7. antigen,mhc (reuploaded)

8/13/2019 7. Antigen,MHC (Reuploaded)

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Assoc. Prof. Ma. Jennifer R. Tiburcio, MSMTDepartment of Med TechUST Faculty of Pharmacy


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AntigenMacromoleculeFormation of immunoglobulin (orantibodies) or sensitized cells

ImmunogenInducing an immuneresponse


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Properties of an antigen

ImmunogenicityInduce an immune response

Antigenicity or specific reactivityReact with antibody or sensitized lymphocytes


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Factors Influencing the Immune Response1. Ageolder individuals are more likely to have a

decreased response to antigenic stimulation. At the otherend of the age scale, neonates do not fully respond to

immunogens.


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Factors influencing the strength of the IR2. Overall Health

fatigued, stressed or malnourished individuals are

less likely to mount a successful IR

3.Genetic capacityParticular MHC should be present

4. Route of administrationSC or IM routes best for soluble antigens

IV more effective for cellular antigens


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Characteristics of immunogensChemical complexityWith the exception of pure lipids, most macromolecules

are immunogenic

1. Proteinsthe strongest immunogens because of thelargest array of building blocks (20 amino acids). Thisdiversity imparts epitopes of differing specificities to amolecule

2. Glycoproteinssuch as the ABO & Rh antigens,inducing an IR to the carbohydrate epitope of amolecule


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Characteristics of immunogens3. Small polypeptides such as insulin and growth hormones

weakly immunogenic

IR is usually induced after prolonged exposure to the antigenor by the use of adjuvant

4. PolysaccharidesNonimmunogenic

do not possess sufficient chemical diversity for complete

immunogenicity

rapidly degraded by the plasma enzymes before reaching theIS


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Characteristics of immunogens5. Nucleic acids

nonimmunogenic

combination with basic proteins can act as an

immunogen

6. Lipidsnonimmunogenic

cardiolipin impart specificity to the antigen when

appropriately presented to the IS


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Characteristics of immunogensMolecular Size

The larger the molecule the better

Exceptions:

insulin is small immunogenic

carbon particle is large but nonimmunogenicMolecules smaller than 5 10 daltons are nonimmunogenic.Reasonable responses are induced by molecule such as

albumin (69KDa)

1. The number & variety of epitopes increaseproportionately with the size of the proteins. With othermolecules (carbohydraten antigens) increase with size but notwith diversity monotonously repeating antigens


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Characteristics of immunogens2. Large molecules are phagocytized

The antibodies to antigens are formed

efficiently if the antigen is processed first within the

phagocytic cell

Molecules must be susceptible to theintracellular catabolism within the phagocytic cell.

Antigens difficult or impossible to phagocytized are not

immunogenic

Ex. Polystyrene particles although readily engulfed

by macrophages are nonimmunogenic bec the

phagocytic cell lacks the enzymes to degrade

polystyrene


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Epitopes or Determinant siteskey portions of the immunogen

molecular shapes or configurations

valence - multivalent

equal to the number of epitopes in an

antigen molecule

(1 epitope per increase of 10,000)


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Epitopes or Determinant sitesdominant epitopes (the most exposed regions)

small in size (4 to 5 amino acids)

conformation

linear amino acid sequence of a molecule

conformational amino acids that end up on the same area

of the proteins but not adjacent to the peptide chains


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Epitopes or Determinant sitessites

some are found on the surface of the antigen; others

are internal (internal epitopes are expressed only after the

antigen is partially degraded in vivo)

functions

determine the specificty of an antigen

immunoreactive only if they are spatially accessible

as a result of the tertiary protein structurecombines with paratopes (found in Ab molecule)


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Hapten

Determinant sites or

Antigenic determinants

Nonprotein w/ lowmolecular weight

Nonimmunogenic

unless coupled with a

carrier molecule

Determines specificity

Carrier

Protein with highmolecular weight

Immunogenic but not

reactive

Provides the required

size


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Classification of antigens

Autoantigens (autograft,sequestered)within the same individual

Ex. A skin graft from a mans thigh to his chest

Syngeneic antigens (isograft)genitically identical individuals

Ex. A graft from members of an inbred strain

Allogeneic antigens (Allograft)genetically dissimilar members of the same speciesEx. A kidney transplant from mother to daughter


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Xenogeneic antigens (xenograft or heterograft)in different species

Ex. Monkeys kidney transplanted to human

Heterogenetic antigens

widely separated places in phylogenetic tree

Ex. Forsmann antigen

Heterophile antigenshave in common one or more epitopes

cross reacting bec of shared epitopes

Classification of antigens


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Activators of lymphocytes

Monoclonal Oligoclonal Polyclonal

T dependent T independent

superantigens

T- cellsubsets

T-lymphocytes B-lymphocytes

PWM

Con A

PHA

PWM

LPS

protein

Type 1

Pneumococcal

polysaccharide

Type 2

Lipopoly-

saccharide


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MHC in mice H2 complex (chromosome 17)H2 map K, I, S, D, L, T1a Qa

In humans Human Leukocyte antigen (HLA)Chromosome 6


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Biochemical Composition Traits under their controlClass IA, B, C, E, F, G, H, X Transplantation antigens

Serologically detected membrane antigensCellular target antigens for cell mediated

lympholysis

Class IIDP, DQ, DR, DM, DN,

DO

I-region leukocyte antigen

T & B cell interaction

Immune responseMixed leukocyte reaction

Graft versus host reaction

Tumor virus susceptibility

Peptide transport

Generation of peptides from cytosolicproteins

Class IIIC components

Cytochrome p450, 21, hydrolases

& tumor necrosis factor

Serum protein molecule

Complement levels cytokines & enzymes


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Reactions (MHC Restricted)

Antigen presentation

T and B cell cooperationCytotoxic T cell interaction with target cells


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Applications of HLA TypingOrgan transplantationPaternity testingDisease AssociationForensic medicine, AnthropologyStudies of Racial ancestry MigrationFor diagnostic genetic counsellingBasic research in immunology


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Detection of HLA

1. Serological ApproachLymphocyte Microtoxicity Mtd2. Cellular ApproachMixed Lymphocyte Reaction

3. Molecular Approach (DNA based typing)PCRRestriction Fragment LengthPolymorphism (RFLP)


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7. antigen,mhc (reuploaded)

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