Two pathways of immunocompetent cell development
The progenitor of all immune cells is the hematopoietic stem cell. The process of its differentiation is divided into two main branches, each responsible for its own type of body defense.
- Myelopoiesis. Forms cells responsible for innate immunity. The myeloid lineage includes basophils, eosinophils, neutrophils, and mast cells. It also includes monocytes, which are capable of migrating into tissues and transforming into macrophages and dendritic cells there.
- Lymphopoiesis. Provides adaptive immunity reactions. The lymphoid lineage includes NK cells (natural killers), B lymphocytes (divided into B1 and B2 subpopulations), and T lymphocytes. The latter are classified by the type of antigen receptor (TCR) into $\gamma\delta$ and $\alpha\beta$. Cells with the $\alpha\beta$ receptor are additionally divided into CD4+ and CD8+ depending on the presence of specific co-receptors.
Primary (central) lymphoid organs
Antigen-independent cell maturation takes place here. This is a kind of "school" where lymphocytes acquire their specialization before encountering real threats.
- Bone marrow. The main site of hematopoiesis and lymphopoiesis. Myeloid cells, B lymphocytes, and natural killer cells are formed here. Interestingly, the bone marrow also serves as a depot for some effector cells of adaptive immunity, such as plasmocytes.
- Thymus. Exclusively a central organ whose sole task is to ensure the proper development of T lymphocytes.
- Bursa of Fabricius. A specific organ characteristic of birds, some reptiles, and ruminant mammals. B lymphocytes develop within it.
Secondary (peripheral) organs and tissues
It is here that mature cells encounter an antigen, after which a full-scale immune response unfolds. They are divided into encapsulated (structurally isolated) and unencapsulated.
Encapsulated organs include:
- Lymph nodes. Have clear zoning: paracortical areas for T lymphocytes, follicles for B lymphocytes, and areas of their coexistence.
- Spleen. Only its white pulp, organized analogously to lymph nodes, participates in immune defense. The red pulp has a fundamentally different structure and is only partially related to immunity.
- Peyer's patches of the intestine. Analogues of lymph nodes. Their most important feature is the presence of epithelial M cells, which actively transport antigens across the epithelial barrier.
Unencapsulated lymphoid tissue associated with mucous membranes is called MALT (Mucosa-associated lymphoid tissue). It unites tonsils, solitary follicles, the appendix, regional lymph nodes, and diffusely scattered lymphocytes. To maintain survival and attract cells of the required type, special stromal cells operate in MALT and other organs, forming a suitable microenvironment.
Recirculation and cell life cycle
The immune system is not static: cells constantly circulate between central and peripheral compartments, as well as peripheral tissues. This continuous exchange follows two transport mainlines:
- Blood distributes cells from the bone marrow and thymus to the periphery, ensuring systemic circulation.
- Lymph collects lymphocytes and antigens from the skin, mucous membranes, and internal organs, drives them through lymph node filters, and returns them back into the bloodstream.
The life cycle of myeloid cells is also noteworthy. Having appeared in the bone marrow, they enter the blood, circulate there for a short time, and migrate into tissues where they can live from several days to months and even years. Their migration is of two types: constitutive (background, baseline movement into tissues) and emergency (massive exit from the bloodstream directly into the focus of inflammation or the site of pathogen contact).
Briefly: answers to topical questions
What zones are distinguished in the structure of a lymph node, and how are T and B lymphocytes distributed within them?
The parenchyma of the lymph node is divided into the cortex, paracortical zone, and medulla. The distribution of lymphocytes across zones is as follows:
- Cortex (outer part of the cortex) — is the B zone, where B lymphocytes are concentrated in lymphoid follicles (nodules).
- Paracortical zone (deep layers of the cortex) — represents the T zone, serving as the localization site for T lymphocytes.
- Mixed zone — the space between follicles and the paracortical zone, containing a mixed population of T and B lymphocytes.
- Medulla — located in the center of the node and represented by medullary cords and sinuses.
What specific functions does the thymus perform during the maturation of T lymphocytes?
The thymus provides antigen-independent differentiation, selection, and functional maturation of T lymphocytes. The following functions are implemented during maturation:
- Differentiation — formation of CD4+ and CD8+ T cell subpopulations, as well as regulatory T cells (Treg).
- Negative selection (clonal deletion) — destruction of autoreactive clones at the double-positive thymocyte stage to ensure central self-tolerance.
- Receptor editing — modification of the V$\alpha$ gene to eliminate autoaggressiveness.
- Agonist-driven selection — selection of Treg clones upon contact with autologous peptides.
- Preparation for migration — sialylation of membrane glycoproteins for protection against phagocytosis and expression of adhesion molecules.
How does the white pulp of the spleen differ morphologically and functionally from the red pulp?
The white and red pulp of the spleen have significant morphological and functional differences.
| Characteristic | White pulp (pulpa alba) | Red pulp |
|---|---|---|
| Morphology | Lymphoid tissue organized around arteries (lymphoid nodules and periarterial sheaths). | Stroma of reticular tissue with numerous sinusoidal capillaries. |
| Cellular composition | Contains T, B, and NK cells, macrophages, interdigitating cells. | Myeloid and erythroid cells, plasmocytes, and blasts predominate. |
| Function | Secondary lymphoid organ: trapping antigens from the blood, antigen-dependent proliferation and differentiation of lymphocytes. | Blood cell homeostasis, creation of a microenvironment for memory cells and antibody-producing cells. |
What stages does a B lymphocyte go through during antigen-dependent differentiation in secondary lymphoid organs?
During antigen-dependent differentiation in secondary lymphoid organs, a B lymphocyte goes through several successive stages.
- B centroblasts — activated and proliferating cells of the dark zone of the germinal center, where somatic hypermutation of V genes takes place.
- Centrocytes — cells of the light basal zone, among which cells with the highest affinity for antigen are selected during affinity maturation.
- B immunoblasts — dividing activated cells of the light apical zone.
- Plasmablasts — mobile cells that retain the ability to proliferate and leave the germinal center.
- Plasma cells (plasmocytes) and B memory cells — terminal stages of differentiation.
The names of lymphocytes hint at their maturation site. T lymphocytes are thymus-dependent (mature in the thymus). B lymphocytes are bursa-dependent (from the word bursa — bursa of Fabricius). And NK cells (natural killers) are named exclusively after their function.
Class and exam questions
What is the difference between central and peripheral lymphoid organs?
In central organs, cells differentiate without contact with antigen. In peripheral ones, mature lymphocytes encounter foreign agents and trigger an immune response.
Where do tissue macrophages come from?
They develop from monocytes — myeloid lineage cells that leave the bloodstream and migrate into tissues.
What is MALT?
This is lymphoid tissue associated with mucous membranes (Mucosa-associated lymphoid tissue). It includes tonsils, Peyer's patches, the appendix, and diffuse lymphocytes.
What else to study on this topic
- T-lymphocyte subpopulations (CD4+, CD8+, αβ, γδ) and their receptor structure
- Structural features of the white and red pulp of the spleen
- Role of M cells in antigen transport across the epithelial barrier
- Mechanisms of emergency myeloid cell migration to the site of inflammation
- Structure of encapsulated lymphoid organs and functions of their zones
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