immunogens, antigens, and haptens - judoctors€¦ · immunogens, antigens, and haptens. initiation...

Immunogens, Antigens, and

Haptens

Initiation of immune response

Interaction between receptor and ligand

Affinity

Avidity

strongbinding

strongbinding

weakbinding

Affinity: high low low

Introduction

Immune responses arise as a result of exposure to

foreign stimuli

The compound that evokes an immune response is

referred to as “antigen” or “immunogen.”

The distinction between the two is functional but

they are commonly used as synonyms.

Definitions

An immunogen is any substance capable of

inducing an immune response

An antigen is any substance capable of binding

specifically to the products of the immune response

All immunogens are antigens but not all antigens

need be immunogens

Special Types of Antigens

Allergen

Mitogen

Super antigen

Tolerogen

According to source of antigen:

- Xenoantigen

- Heteroantigen

- Alloantigen

- Autoantigen

Haptens are low molecular weight compounds

(antibiotics and drugs) that by themselves are

incapable of inducing an immune response, but they

can react with its products

When haptens are coupled with large molecules

such as proteins (carriers), the resultant conjugate

induces an immune response directed against the

hapten and the carrier

Factors influencing immunogenicity

Factors

Contribution of immunogen

Contribution of biological

system

Method of administration

Contribution of the immunogen

Foreignness

High Molecular Weight

- <1000 Daltons : nonimmunogenic

- 1000-6000 Daltons: may be immunogenic

- > 6000 immunogenic

Chemical Nature and Complexity

- Homopolymers Vs Heteropolymers

- Primary, secondary, tertiary, and quaternary structures

Antigenic Determinants or Epitopes

- Linear

- Discontinuous

Paratope: “The site in the variable (V) domain of an

antibody or T-cell receptor that binds to an epitope

on an antigen

Physical Form

Particulate > Soluble

Denatured > Native

Degradability

Ag processing by Ag Presenting Cells (APC)

Factors Influencing ImmunogenicityContribution of the Biological System

Genetics

Species

Individual

Responders vs. Non-responders

Age

Factors Influencing ImmunogenicityMethod of Administration

Dose

Route

Subcutaneous > Intravenous > Intragastric

Rate of elimination

Adjuvant

Substances that enhance an immune response to an Ag

Adjuvants

Substances which when mixed with an immunogen enhance

the immune response against the immunogen

They differ from carriers as they do not enhance immunity

to haptens

Release immunogens slowly but continuously

Types: Freund’s incomplete or complete adjuvants, BCG,

Corynebacterium parvum, Bordetella pertussis, LPS, and

Alum precipitate (most widely used )

Major Classes of Immunogens

Proteins: Best immunogens

Carbohydrates: Usually but not always good

immunogens

Nucleic Acids: Poor immunogens by themselves

unless coupled to carriers

Lipids: Non immunogens unless coupled to carriers

Cross Reactivity

Modification of a molecule; toxins and toxoids

Sharing epitopes between unrelated macromolecules

Structural resemblance (molecular mimicry)

Significance in

- tolerance and autoimmunity

- Isohemagglutinins

Antigens: T-independent

Activate B cells without MHC class II T help

Polysaccharides

Properties

Polymeric structure

Polyclonal B cell activation, but poor memory

Resistance to degradation

Examples

Pneumococcal polysaccharide, LPS

Flagella

Antigens: T-dependent

Require T help to activate B cells

Proteins

Structure

Examples

Microbial proteins

Non-self or altered-self proteins

Hapten-carrier conjugates

Definition

Ag only if bound to carrier protein

Structure

Native determinants

Haptenic determinants

Sequential (or linear) determinants

Epitopes formed by several adjacent amino acid

residues are called linear determinants.

They exist on the surface of antigen molecules or

inside of antigen molecules.

They are mainly recognized by T cells, but some can

also be recognized by B cells.

Conformational determinants

Conformational determinants are formed by amino

acid residues that are not in a sequence but become

spatially juxtaposed in the folded protein.

They normally exist on the surface of antigen

molecules.

They are recognized by B cells or antibody.

Antigenic Determinants

Recognized by B cells and Ab

Composition

Proteins, polysaccharides, nucleic acids

Sequence (linear) determinants

Conformational determinants

Size

4-8 residues

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)

Size

8 -15 residues

Number

Limited to those that can bind to MHC

T cell

TCR

T cell

TCR

APC

MHC

APC

MHC

Ag Super Ag

Superantigens

Definition

Polyclonal T cell

response

Examples

Staphylococcal

enterotoxins

Toxic shock toxin

Superantigens

Conventional Antigen

Monoclonal/ Oligoclonal

T cell response

1:104 - 1:105

Superantigen

Polyclonal T cell response

1:4 - 1:10

Definition

Most Important Human

Antigens

Membrane molecules of immune cells

Receptors: TCR, BCR, CR, CKR, FcR

Class I and class Ⅱ MHC molecules

CD molecules: CD1~339

Cell Adhesion Molecules

Cytokine Receptors

Blood Group Antigens

Pathogen recognition by adaptive immunity: great

variety, selectivity

T Lymphocytes

• Distinguishing cell-surface markers include TCR, CD3,

CD2, CD4 or CD8, CD28, and CD45

• Similarities between T and B cells:

• Antigen receptor on surface

(TCR)

• Recognize single, specific antigen

• Expand through clonal selection

• Some T cells exist as long-lived memory cells

B Lymphocytes

• Recognize antigen by

means of surface-expressed

antigen receptor

• Distinguishing cell-surface

markers include: B220 (CD45),

MHC Class II, CD80 (B7-1) and

CD86 (B7-2), CD40, CD19,

CD21, etc.

Bursa of

fabricius

Figure 3-13 part 1 of 2

Figure 3-15The peptide-binding groove of MHC molecules

Present Ag to

CD4 T cells

Present Ag to

CD8 T cells

Help peptide loading

Present antigen peptides

to CD4+ T cells

Polymorphism allows the population to handle a variety of pathogens.

Polymorphism: presence of

multiple alternative forms

(alleles) of a gene.

Figure 3-22• Almost all cells express MHC I for comprehensive surveillance by CD8 T cells

• Only some cells express high levels of MHC II and MHC I

• These are B cells, macrophages, dendritic cells and thymic epithelial cells.

• B cells, macrophages and dendritic cells are called professional antigen-presenting cells (APC).

• IFN-g increases the expression of MHC II in APC and induces the expression in non-APC cells at sites of infection

Different cell distribution of MHC class I and II

Leukocyte Differentiation Antigens and CD

Leukocyte differentiation antigen: Cell

surface molecules expressed (or disappeared)

during different developmental and differential

phases, activation or inactivation process of

blood cells.

Identifying Cell Using the CD

Nomenclature

CD Cluster Of Differentiation

Over 300 CD Markers

T cells, CD4 or CD8 and CD3

B cells, CD19

NK cells, CD56

Monocytes /Macrophages CD14

Dendritic Cells, CD1c

Table 2-4

CD - Cluster of Differentiation

CDs which take part in T cell recognition,

adhesion and activation

CDs which take part in B cell recognition,

adhesion and activation

Adhesion Molecules

Cell adhesion molecules (CAMs) are cell surface

proteins involved in the interaction of cell-cell or

cell-extracellular matrix.

CAMs take effect by the binding of receptor and

ligand.

Ⅱ. Classification

Integrin family

Selectin family

Immunoglobulin (Ig) superfamily

Cadherin family

Mucin - like family

Other adhesion molecules

1. Integrin family

Integrins consist of α and β chains.

According to β subunits, Integrins are divided into

eight groups: β1- β8

VLA-4(Very Late Antigen-4)------VCAM-1

LFA-1(Lymphocyte Function-associated Antigen-1)

ICAM-1,2,3

MAdCAM-1 (Mucosal Addressin Cell Adhesion

Molecule-1)

TSP-1 ((Thrombospondin一1)

2. Selectin family

Selectins consist of one peptide chain.

The three family members include: E- selectin,

L-selectin, and P-selectin.

3. Ig superfamily(IgSF)

The structure of these adhesion molecules resemble

that of Ig.

CD4, CD8, CD2(LFA-2), CD58(LFA-3), VCAM-1,

ICAM-1,2,3

4. Cadherin family

E- cadherin------ Epithelia cell

N- cadherin------ Nerve cell

P- cadherin-------Placenta

5. Mucin -like family

CD34, GlyCAM-1(glycosylation dependent cell

adhesion molecule-1)

PSGL-1(P-selectin glycoprotein ligand-1)

6. Other adhesion molecules

CD44

Ⅲ. Functions

1. Participate in development and differentiation of immune cells

CD2----LFA-3

LFA-1----ICAM-1

Participate in development and maturation of thymocytes.

2. Participate in immune response and regulation

IL-21

IL-10

Cytokine Receptor Families

TLRs