Dealing with Garbage is the Immune System’s Main Job

Abstract

The classical analogy for the immune system is of a military response to invasion. This is appropriate for explaining the complexities of the system's response to infectious challenges but does not deal with the normal, routine, status quo functions of the system, as would occur during peacetime. As with the military, understanding the function of the immune response and its components requires an understanding of their responses and roles in maintenance of normal, status quo, everyday situations of the body and their ability to react to sporadic challenges. What follows is not meant to be a detailed or referenced review but more of an opinion to be shared with others besides my own students. Like a city, the body is constantly creating cellular and molecular garbage.Cells die, proteins denature and without a means for disposing and recycling of these materials, they would build up and clog the system. Macrophages are usually thought of as the garbage processors of the body. Macrophages pick up and recycle the dead (apoptotic, necrotic), broken (denatured proteins) and discarded parts (e.g. exosomes) of our cells, tissues and body. Tissue and bone marrow derived macrophages carry out this boring task every single day without getting excited or angry. Dendritic cells, including Langerhans cells, are garbage pickers, possibly more selective and more reactive to the type of trash that they pick up than the macrophage. Their role will be described later.Like garbage persons (they are genderless), macrophages take up garbage indiscriminately and the material may or may not be in containers. Dead cells and exosomes [1] provide receptacles for garbage but degraded, denatured proteins and particles are strewn across the body's terrain. Dead and denatured material exposes unique structures that distinguish them from viable materials. These structures can be recognized by opsonins, one end of which binds to the molecular or cellular garbage and the other end to a receptor on the macrophage. As such, the opsonins facilitate the cleanup process. Opsonins include pentraxins, collectins, ficolins, complement, and antibodies. These molecules bind the structures on proteins, glycoproteins, carbohydrates, lipids and glycolipids, which may be exposed on native or denatured proteins, other molecules, exosomes, particles, apoptotic or necrotic dead cells, and also microbes and their components. The importance of proper trash marking is indicated by the consequences of defects in the early components of complement leading to autoimmune diseases, such as lupus [2].Like many garbage trucks, the surface of macrophages is decorated with pieces of the collected garbage. During recycling of the garbage, phagocytosed proteins are processed and peptides of 11-13 amino acid length are selected to decorate the cell surface in major histocompatibility protein (MHC) II holders. The dendritic cell also picks up garbage but decorates its surface using MHC II holders and also MHC I holders. MHC I molecules acquire their 8-9 amino acid peptides by ...

Vaccine Immunomodulation of Disease: Targeting the Treatment of Autoimmune Diseases

“…This is especially true for the immune system which maintains a balance between the status quo (maintenance of homeostasis) and activation of effector and inflammatory responses. 1,2 Challenges from trauma, infections, neoplasms, and autoimmunity disrupt the normal balance by promoting a cycle of immune/inflammatory responses that continue as long as there are stimuli (tissue disruption, pathogenic microbes, antigens) and drivers (effector cells and molecules e.g. cytokines, chemokines, antibodies).…”