Vertebrates resist infection by pathogenic microorganisms in several ways. The innate defenses can act immediately and may succeed in repelling the infection, but if not, they are followed by a series of induced early responses that help to contain the infection as adaptive immunity develops. These first two phases of the immune response rely on recognizing the presence of infection by using the nonclonotypic receptors of the innate immune system. They are summarized in Fig. 11.35 and covered in detail in Chapter 3. Several specialized subsets of immune cells, which can be viewed as intermediates between innate and adaptive immunity, act next and include the innate lymphoid cells, or ILCs, which are rapid responders to cytokines produced by innate sensor cells and can help to bias the CD4 T-cell response toward parallel subsets of effector T cells; and NK cells, which can be recruited to lymph nodes and secrete IFN-γ, and thus promote a TH1 response. The third phase of an immune response is the adaptive immune response (see Fig. 11.35), which is mounted in the peripheral lymphoid tissue that serves the particular site of infection and takes several days to develop, because T and B lymphocytes must encounter their specific antigen, proliferate, and differentiate into effector cells. T-cell dependent B-cell responses cannot be initiated until antigen-specific TFH cells have had a chance to proliferate and differentiate. Once an adaptive immune response has occurred, the antibodies and effector T cells are dispersed via the circulation and recruited into the infected tissues; the infection is usually controlled and the pathogen is contained or eliminated. The final effector mechanisms used to clear an infection depend on the type of infectious agent, and in most cases they are the same as those employed in the early phases of immune defense; only the recognition mechanism changes and is now more selective (see Fig. 11.35).
Fig. 11.35 The components of the three phases of the immune response against different classes of microorganisms. The mechanisms of innate immunity that operate in the first two phases of the immune response are described in Chapters 2 and 3, and thymus-independent (T-independent) B-cell responses are covered in Chapter 10. The early phases contribute to the initiation of adaptive immunity, and they influence the functional character of the antigen-specific effector T cells and antibodies that appear on the scene in the late phase of the response. There are striking similarities in the effector mechanisms at each phase of the response; the main change is in the recognition structure used.
An effective adaptive immune response leads to a state of protective immunity. This state consists of the presence of effector cells and molecules produced in the initial response, and of immunological memory. Immunological memory is manifested as a heightened ability to respond to pathogens that have previously been encountered and successfully eliminated. Memory T and B lymphocytes have the property of being able to transfer immune memory to naive recipients. The mechanisms that maintain immunological memory include certain cytokines, such as IL-7 and IL-15, as well as homeostatic interactions between the T-cell receptors on memory cells with self peptide:self MHC complexes. The artificial induction of protective immunity, which includes immunological memory, by vaccination is the most outstanding accomplishment of immunology in the field of medicine. The understanding of how this is accomplished is now catching up with its practical success. However, as we will see in Chapter 13, many pathogens do not induce protective immunity that completely eliminates the pathogen, so we will need to learn what prevents this before we can prepare effective vaccines against these pathogens.
Questions.
11.1 True or False: The immune response is a dynamic process that initiates with an antigen-independent response, which becomes more focused and powerful as it develops antigen specificity. Once the adaptive immune system develops, a single type of response is capable of eliminating any type of pathogen.
11.2 Multiple Choice: Which statement is incorrect?