What Is Immunological Memory?
Memory is a key feature of adaptive immune responses involving lymphocytes (key cells of the immune system). When an infection causes a lymphocyte response, it causes a small number of pre-existing B and T cells (two types of lymphocytes) to proliferate, resulting in a small army of cells that are specific for the infectious agent and thus capable of combating it. B and T cells are activated to respond by recognizing a portion of the pathogen with their antigen receptors.
All potential invaders have their own already-existing, matching B and T cells that are prepared to respond if and when necessary. This is possible because each B and T cells express an antigen receptor on its surface, distinct from all others. Antibodies circulate throughout the body and bind to the pathogen that triggers the response. A small number of these recent combatants of B cells, T cells, and antibody-secreting plasma cells (PCs) persist as specialized, long-lived immune memory cells after the pathogen has been defeated.
How Does the B Cell-Mediated Memory Occur?
The release of high-affinity Abs is one of our body's most powerful immune defense mechanisms. Immunoglobulin IgM, IgG, IgA, and IgE are classes or isotypes of antibodies that change over the course of an infection, improving their affinity for antigen (binding strength) and allowing antibodies to bind better and neutralize pathogens. The term "isotype" refers to the part of the antibody (Ab) that does not directly bind antigen but instead activates immune effector mechanisms like activating the complement cascade or attaching to immune cell receptors to direct pathogen responses.
Initiation:
Germinal centers (GCs), which form in secondary lymphoid organs like lymph nodes and spleen following an immune challenge, are crucial to creating immunological memory. Germinal centers are specialized, transient, micro-anatomical structures that improve B cell affinity. Activated pathogen-specific CD4+ T cells and B cells interact soon after infection or vaccination. The T cells control the B cells proliferation, antigen receptor class switch (to surface-bound Ab), and GC establishment. Some B cells differentiate into the precursor stage of Ab-secreting cells known as plasmablasts (PBs). Within days of the infection, PBs appear and release antibodies (Abs) that represent the initial, best-available response to the pathogen in the blood throughout the body. The B cells stimulate T cell differentiation into specialized T follicular helper (Tfh) cells, which then control the behavior of the B cells in the immune response.
Germinal Center Reaction:
B cells multiply quickly inside GCs and, remarkably, change the DNA encoding the antigen-binding receptor's epitope-binding component. It potentially alters the receptor's affinity. Repeated B cell proliferation and mutation cycles occur, and only the B cells with the best antigen-binding affinities survive. This selection of the fittest persists throughout the response or until antigen receptor binding strength reaches a maximum, indicating that B cell affinity increases as the response develops. Circulating memory B cells (MBCs) and PC-secreting high-affinity Ab are two long-lived "Ab memory" types that GCs gradually produce.
Germinal Centre Derived Memory:
Germical center-produced plasma cells eventually settle in the spleen and bone marrow, where they can persist in specialized niches for years to decades while continuously secreting antibodies regardless of the presence of pathogens. These circulating antibodies will provide protection as long as there is enough of them to neutralize a pathogen inoculum without inducing an immune response or symptoms. There is a strong correlation between the type of immune response and plasma cell longevity. Viral infections typically produce very long-lived plasma cells, whereas vaccines based on virus components typically produce short-lived plasma cells.
Additionally, regardless of whether the antibodies neutralize or not, plasma cell-derived antibodies will opsonize the target, facilitating recognition by other immune system cells and inducing a secondary immune response. Since different antibody classes stimulate different aspects of the immune response, these outcomes are determined by the isotype of the antibody bound to the pathogen. The soluble mediators (cytokines) secreted by CD4+ T cells, which assist the B cells in the initial phases of the response, control the switching of the antibody class. When CD4+ T cells are activated, their cytokine profile is built based on the persistent features of the infection and the pathogen.
Information about the pathogen is reflected in the antibodies. Thus, the B cells, PBs, MBCs, and PCs produce antibodies by programming CD4+ T cells with pathogen characteristics. This allows for the independent recruitment of the immune system components for each infection, regardless of antibody specificity and affinity. The antibody class also influences antibody half-life and tissue distribution.
How Does the Site of Infection Affect B Cell Memory?
The site of infection, such as the respiratory tract, blood, or gut, is another crucial factor in the immune response and, consequently, immunological memory. This can be seen in the choice of isotype for antibodies (for example, IgG circulates in the blood and lymphatics while IgA is primarily secreted into the mucosa) and the location of memory PC (gut, spleen). The site and mechanism of initial entry may be distinct from the rest of the infection because pathogens do not always finish their entire life cycle in one place. As a result, an immune response that targets a late-stage infection may not necessarily be successful in producing an immune response that stops the infection from occurring. Because, at that point, entry into the host is not a requirement for host survival.
How Does Vaccination Provide B Cell Memory?
The success of a vaccine depends on selecting the proper vaccine formulation and vaccination schedule to guarantee a potent and long-lasting immune response that induces protective immune memory in as many people as possible. Vaccines administered in the absence of infection can use delivery schedules that encourage prolonged immune responses to achieve long-lived protective immunity.
Conclusion:
A hallmark of immune responses to pathogens is to create a memory of the response. The persistence of small numbers of pathogen-specific B and T cells and PCs that secrete pathogen-specific antibodies is a hallmark of immune responses to pathogens. Immune memory may prevent future infections without causing symptoms by continuing to produce neutralizing antibodies from long-lived PCs. If that antibody amount decreases, memory B and T cells rapidly produce new PBs, restoring high affinity and neutralizing antibodies in circulation. Vaccination also provides infection protection, relying on the continued or restored production of pathogen-specific, neutralizing antibodies.
