02 Antigens

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Antigens

Jennifer Nyland, PhD

Office: Bldg#1, Room B10

Phone: 733-1586Email: [email protected]

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Teaching objectives

To compare and contrast immunogen, antigen &hapten

To describe the factors influencing immunogenicity

To define the chemical nature of immunogens To compare the structures of T-independent and T-

dependent antigens

To introduce the concept of hapten-carrier conjugates

and their structure To characterize antigenic determinants

To define superantigens

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Overview of the immune system

Immune system

Innate(nonspecific)

1stline of defense

Cellularcomponents

Humoralcomponents

Adaptive

(specific)

2ndline of defense

Cellularcomponents

Humoralcomponents

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Vocabulary

Immunogen

Antigen (Ag)

Hapten Epitope or antigenic determinant

Antibody (Ab)

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Factors influencing immunogenicity

Factors

Contribution

of

immunogen

Contribution

of biological

system

Method of

administration

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Immunogenicity: contribution of

immunogen

Foreignness

Size

Chemical composition Primary structure --- sequence determinants

Secondary structure

Tertiary structure

Quarternary structure

Conformational

determinants

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Immunogenicity: contribution of

immunogen

Foreigness

Size

Chemical composition Physical form

Particular > Soluble

Denature > Native

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Immunogenicity: contribution of

immunogen

Foreigness

Size

Chemical composition Physical form

Degradability

Ag processing by Ag-presenting cells (APC)

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Immunogenicity: contribution of

biological system

Genetics

Species

Individual

Responders vs Non-responders

Age

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Immunogenicity: method of

administration

Dose

Route

Subcutaneous > Intravenous > Intragastric

Adjuvant

Substances that enhance immune response to Ag

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Chemical nature of immunogen

Proteins

Polysaccharides

Nucleic acids Lipids

Some glycolipids and phospholipids can be

immunogenic for T cells and illicit a cell-mediated

immune response

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Antigens: T-independent

Activate B cells without MHC class IIT help

Polysaccharides

Properties

Polymeric structure

Polyclonal B cell activation, but poormemory

Resistance to degradation

Examples Pneumococcal polysaccharide, LPS

Flagella

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Antigens: T-dependent

Require T help to activate B

cells

Proteins

Structure

Examples

Microbial proteins

Non-self or altered-selfproteins

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Hapten-carrier conjugates

Definition

Ag only if bound to carrier protein

Structure

Native determinants

Haptenic determinants

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Antigenic determinants recognized by

B cells and Ab

Composition

Proteins, polysaccharides, nucleic acids, haptens

Sequence (linear) determinants

Conformational determinants

Size

4-8 residues

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Antigenic determinants recongized by

B cells and Ab

Composition

Size

Number Limited (immunodominant epitopes)

Located on the external surface of the Ag

(exposed)

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Antigenic determinants recognized by

T cells

Composition

Proteins (some lipids)

Sequence determinants

Processed MHC presentation (lipid presentation by MHC-like CD1)

Size

8-15 residues

Number

Limited to those that can bind MHC

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T cell

TCR

T cell

TCR

APC

MHC

APC

MHC

Ag SuperAg

Superantigens

Definition

Polyclonal T cell

response

Examples

Staphlycoccal

enterotoxins

Toxic shock toxin

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Summary of immune response

Adaptive immune response

Discrete determinants

Reacts with specific pathogen

Innate immune response

Broad molecular patterns

Reacts with a variety of pathogens