Humoral immunity

Structural organization and localization

The morphological basis of humoral immunity is formed by B-zones — areas of lymphoid tissue dominated by B lymphocytes (despite the presence of T cells there as well). Structurally, they are represented by lymphoid follicles (nodules).

Depending on the organ, follicles are located in different areas:

• Lymph nodes: in the cortex. An additional localization site for B cells here is the medullary cords (accumulations of tissue in the medulla).
• Spleen: make up the bulk of the white pulp.
• Mucous membranes: located in the lamina propria, sometimes penetrating into the submucosa.

The spatial dynamics of the humoral response differs significantly from cellular immunity. While cellular reactions occur strictly in the T-zones, the humoral process migrates. It starts in the T-zone, then the primary response unfolds at the border with the follicles, and the advanced phase moves directly inside the B-zones (into the follicles and medullary cords). Finally, the effector phase is carried out by antibodies throughout the body.

Cellular participants and reaction initiation

Initiating a humoral response requires a strict sequence of interactions between several cell types. The main effectors are B lymphocytes, which recognize dissolved antigens or antigens on the surface of extracellular parasites using their specific receptors (BCR).

Triggering the immune response requires the participation of helpers:

1. Antigen-presenting cells (APCs): Macrophages or B lymphocytes themselves process the antigen and display its antigenic determinant (AD) on their membrane.
2. Helper activation: APCs stimulate corresponding clones of naive $T_0$ helpers. In a humoral response, $T_0$ helpers repeatedly contact APCs and differentiate into $T_{h2}$ cells (B-cell helpers).
3. Cooperation: $T_{h2}$ cells meet with B lymphocytes. An important condition: by this time, the B lymphocyte must have engulfed the antigen and presented its determinant in a complex with MHC-II proteins. The result of this interaction is the activation of the B cell and its transformation into an immunoglobulin-producing plasmacyte.

Simplified plasmacytogenesis (primary response)

In the early stages of humoral immunity, plasmacyte development follows a simplified pathway.

This process is localized in the paracortical zone and at the border of the T- and B-zones of lymphoid structures, where small centers of cell proliferation are formed. Activated B cells divide intensively here and differentiate very rapidly.

As a result, plasmacytes are formed that secrete class M immunoglobulins (IgM). These early antibodies possess moderate specificity and relatively low antigen-binding efficiency, yet they provide the first line of specific humoral defense.

Full plasmacytogenesis (secondary response)

At later stages of the response (upon secondary contact with the antigen), the full variant of plasmacytogenesis is implemented. It takes place in the germinal center of the lymphoid follicle and includes three sequential stages of B-cell genome modification:

1. Somatic hypermutation: DNA repair mechanisms are temporarily switched off in stimulated B lymphocytes, causing numerous mutations to arise in immunoglobulin genes.
2. Selection: Mutated cells are checked for affinity (binding strength) to the antigen presented in a complex with existing IgM. Cells with low receptor efficiency undergo apoptosis, and only the most effective clones survive.
3. Class switching ($C_H$ switching): While initially in the red bone marrow the heavy chain gene encoded the constant part of IgM, this fragment is now replaced. Plasmacytes begin to synthesize more specific antibody classes: IgG, IgA, or IgE.

Following genetic rearrangements, the cells divide rapidly and migrate to the follicle periphery (the corona). There they divide into memory B cells and proplasmacytes. The final maturation of proplasmacytes occurs outside the follicles (e.g., in the medullary cords of lymph nodes or in the loose connective tissue of mucous membranes), from where they actively secrete antibodies into the blood and tissue fluid.

Differences from initial stages of cellular immunity

To fully understand the topic, it is important to contrast the initiation of the humoral response with the mechanisms of cellular immunity.

In the cellular response, $T_0$ helpers, having recognized antigenic determinants on the surface of APCs, differentiate not into $T_{h2}$ but into $T_{h1}$ cells (type 1 T-helpers). Subsequently, $T_{h1}$ lymphocytes activate T-killers (possibly via the formation of a "$T_{h1}$ — APC — T-killer" triple complex). This process concludes with the active proliferation and maturation of T-killers, as well as the formation of memory T cells, without the participation of B lymphocytes or antibody production.

Class and exam questions

What else to study on this topic

• Morphological structure of the lymphoid follicle and germinal center
• Structure and functions of the major histocompatibility complex class II (MHC-II)
• Ultrastructural organization of a mature plasmacyte
• Mechanisms of antigen processing in antigen-presenting cells
• Differences in the activation mechanisms of Th1 and Th2 lymphocytes

Other topics in the section "Hematopoietic and lymphoid organs"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.