Role and Development of Th1/Th2 Immune Responses in the Lungs
Role and Development of Th1/Th2 Immune Responses in the Lungs
The development of T helper 1 (Th1) and Th2 responses is dependent on the cells and early signals of the innate immune system. Following inhalation of pulmonary pathogens, lung antigenpresenting cells (APCs) ingest the microbe, begin to process antigen, and migrate to peripheral lymphoid tissues (i.e., LALNs). It is in the lymph node that the APCT cell interaction takes place; therefore, the microenvironment of the lymph node significantly influences the developing T cell response (Th1 vs Th2). Several factors can determine the nature of the T cell response, including cytokines, chemokines, microbial virulence factors, and dendritic cell phenotype. A shift in the Th1/Th2 balance in the lungs can result in chronic infection, allergic disease, and immunopathology. This review discusses the mechanisms of developing Th1/Th2 pulmonary responses, the counterregulation of Th1/Th2 immunity, and the consequences of immune deviation in the lungs.
Objectives: Upon completion of this article, the reader should understand that: (1) developing Th1/Th2 responses are dependent on innate immunity; (2) shifts in the Th1/Th2 balance can result in chronic infection and/or allergy; and (3) mechanisms exist to counterregulate Th1/Th2 responses.
Accreditation: The University of Michigan is accredited by the Accreditation Council for Continuing Medical Education to sponsor continuing medical education for physicians.
Credits: The University of Michigan designates this educational activity for amaximumof 1 category 1 credit toward the AMAPhysician's Recognition Award.
The type of host response mounted during a pulmonary infection is determined by multiple factors, including the host innate response, host genetics, and microbial virulence factors. It is the combination of these components that determines whether T1 or T2 immune responses develop in the lungs (Fig. 1). The innate response can destroy a pathogen or limit the infection until adaptive immunity develops. The cells and signals of innate immunity provide the major immunoregulatory functions that link innate and adaptive immunity. Dendritic cells (DCs) are at the gateway between innate and adaptive immunity. The phenotype of the DC and the proinflammatory mediators they produce strongly influence the developing T cell response. An alteration in the innate immune response or a change in T1/T2 counterregulation can result in immune deviation and chronic pulmonary infection.
(Enlarge Image)
The infection triad. The interplay between the host innate response, microbial virulence factors, and host genetics determines the type of T cell response (T1 vs T2). Each component has the ability to influence the other components or to be influenced by the other components. Thus the development of T1 or T2 responses is determined by multiple factors.
Microbial virulence factors can also modulate the development of T1/T2 immune responses in the lungs. Virulence factors allow the microbe to escape elimination by host defenses. Mechanisms of immune evasion by virulence factors include (1) the modulation of afferent cytokine signals, (2) the alteration of antigen processing, and (3) the inhibition of adaptive immune effector mechanisms. For example, virulent strains of Cryptococcus neoformans inhibit the production of tumor necrosis factor alpha (TNF-α), interleukin (IL)-12 and IL-18, and interferon gamma (IFN-γ) during the first week of infection.
The development of T helper 1 (Th1) and Th2 responses is dependent on the cells and early signals of the innate immune system. Following inhalation of pulmonary pathogens, lung antigenpresenting cells (APCs) ingest the microbe, begin to process antigen, and migrate to peripheral lymphoid tissues (i.e., LALNs). It is in the lymph node that the APCT cell interaction takes place; therefore, the microenvironment of the lymph node significantly influences the developing T cell response (Th1 vs Th2). Several factors can determine the nature of the T cell response, including cytokines, chemokines, microbial virulence factors, and dendritic cell phenotype. A shift in the Th1/Th2 balance in the lungs can result in chronic infection, allergic disease, and immunopathology. This review discusses the mechanisms of developing Th1/Th2 pulmonary responses, the counterregulation of Th1/Th2 immunity, and the consequences of immune deviation in the lungs.
Objectives: Upon completion of this article, the reader should understand that: (1) developing Th1/Th2 responses are dependent on innate immunity; (2) shifts in the Th1/Th2 balance can result in chronic infection and/or allergy; and (3) mechanisms exist to counterregulate Th1/Th2 responses.
Accreditation: The University of Michigan is accredited by the Accreditation Council for Continuing Medical Education to sponsor continuing medical education for physicians.
Credits: The University of Michigan designates this educational activity for amaximumof 1 category 1 credit toward the AMAPhysician's Recognition Award.
The type of host response mounted during a pulmonary infection is determined by multiple factors, including the host innate response, host genetics, and microbial virulence factors. It is the combination of these components that determines whether T1 or T2 immune responses develop in the lungs (Fig. 1). The innate response can destroy a pathogen or limit the infection until adaptive immunity develops. The cells and signals of innate immunity provide the major immunoregulatory functions that link innate and adaptive immunity. Dendritic cells (DCs) are at the gateway between innate and adaptive immunity. The phenotype of the DC and the proinflammatory mediators they produce strongly influence the developing T cell response. An alteration in the innate immune response or a change in T1/T2 counterregulation can result in immune deviation and chronic pulmonary infection.
(Enlarge Image)
The infection triad. The interplay between the host innate response, microbial virulence factors, and host genetics determines the type of T cell response (T1 vs T2). Each component has the ability to influence the other components or to be influenced by the other components. Thus the development of T1 or T2 responses is determined by multiple factors.
Microbial virulence factors can also modulate the development of T1/T2 immune responses in the lungs. Virulence factors allow the microbe to escape elimination by host defenses. Mechanisms of immune evasion by virulence factors include (1) the modulation of afferent cytokine signals, (2) the alteration of antigen processing, and (3) the inhibition of adaptive immune effector mechanisms. For example, virulent strains of Cryptococcus neoformans inhibit the production of tumor necrosis factor alpha (TNF-α), interleukin (IL)-12 and IL-18, and interferon gamma (IFN-γ) during the first week of infection.