Major Histocompatibility (MHC)

T Cell Antigen Recognition

• T lymphocytes recognize antigens only when presented by MHC molecules on the surface of cells.

• MHC Class I and MHC Class II molecules are responsible for antigen presentation to T cells.

• MHC I presents processed antigen to Cytotoxic T cells.

• MHC II presents processed antigen to T Helper cells.

Antigen Presenting Cells (APCs)

• Three professional APCs exist: macrophages, dendritic cells, and B cells.

• APCs process antigens by breaking them down and presenting them on their MHC II molecules.

• APCs activate an immune response by presenting antigens to T Helper cells.

MHC Class 1: Intracellular Antigen Presentation

• All cells express MHC I molecules to present intracellular antigens, primarily from viral infections.

• MHC I molecules with bound antigen stimulate Cytotoxic T cells to destroy infected cells.

• This process facilitates the clearance of intracellular pathogens, especially viruses.

MHC Class 1: Cellular Functions

• Macrophages release cytokines which enhance phagocytosis.

• Dendritic cells bring antigens to lymph nodes, where T cell responses are mounted.

• Macrophages reside in the skin, nasopharynx, stomach, lungs, and intestines.

• B cells can present antigens to T cells, crucial for specific antibody responses.

Intracellular and Extracellular Antigen Processing

• Intracellular antigens, typically from viruses and intracellular bacteria, are processed in the cytosol by the proteasome, transported to the endoplasmic reticulum via TAP, and then presented through MHC I.

• Extracellular antigens are engulfed by endocytosis, fuse with Golgi vesicles containing MHC II, and are ultimately presented by MHC II on the cell surface.

T Cell Recognition

• T lymphocytes do not recognize free-floating antigens or antigens on pathogen surfaces.
• T cells specifically recognize antigens presented on the surface of cells by Major Histocompatibility Complex (MHC) molecules.

MHC Molecules

• MHC class I and MHC class II molecules are involved in antigen presentation.
• Both MHC classes process antigens and transport them to the cell surface.
• MHC class I presents antigens to cytotoxic T cells.
• MHC class II presents antigens to T helper cells.

Antigen Presenting Cells (APCs)

• Macrophages, dendritic cells, and B cells are professional APCs.
• APCs possess MHC class II receptors and present antigens to T helper cells, initiating an immune response.
• APCs engulf antigens and process them by breaking them down into smaller fragments.
• These fragments are then presented on the cell surface bound to MHC molecules.
• The combination of MHC and antigen fragment is recognized by the T cell receptor.
• Several cell types express MHC I to present intracellular antigens.
• This facilitates recognition by cytotoxic T cells, leading to the destruction of infected cells.
• MHC I expression is crucial for combating intracellular pathogens, especially viruses.

APC Functions

• Macrophages stimulate T cells to release cytokines that enhance phagocytosis.
• Dendritic cells phagocytose pathogens and transport antigens to lymph nodes.
• Lymph nodes are crucial sites for T cell responses against pathogens in interstitial tissues.
• B cells can present antigens to T cells, contributing to antibody responses.

Intracellular vs. Extracellular Antigens

• Intracellular antigens, often from viruses or intracellular parasites, are processed in the cytosol by the proteasome.

• These antigens are then transported to the endoplasmic reticulum by the transporter associated with antigen processing (TAP).

• Inside the endoplasmic reticulum, they associate with MHC I molecules and are transported to the cell surface.

• Extracellular antigens, typical of bacteria, parasites, and fungi, are internalized by receptor-mediated endocytosis.

• The resulting vesicles fuse with Golgi vesicles containing pre-formed MHC II molecules.

• This fusion leads to the association of antigen and MHC II, followed by transport to the cell surface.

Antigen-Presenting Cells (APCs)

• APCs present antigens to T cells to trigger an immune response.
• APCs express MHC molecules on their surface.
• MHC class I is expressed by all cells and presents antigens to cytotoxic T cells.
• MHC class II is expressed by macrophages, dendritic cells, and B cells.
• Macrophages are phagocytic and engulf pathogens.
• They present antigens to T helper cells at the site of infection.
• Dendritic cells are phagocytic in tissues and migrate to lymph nodes to present antigens to T helper cells.
• B cells can internalize antigens via their surface immunoglobulin receptors and present them to T helper cells to trigger antibody secretion.

Antigen-presenting Cells - MHC Class One

• All cells present MHC class one molecules
• MHC class one does not engage in phagocytosis
• Presents antigen to cytotoxic T cells
• Triggers cytotoxic T cell responses

Antigen-presenting Cells - MHC Class Two

• MHC class two molecules are expressed on macrophages, dendritic cells, and B cells
• Macrophages engulf and destroy pathogens through phagocytosis
• Macrophages present antigens to T helper cells at the site of infection
• Dendritic cells phagocytose in tissues
• Dendritic cells then migrate to lymph nodes and present antigen to T helper cells
• B cells present antigen to T helper cells
• B cells internalize antigens via surface immunoglobulin
• B cells undergo differentiation and promote antibody secretion