Immunologic Adjuvant - Adjuvants and The Adaptive Immune Response

Adjuvants and The Adaptive Immune Response

One misconception concerning adjuvant function is that an adjuvant-enhanced innate immune response should affect only the transient reaction of the innate immune response and not the more long-lived effects of the adaptive immune response. Although it may appear fitting to separate the two systems, it is however important to realize the interconnected nature of the two systems. When the amount of communication that takes place between the innate immune response and the adaptive immune response with the onset of infection is considered it becomes difficult to separate the two systems.

In order to understand the links between the innate immune response and the adaptive immune response to help substantiate an adjuvant function in enhancing adaptive immune responses to the specific antigen of a vaccine, the following points should be considered:

• Innate immune response cells such as Dendritic Cells (DCs) engulf pathogens through a process called phagocytosis.
• DCs then migrate to the lymph nodes where T cells (adaptive immune cells) wait for signals to trigger their activation.
• In the lymph nodes, DCs mince the engulfed pathogen and then express the pathogen clippings as antigen on their cell surface by coupling them to a special receptor known as a major histocompatibility complex (MHC).
• T cells can then recognize these clippings and undergo a cellular transformation resulting in their own activation.
• γδ T cells possess characteristics of both the innate and adaptive immune responses.
• Macrophages can also activate T cells in a similar approach (but do not do so naturally).

This process carried out by both DCs and macrophages is termed antigen presentation and represents a physical link between the innate and adaptive immune responses.

Upon activation, mast cells release heparin and histamine to effectively increase trafficking to and seal off the site of infection to allow immune cells of both systems to clear the area of pathogens. In addition, mast cells also release chemokines which result in the positive chemotaxis of other immune cells of both the innate and adaptive immune responses to the infected area.

Due to the variety of mechanisms and links between the innate and adaptive immune response, an adjuvant-enhanced innate immune response results in an enhanced adaptive immune response. Specifically, a recent study has observed that adjuvants may exert their immune-enhancing effects according to five immune-functional activities.

• First, it was found that adjuvants all help in the translocation of antigens to the lymph nodes where they can be recognized by T cells. This will ultimately lead to greater T cell activity resulting in a heightened clearance of pathogen throughout the organism.
• Second, adjuvants provide physical protection to antigens which grants the antigen a prolonged delivery. This means that the organism will be exposed to the antigen for a longer duration, making the immune system more robust as it makes use of the additional time by upregulating the production of B and T cells needed for greater immunological memory in the adaptive immune response.
• Third, adjuvants help to increase the capacity to cause local reactions at the injection site (during vaccination), inducing greater release of danger signals by chemokine releasing cells such as helper T cells and mast cells.
• Fourth, they induce the release of inflammatory cytokines which helps to not only recruit B and T cells at sites of infection but also to increase transcriptional events leading to a net increase of immune cells as a whole.
• Finally, adjuvants are believed to increase the innate immune response to antigen by interacting with pattern recognition receptors (PRRs), specifically Toll-like receptors (TLRs), on accessory cells.