Immunology

Cluster of differentiation 74 (CD74) is an important integral membrane protein that serves as a chaperone for MHC class II molecules. CD74, also known as the invariant chain or Ii, is needed for the proper folding and trafficking of MHC class II in antigen presenting cells. CD74 serves as a scaffold for MHC class II assembly. During assembly CD74 blocks the peptide binding cleft of MHC class II to prevent binding of antigenic peptides.

The mammalian target of rapamycin (mTOR) signaling pathway allows cells to monitor environmental signals like nutrient availability and oxygen levels. mTOR is a phosphoinositide 3-kinase (PI3K)-related protein that assembles into large protein complexes (mTORC1 and mTORC2) capable of regulating cell metabolism, growth, and proliferation.

What is the Cellular Role of the CD11 Protein?

The CD11 protein is actually a heterodimer complex that consists of CD11b and CD18. CD11 is involved in numerous adhesion-related associations between cells such as monocytes, macrophages, natural killer (NK) cells, and granulocytes. CD11 also regulates the uptake of complement-coated particles within cells. It has also gained usage as a microglial marker for tissues derived from the nervous system.

IL-1 was originally identified and cloned as a lymphocyte mitogen and much later, was found to be comprised of two closely related but distinct proteins, interleukin 1 alpha (IL-1 alpha) and interleukin 1 beta (IL-1 beta). Both these proteins bind to the same cell surface receptor. IL-1 is primarily released from stimulated macrophages, but is also released from several other cell types. Along with other IL-1 gene family members, IL-1 beta falls within a cytokine gene cluster on chromosome 2.

The complement system is made up of a collection of proteins found in the bloodstream and is comprised of nine major complement proteins; complement C3 is one of them. The complement system is a crucial component of the cellular immune system because it kills unwanted bacteria and initiates inflammation. Within the complement system family of proteins, C3 is the most plentiful as well as most central protein, and consists of an alpha and a beta chain. The C3 activation step represents the convergence of the lectin, classical, and alternative complement activation pathways.

Chemokines play a central role in inflammation and are crucial for recruitment of immune cells to sites of infection. The chemokine-dependent activation of leukocytes occurs through binding to G-protein coupled receptors. These chemokine receptor subtypes can be divided into two major groups, CXCR and CCR.

The protein P2Y2 is a G-protein coupled metabotropic receptor that belongs to a larger family consisting of several receptor subtypes that each has a different pharmacological selectivity for various adenosine and uridine nucleotides. (This selectivity overlaps in some cases).

IL-33 is a member of the interleukin family of cytokines that regulates a wide variety of cellular functions. Its receptor is ST2, an IL-1 receptor family member that also acts as a negative regulator of TLR-IL-1R signaling and the IL-1R accessory protein (IL-1RAcP). Receptor binding of IL-33 activates NF-kB and MAP kinases, stimulating downstream expression of TH2-associated cytokines such as IL-4, IL-5 and IL-6.

Beta-defensin 3 is a novel, non-hemolytic antimicrobial cationic peptide originally isolated from human lesional psoriatic scales and keratinocyte clones. It is a very small (2-6 kD) yet potent salt-insensitive broad spectrum antimicrobial that targets many pathogenic microbes such as multiresistant S. aureus, vancomyosin-resistant Enterococcus faecium, Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses.