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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