User:Immcarle6/sandbox

Carleton College student here, studying Immunology.

Immunology

Antigen-presenting cell – there are some issues with this article. It's quite short, and it lacks sufficient citations, relying too heavily on a single source. It's also not comprehensive. I'm adding some new citations and hope for an all-round improvement.

On artificial APCs, used in the lab and possible clinical applications. Some of these applications include immunotherapy for cancer. Research is ongoing about 'tumor vaccines' that would present tumor-associated antigen to T helper cells, which would recruit other immune components to destroy cancer cells.

An overview of APC function, plus indications that more than just B cells, dendritic cells, and macrophages can present antigen to T helper cells.

APC function in the gut, two articles.

A general overview of signaling and "collaboration" between T cells and APCs.

Some notes about APCs and vaccination in the skin.

Microdomains on immune cell surface, with discussion of their function in APCs.

New lead section draft
[This is the original lead section from the APC page]: An antigen-presenting cell (APC) or accessory cell is a cell that displays foreign antigens complexed with major histocompatibility complexes (MHCs) on their surfaces; this process is known as antigen presentation. T-cells may recognize these complexes using their T-cell receptors (TCRs). These cells process antigens and present them to T-cells.

New version:

Almost all cell types can serve as some form of APC, and APCs are found in a large variety of tissue types. Professional antigen-presenting cells, including macrophages, B cells, and dendritic cells, are specialized to present foreign antigen to T helper cells, while other cell types can present antigen originating inside the cell to cytotoxic T cells. Antigen presentation relies on the major histocompatibility complex family of proteins as well as other specialized molecules on the surfaces of both APCs and T cells.

Antigen-presenting cells are vital for an effective adaptive immune response, as the functioning of both cytotoxic and helper T cells is dependent on APCs. Antigen presentation allows for the extreme specificity of adaptive immunity and can contribute to immune responses against both intracellular and extracellular pathogens. It is also involved in defense against tumors. Some new therapies against cancer involve the creation of artificial APCs to prime the adaptive immune system to target malignant cells.

Role of APCs in adaptive immunity
Helper and cytotoxic T cells cannot interact with free antigen. In order for a T cell to bind antigen with its T cell receptor, it must recognize and bind to a peptide bound by a major histocompatibility complex (MHC) on the surface of an antigen-presenting cell. T helper cells interact with MHC class II molecules, which present antigen that originates outside the APC; cytotoxic T cells interact with MHC class I molecules, which present antigen that originates within the APC. T cell receptors have high specificity and once binding occurs, the T cell can perform its effector functions. In the case of T helper cells, these functions include activating other immune cells. For cytotoxic T cells, this could mean initiating cell death of the APC.

T cells must be activated by interacting with an APC, usually a dendritic cell, before they can divide and perform their function.

Types of APC
Antigen-presenting cells fall into two categories: professional and non-professional.

Professional
Professional APCs specialize in presenting antigen to T cells. They are very efficient at internalizing antigens, either by phagocytosis or by receptor-mediated endocytosis, processing the antigen into peptide fragments, and then displaying peptides, bound to a class II MHC molecule, on their membrane. The T cell recognizes and interacts with the antigen-class II MHC molecule complex on the membrane of the antigen-presenting cell. An additional co-stimulatory signal is then produced by the antigen-presenting cell. The expression of co-stimulatory molecules and MHC class II are defining features of professional APCs. All professional APCs also express MHC class I molecules as well.

The main types of professional antigen-presenting cells are dendritic cells, macrophages, and B cells. However, it has been observed that antigen presentation to CD4+ cells via MHC class II is not restricted to the classically professional APCs. Other leukocytes, including granulocytes such as mast cells and neutrophils, can be induced to do so, as can endothelial and epithelial cells under certain circumstances. However, there is little evidence that these atypical APCs are able to activate naive CD4+ T cells.

Dendritic cells
Dendritic cells (DCs), which have the broadest range of antigen presentation. They present antigen to both helper and cytotoxic T cells. Dendritic cells can also perform cross-presentation, a process by which they present exogenous antigen on MHC class I molecules to cytotoxic T cells. Cross-presentation plays an important role in the activation of these T cells.

Prior to encountering foreign antigen, dendritic cells express very low levels of MHC class II and co-stimulatory molecules on their cell surface. These immature dendritic cells are ineffective at presenting antigen to T helper cells. Once a dendritic cell's toll-like receptors recognize a pathogen-associated molecular pattern, antigen is phagocytosed, and the dendritic cell becomes activated, upregulating the expression of MHC class II molecules as well as the co-stimulatory molecule CD40. The co-stimulatory molecule B7, formed via a complex of CD80 and CD86, is also expressed, and can interact with CD28 on the surface of a CD4+ T cell. The dendritic cell is then a fully mature professional APC. It moves from the tissue to lymph nodes, where it encounters and activates T cells.

Macrophages
Macrophages can be stimulated by T cell secretion of interferon gamma. After this activation, macrophages are able to express MHC class II and co-stiumulatory molecules, including the B7 complex, and can present phagocytosed peptide fragments to helper T cells. Activation can assist pathogen-infected macrophages in clearing the infection.

B cells
B cells can internalize antigen that binds to their B cell receptor and present it to helper T cells. Unlike T cells, B cells can recognize soluble antigen for which their B cell receptor is specific. They can then process the antigen and present peptides using MHC class II molecules. When a T helper cell with a TCR specific for that peptide binds, the B cell marker CD40 binds to CD40L on the T cell surface. When activated by a T cell, a B cell can undergo antibody isotype switching, affinity maturation, as well as formation of memory cells.

Non-professional
Non-professional antigen presenting cells include all nucleated cell types in the body. They use an MHC class I molecule coupled to beta-2 microglobulin to display endogenous antigen on the cell membrane. These peptides originate within the cell itself, in contrast to the exogenous antigen displayed by professional APCs using MHC class II molecules. Cytotoxic T cells are able to interact with endogenous antigen presented using an MHC class I molecule.

Antigen-presenting cells in cancer therapy
APCs naturally have a role in fighting tumors, via stimulation of B and cytotoxic T cells to produce antibodies against tumor-related antigen, and kill malignant cells, respectively. Dendritic cells, presenting tumor-specific antigen to T cells, are key to this process. Cancer therapies have included treating the patient with increased numbers of dendritic cells or cancer-specific T cells. However, newer therapies have turned to genetically engineered artificial antigen-presenting cells designed to prime the immune system to attack malignant cells. Some artificial APCs are derived from human cells; others are acellular, containing MHC proteins, co-stimulatory molecules, and the necessary peptides.

Workups
Macrophages are better able resist infection by HIV-1 than CD4+ T cells, although susceptibility to HIV infection differs among macrophage subtypes.