Lecture 3 clinical immunology

Antigen Presenting Cells

By Dr. Dalia Galal Hamouda

Objectives1. Antigen Presenting Cells

• Professional antigen presenting cells (dendritic cells, macrophages and B cells) present antigen to CD4+ T cells.

• Target cells present antigen to CD8+ T cells

2. Antigen Presenting Molecule: Class I MHC Molecules

3. Antigen Presenting Molecules: Class II MHC Molecules

Antigen presented on molecules to T cells by cells:

1. Extracellular antigen presented on major histocompatibility complex molecule (MHC class II) to CD4+ T cells by Professional antigen presenting cells (dendritic cells, macrophages and B cells).

2. Intracellular antigen presented on major histocompatibility complex molecule (MHC class I) to CD8+ T cells by target cells (Any nucleated cell is a potential target cell)

The structures of CD4 and CD8

MHC class I molecules present antigens to CD8+ T cells, and MHC class II molecules present antigens to

CD4+ T cells:

Dendritic cells

• Dendritic cells are the most professional antigen presenting cells during primary immune response which occur in secondary lymphoid tissues.

• Immature dendritic cells are found in all lymphoid and nonlymphoid tissues (except the brain).

• In nonlymphoid tissues, dendritic cells become immature that capture (endocytose) antigens, processed, carry them and transport them to lymphoid tissues.

• In lymphoid tissues, dendritic cells become mature and cannot endocytose antigen but their role is to present antigen to T-cell.

Macrophages

• The role of macrophages in antigen presentation appears during secondary immune responses which occur at the site of infection.

• Like dendritic cells, macrophages capture (endocytose) antigens, processed, and presented them to CD4+ T cells.

Role of CD4+ molecule in the disease

• Human immunodeficiency virus, type 1 (HIV-1) causes a disease called AIDS.

• HIV-1 interact with CD4 molecule found on the surface of T cells, dendritic cells and macrophage.

B cells

• B cells recognize antigen through antigen specific receptors (membrane antibody).

• B cells can bind antigen even when antigen is in low concentration.

• After binding, B cell endocytose antigens, processed, and presented them to CD4+ T cells.

ANTIGEN PRESENTING MOLECULEAntigen presenting molecules are two classes (Fig. 3.2):• Major histocompatibility complex molecule (MHC Class

I)• Major histocompatibility complex molecule (MHC Class

II)

All nucleated cells express MHC class I molecules while only professional antigen presenting cells (dendritic, macrophage and B cells) express MHC class II molecules.

In humans, the MHC located on chromosome 6, and is also called the human leukocyte antigens “HLA”.

Structure of class I MHC and class II MHC

ANTIGEN PRESENTING MOLECULE CLASS I MHC MOLECULES

• CD8+ T cells, ONLY recognize MHC class I molecules on the surface of a target cell (infected cell).

• After CD8+ T cells recognize MHC class I molecules, CD8+ T cells destroy and kill the target cell

Antigen processing by target cells

Microorganisms that are present in the cell (intracellular) are degraded into peptide fragments by proteolytic action of an enzyme called proteosome.

Then, peptide fragments bind to the transporter of antigen processing (TAP) proteins, and are transported into the Endoplasmic Reticulum (ER).

In the Endoplasmic Reticulum, peptide fragments bind to class I MHC molecules forming complexes.

Complexes (antigen peptide/class I MHC complex)are released to the surface of the cell membrane

Antigen processing is required to present antigen peptides to TCR.TCRs bind short antigen peptides but not whole antigen proteins

ANTIGEN PRESENTING MOLECULESCLASS II MHC MOLECULES

Role of class II MHC molecules and class II MHC restriction

• Class II MHC molecules present antigen to CD4+ T cells.

• CD4+T cells ONLY recognize antigenic peptides if they are binding to class II MHC molecules that present on the surface of “professional” antigen presenting cells.

• class II MHC restriction: CD4+ T cells are RESTRICTED to “see” antigen bind with class II MHC.

• Therefore, T cells are activated to secrete cytokines.

Antigen processing by antigen presenting cells cancelled

• When extracellular microbes penetrate the host’s physical defenses, they endocytosed by antigen presenting cells.(Fig. 3.9)

• Then the endocytotic vesicle fused with lysosomes that release their lysosomal enzymes into the endosome to degrade the microbes into antigenic peptide.

• At the same time, a second fusion process forming another endosome that contains the class II MHC.

• The antigenic peptide binds to the class II MHC and transport to, and fuses with, the cell surface of antigen presenting cell forming the antigen peptide/class II MHC complex.

• • When these complexes are recognized by CD4+ T cells, the T cell is activated to

secrete cytokines.

Disease association with class I and class II MHC expression

In Ankylosing spondylitis, patients are males who have inherited the HLA-B27 allele.

Type 1 diabetes is an autoimmune disorder associated with destruction of the insulin producing beta cells of the pancreatic islets of Langerhans, express either HLA-DR3 or HLA-DR4.

Two different types of antigens:Extracellular for MHC II and intracellular for MHC I

They are generated in different compartments