Introduction Introduction To To

ImmunologyImmunologyDr. yasmeen tajDr. yasmeen taj

DefinitionDefinition

The word “Immuis” means free The word “Immuis” means free from burden and “immunitas” from burden and “immunitas” means exemption from means exemption from government taxes and this government taxes and this provided the English terminology provided the English terminology Immunity.Immunity.

Immunity is a broad definition: Immunity is a broad definition: This is a protective or defense This is a protective or defense mechanism of our body, which mechanism of our body, which leads us to a healthy life.leads us to a healthy life.

Types Of ImmunityTypes Of Immunity Inborn or innate immunityInborn or innate immunity: It is present at : It is present at

birth; This is our First Line Of Defense.birth; This is our First Line Of Defense.

Acquired or specificAcquired or specific: It is not present at birth : It is not present at birth but becomes part of our immune system as the but becomes part of our immune system as the lymphoid system develops.lymphoid system develops.

1970: WHO defined immunity as immune 1970: WHO defined immunity as immune response to antigen ( Foreign body) in form ofresponse to antigen ( Foreign body) in form of

Humoral Humoral ( activation of B-lymhocytes)( activation of B-lymhocytes) Cellular Cellular (by activation of T-lymphocytes (by activation of T-lymphocytes

Cells Involved in Cells Involved in ImmunityImmunity

MacrophagesMacrophages B cellsB cells T cellsT cells

Important components of innate Important components of innate immunityimmunity

Factors that limit entry of microorganisms into the Factors that limit entry of microorganisms into the bodybody

Factor Factor Mode Of Mode Of ActionAction

-Keratin layer of intact skin -Acts as mechanical barrier-Keratin layer of intact skin -Acts as mechanical barrier

-Lysozyme in tears and other secretions -Degrades peptidoglycan in -Lysozyme in tears and other secretions -Degrades peptidoglycan in bacteria bacteria

cell wall cell wall

-Respiratory cilia -Elevate mucus containing -Respiratory cilia -Elevate mucus containing trapped organismstrapped organisms

-Low pH in stomach and vagina; -Retards growth of microbes-Low pH in stomach and vagina; -Retards growth of microbes

fatty acids in skinfatty acids in skin

-Surface phagocytes -Ingest and destroy microbes-Surface phagocytes -Ingest and destroy microbes

(eg. alveolar macrophages)(eg. alveolar macrophages)

-Defensins (cationic peptides) -Create pores in microbial -Defensins (cationic peptides) -Create pores in microbial membranemembrane

-Normal flora of throat, colon -Occupy receptors which -Normal flora of throat, colon -Occupy receptors which preventprevent

and vagina colonization by pathogens and vagina colonization by pathogens

Important components of innate Important components of innate immunityimmunity

Factors that limit growth of Factors that limit growth of microorganisms within the bodymicroorganisms within the body Natural killer cellsNatural killer cells

NeutrophilsNeutrophils Macrophages and dendritic Macrophages and dendritic

cellscells InferonsInferons ComplementComplement

Transferrin and lactoferrinTransferrin and lactoferrin

FeverFever

Inflammatory response Inflammatory response APOBEC3GAPOBEC3G ( (apolypoprotein is apolypoprotein is

RNA editing enzyme)RNA editing enzyme)

Kill virus infected cellsKill virus infected cells Ingest and destroy microbesIngest and destroy microbes Ingest and destroy microbes, and Ingest and destroy microbes, and

present antigen to helper T-cellspresent antigen to helper T-cells Inhibit viral replication Inhibit viral replication C3b is an opsonin, membrane C3b is an opsonin, membrane

attack complex creates holes in attack complex creates holes in bacterial membranesbacterial membranes

Sequester iron required for Sequester iron required for bacterial growthbacterial growth

Elevated temperature retards Elevated temperature retards bacterial growthbacterial growth

Limits spread of microbesLimits spread of microbes Causes hypermutation in Causes hypermutation in

retroviral DNA and mRNAretroviral DNA and mRNA

Macrophages and other antigen presenting cells such as Macrophages and other antigen presenting cells such as dendritic cells, participate in both the innate arm and dendritic cells, participate in both the innate arm and acquired arm of the immune system. They are in effect a acquired arm of the immune system. They are in effect a bridge between the two arms. As part of the innate arm they bridge between the two arms. As part of the innate arm they ingest and kill various microbes. They also present antigens ingest and kill various microbes. They also present antigens to helper T cells which is the essential first step in the to helper T cells which is the essential first step in the activation of the acquired arm.activation of the acquired arm.

Main Components of Innate and Main Components of Innate and acquired Immunity that contribute to acquired Immunity that contribute to

humoral ( antibody-mediated ) humoral ( antibody-mediated ) immunity and cell mediated immunityimmunity and cell mediated immunity

HumoralHumoral

ImmunityImmunityCell Cell mediatedmediated

ImmunityImmunity

InnateInnate ComplementComplement

NeutrophilNeutrophilMacrophageMacrophagess

Natural Natural killer cellskiller cells

AcquiredAcquired B cellsB cells

AntibodiesAntibodiesHelper TcellsHelper Tcells

Cytotoxic T Cytotoxic T cellscells

Specificity Of The Immune Specificity Of The Immune ResponseResponse

-Recognition of the foreign organisms by specific -Recognition of the foreign organisms by specific immune cellsimmune cells

-Activation of these immune cells to produce a -Activation of these immune cells to produce a specific response (eg,antibodies)specific response (eg,antibodies)

-Response that specifically targets the -Response that specifically targets the organisms for destruction organisms for destruction

Major Functions Of T Cells and B Major Functions Of T Cells and B cellscells

Antibody-Mediated Antibody-Mediated Immunity (B Cells)Immunity (B Cells)

1)1) Host defense against Host defense against infectioninfection

2)2) (Opsonize bacteria, (Opsonize bacteria, neutralize toxins and neutralize toxins and viruses)viruses)

3)3) Allergy (hypersensitivity) Allergy (hypersensitivity) eg, hay fever eg, hay fever anaphylactic shockanaphylactic shock

4)4) AutoimmunityAutoimmunity

Cell Mediated ImmunityCell Mediated Immunity

1) Host defense against 1) Host defense against infection (especially infection (especially M.tuberculosis, fungi and M.tuberculosis, fungi and virus infected cells)virus infected cells)

2) Allergy (hypersensitivity )eg 2) Allergy (hypersensitivity )eg poison oakpoison oak

3) Graft and tumor rejection3) Graft and tumor rejection

4) Regulation of antibody 4) Regulation of antibody response (help and response (help and suppression)suppression)

Important features Of Innate and Acquired Important features Of Innate and Acquired ImmunityImmunity

Type of Immunity Specificity Effective immediately Improves Type of Immunity Specificity Effective immediately Improves Has Has

after exposure to After after exposure to After Exposure memoryExposure memory

microbemicrobe

Innate Innate Nonspecific Yes in No Nonspecific Yes in No No No

minutesminutes

Acquired Acquired Highly No--requires Yes Highly No--requires Yes Yes Yes

specific several daysspecific several days

before becomingbefore becoming

effective effective

Active Active and and PassivePassive Immunity Immunity

Active Active immunity is resistance acquired after immunity is resistance acquired after contact withcontact with

foreign antigens, eg, microorganisimsforeign antigens, eg, microorganisims This contact may consist of :This contact may consist of : Clinical or subclinical infectionsClinical or subclinical infections Immunization with live or killed infectious Immunization with live or killed infectious

agents or their antigens.agents or their antigens. Exposure to microbial products (eg, toxins and Exposure to microbial products (eg, toxins and

toxoids)toxoids)

Passive immunityPassive immunity Passive immunity is resistance Passive immunity is resistance

based on antibodies preformed in based on antibodies preformed in another host.another host.

Other forms of passive immunity Other forms of passive immunity are IgG passed from the mother to are IgG passed from the mother to the fetus during pregnancy.the fetus during pregnancy.

IgA passed from the mother to the IgA passed from the mother to the newborn during breast feeding.newborn during breast feeding.

Passive activePassive active immunityimmunity

Passive-active immunity involves giving Passive-active immunity involves giving both preformed antibodies (immune both preformed antibodies (immune globulins) to provide immediate protection globulins) to provide immediate protection andand

Vaccine to provide long term protectionVaccine to provide long term protection These preparations should be given at These preparations should be given at

different sites in the body to prevent the different sites in the body to prevent the antibodies from neutralizing the antibodies from neutralizing the immunogen in the vaccine.immunogen in the vaccine.

This approach is used in the prevention of This approach is used in the prevention of Tetanus, Rabies and Hepatitis B Tetanus, Rabies and Hepatitis B

Immunogen and AntigenImmunogen and Antigen

When foreign substances (Ag) are introduced into When foreign substances (Ag) are introduced into the body, they lead to anti-foreign substance the body, they lead to anti-foreign substance

( Anti-body ) formation( Anti-body ) formation ImmunogenicImmunogenic when they are able to produce when they are able to produce

specific immune response; that they will stimulate specific immune response; that they will stimulate immune cells and then give rise to immunological immune cells and then give rise to immunological reaction (Humoral or cellular).reaction (Humoral or cellular).

AntigenicAntigenic substances cannot directly yield immune substances cannot directly yield immune response, but need some help by some proteins) response, but need some help by some proteins) and then and then

They can react with antibodies.They can react with antibodies. All immunogens are antigenic but not all All immunogens are antigenic but not all

antigens are immunogenicantigens are immunogenic

AntigenAntigenAntigen may be: A) CompleteAntigen may be: A) Complete

B) Incomplete B) Incomplete Properties of antigen( Foreign Properties of antigen( Foreign

substances) to be Immunogenicsubstances) to be Immunogenic 1) 1) ForeignnessForeignness A) A) Autologous antigens Autologous antigens are self antigens and there will are self antigens and there will

be no immune response. be no immune response. B) B) Allogenic antigens Allogenic antigens are from the same species and are from the same species and

there may be reaction, eg. Blood transfusion, kidney there may be reaction, eg. Blood transfusion, kidney transplant.transplant.

C) C) Heterologous antigens Heterologous antigens are from different speciesare from different species These antigens will be rejected and there will be severe These antigens will be rejected and there will be severe

immune responseimmune response

CChemical-Structural complexityhemical-Structural complexity A certain amount of chemical complexity is required; eg A certain amount of chemical complexity is required; eg

aminoacidaminoacid Homoplymers are less immunogenic then heteropolymers Homoplymers are less immunogenic then heteropolymers

containing containing Two or three different aminoacidsTwo or three different aminoacids

Molecular SizeMolecular Size The most potent imunogens are proteins with high The most potent imunogens are proteins with high

molecular weightmolecular weight ie, above 100,000.ie, above 100,000. Generally, molecules with molecular weight below 10,000 Generally, molecules with molecular weight below 10,000

are weakly immunogenic, and very small ones eg an are weakly immunogenic, and very small ones eg an aminoacid are nonimmunogenicaminoacid are nonimmunogenic

EpitopeEpitope Epitopes are small chemical groups on the antigen Epitopes are small chemical groups on the antigen

molecule that can elicit and react with antibodymolecule that can elicit and react with antibody The antigen has variable number of epitopes and this is The antigen has variable number of epitopes and this is

called the valency of the antigen called the valency of the antigen

HaptenHapten

Hapten is a greek word meaning to fasten. Hapten is a greek word meaning to fasten. These are partial antigens. These are not These are partial antigens. These are not immunogenic.immunogenic.

Hapten needs carrier proteins like albumin, Hapten needs carrier proteins like albumin, globulin and synthetic polypeptide to become globulin and synthetic polypeptide to become immunogenic.immunogenic.

Hapten (Hp)+Carrier Protein (Cp) Hapten (Hp)+Carrier Protein (Cp) Hp+Cp-Hp+Cp-Ab formation against haptenAb formation against hapten

Antibiotics, analgesics, penicilin and alpha-Antibiotics, analgesics, penicilin and alpha-methyldopamethyldopa

Therefore haptens are antigenic and not Therefore haptens are antigenic and not immunogenicimmunogenic

ADJUVANTSADJUVANTS

Adjuvant word is from Latin means Adjuvant word is from Latin means “aiding”and these are “aiding”and these are immunopotentiating agents.immunopotentiating agents.

These are of two typesThese are of two types ( Ag+Ab)---( Ag+Ab)---Injected---->Increased Injected---->Increased

immune response immune response

Today, adjuvants play an important role in the efficacy Today, adjuvants play an important role in the efficacy of vaccines. Stimulating the correct immune response of vaccines. Stimulating the correct immune response is a must when selecting an adjuvant to use for a new is a must when selecting an adjuvant to use for a new vaccine. Since one adjuvant alone is rarely optimal for vaccine. Since one adjuvant alone is rarely optimal for all antigens, it is critical to have a selection of different all antigens, it is critical to have a selection of different types of adjuvants for evaluation with your antigen.types of adjuvants for evaluation with your antigen.   MVP offers a selection of oil emulsion based adjuvants, MVP offers a selection of oil emulsion based adjuvants, polymer based adjuvants and co-polymer based polymer based adjuvants and co-polymer based

adjuvants.adjuvants.  

Enhance the response to immunogens with Enhance the response to immunogens with Imject Adjuvants.Imject Adjuvants.

Adjuvants are nonspecific stimulators Adjuvants are nonspecific stimulators of the immune response. When mixed of the immune response. When mixed with an antigen or immunogen, with an antigen or immunogen, adjuvants help to deposit or sequester adjuvants help to deposit or sequester the injected material thereby helping to the injected material thereby helping to increase antibody response. Adjuvants increase antibody response. Adjuvants enhance the immune response to enhance the immune response to compounds that are already compounds that are already immunogenic; they do not confer immunogenic; they do not confer immunogenicity to non-immunogenic immunogenicity to non-immunogenic haptens. To make prospective antigens haptens. To make prospective antigens more immunogenic, it is necessary to more immunogenic, it is necessary to conjugate them to a carrier protein or conjugate them to a carrier protein or some other complex, immunogenic some other complex, immunogenic molecule.molecule.

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