Impact of the Microbiome on the Immune System

Abstract

Higher organisms are all born with general immunity as well as with, increasingly, more specific immune systems. All immune mechanisms function with the intent of aiding the body in defense against infection. Internal and external factors alike have varying effects on the immune system, and the immune response is tailored specifically to each one. Accompanying the components of the human innate and adaptive immune systems are the other intermingling systems of the human body. Increasing understanding of the body's immune interactions with other systems has opened new avenues of study, including that of the microbiome. The microbiome has become a highly active area of research over the last 10 to 20 years since the NIH began funding the Human Microbiome Project (HMP), which was established in 2007. Several publications have focused on the characterization, functions, and complex interplay of the microbiome as it relates to the rest of the body. A dysfunction between the microbiome and the host has been linked to various diseases including cancers, metabolic deficiencies, autoimmune disorders, and infectious diseases. Further understanding of the microbiome and its interaction with the host in relation to diseases is needed in order to understand the implications of microbiome dysfunction and the possible use of microbiota in the prevention of disease. In this review, we have summarized information on the immune system, the microbiome, the microbiome's interplay with other systems, and the association of the immune system and the microbiome in diseases such as diabetes and colorectal cancer.

FIG. 1:

Infection course in adaptive immunity. An APC recognizes antigen of an invading pathogen, processes it, and brings it to the draining lymph nodes. In the lymph nodes, the presentation of antigen on MHC class I or class II occurs. CD8+ T cells are MHC-I restricted and CD4+ T cells are MHC-II restricted. Further differentiation of CD4+ T cells helps to activate the immune components and, with the CD8+ T cells (cytotoxic T lymphocytes), the CD4+ T cells attack the original infection.

FIG. 2:

Hematopoietic stem cells are multipotent precursor cells with the ability to differentiate into all cells of the blood. Thrombopoiesis is the formation of platelets, the cells involved in primary hemostasis, and platelet plug formation. Erythropoiesis is the formation of erythrocytes, the cells involved in oxygen and CO₂ transport in the blood. Granulocytopoiesis is the formation of granulocytes (neutrophils, basophils, and eosinophils), the cells involved in the immediate response of the innate immune system. Monocytopoiesis is the formation of monocytes; these cells further differentiate into macrophages, which are involved in the innate immune response as well as the adaptive immune response as APCs. Lymphopoiesis is the formation of B and T lymphocytes as well as NK cells. B and T-lymphocytes are involved in the adaptive immune response while NK cells are involved in the innate immune system.

FIG. 3:

Effector T cell functions. Activation of CD4 helper T cells via recognition of antigens presented on MHC II molecules on an APC leads to a subsequent release of cytokines that stimulate the activity of B cells to differentiate into an antibody-secreting plasma cell. Activated CD4 helper T cells, upon contact with a macrophage engaged in the phagocytosis of bacteria, secrete cytokines that increase the microbicidal power of the macrophages by secretion of inflammatory cytokines. A naïve CD8 T cell can be activated directly by a virus-infected dendritic cell or indirectly by help from a CD4 helper T cell, which makes it a killer T cell.

FIG. 4:

Bacterial composition of microbiota. The microbiome consists of varying bacterial compositions. The Human Microbiome Project and outside studies have worked to characterize the microbiome through 16S rRNA and metagenomic sequencing. Listed are a few of the prominent bacteria from three major sites of the microbiome. Similar families of bacteria are seen across most sites in the body, but vary in composition due to their role in certain environments.