IMMUNITY IMMUNITY Concepts Concepts (Immunity, antigens, (Immunity, antigens, antibodies, antigen antibody antibodies, antigen antibody reactions, vaccines) reactions, vaccines) Dr. Ashish V. Jawarkar Dr. Ashish V. Jawarkar M.D M.D.
May 07, 2015
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