A brief journey through the immune system

Abstract

This review serves as an introduction to an Immunology Series for the Nephrologist published in CJASN. It provides a brief overview of the immune system, how it works, and why it matters to kidneys. This review describes in broad terms the main divisions of the immune system (innate and adaptive), their cellular and tissue components, and the ways by which they function and are regulated. The story is told through the prism of evolution in order to relay to the reader why the immune system does what it does and why imperfections in the system can lead to renal disease. Detailed descriptions of cell types, molecules, and other immunologic curiosities are avoided as much as possible in an effort to not detract from the importance of the broader concepts that define the immune system and its relationship to the kidney.

Keywords: ARF; GN; immunology; renal transplantation; tolerance.

Figure 1.

Evolution of the immune system. Adaptive immunity as we know it in humans did not evolve until the emergence of the first jawed vertebrates (fish) around 450 million years (my) ago. Evolution of adaptive immunity was heralded by the appearance of lymphocytes, the major histocompatibility complex (MHC), immunoglobulin (Ig) molecules, T-cell receptor for antigen (TCR), and recombinase activating genes (RAG) responsible for the diversity in these recognition molecules. Our more ancient ancestors, such as the sponges (−700 my), relied on basic defense systems without the benefit of lymphocytes, antigen receptors with fine molecular specificity, or any noteworthy immunologic memory. An approximate timeline for evolution of innate immune components (antimicrobial peptides, phagocytosis, complement, and Toll-like receptors) is also shown.

Figure 2.

A two-dimensional view of the adaptive (lymphocyte) immune response. Foreign antigen triggers the exponential proliferation of lymphocytes, which then differentiate into helper and effector cells. Regulatory mechanisms kick in at the peak of the response, the most conspicuous of which is the death of the majority of the lymphocytes by apoptosis. The few that survive become memory precursors and later memory cells. Lymphocyte death is necessary to prevent unwanted immunopathology.

Figure 3.

The role of the innate immune system in activating adaptive immunity. The innate immune system can be envisioned as a doorbell that awakens the adaptive immune system (lymphocytes) upon sensing microbes (bacteria, viruses, fungi, and parasites). The dendritic cell (DC) acts as the link between the innate and adaptive systems by phagocytosing, processing, and presenting microbial antigens to lymphocytes and providing them with the necessary costimulatory signals. Endogenous molecules released by stressed or dying cells participate in acute kidney injury, transplant rejection, or autoimmunity by triggering the same innate immune receptors that sense microbes leading to stimulation of the adaptive immune response.

Figure 4.

The relationship between the immune system and kidney disease. The principal renal afflictions in which the immune system plays a major or important role are shown. Conversely, renal insufficiency affects the immune system by weakening immune defenses and by causing systemic inflammation that contributes to cardiovascular disease.