Immune Tolerance vs. Immune Resistance: The Interaction Between Host and Pathogens in Infectious Diseases

Abstract

The immune system is most likely developed to reduce the harmful impact of infections on the host homeostasis. This defense approach is based on the coordinated activity of innate and adaptive immune system components, which detect and target infections for containment, killing, or expulsion by the body's defense mechanisms. These immunological processes are responsible for decreasing the pathogen burden of an infected host to maintain homeostasis that is considered to be infection resistance. Immune-driven resistance to infection is connected with a second, and probably more important, defensive mechanism: it helps to minimize the amount of dysfunction imposed on host parenchymal tissues during infection without having a direct adverse effect on pathogens. Disease tolerance is a defensive approach that relies on tissue damage control systems to prevent infections from causing harm to the host. It also uncouples immune-driven resistance mechanisms from immunopathology and disease, allowing the body to fight infection more effectively. This review discussed the cellular and molecular processes that build disease tolerance to infection and the implications of innate immunity on those systems. In addition, we discuss how symbiotic relationships with microbes and their control by particular components of innate and adaptive immunity alter disease tolerance to infection.

Keywords: adaptive immunity; disease resistance; immune tolerance; infectious diseases; pathogens.

Figure 1

Central T-cell tolerance mechanism. The T-cells mature in the thymus by attaching themselves to self MHC molecules. If the interaction is not strong, the T-cell survives called “positive selection.” If the interaction is too strong, it leads to programmed cell death called “negative selection”.

Figure 2

Peripheral T cell tolerance prevents T cell activation or controls the immune responses by switching on certain signaling pathways. However, to present T cell activation, the DC representing antigen either attaches to autoreactive T cell or starts apoptosis because the stimulatory component was absent on DC. This is called peripheral clonal deletion of T cells. If the T cell is inactivated, the process is called anergy.

Figure 3

Innate immunity: pathogen-associated molecular patterns are recognized by Toll-like receptors. When the pathogen invades the host cell, the neutrophil and natural killer cells start digesting the pathogen. However, the macrophages and DC phagocytose the pathogen and act as antigen-presenting cells, producing a cytokine storm for attracting other immune cells to amplify the response.

Figure 4

Acquired immunity: immune cells show two types of responses. Humoral immunity involves the B cells that mature into plasma cells that secrete antibodies and attach to the pathogen. B cells also produce memory cells for the future attack of the same pathogen. Cytotoxic T lymphocytes (CTLs) are immune cells that play an important role in the fight against infections and tumor immunology. T cell matures into an active killer T cell called cytotoxic T lymphocytes, which attach to the infected cell and kill it. The lymphokines attract additional immune cells for stimulation and cascade the effect.