antigens and immunogens

8/9/2019 Antigens and Immunogens

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Antigens and immunogens



There are two major branches of theThere are two major branches of the

adaptive immune responsesadaptive immune responses::

11..Humoral immunityHumoral immunity: humoral immunity: humoral immunity

involves the production of involves the production of antibody moleculesantibody

molecules

in response to an antigenin response to an antigen and is mediated byand is mediated byB-lymphocytesB-lymphocytes..

22..Cell-mediated immunityCell-mediated immunity: Cell-mediated: Cell-mediatedimmunity is mediated byimmunity is mediated by T-lymphocytesT-lymphocytes..



DEFINITIONS

A. Immunogen - A substance that

induces a specific immune response.

B. Antigen (Ag) - A substance that reacts

with the products of a specific immune

response.



DEFINITIONS

C. Hapten - A substance that is non-immunogenic but which can react with theproducts of a specific immune response.

Haptens are small molecules which couldnever induce an immune response whenadministered by themselves but which canwhen coupled to a carrier molecule. Free

haptens, however, can react with products of the immune response after such productshave been elicited. Haptens have the propertyof antigenicity but not immunogenicity.



DEFINITIONS

D. Epitope or Antigenic Determinant -

That portion of an antigen that combines

with the products of a specific immune

response.

E. Antibody (Ab) _ A specific protein

which is produced in response to an

immunogen and which reacts with anantigen.



FACTORS INFLUENCINGFACTORS INFLUENCING

IMMUNOGENICITY IMMUNOGENICITY A.A. Contribution of the ImmunogenContribution of the Immunogen

11..ForeignnessForeignness - The immune system- The immune system normallynormally

discriminates between self and non-self suchdiscriminates between self and non-self suchthat only foreign molecules are immunogenicthat only foreign molecules are immunogenic..

22..SizeSize - There is not absolute size above which- There is not absolute size above which

a substance will be immunogenic. However, ina substance will be immunogenic. However, ingeneral, the larger the molecule the moregeneral, the larger the molecule the moreimmunogenic it is likely to beimmunogenic it is likely to be..



33..Chemical CompositionChemical Composition - In general, the- In general, themore complex the substance is chemically themore complex the substance is chemically themore immunogenic it will be. The antigenicmore immunogenic it will be. The antigenicdeterminants are created by thedeterminants are created by the primaryprimary sequence of residues in the polymer and/or bysequence of residues in the polymer and/or bythethe secondarysecondary,, tertiarytertiary or or quaternaryquaternary structurestructure

of the moleculeof the molecule..

44..Physical formPhysical form - In general- In general particulate particulate

antigens are more immunogenic thanantigens are more immunogenic than solublesoluble ones andones and denatured denatured antigens moreantigens moreimmunogenic than theimmunogenic than the nativenative formform..



B.B. Contribution of the Biological SystemContribution of the Biological System

11..Genetic FactorsGenetic Factors - Some substances are- Some substances areimmunogenic in oneimmunogenic in one speciesspecies but not in another. Similarly,but not in another. Similarly,some substances are immunogenic in onesome substances are immunogenic in one individualindividual butbutnot in others (not in others (i.e.i.e. responders and non-responders). Theresponders and non-responders). Thespecies or individuals may lack or havespecies or individuals may lack or have altered genesaltered genes

that code for the receptors for antigen on B cells and Tthat code for the receptors for antigen on B cells and Tcells or they maycells or they may not have the appropriate genesnot have the appropriate genes neededneededfor the APC to present antigen to the helper T cellsfor the APC to present antigen to the helper T cells..

22..AgeAge - Age can also influence immunogenicity. Usually- Age can also influence immunogenicity. Usually

thethe very youngvery young and theand the very oldvery old have ahave a diminished abilitydiminished ability to mount an immune response in response to anto mount an immune response in response to animmuonogenimmuonogen..



C.C. Method of AdministrationMethod of Administration

11..DoseDose - The dose of administration of an immunogen- The dose of administration of an immunogen

can influence its immunogenicity. There is a dose of can influence its immunogenicity. There is a dose of

antigen above or below which the immune response willantigen above or below which the immune response will

not be optimalnot be optimal..

22..RouteRoute - Generally the- Generally the subcutaneoussubcutaneous route is better route is better

than thethan the intravenousintravenous or intra gastric routes. The route of or intra gastric routes. The route of

antigen administration can also alter theantigen administration can also alter the naturenature of theof the

responseresponse



Intravenous (iv): into a veinIntradermal (id): into the skin

Subcutaneous (sc): beneath the skinIntramuscular (im): into a muscle

Intraperitoneal (ip): into the peritoneal cavity

The administration route strongly influences which immune organs and cell populations will be involved in the response.

Antigen administered intravenously is carried first to thespleen, whereas antigen administered subcutaneously moves

first to local lymph nodes. Differences in the lymphoid cellsthat populate these organs may be reflected in the subsequent

immune response.



33..AdjuvantsAdjuvants -Substances that can enhance-Substances that can enhance

the immune response to an immunogen arethe immune response to an immunogen are

calledcalled adjuvantsadjuvants. The use of adjuvants,. The use of adjuvants,

however, is often hampered by undesirablehowever, is often hampered by undesirable

side effects such as fever and inflammationside effects such as fever and inflammation..



Adjuvants are often used to

boost the immune response

when an antigen has low immunogenicity

or when only small amounts of an antigen

are available.



CHEMICAL NATURE OFCHEMICAL NATURE OF

IMMUNOGENSIMMUNOGENS►A.A. ProteinsProteins -The vast majority of immunogens-The vast majority of immunogens

are proteins. These may beare proteins. These may be pure proteinspure proteins or theyor theymay bemay be glycoproteinsglycoproteins oror lipoproteinslipoproteins. In general,. In general,proteins are usuallyproteins are usually very goodvery good immunogensimmunogens..

►B.B. PolysaccharidesPolysaccharides -- Pure polysaccharidesPure polysaccharides andandllipopolysaccharidesipopolysaccharides areare goodgood immunogensimmunogens..►C.C. Nucleic AcidsNucleic Acids - Nucleic acids are usually- Nucleic acids are usually

poorlypoorly immunogenic. However they may becomeimmunogenic. However they may becomeimmunogenic when they are single stranded orimmunogenic when they are single stranded or

complexed with proteinscomplexed with proteins.. ►D.D. LipidsLipids - In general lipids are- In general lipids are non-non-immunogenicimmunogenic, although they may be haptens., although they may be haptens.SomeSome glycolipidsglycolipids andand phospholipidsphospholipids can stimulatecan stimulate

T cells and produce a cell-mediated immune T cells and produce a cell-mediated immuneresponseresponse..



TYPES OF ANTIGENSTYPES OF ANTIGENS

►A.A. T-independent AntigensT-independent Antigens – T-– T-

independent antigens are antigensindependent antigens are antigens

which can directly stimulate the B cellswhich can directly stimulate the B cells

to produce antibodyto produce antibody without thewithout therequirement for T cell helprequirement for T cell help. In general,. In general,

polysaccharidespolysaccharides are T-independentare T-independent

antigens. The responses to theseantigens. The responses to theseantigens differ from the responses toantigens differ from the responses to

other antigensother antigens..



►Properties of T-independent Properties of T-independent antigensantigens::

►

►a. Polymeric structurea. Polymeric structure - These- These

antigens are characterized byantigens are characterized by thethesamesame antigenic determinantantigenic determinantrepeated many timesrepeated many times as illustratedas illustratedin Figure 1in Figure 1..

►



►b. Polyclonal activation of B cellsb. Polyclonal activation of B cells - Many of these- Many of these

antigens can activate B cell clones specific forantigens can activate B cell clones specific for

other antigens (other antigens (polyclonal activationpolyclonal activation). T-). T-independent antigens can be subdivided into Typeindependent antigens can be subdivided into Type

1 and Type 2 based on their ability to polyclonally1 and Type 2 based on their ability to polyclonally

activate B cells.activate B cells. Type 1 Type 1 T-independent antigens are T-independent antigens are

polyclonal activators whilepolyclonal activators while

Type 2 Type 2

antigens are notantigens are not

.

.

►c. Resistance to degradationc. Resistance to degradation - T-independent- T-independent

antigens are generally more resistant toantigens are generally more resistant to

degradation and thus theydegradation and thus they persist for longerpersist for longerperiods of timeperiods of time and continue to stimulate theand continue to stimulate the

immune systemimmune system..



►B.B. T-dependent AntigensT-dependent Antigens – T-– T-

dependent antigens are those that dodependent antigens are those that do

not directly stimulate the production of not directly stimulate the production of

antibody without the help of T cells.antibody without the help of T cells.

ProteinsProteins are T-dependent antigens.are T-dependent antigens.

Structurally these antigens areStructurally these antigens arecharacterized by a few copies of characterized by a few copies of manymany different antigenic determinantsdifferent antigenic determinants asas

illustrated in the Figure 2illustrated in the Figure 2..



HAPTEN-CARRIERHAPTEN-CARRIER

CONJUGATESCONJUGATES►A.A. DefinitionDefinition – Hapten-carrier conjugates– Hapten-carrier conjugates

are immunogenic molecules to whichare immunogenic molecules to which

haptens have been covalently attached. Thehaptens have been covalently attached. The

immunogenic molecule is called the carrierimmunogenic molecule is called the carrier..



►B.B. StructureStructure - Structurally these conjugates- Structurally these conjugates

are characterized by havingare characterized by having native antigenicnative antigenic

determinantsdeterminants of the carrier as well as newof the carrier as well as newdeterminants created by the hapten (determinants created by the hapten (haptenichaptenic determinantsdeterminants) as illustrated in the Figure 3) as illustrated in the Figure 3..

► The actual determinant created by the The actual determinant created by the

hapten consists of thehapten consists of the haptenhapten and aand a few of thefew of theadjacent residuesadjacent residues, although the antibody, although the antibody

produced to the determinant will also reactproduced to the determinant will also react

with free hapten. In such conjugates the typewith free hapten. In such conjugates the type

of carrier determines whether the response willof carrier determines whether the response willbe T-independent or T-dependentbe T-independent or T-dependent..



33..Number Number - Although, in theory, each 4-8- Although, in theory, each 4-8

residues can constitute a separate antigenicresidues can constitute a separate antigenic

determinant,determinant, in practicein practice, the number of , the number of antigenic determinants per antigenantigenic determinants per antigen is muchis much

lower lower than what would theoretically bethan what would theoretically be

possiblepossible.. Usually the antigenic determinants areUsually the antigenic determinants are

limited to thoselimited to those portions of the antigen thatportions of the antigen that

are accessibleare accessible to antibodies as illustrated into antibodies as illustrated inthe Figure 4 (antigenic determinants arethe Figure 4 (antigenic determinants are

indicated in blackindicated in black).).



A-Lock and key concept A-Lock and key concept

B-Non covalent bondsB-Non covalent bonds

** Hydrogen bondsHydrogen bonds

** Electrostatic bondsElectrostatic bonds

** Van der Waals forecesVan der Waals foreces

** Hydrophobic bondsHydrophobic bonds

C-ReversibleC-Reversible



B-Determinants recognized by T cellsB-Determinants recognized by T cells

11..CompositionComposition - Antigenic determinants recognized by T- Antigenic determinants recognized by Tcells are created by thecells are created by the primary sequenceprimary sequence of amino acids inof amino acids inproteins.proteins. T cells do not recognize polysaccharide or nucleicT cells do not recognize polysaccharide or nucleicacid antigens. This is why polysaccharides are generally T-acid antigens. This is why polysaccharides are generally T-independent antigens andindependent antigens and proteinsproteins are generally T-dependentare generally T-dependent

antigensantigens.. The determinantsThe determinants needneed notnot be located on the exposedbe located on the exposedsurface of the antigensurface of the antigen since recognition of the determinant bysince recognition of the determinant byT cells requires that the antigen be proteolytically degradedT cells requires that the antigen be proteolytically degradedinto smaller peptidesinto smaller peptides..

Free peptides are not recognized by T cells, rather theFree peptides are not recognized by T cells, rather thepeptides associate with molecules coded for by the major peptides associate with molecules coded for by the major histocompatibility complex (MHC) and it is thehistocompatibility complex (MHC) and it is the complex of complex of MHC molecules + peptideMHC molecules + peptide that is recognized by T cells. Somethat is recognized by T cells. SomeT cells can recognizeT cells can recognize lipidslipids in conjunction with a MHC-likein conjunction with a MHC-likemolecule calledmolecule called CD1CD1..



T helper cells → peptde + MHC (2T helper cells → peptde + MHC (2))

Cytotoxic T cells → peptde + MHC (1Cytotoxic T cells → peptde + MHC (1))



22..SizeSize - In general antigenic determinants are small- In general antigenic determinants are smalland are limited to approximately 8-15 amino acidsand are limited to approximately 8-15 amino acids..

33..Number Number -Although, in theory, each 8-15 residues-Although, in theory, each 8-15 residues

can constitute a separate antigenic determinant, incan constitute a separate antigenic determinant, inpractice, the number of antigenic determinants per practice, the number of antigenic determinants per

antigen is much less than what would theoretically beantigen is much less than what would theoretically bepossible. The antigenic determinants are limited topossible. The antigenic determinants are limited tothosethose portions of the antigen that can bind to MHCportions of the antigen that can bind to MHCmolecules.molecules. This is why there can be differences inThis is why there can be differences in

the responses of different individualsthe responses of different individuals..



Examples of superantigens include:Examples of superantigens include:

Staphylococcal enterotoxinsStaphylococcal enterotoxins (food poisoning),(food poisoning),

Staphylococcal toxic shockStaphylococcal toxic shock toxintoxin (toxic shock(toxic shocksyndrome),syndrome), Staphylococcal exfoliating toxinsStaphylococcal exfoliating toxins

(scalded skin syndrome) and(scalded skin syndrome) and StreptococcalStreptococcal

pyrogenic exotoxinspyrogenic exotoxins (shock). Although the(shock). Although the

bacterial superantigens are the best studied therebacterial superantigens are the best studied thereare superantigens associated with viruses andare superantigens associated with viruses and

other microorganisms as wellother microorganisms as well..

The diseases associated with exposure toThe diseases associated with exposure to

superantigens are, in part, due tosuperantigens are, in part, due to hyper activationhyper activation

of the immune systemof the immune system and subsequent release of and subsequent release of

biologically activebiologically active cytokinescytokines by activated T cellsby activated T cells..

DETERMINANTS RECOGNIZEDDETERMINANTS RECOGNIZED



DETERMINANTS RECOGNIZEDDETERMINANTS RECOGNIZEDBY THE INNATE IMMUNEBY THE INNATE IMMUNE

SYSTEMSYSTEM

► Determinants recognized by components of theDeterminants recognized by components of theinnate (nonspecific) immune system differ from thoseinnate (nonspecific) immune system differ from thoserecognized by the adaptive (specific) immune system.recognized by the adaptive (specific) immune system.Antibodies, and the B and T cell receptors recognizeAntibodies, and the B and T cell receptors recognizediscrete determinants and demonstrate a high degree of discrete determinants and demonstrate a high degree of specificity, enabling the adaptive immune system tospecificity, enabling the adaptive immune system to

recognize and react to arecognize and react to a particular pathogenparticular pathogen..► In contrast, components of the innate immuneIn contrast, components of the innate immune

system recognizesystem recognize broad molecular patternsbroad molecular patterns found infound inpathogens but not in the host. Thus, they lack a highpathogens but not in the host. Thus, they lack a highdegree of specificity seen in the adaptive immunedegree of specificity seen in the adaptive immunesystem. The broad molecular patterns recognized by thesystem. The broad molecular patterns recognized by the

innate immune system have been calledinnate immune system have been called PAMPSPAMPS((pathogen associated molecular patterns)pathogen associated molecular patterns) and theand thereceptors for PAMPS are calledreceptors for PAMPS are called PRRsPRRs (pattern recognition(pattern recognitionreceptors).receptors). A particular PRR can recognize a molecularA particular PRR can recognize a molecularpattern that may be present on a number of differentpattern that may be present on a number of differentpathogens enabling the receptor to recognize a varietypathogens enabling the receptor to recognize a varietyof different pathogens. Examples of some PAMPs andof different pathogens. Examples of some PAMPs andPRRs are illustrated in Table 1PRRs are illustrated in Table 1..

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