Kuby Immunology, 7e: Chapter 2 Cells, Organs, and Microenvironments of the Immune System

Cells of the immune system Immune responses result from coordinated activities of many cells, organs, and microenvironments in the body Hematopoietic stem cells (HSCs) have the ability to differentiate into many types of blood cells All red and white blood cells develop from a pluripotent HSC during hematopoiesis Hematopoiesis is a highly regulated process

Cells of the immune system In adult vertebrates, hematopoiesis occurs in the bone marrow Within the bone marrow, HSCs are constantly renewed and directed to differentiate into two major types of progenitors Common myeloid progenitor cells Common lymphoid progenitor cells

Cells of the immune system Four main types of cells develop from common myeloid progenitors Red blood cells (erythrocytes) Monocytes Granulocytes Megakaryocytes (form platelets―cell fragments placed into circulation for clotting)

Cells of the immune system Four main types of cells develop from common myeloid progenitors Red blood cells (erythrocytes) Monocytes Granulocytes Neutrophils―direct harm to pathogens Basophils/mast cells―inflammation/allergies Eosinophils―antiviral activity, antiparasite activity Megakaryocytes

Cells of the immune system Four main types of cells develop from common myeloid progenitors Red blood cells (erythrocytes) Monocytes Migrate into tissues and differentiate into macrophages―function to repair/remodel, destroy pathogens, present antigens Can also differentiate into dendritic cells―HIGH degree of function as ingesters of antigens, followed by presentation to naïve T lymphocytes for initial activation Granulocytes Megakaryocytes

Cells of the immune system Macrophages and neutrophils are specialized for phagocytosis Macrophages can also present antigens to T cells via MHC molecules Immature dendritic cells capture antigen, then mature and migrate out of that location to another to present antigen to T cells Dendritic cells are the most potent antigen-presenting cells for activating naïve T cells

Cells of the immune system Three main types of cells develop from the common lymphoid progenitor B lymphocytes T lymphocytes There is a subset that appears more similar to Natural Killer cells that are known as NKT cells NK cells Lymphocytes appear very similar, but different sets carry different cluster of differentiation (CD) molecules on their surface

Primary lymphoid organs―Where immune cells develop B lymphocytes develop in the niche of the bone marrow

Primary lymphoid organs―Where immune cells develop T cells develop initially in the bone marrow, but then migrate to the thymus to achieve full maturity

Secondary lymphoid organs―Where the immune response is initiated Areas where lymphocytes encounter antigen, become activated, undergo clonal expansion, and differentiate into effector cells Secondary lymphoid organ areas include: Lymph nodes Spleen Mucosa-associated lymphoid tissue (MALT) Other diffuse and loosely organized areas These are connected to each other via the blood and lymphatic circulatory systems

Secondary lymphoid organs―Where the immune response is initiated Lymph nodes and spleen are the most highly organized secondary lymphoid organs T-cell and B-cell activity are separated into distinct microenvironments The cells will actively migrate toward each other during activation events for their required interactions

Secondary lymphoid organs―Where the immune response is initiated Differentiation into effector cells takes place in follicles of secondary lymphoid organs T lymphocytes CD4+ T cells differentiate into helper T cells that assist in B-cell differentiation CD8+ T cells differentiate into killer (or cytotoxic) T cells that attack and destroy virally infected cells

Secondary lymphoid organs―Where the immune response is initiated Differentiation into effector cells takes place in follicles of secondary lymphoid organs B cells further mature in germinal centers in such tissues Antigen affinity is increased Class switching can take place Both B and T lymphocytes will develop into long-lived memory cells in these areas, as well

Secondary lymphoid organs―Where the immune response is initiated The spleen is the first line of defense against blood-borne pathogens Red blood cells are compartmentalized in red pulp White blood cells are segregated in white pulp A specialized region of macrophages and B cells known as the marginal zone borders the white pulp

Secondary lymphoid organs―Where the immune response is initiated Mucosa-associated lymphoid tissue (MALT) Important layer of defense against infection at mucosal and epithelial layers Organizes responses to antigens that enter mucosal tissues Includes a network of follicles and lymphoid microenvironments associated with the intestines (gut-associated lymphoid tissue, or GALT)

Secondary lymphoid organs―Where the immune response is initiated MALT M cells in the lining of the gut are unique They function to deliver antigen from the intestinal spaces to lymphoid cells in the gut wall

Secondary lymphoid organs―Where the immune response is initiated Various loosely organized and diffuse lymphoid tissue are also found under the skin, mucosae, and tertiary tissues at sites of infection

Summary While blood cell development is a necessary part of immune responses, it’s only a first step Multiple other organs and tissues of the body must receive those blood cells and interface them with each other to achieve proper immune responses These interfaces and the tissues involved are complex and multifaceted, as shown in this chapter’s materials