The immune response is a dynamic process, and both its nature and its intensity change over time. It begins with the antigen-independent responses of innate immunity and becomes both more focused on the pathogen and more powerful as the antigen-specific adaptive immune response matures. The character of the response differs contingent on the type of pathogen. Different types of pathogens (for example, intracellular and extracellular bacteria, viruses, helminthic parasites, and fungi) elicit different types of immune response (for example, type 1, 2, or 3), so that the most effective immune response is induced for effective elimination of the pathogen. The innate immune system not only anticipates and initiates the adaptive Tand B-cell responses, but continues to provide effector cells and reinforcing pathways of the different types of immunity throughout infection. Early in the response, different subsets of innate lymphoid cells (ILCs) are activated by cytokines produced by innate sensor cells. This early response acts to constrain pathogen entry at the initial site of infection to prevent dissemination while the adaptive response develops. However, the more sensitive and specific actions of effector T cells and class-switched, affinity-matured antibodies are often required for the complete elimination of infection, or sterilizing immunity. In this part of the chapter, we provide an overview of how the different phases of an immune response are orchestrated in space and time and then discuss how distinct cytokines from innate sensor cells activate different innate lymphoid cell subsets to restrain pathogen invasion and direct pathogen-specific defenses while the adaptive response is developing.
11-1 The course of an infection can be divided into several distinct phases.
Although some of the microbe-associated molecular patterns (MAMPs) of different types of pathogens are shared, others are not, and these differences underlie the induction of distinct patterns of innate and adaptive immunity that can be broadly grouped into type 1, type 2, and type 3 responses, as will be discussed below. Irrespective of the inciting pathogen and the pattern of immune response it provokes, however, the tempo of the host response is similar and can be broken down into various stages (Fig. 11.1, and see Fig. 3.38).
In the first stage of infection, a new host is exposed to infectious particles either shed by an infected individual or present in the environment. The numbers, route, mode of transmission, and stability of an infectious agent outside the host determine its infectivity. The first contact with a new host occurs through an epithelial surface, such as the skin or the mucosal surfaces of the respiratory, gastrointestinal, or urogenital tracts. After making contact, an infectious agent must establish a focus of infection. It must either adhere to the epithelial surface and colonize it, or penetrate it to replicate in the tissues (Fig. 11.2). Bites by arthropods (insects and ticks) and wounds breach the epidermal barrier and help some microorganisms gain entry through the skin.
Integration of innate and adaptive immunity in response to specific types of pathogens.
Fig. 11.2 Infections and the responses to them can be divided antigen and antigen-loaded dendritic cells to lymphatics (second into a series of stages. These are illustrated here for a pathogenic panel) and thence to local lymph nodes (third panel). This leads to microorganism (red) entering across a wound in an epithelium. The an adaptive immune response in the lymph node that involves the microorganism first adheres to epithelial cells and then invades activation and further differentiation of B cells and T cells with the beyond the epithelium into underlying tissues (first panel). A local eventual production of antibody and effector T cells, which clear the innate immune response helps to contain the infection, and delivers infection (fourth panel).