Premed · Premed · Immunology

Lecture 2: Cells and Tissues of the Immune System

Immunology

Learning Objectives

By the end of this lecture, students will be able to:

1. Identify and describe the major cell types of the innate and adaptive immune systems
2. Distinguish between primary and secondary lymphoid organs and their functions
3. Describe the structure and function of lymph nodes, spleen, and mucosal-associated lymphoid tissue
4. Explain the patterns of lymphocyte recirculation and homing
5. Recognize key surface markers used to identify immune cell populations

Lecture Content

I. Cells of the Innate Immune System

Neutrophils, also known as polymorphonuclear leukocytes, are the most abundant circulating white blood cells, making up 60-70% of the total. They have a characteristic multilobed nucleus and granular cytoplasm, and they serve as the first responders to sites of infection, arriving within hours. Neutrophils kill pathogens through phagocytosis, degranulation, and the release of neutrophil extracellular traps (NETs). They are short-lived cells, surviving only 6-8 hours in circulation and 1-2 days in tissues. Key surface markers include CD66b, CD16, and CD15.

Monocytes and macrophages form a continuous lineage in which monocytes circulate in the blood and differentiate into macrophages or dendritic cells upon entering tissues. Tissue-resident macrophages carry specialized names depending on their location: Kupffer cells in the liver, alveolar macrophages in the lungs, microglia in the brain, osteoclasts in bone, and Langerhans cells in the skin (which are actually of dendritic cell lineage). Their functions include phagocytosis, antigen presentation, cytokine production, and tissue repair. Key markers are CD14, CD68, and CD163.

Dendritic cells (DCs) are professional antigen-presenting cells and the most potent activators of naive T cells. They come in two major types: conventional or classical DCs (cDC1 and cDC2), which specialize in antigen presentation, and plasmacytoid DCs (pDCs), which are major producers of type I interferons for antiviral defense. Immature DCs reside in tissues where they capture antigen, then migrate to lymph nodes where they mature and upregulate MHC II and co-stimulatory molecules such as CD80 and CD86. Key markers include CD11c, MHC II, and CD83 (on mature DCs).

Mast cells reside in tissues, particularly at mucosal surfaces and near blood vessels. Their granules contain histamine, heparin, and proteases, and they play a central role in allergic reactions (type I hypersensitivity) through their high-affinity IgE receptor (FcεRI). Basophils account for less than 1% of circulating white blood cells and serve a similar function to mast cells, participating in allergic responses and anti-parasitic immunity through the release of histamine and IL-4. Eosinophils make up 1-3% of circulating white blood cells and are recognized by their bilobed nucleus and large eosinophilic granules. They are specialized for defense against helminth parasites, releasing major basic protein and eosinophil cationic protein, and they also contribute to allergic inflammation. Key eosinophil markers include CD193 (CCR3) and Siglec-8.

Natural killer (NK) cells are large granular lymphocytes classified as innate lymphoid cells. They kill virus-infected cells and tumor cells without requiring prior sensitization, recognizing their targets through a balance of activating and inhibitory receptors. Their inhibitory receptors recognize MHC class I, following the "missing-self hypothesis," and they can also perform antibody-dependent cellular cytotoxicity (ADCC). Key markers are CD56, CD16, and NKp46. Beyond NK cells, innate lymphoid cells (ILCs) are tissue-resident cells that mirror T helper subsets but lack antigen-specific receptors: ILC1s produce IFN-γ (like Th1 cells), ILC2s produce IL-5 and IL-13 (like Th2 cells), and ILC3s produce IL-17 and IL-22 (like Th17 cells).

<image>A composite panel of immune cell morphology illustrations. Panel A: Neutrophil with multilobed nucleus and fine granules. Panel B: Monocyte with kidney-shaped nucleus transitioning into a larger macrophage with pseudopods and phagosomes. Panel C: Dendritic cell with long branching processes extending outward. Panel D: Mast cell packed with purple metachromatic granules. Panel E: Eosinophil with bilobed nucleus and large red-orange granules. Panel F: NK cell as a large granular lymphocyte with azurophilic granules. Each panel includes the cell name, key surface markers, and primary functions listed below.</image>

II. Cells of the Adaptive Immune System

T lymphocytes (T cells) develop in the thymus and express a T cell receptor (TCR) that recognizes antigen presented by MHC molecules. Several subsets exist: CD4+ T helper cells recognize antigen on MHC class II and coordinate immune responses through cytokine secretion; CD8+ cytotoxic T cells (CTLs) recognize antigen on MHC class I and kill infected or abnormal cells; regulatory T cells (Tregs), characterized by the markers CD4+CD25+FoxP3+, suppress immune responses and maintain tolerance; and memory T cells are long-lived cells that provide rapid recall responses upon re-encounter with a previously seen antigen. All T cells express CD3, along with either CD4 or CD8 and either the αβ or γδ form of the TCR.

B lymphocytes (B cells) develop in the bone marrow and express a B cell receptor (BCR), which is essentially surface immunoglobulin that recognizes native, unprocessed antigen. Upon activation, B cells differentiate into plasma cells, which secrete large quantities of antibody (up to 2,000 molecules per second), and memory B cells, which are long-lived cells primed for rapid secondary responses. B cells also function as antigen-presenting cells. Key markers include CD19, CD20, CD21, and surface immunoglobulin (IgM and IgD on naive B cells).

Two additional lymphocyte populations bridge innate and adaptive immunity. NKT cells express both NK markers and a semi-invariant TCR and recognize lipid antigens presented by CD1d molecules. Gamma-delta (γδ) T cells express the γδ TCR instead of the αβ TCR, are enriched in epithelial tissues such as the skin, gut, and reproductive tract, and recognize non-peptide antigens including phosphoantigens and lipids without requiring MHC-restricted antigen presentation.

III. Primary (Central) Lymphoid Organs

The bone marrow is the site of hematopoiesis, where all blood cells originate from hematopoietic stem cells (HSCs). It is also the site of B cell development and maturation. In adults, active red marrow (where hematopoiesis occurs, as opposed to yellow marrow that contains fat) is found in flat bones including the pelvis, sternum, vertebrae, ribs, and skull. The bone marrow provides the microenvironment -- consisting of stromal cells and cytokines -- necessary for lymphocyte development.

The thymus is a bilobed organ located in the anterior mediastinum where T cell development and selection take place. Its structure includes a densely packed cortex containing immature thymocytes along with cortical epithelial cells and macrophages, and a less dense medulla where medullary epithelial cells express AIRE (autoimmune regulator) to drive negative selection. The corticomedullary junction serves as the entry point for bone marrow progenitors, and Hassall's corpuscles -- concentric whorls of epithelial cells in the medulla -- play a role in Treg development. The thymus involutes with age, being replaced by fat, though it is most active in early life and still maintains some function in adults through residual thymic tissue.

<image>Cross-sectional histological diagram of the thymus. Panel A: Low-magnification view showing lobular architecture with distinct dark cortex and lighter medulla separated by connective tissue septa (trabeculae). Blood vessels enter at corticomedullary junction. Panel B: High-magnification of cortex showing densely packed immature thymocytes (small dark cells) interspersed with cortical epithelial nurse cells. Panel C: High-magnification of medulla showing mature thymocytes, medullary epithelial cells, dendritic cells, and a Hassall's corpuscle (concentric keratinized epithelial layers). Arrows indicate the path of thymocyte migration from cortex to medulla during maturation.</image>

IV. Secondary (Peripheral) Lymphoid Organs

Lymph nodes are small bean-shaped organs distributed along lymphatic vessels that filter lymph and facilitate encounters between antigen and lymphocytes. Their structure is organized into a cortex containing B cell follicles (both primary and secondary or germinal center types), a paracortex rich in T cells, dendritic cells, and high endothelial venules (HEVs), and a medulla containing medullary cords (with plasma cells and macrophages) and medullary sinuses. Afferent lymphatics bring antigen and antigen-presenting cells into the node, while an efferent lymphatic exits at the hilum. Lymphocytes enter via HEVs from the blood or through afferent lymphatics.

The spleen is the largest secondary lymphoid organ and filters blood rather than lymph, making it particularly important for clearing blood-borne pathogens. Its white pulp consists of the periarteriolar lymphoid sheath (PALS), which is the T cell zone surrounding the central arteriole, and B cell follicles at the margins. The red pulp contains sinusoids and splenic cords and serves as the site of red blood cell recycling and macrophage filtration. The marginal zone at the border between white and red pulp contains marginal zone B cells and macrophages that capture blood-borne antigens. Asplenic patients are notably susceptible to encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis.

Mucosal-associated lymphoid tissue (MALT) protects the mucosal surfaces of the gut, respiratory tract, and urogenital tract. The gut-associated lymphoid tissue (GALT) includes Peyer's patches in the small intestine, isolated lymphoid follicles, and mesenteric lymph nodes, along with specialized M cells that sample luminal antigens and deliver them to underlying antigen-presenting cells. Bronchus-associated lymphoid tissue (BALT) protects the airways, and nasopharynx-associated lymphoid tissue (NALT), which includes the tonsils and adenoids, guards the upper respiratory tract. A hallmark of mucosal immunity is the production of secretory IgA, the major antibody at mucosal surfaces.

<image>Detailed anatomical cross-section of a lymph node. The outer cortex contains primary follicles (dense B cell aggregates) and secondary follicles with pale germinal centers. The paracortex (T cell zone) sits deep to the cortex and contains high endothelial venules (HEVs) shown in cross-section with lymphocytes transmigrating through the vessel wall. The medulla shows medullary cords and sinuses. Afferent lymphatic vessels enter at the convex surface; efferent lymphatic vessel exits at the hilum alongside blood vessels. A legend identifies: B cells (blue), T cells (green), dendritic cells (yellow), macrophages (red), and follicular dendritic cells (orange) within the germinal center.</image>

V. Lymphocyte Recirculation and Homing

Lymphocytes continuously recirculate between blood, lymphoid tissues, and lymphatic vessels, a process that maximizes their chance of encountering their cognate antigen. Naive lymphocytes preferentially home to secondary lymphoid organs by expressing L-selectin (CD62L) and CCR7, which bind to addressins on HEVs such as PNAd in lymph nodes and MAdCAM-1 in the gut. Effector and memory lymphocytes, by contrast, home to peripheral tissues at sites of inflammation. These cells downregulate L-selectin and upregulate tissue-specific integrins and chemokine receptors -- for example, gut-homing lymphocytes express α4β7 integrin and CCR9, while skin-homing lymphocytes express CLA (cutaneous lymphocyte antigen) and CCR4.

The process by which lymphocytes enter tissues follows a multi-step adhesion cascade. First, rolling occurs through selectin-mediated transient, low-affinity interactions. Next, activation takes place when chemokine signaling activates integrins on the lymphocyte surface, switching them to a high-affinity state. This leads to firm adhesion as the activated integrins bind to ICAMs and VCAMs on the endothelium. Finally, transmigration (diapedesis) occurs as the lymphocyte moves through endothelial junctions into the tissue.

VI. Key Surface Markers -- Summary Table

Read this lecture as Markdown