exposure to an Ag mucosal or secretory immune system

HERD IMMUNITY Overall level of immunity in a community of importance in control of epidemics Eradication of communicable diseases depend on development of herd immunity

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