Unlike adaptive immunity, innate immunity does not recognize every possible antigen. Instead, it is designed to recognize a few highly conserved structures present in many different microorganisms. The structures recognized are called pathogen-associated molecular patterns and include LPS from the gram-negative cell wall, peptidoglycan, lipotechoic acids from the gram-positive cell wall, the sugar mannose (common in microbial glycolipids and glycoproteins but rare in those of humans), bacterial DNA, N-formylmethionine found in bacterial proteins, double-stranded RNA from viruses, and glucans from fungal cell walls. Most body defense cells have pattern-recognition receptors for these common pathogen-associated molecular patterns and so there is an immediate response against the invading microorganism. Pathogen-associated molecular patterns can also be recognized by a series of soluble pattern-recognition receptors in the blood that function as opsonins and initiate the complement pathways. In all, the innate immune system is thought to recognize approximately 103 molecular patterns. All of this will be discussed in greater detail in upcoming pages.
The innate immune responses involve:
phagocytic cells (neutrophils, monocytes, and macrophages);
cells that release inflammatory mediators (basophils, mast cells, and eosinophils);
natural killer cells (NK cells); and
molecules such as complement proteins, acute phase proteins, and cytokines.
Examples of innate immunity include anatomical barriers, mechanical removal, bacterial antagonism, pattern-recognition receptors, antigen-nonspecific defense chemicals, the complement pathways, phagocytosis, inflammation, and fever. In the next several pages we will look at each of these in greater detail.
We will now take a closer look at phagocytosis.
An Overview of Phagocytic Defense
Phagocytosis is the primary method used by the body to remove free microorganisms in the blood and tissue fluids. The body’s phagocytic cells are able to encounter these microorganisms in a variety of ways:
a. Infection or tissue injury stimulates cells such as mast cells and basophils to release vasodilators to initiate the inflammatory response (discussed later in this unit). As a result of vasodilation and increased capillary permeability, phagocytic white blood cells (neutrophils, monocytes/macrophages, eosinophils) and other white blood cells enter the tissue around the injured site and are chemotactically attracted to the area of infection. In other words, inflammation allows phagocytes to enter the tissue and go to the site of infection. Neutrophils are the first to appear and are later replaced by macrophage.
b. Lymph nodules are unencapsulated masses of lymphoid tissue containing fixed macrophages and ever changing populations of B-lymphocytes and T-lymphocytes. They are located in the respiratory tract, the liver, and the gastrointestinal tract and are collectively referred to as mucosa-associated lymphoid tissue or MALT. Examples include the adenoids and tonsils in the respiratory tract and the Peyer’s patches on the small intestines. Organisms entering these systems can be phagocytosed by fixed macrophages and dendritic cells and presented to B-lymphocytes and T-lymphocytes to initiate adaptive immune responses. In addition, beneath the skin surface is skin-associated lymphoid tissue (SALT) that contains phagocytic cells for killing microbes and sampling antigens on the skin in order to start adaptive immune responses against them.
c. Tissue fluid picks up microbes and then enters the lymph vessels as lymph. Lymph vessels carry the lymph to regional lymph nodes . Lymph nodes contain many reticular fibers that support fixed macrophages and dendritic cells as well as everchanging populations of circulating B-lymphocytes and T-lymphocytes. Microbes picked up by the lymph vessels are filtered out and phagocytosed in the lymph nodes by these fixed macrophages and dendritic cells and presented to the circulating B-lymphocytes and T-lymphocytes to initiate adaptive immune responses. The lymph eventually enters the circulatory system at the heart to maintain the fluid volume of the circulation.
In addition, dendritic cells are located throughout the epithelium of the skin, the respiratory tract, and the gastrointestinal tract where in their immature form they are attached by long cytoplasmic processes. Upon capturing antigens through pinocytosis and phagocytosis and becoming activated by proinflammatory cytokines, the dendritic cells detach from the epithelium, enter lymph vessels, and are carried to regional lymph nodes. By the time they enter the lymph nodes, they have matured and are now able to present antigen to the everchanging populations of naive T-lymphocytes located in the cortex of the lymph nodes.
d. The spleen contains many reticular fibers that support fixed macrophages and dendritic cells as well as everchanging populations of circulating B-lymphocytes and T-lymphocytes. Blood carries microorganisms to the spleen where they are filtered out and phagocytosed by the fixed macrophages and dendritic cells and presented to the circulating B-lymphocytes and T-lymphocytes to initiate adaptive immune responses.
e. As mentioned above under fixed macrophages, there are also specialized macrophages and dendritic cells located in the brain (microglia), lungs (alveolar macrophages), liver (Kupffer cells), kidneys (mesangial cells), bones (osteoclasts), the gastrointestinal tract (peritoneal macrophages), and the skin and mucous membranes (Langerhans’ cells).