Molecular, Cellular and Structural Immunology

Immune system must rapidly respond to small numbers of many different microbes that may be introduced at any site in the body.

The major cells and tissues of the immune system are macrophages, neutrophils, peripheral lymphoid organs, dendritic cells (antigen presenting cells), naive lymphocytes and effector/memory lymphocytes.

Phagocytes are neutrophils and macrophages. The function of the phagocyte is to identify, ingest and destroy microbes. Through direct contact and the secretion of proteins, phagocytes cna communicate with other immune cells to promote or regulate immune responses.

Neutrophils (polymorphonuclear leukocytes) are the most abundant population of white blood cells, mediating the earliest phases of inflammatory reactions. They are spherical about 12-15um diameter and have numerous membrane projections. The neutrophil nucleus is segmented into 3/5 connected lobules. The cytoplasm has specific granules and azurophilic granules.

The specific granules have enzymes such as lysozyme, collagenase and elastase The granules dont stain strongly with either basic or acidic dyes. Azurophilic granules are lysosomes containing enzymes, defensins and cathelicidins.

Neutrophils are produced in the bone marrow, they are stimulated by the granulocyte colony stimulating factor. Neutrophils only circulate for about 6 hours. They migrate to sites of infection within a few hours after a microbial entry. If there is no site of inflammation the neutrophil undergoes apoptosis.

Mononuclear phagocyte systems primary function is phagocytosis, playing in innate and adaptive immunity. The cells originate in the bone marrow, circulating in blood, maturing and activating in various tissues.

Monocytes are 10-15um in diameter, bean-shaped nuclei and granular cytoplasm with lysosomes, phagocytic vesicles and cytoskeletal filaments. They are heterogenous, distinguishable by cell surface proteins and kinetics of migration into tissues. Monocytes mature in the tissues to become macrophages.

Macrophages in the CNS are called microglial cells, in the liver Kupffer cells, in the pulmonary airways they are called alveolar macrophages, in the bone they are known as osteoclasts.

The major function of macrophages in host defence is to ingest and kill microbes. The mechanisms involve enzymatic generation of reactive oxygen and nitrogen species that are toxic to microbes and proteolytic digestion.

Macrophages ingest dead host cells after infection or sterile tissue injury. They also recognize and engulf apoptotic cells before they release their contents and induce inflammatory responses.

Activated macrophages secrete cytokines which bind to signalling receptors on other cells, instructing them to respond in ways that contribute to host defence.

Macrophages act as APCs displaying antigens and to activate T lymphocytes. They are important in the effector phase of T cell mediated immune responses. They can also promote repair of damaged tissues by stimulating new blood vessel growth and synthesis of collagen-rich extracellular matrix. 

Activating molecules bind to specific signalling receptors on the macrophage surface e.g. Toll like receptors.

Binding of opsonins on macrophage plasma membrane from the surface of microbes stimulates activation. Opsonins coat particles for phagocytosis.

During adaptive immunity macrophages are activated by secreted cytokines and membrane proteins made by T lymphocytes.

Some T cell cytokines activate macrophages to become efficient at killing microbes (classical activation).…