IMSE_LEC_ANTIGENS AND MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)

What is an immunogen?

A macromolecule capable of inducing an immune response by activating T cells and stimulating antibody production.

What is an antigen?

A substance that reacts with antibodies or sensitized T cells but may not necessarily induce an immune response.

Give examples of antigens

• Bacteria

• fungi

• viruses

• protozoa

• and some non-living substances

How does age affect immune response?

Newborns have underdeveloped immunity and are more prone to infections; immunity improves with age.

FACTORS INFLUENCING THE IMMUNE RESPONSE

• Age

• Over health status

• Dose

• Route of Inoculation

How does overall health status affect immunity?

Underlying diseases weaken the immune system, making the host more susceptible to infections.

What is the role of dose in immune response?

Depends on the pathogenicity and virulence of the organism; not all exposures cause disease.

What is route of inoculation?

The portal of entry of pathogens (skin, mucous membranes such as mouth, nose, eyes).

What is the minimum molecular weight of an immunogen?

At least 10,000 daltons.

Which molecules are the best immunogens?

Proteins (most immunogenic) and polysaccharides.

Why are synthetic materials (e.g., nylon, teflon) not rejected in surgeries?

They are non-immunogenic and do not trigger an immune response.

Are pure lipids and nucleic acids immunogenic?

No, unless combined with proteins or carbohydrates (e.g., lipoproteins).

What is an epitope?

The determinant site of an immunogen that is recognized by B or T cells.

How many amino acids can make up a protein epitope?

As few as 6–15 amino acids.

What are the two types of epitopes?

Linear (sequential) and conformational.

What is a linear epitope?

An epitope formed by a continuous sequence of amino acids in a single chain

What is a conformational epitope?

An epitope formed by protein folding, bringing distant amino acids together.

Which epitopes can B cells recognize?

Both linear and conformational epitopes.

Which epitopes can T cells recognize?

Only linear epitopes

Why can T cells recognize only linear epitopes?

Antigens must be processed into peptides by APCs before presentation.

What is a hapten?

An incomplete, non-immunogenic antigen that requires a carrier to induce an immune response.

How do haptens become immunogenic?

By binding to a carrier protein, forming a new antigenic determinant.

Example of a hapten-related disease?

Poison ivy contact dermatitis (catechols binding to skin proteins).

Who explained hapten mechanisms?

Karl Landsteiner (1917).

What are autoantigens?

Antigens belonging to the same host (normally no antibody production).

What are alloantigens?

Antigens from another individual of the same species.

What is an autograft?

Transplantation within the same individual.

What is an allograft?

Transplant between genetically different individuals of the same species.

What is an isograft?

Transplant between genetically identical individuals (identical twins).

What is a xenograft?

Transplant between different species (e.g., pig to human).

What is an adjuvant?

A substance that enhances the immune response to an immunogen.

Approved adjuvant for human use?

Aluminum salts.

Why is Freund’s adjuvant not used in humans?

It causes localized granuloma formation.

What is the function of MHC?

Determines tissue compatibility and presents antigens to T cells.

Where are MHC genes located?

Short arm of chromosome 6.

Enumerate cells that express MHC Class II (any 4)

1. B cells

2. Macrophages

3. Dendritic cells

4. Monocytes

MHC Class I gene loci?

• HLA-A

• HLA-B

• HLA-C

MHC Class II gene loci?

• HLA-DP

• HLA-DQ

• HLA-DR

What does MHC Class III code for?

Complement proteins and cytokines (not involved in antigen presentation).

Which cells express MHC Class I?

All nucleated cells.

Which T cell recognizes MHC Class I?

CD8⁺ cytotoxic T cells.

Endogenous antigens examples?

• Viruses

• tumors

• parasites

Components of MHC Class I molecule?

Alpha chain (α1, α2, α3) + β2-microglobulin

Which cells express MHC Class II?

APCs (B cells, macrophages, dendritic cells).

Which T cell recognizes MHC Class II?

CD4⁺ helper T cells.

What is the role of invariant chain?

Prevents endogenous peptide binding in ER.

What is CLIP?

Fragment of invariant chain occupying peptide-binding groove before exogenous peptide loading.

Clinical applications of MHC typing?

Organ transplantation, disease association, paternity testing, forensics.

Major Histocompatibility Complex (MHC)

Antigen-presenting molecules responsible for tissue compatibility

Enumerate the characteristics of an effective immunogen (4)

1. Macromolecular size

2. Chemical composition

3. Molecular complexity

4. Ability to be processed and presented by MHC

Enumerate the components of MHC Class I molecule

1. Alpha chain (α1, α2, α3)

2. β2-microglobulin

Enumerate the steps in antigen presentation by MHC Class I (3)

1. Proteasomal degradation of endogenous proteins

2. Transport of peptides via TAP1/TAP2 into ER

3. Peptide loading and transport to cell surface

Enumerate the functions of adjuvants (any 4)

1. Increase antigen size

2. Prevent rapid antigen escape

3. Enhance antigen processing

4. Stimulate T cells

5. Stimulate B cells

6. Activate phagocytic cells