immunity - concepts - antigen, antibody, ag-ab reactions, vaccines

IMMUNITYIMMUNITYConceptsConcepts

(Immunity, antigens, antibodies, antigen (Immunity, antigens, antibodies, antigen antibody reactions, vaccines)antibody reactions, vaccines)

Dr. Ashish V. JawarkarDr. Ashish V. JawarkarM.DM.D..

INFECTIONINFECTION

Relationship between host and Relationship between host and infectious agentinfectious agent

Saprophytes – live on dead tissue – do not Saprophytes – live on dead tissue – do not cause diseasescause diseases

Parasites – multiply in hosts Parasites – multiply in hosts Pathogens – cause diseasesPathogens – cause diseases Commensals – donot cause diseases Commensals – donot cause diseases

normally – only during immunosuppressionnormally – only during immunosuppression

InfectionInfection

Lodging of parasite in tissues of hostLodging of parasite in tissues of host This is not necessarily diseaseThis is not necessarily disease

DiseaseDisease

Any deviation from good healthAny deviation from good health

Infectious diseaseInfectious disease

Any deviation from good health due to Any deviation from good health due to infectious agentinfectious agent

InfectionInfection

Primary infection – in healthy hostPrimary infection – in healthy host Re-infection – repeat infection by the Re-infection – repeat infection by the

same agentsame agent Secondary infection – second infection by Secondary infection – second infection by

a new agenta new agent

InfectionInfection

Acute – rapid progressAcute – rapid progress typhoidtyphoid

Chronic – slow onset and progressChronic – slow onset and progress tuberculosistuberculosis

InfectionInfection

Localised – restricted to specific areaLocalised – restricted to specific area SystemicSystemic

InfectionInfection

Clinical – with symptomsClinical – with symptoms Subclinical – no obvious symptomsSubclinical – no obvious symptoms

InfectionInfection

Oppurtunistic – when host resistance is Oppurtunistic – when host resistance is loweredlowered

Nosocomial – acquired from hospital, not Nosocomial – acquired from hospital, not present on admissionpresent on admission

Laboratory acquired – from laboratoryLaboratory acquired – from laboratory

Sources of infectionSources of infection

Humans – carriersHumans – carriers Animals – zoonosesAnimals – zoonoses InsectsInsects Soil and waterSoil and water FoodFood

Methods of transmissionMethods of transmission

Contact – direct, indirect, sexualContact – direct, indirect, sexual InhalationInhalation IngestionIngestion InoculationInoculation InsectsInsects Congenital – verticalCongenital – vertical IatrogenicIatrogenic

PathogenicityPathogenicity

Capacity of micro organisms to cause Capacity of micro organisms to cause diseasesdiseases

VirulenceVirulence

Degree of pathogenicityDegree of pathogenicity

Factors predisposing to Factors predisposing to pathogenicitypathogenicity

Adhesion – attachment due to receptors Adhesion – attachment due to receptors and ligandsand ligands

Factors predisposing to Factors predisposing to pathogenicitypathogenicity

InvasivenessInvasiveness Highly invasive – septicemia following wound Highly invasive – septicemia following wound

infection by streptococciinfection by streptococci Less invasive – staphylococcal abscessLess invasive – staphylococcal abscess

Factors predisposing to Factors predisposing to pathogenicitypathogenicity

ToxinsToxins Exo toxins – released outsideExo toxins – released outside Endotoxins – LPS (part of cell wall)Endotoxins – LPS (part of cell wall)

Factors predisposing to Factors predisposing to pathogenicitypathogenicity

CommunicabilityCommunicability Ability to spread from one host to otherAbility to spread from one host to other Ensures survivalEnsures survival

Types of infectious diseasesTypes of infectious diseases

Endemic – constantly present in a Endemic – constantly present in a particular area particular area Eg typhoidEg typhoid

Epidemic – one that spreads rapidly Epidemic – one that spreads rapidly involving many persons at the same timeinvolving many persons at the same time influenzainfluenza

Pandemic – spreads through many areas Pandemic – spreads through many areas of the world at the same timeof the world at the same time

IMMUNITYIMMUNITY

ImmunityImmunity

Resistance exhibited by host towards Resistance exhibited by host towards micro organismsmicro organisms

Types of immunityTypes of immunity

Innate Innate Immunity that a person possesses due to Immunity that a person possesses due to

genetic make upgenetic make up AcquiredAcquired

ActiveActive• Acquired after an exposure to infection (natural) / Acquired after an exposure to infection (natural) /

artificially induced (vaccine)artificially induced (vaccine) PassivePassive

• Injection of antibodiesInjection of antibodies

Innate immunityInnate immunity Epithelial surfacesEpithelial surfaces

SkinSkin MucosaMucosa SalivaSaliva UrineUrine

Antibacterial systems in blood and tissuesAntibacterial systems in blood and tissues Complement systemComplement system Interferons Interferons

Microbial antagonismMicrobial antagonism FloraFlora

CellsCells macrophagesmacrophages NeutrophilsNeutrophils NK cellsNK cells

InflammationInflammation FeverFever Acute phase proteinsAcute phase proteins

CRPCRP

Acquired (Active)Acquired (Active)

Due to stimulation by an antigen (like Due to stimulation by an antigen (like microorganism)microorganism) Long lastingLong lasting Associated with memoryAssociated with memory

Active immunityActive immunity

Natural activeNatural active Clinical or subclinical infectionClinical or subclinical infection Eg chicken poxEg chicken pox

Artificial activeArtificial active vaccinesvaccines

Passive immunityPassive immunity

Natural passiveNatural passive PlacentaPlacenta Breast milkBreast milk

Artificial passiveArtificial passive Rh iso immunisationRh iso immunisation

HERD IMMUNITYHERD IMMUNITY

Overall level of immunity in a communityOverall level of immunity in a community Useful in case of epidemicsUseful in case of epidemics

OVERVIEW OF STRUCTURE OVERVIEW OF STRUCTURE AND FUNCTION OF IMMUNE AND FUNCTION OF IMMUNE

SYSTEMSYSTEM

LymphocytesLymphocytes

B lymphocytes – produce antibodies – B lymphocytes – produce antibodies – Humoral immunityHumoral immunity

T lymphocytes – cell mediated immunityT lymphocytes – cell mediated immunity

T cell maturationT cell maturation(central lymphoid organs)(central lymphoid organs)

Central lymphoid organsCentral lymphoid organs

Bone marrowBone marrow ThymusThymus

B cell maturationB cell maturation(Peripheral lymphoid organs)(Peripheral lymphoid organs)

Peripheral lymphoid organsPeripheral lymphoid organs

Lymph nodesLymph nodes SpleenSpleen Mucosa associated lymphoid tissue Mucosa associated lymphoid tissue

(MALT)(MALT) TonsilsTonsils Peyer’s patchesPeyer’s patches

Other cells of the immune systemOther cells of the immune system

ANTIGEN PRESENTING CELLS (APCs)ANTIGEN PRESENTING CELLS (APCs)

Phagocytes (macrophages)Phagocytes (macrophages)

Dendritic cellsDendritic cellseg Langerhan’s celleg Langerhan’s cell

MAJOR HISTOCOMPATIBILITY MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)COMPLEX (MHC)

Differentiates between self and foreignDifferentiates between self and foreign

ANTIGENS AND ANTIBODIESANTIGENS AND ANTIBODIES

ANTIGENANTIGEN

Any substance which, when introduced Any substance which, when introduced into the body stimulates production of into the body stimulates production of antibodyantibody

ANTIBODYANTIBODY

Substance that is produced by the body Substance that is produced by the body against the antigen is an antibodyagainst the antigen is an antibody

It is a protein It is a protein Almost 25% of our body proteins are Almost 25% of our body proteins are

ImmunoglobulinsImmunoglobulins

Types of antigensTypes of antigens

Xenoantigens – from different speciesXenoantigens – from different species Alloantigens – from same speciesAlloantigens – from same species Autoantigen – lens protein, testisAutoantigen – lens protein, testis Heterophile antigen – closely related Heterophile antigen – closely related

antigens from different speciesantigens from different species

Antigens – on the basis of ability to Antigens – on the basis of ability to cause diseasecause disease

Immunogen – develop undesired response Immunogen – develop undesired response – transplants– transplants

Tolerogens – induce immunological Tolerogens – induce immunological tolerance due to memorytolerance due to memory

Allergens – over reactionsAllergens – over reactions Vaccines – protective responseVaccines – protective response

Biological classes of antigensBiological classes of antigens

T cell dependentT cell dependent T cell independentT cell independent

Antibodies - typesAntibodies - types

Ig G Ig G Ig AIg A Ig MIg M Ig DIg D Ig EIg E

StructureStructure

IgGIgG

Can be transported across placenta, Can be transported across placenta, provides immunity to new bornprovides immunity to new born

Neutralize virusesNeutralize viruses Encourage phagocytosisEncourage phagocytosis

IgAIgA

Main immunoglobulin in mother’s milk, Main immunoglobulin in mother’s milk, saliva and tearssaliva and tears

Called secretory IgCalled secretory Ig Local immunityLocal immunity

IgMIgM

Earliest Ig to be synthesized by fetusEarliest Ig to be synthesized by fetus Not transported across placentaNot transported across placenta Presence useful in diagnosis of congenital Presence useful in diagnosis of congenital

infections such as syphilis, rubella, HIV infections such as syphilis, rubella, HIV and toxoplasmosisand toxoplasmosis

Responsible for protection from blood Responsible for protection from blood invasion by microorganismsinvasion by microorganisms

IgDIgD

Occur on the surface of B lymphocytes Occur on the surface of B lymphocytes (with IgM) and act as receptors for (with IgM) and act as receptors for antigens antigens

IgEIgE

On mast cells and basophilsOn mast cells and basophils Responsible for anaphylaxis Responsible for anaphylaxis

(hypersensitivity)(hypersensitivity)

In shortIn short

IgG - protects body fluidsIgG - protects body fluids IgA – protects body surfacesIgA – protects body surfaces IgM – protects the blood streamIgM – protects the blood stream IgD – receptor on surface of B IgD – receptor on surface of B

lymphocyteslymphocytes IgE – mediates anaphylaxisIgE – mediates anaphylaxis

Antigen – Antibody reactionsAntigen – Antibody reactions

Antigen and antibody can react and causeAntigen and antibody can react and cause PrecipitationPrecipitation AgglutinationAgglutination Lysis Lysis Killing of live antigens (micro organisms)Killing of live antigens (micro organisms)

PrecipitationPrecipitation

AgglutinationAgglutination

LysisLysis

Killing of microorganismsKilling of microorganisms

General features of antigen – General features of antigen – antibody reactionantibody reaction

Reaction is specificReaction is specific Combination occurs at surface – so Combination occurs at surface – so

surface antigens are relevantsurface antigens are relevant Combination is firm but reversibleCombination is firm but reversible Antigen and antibody can combine in Antigen and antibody can combine in

variable proportionsvariable proportions

Combinations occur at surfaceCombinations occur at surface

Combination is reversibleCombination is reversible

Affinity – intensity of attractionAffinity – intensity of attraction

Avidity – strength of bondAvidity – strength of bond

Combine in variable proportionsCombine in variable proportions

ApplicationsApplications

Precipitation reactionsPrecipitation reactions Agglutination reactionsAgglutination reactions Complement fixation testsComplement fixation tests Neutralization testsNeutralization tests Labelled immunoassaysLabelled immunoassays

ImmunofluorescenceImmunofluorescence Radio immunoassayRadio immunoassay Enzyme linked immunosorbent assay (ELISA)Enzyme linked immunosorbent assay (ELISA)

Precipitation reactionsPrecipitation reactions

Precipitation – when a soluble antigen Precipitation – when a soluble antigen combines with its antibody – antigen combines with its antibody – antigen antibody complex forms an insoluble ppt in antibody complex forms an insoluble ppt in the mediumthe medium

Prozone

Ring test – to group streptococciRing test – to group streptococci

Slide test – VDRL for syphilisSlide test – VDRL for syphilis Tube test – Widal testTube test – Widal test

Agglutination reactionsAgglutination reactions

For blood groupingFor blood grouping

Labelled immunoassaysLabelled immunoassays

Radio immuno assayRadio immuno assay

ELISAELISA

HIVHIV

HYPERSENSITIVITY REACTIONS(ALLERGY)

.

Definition

• Hypersensitivity – exaggerated immune response

• Allergen – substance which causes hypersensitivity

• Hypersensitivity reaction occurs after second exposure to antigen

• First exposure causes sensitisation

Types

• Based on time between second exposure and clinical reaction – – Immediate hypersensitivity– Delayed hypersensitivity

Types

• Type I – anaphylactic

• Type II – cytotoxic

• Type III – immune complex

• Type IV – delayed type

Type I hypersensitivity (Allergy)

• a/k/a anaphylaxis (ana – without, phylaxis – protection)

degranulation

• Releases histamine, serotonin, cytokines and prostaglandins

• These cause– Smooth muscle contraction (larynx, lungs)– Leaky blood vessels (rhinorrhoea, oral

secretions)– Intestinal fluid secretion (diarrhoea and

vomitting)

• Systemic anaphylaxis is fatal within minutes

• Unless given adrenaline immediately

allergens

• Nuts

• Seafood

• Eggs

• Insect venom

• Drugs

Atopy

• Anaphylaxis in a localised area

• Eg asthma, hay fever

• Allergens here include– Dust– Pollen– Eggs – milk

TYPE II HS

• Mediated by IgG or IgM (with complement) antibodies

• Examples are autoimmune hemolytic anemias and hemolytic disease of newborn

Type III HS

• Complexes of antigen and antibody get deposited in various sites of the body like– Kidneys– Joints– Skin– Eye

• Examples– Vasculitis– Arthus reaction– Serum sickness

Type IV HS

• Take 2-3 days to occur

• Delayed HS

• Mediated by T cells – antibodies not involved

• Examples– Tuberculin reaction– Contact dermatitis

Tuberculin reaction(Montaux test)

• To know whether the person is infected by TB

• Injection of PPD into skin

• Look for raised area (induration) after 48 hours

Contact dermatitis

• Skin reaction caused by application of various chemicals such as nickel, chromium, drugs such as penicillin and toiletries.

Contact dermatitis

Granulomatous reactions

• Occur due to intracellular pathogens such as Mycobacteria, fungi and Leishmania

• Phagocytes are unable to remove and digest them and become giant cells with multiple nuclei

Summary

VACCINES AND IMMUNISATION

Immunising agents

• Vaccines (active – slower, long lasting)

• Immunoglobulins (passive – faster, short lasting)

Vaccine

• Substance designed to induce production of antibodies against a specific disease causing organism

Types

• Live – live but attenuated organisms– Eg BCG, oral typhoid vaccine, oral polio

vaccine

• Killed – typhoid, cholera, injectable polio vaccine

• Toxoids - DPT

Immunoglobulins (Passive)

• Administering directly antibodies

• Newborns receive passive immunisation from colostrum

• Eg – Hep B antibodies given after accidental exposure

• Protect immunodeficient individuals

Vaccines available

Herd immunity

Contact immunity

• Children immunised with live OPV shed virus in feces

• An unimmunised family member / community member who is exposed to this shed virus develops immunity as well

National immunisation schedule (Indian academiy of Paediatrics)

Optional immunisation

• Chicken pox

• Influenzae

• HPV

• Yellow fever

• Japanese encephalitis

• Pneumococcal vaccine