Antigens 2022-2023

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Antigens

Overview of the Immune System

Immune System

Innate Adaptive
(Nonspecific) (Specific)

Cellular Humoral Humoral


Cell-Mediated
Components Components (Ab)
Definitions
• Immunogen
• Antigen (Ag)
• Hapten
• Epitope or Antigenic Determinant
• Antibody (Ab)
• An antigen is any substance that is
specifically recognized and bound by the
antigen receptors of T or B lymphocytes
• An immunogen is any substance that
elicits an adaptive immune response.
• All immunogens are antigens but not all
antigens are immunogens
Factors Influencing Immunogenicity
Contribution of the Immunogen
• Foreignness (receptors that are reacting with self are
eliminated in the process of tolerance)
• Size
• Chemical Composition
– Primary Structure Sequence determinants
– Secondary Structure
– Tertiary Structure Conformational
determinants
– Quarternary Structure
Factors Influencing Immunogenicity
Contribution of the Immunogen

• Foreigness
• Size
• Chemical
Composition
• Physical Form
– Particulate > Soluble
– Denatured > Native
Factors Influencing Immunogenicity
Contribution of the Immunogen

• Foreigness
• Size
• Chemical Composition
• Physical Form
• Degradability
– Ag processing by Ag Presenting Cells (APC)
Factors Influencing Immunogenicity
Contribution of the Biological System
• Genetics
– Species
– Individual
• Responders vs Non-responders
• Age
Factors Influencing Immunogenicity
Method of Administration
• Dose
• Route
– Subcutaneous > Intravenous > Intragastric
• Adjuvant (adjuvare =help)
– Substances that enhance an immune
response to an Ag
– Aluminum potassium sulfate (alum) –
prolongs the exposure to antigen
– Freund’s incomplete adjuvant ( water in oil +
emulsyfing agent)
– Freund’s complete adjuvant ( +extract of
mycobacterium cell wall)
Chemical Nature of
Immunogens
• Proteins
• Polysaccharides
• Nucleic Acids
• Lipids
– Some glycolipids and phosopholipids can be
immunogenic for T cells and illicit a cell
mediated immune response
Types of Antigens
T-independent
Ti-1 and Ti-2
• Repetitive epitopes
• No memory
response
EX: Pneumococcal polysaccharide,
Lipopolysaccharide
Flagella
Types of Antigens
T-dependent
• Proteins

• Structure
• Examples
– Microbial
proteins
– Non-self or
Altered-self
proteins
Hapten
Low MW molecules
Drugs (antibiotics)
Nonimmunogenic – unless are coupled
with high MW molecules (CARRIER)

HAPTENS
Hapten-carrier conjugates
• Definition

• Structure
Haptenic determinants
– native
determinants
– haptenic
determinants
Native determinants
Antigenic Determinants
Recognized by B cells and Ab

• Composition
– Proteins, polysaccharides, nucleic acids
– Sequence (linear) determinants
– Conformational determinants
• Conformational determinants - structures
in which the contributing amino acids may
be located far apart in their linear
sequence but which become juxtaposed
when the protein is folded in its natural or
native shape
• Linear – they are defined by a particular
stretch of consecutive aac
Antigenic Determinants
Recognized by B cells and Ab

• Composition
• Size
• Number
– Limited
(immunodominant
epitopes)
– Located on the
external surfaces
of the Ag
Antigenic Determinants
Recognized by T cells
• Composition
– Proteins (some lipids)
– Sequence determinants
• Processed
• MHC presentation (lipid presentation by MHC-
like CD1)
• Number
– Limited to those that can bind to MHC
Superantigens
• Definition
Conventional Antigen Superantigen

Monoclonal/Oligoclonal Polyclonal T cell response


T cell response
1:4 - 1:10
1:104 - 1:105
Superantigens
• Definition
• Examples
– Staphylococcal enterotoxins
– Staphylococcal toxic shock toxin
– Staphylococcal exfoliating toxin
– Streptococcal pyrogenic exotoxins
Determinants Recognized by the Innate
Immune System
• Adaptive Immune System – Discrete
Determinants
– Reacts with a specific pathogen
• Innate Immune System – Broad Molecular
Patterns
– Reacts with a variety of pathogens
Determinants Recognized by the Innate
Immune System
• PAMPs – Pathogen Associated Molecular
Patterns
• PRRs – Pattern Recognition Receptors
Initiation of Phagocytosis

Attachment via
ScavengerR
IgG FcR
CR
Toll-like R
Biological
PAMP PRR Consequence
of Interaction
Microbial cell wall Complement Opsonization;
components Complement
activation
Mannose- Mannose-binding Opsonization;
containing protein Complement
carbohydrates activation
Polyanions Scavenger Phagocytosis
receptors
Lipoproteins of TLR-2 (Toll-like Macrophage
Gram + bacteria receptor 2) activation;
Yeast cell wall Secretion of
components inflammatory
cytokines
Biological
PAMP PRR Consequence
of Interaction
Double stranded TLR-3 Production of
RNA interferon
(antiviral)
LPS TLR-4 Macrophage
(lipopolysacchari activation;
de of Gram – Secretion of
bacteria inflammatory
cytokines
Flagellin TLR-5 Macrophage
(bacterial activation;
flagella) Secretion of
inflammatory
cytokines
Biological
PAMP PRR Consequence of
Interaction
U-rich single TLR-7 Production of
stranded viral interferon
RNA (antiviral)

CpG containing TLR-9 Macrophage


DNA activation;
Secretion of
inflammatory
cytokines

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