CHAPTER 2 Cells, Organs, and Microenvironments of the Immune System

Scanning electron micrograph of blood vessels in a lymph node.

Learning Objectives

After reading this chapter, you should be able to:

1. Describe the types of blood cells that make up the immune system and outline the main events that occur during hematopoiesis, the process that gives rise to immune cells.
2. Identify the primary, secondary, and tertiary immune organs in vertebrates and describe their function.
3. Recognize and describe the microenvironments where immune cells mature and the immune response develops.
4. Identify several experimental approaches used to understand how blood cells and immune responses develop.

Key Terms

• Hematopoiesis
• Hematopoietic stem cell (HSC)
• Myeloid lineage cells
• Lymphoid lineage cells
• Primary lymphoid organs
  • Bone marrow
  • Thymus
• Secondary lymphoid organs
  • Lymph nodes
  • Spleen
  • Barrier tissues (MALT and skin)
• Lymphatic system
• Tertiary lymphoid tissue
• Paracortex
• B-cell follicle
• Germinal centers
• Follicular dendritic cells (FDCs)

A successful immune response to a pathogen depends on finely choreographed interactions among diverse cell types (see Figure 1-7): innate immune cells that mount the first line of defense against pathogen, antigen-presenting cells that communicate the infection to lymphoid cells, which coordinate the adaptive response and generate the memory cells that prevent future infections. The coordination required for a full immune response is made possible by the specialized anatomy and microanatomy of the immune system, which is dispersed throughout the body and organizes cells in time and space. Primary lymphoid organs—including the bone marrow and the thymus—are sites where immune cells develop from immature precursors. Secondary lymphoid organs—including the spleen, lymph nodes, and specialized sites in the gut and other mucosal tissues—are sites where the mature antigen-specific lymphocytes first encounter antigen and begin their differentiation into effector and memory cells. Two circulatory systems—blood and lymphatic vessels—connect these organs, uniting them into a functional whole.

Remarkably, all mature blood cells, including red blood cells, granulocytes, macrophages, dendritic cells, and lymphocytes, arise from a single cell type, the hematopoietic stem cell (HSC) (Figure 2-1). We begin this chapter with a description of hematopoiesis, the process by which HSCs differentiate into mature blood cells. We describe the features and function of the various cell types that arise from HSCs and then discuss the anatomy and microanatomy of the major primary lymphoid organs where hematopoiesis takes place. We feature the lymph nodes and the spleen in our description of secondary lymphoid organs. The secondary lymphoid tissue in the distinctive mucosal immune system is described in Chapter 13.

FIGURE 2-1 Hematopoiesis. Self-renewing hematopoietic stem cells give rise to lymphoid and myeloid progenitors. Most immune cells mature in the bone marrow and then travel to peripheral organs via the blood. Some, including mast cells and macrophages, undergo further maturation outside the bone marrow. T cells develop to maturity in the thymus.

The hematopoietic cell is a self-renewing cell found in the bone marrow. It forms two different cells – Myeloid progenitor and lymphoid progenitor.

The different types of cells formed by Myeloid progenitor are given below with the forming region mentioned in parenthesis:

Dendritic cell (peripheral tissues) Granulocyte monocyte progenitor (bone marrow), which forms neutrophil and monocyte (peripheral tissues). Monocyte further forms macrophage and Dendritic cell Eosinophil progenitor (bone marrow), which further forms Eosinophil (peripheral tissues) Basophil progenitor (bone marrow), which forms basophil (peripheral tissues) Mast cell (peripheral tissues) Megakaryocyte (bone marrow), which forms platelets (peripheral tissues) Erythroid progenitor (bone marrow), which forms erythrocyte The different types of cells formed by Lymphoid progenitor are given below with the forming region mentioned in parenthesis:

Dendritic cell (peripheral tissues) T-cell progenitor (thymus), which forms T H helper cells and T C cytotoxic cells (thymus) B-cell progenitor (bone marrow), which forms B cell (peripheral tissues) Innate lymphoid cell (peripheral tissues)

Four focused discussions are also included in this chapter. In two Classic Experiment Boxes, we describe the discovery of a second thymus and the history behind the identification of hematopoietic stem cells. In a Clinical Focus Box, we discuss the clinical use and promise of hematopoietic stem cells, and finally, in an Evolution Box, we describe some intriguing variations in the anatomy of the immune system among our vertebrate relatives.