Immunology Immunology (elective)(elective)MLIM-101MLIM-101

Prepared by: Prepared by:

Dr. Mohamed S. Abdel-Dr. Mohamed S. Abdel-LatifLatif

Learning Outcome:Learning Outcome:

At this time you should know the following:At this time you should know the following:

1. To compare and contrast immunogen, antigen and hapten 2. To describe the factors influencing immunogenicity 3. To define the chemical nature of immunogens 4. To compare the structures of T-independent and T-dependent antigens 5. To introduce the concept of hapten-carrier conjugates and to describe their structure 6. To characterize antigenic determinants 7. To introduce the concepts of superantigens, PAMPs and PRRs

AntigensAntigens

Overview of the Overview of the Immune SystemImmune System

Immune System

Innate(Nonspecific)

Adaptive(Specific)

CellularComponents

HumoralComponents

Cell-MediatedHumoral

(Ab)

Definitions

• Immunogen

• Antigen (Ag)

• Hapten

• Epitope or Antigenic Determinant

• Antibody (Ab)

Factors Influencing ImmunogenicityContribution of the Immunogen

• Foreignness

• Size

Conformational determinants

Sequence determinants

• Chemical Composition– Primary Structure– Secondary Structure– Tertiary Structure– Quarternary Structure

Factors Influencing ImmunogenicityContribution of the Immunogen

• Foreigness

• Size

• Chemical Composition

• Physical Form– Particulate > Soluble– Denatured > Native

Factors Influencing ImmunogenicityContribution of the Immunogen

• Foreigness

• Size

• Chemical Composition

• Physical Form

• 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

• Adjuvant– Substances that enhance an immune response to

an Ag

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 AntigensT-independent

• Polysaccharides• Properties

– Polymeric structure

– Polyclonal B cell activation

• Yes -Type 1 (TI-1)

• No - Type 2 (TI-2)

– Resistance to degradation

• Examples– Pneumococcal polysaccharide, lipopolysaccharide

– Flagella

Types of AntigensT-dependent

• Proteins• Structure• Examples

– Microbial proteins

– Non-self or Altered-self proteins

Hapten-carrier conjugates

• Definition

Native determinants

Haptenic determinants• Structure

– native determinants

– haptenic determinants

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

Fe

Antigenic DeterminantsRecognized 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

Superantigens

Conventional Antigen

Monoclonal/Oligoclonal T cell response

1:104 - 1:105

Superantigen

Polyclonal T cell response

1:4 - 1:10

• Definition

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

PAMP PRR

Biological Consequence of

Interaction

Microbial cell wall components

Complement Opsonization; Complement activation

Mannose-containing carbohydrates

Mannose-binding protein

Opsonization; Complement activation

Polyanions Scavenger receptors Phagocytosis

Lipoproteins of Gram + bacteria

Yeast cell wall components

TLR-2 (Toll-like receptor 2)

Macrophage activation; Secretion of inflammatory cytokines

PAMP PRR

Biological Consequence of

Interaction

Double stranded RNA

TLR-3 Production of interferon (antiviral)

LPS (lipopolysaccharide of Gram – bacteria

TLR-4 Macrophage activation; Secretion of inflammatory cytokines

Flagellin (bacterial flagella)

TLR-5 Macrophage activation; Secretion of inflammatory cytokines

PAMP PRR

Biological Consequence of

Interaction

U-rich single stranded viral RNA

TLR-7 Production of interferon (antiviral)

CpG containing DNA

TLR-9 Macrophage activation; Secretion of inflammatory cytokines

Assignment:

As a part of the semester activity, group of students are selected every week to prepare a short seminar about his/her point of interest in one of the lecture topics. That to be discussed and evaluated during the next lecture.