*6.2.2 The role of basal cells in mucociliary clearance*

Basal cells of the respiratory epithelium have the capability to differentiate into ciliated and secretory cells and hence can restore the normal structure of the respiratory epithelium after injury. The stimulus for differentiation into ciliated or secretory cells is by exposure to the luminal air [44]. The differentiation of basal cells into ciliated and secretory cells has been attributed to the activation of the transcription factor forkhead boxJ1 (FOXJ1) and the regulatory factor X [45]. Thus, the basal and intermediate cells impart regeneration capacity to various regions of the airway. In the human respiratory tract, the highest epithelial regeneration capacity is found in the large airways (trachea and bronchi) whose regeneration capacity is estimated to be about 8 times higher than in the smaller airways [36].

#### **6.3 Adaptive immune response of the lower respiratory tract**

The respiratory tract is constantly exposed to the external environment which contains numerous particles and molecules that can potentially trigger an inflammatory reaction. An important anatomical feature of the respiratory system in general and the lungs in particular is that it has a large surface area of epithelium that is constantly exposed to the external environment and, at the same time, is highly vascularized. This anatomical feature makes the respiratory tract and the lungs to be the major portal of entry for many pathogens including a wide array of respiratory viruses [46].

The respiratory immune system must discriminate between potentially harmful pathogens and those that are innocuous. Most diseases of the respiratory tract involve contributions from both the innate and adaptive immune systems. Complex interactions occur during most respiratory tract infections. A number of systems are *Refocusing Functional Anatomy and Immunology of the Respiratory Mucosa in the Advent… DOI: http://dx.doi.org/10.5772/intechopen.96251*

involved in the overall immune responses within the respiratory tract and include epithelium-immune system interactions, early effector mechanisms, the influence of the microbiome and immunomodulatory and regulatory pathways [47].

As opposed to the innate immune system, the adaptive immune system (or acquired immune system) is highly specific to a particular pathogen. The adaptive immunity is also able to provide long-term immune protection. The cells responsible for carrying out the acquired immune response are the lymphocytes.

Many respiratory tract viral infections result in mild, self-limited disease. However, other viruses like the SARS-CoV-2 and certain type A influenza virus strains such as the highly pathogenic avian H5N1 viruses can produce severe and frequently fatal infections and can also target epithelial cells of the conducting airways [5].

Many types of immune cells such as dendritic cells, macrophages, neutrophils, eosinophils, and B and T lymphocytes, contribute to lung immunity. Cell-mediated

**Figure 3.** *Adaptive immune responses build and shape innate immune responses.*

adaptive immune responses are key against all classes of pulmonary pathogens including viruses, various bacteria and fungi. Adaptive immune responses build upon and shape innate immune responses (**Figure 3**). They depend on sequential pairwise interactions between three cell types: T-cells, Natural Killer (NK) cells, and Dendritic Cells (DCs).

Dendritic cells (DCs) are also known as accessory cells whose function is to ingest and process antigen material and then present it on their surfaces to the T cells. DCs migrate to local lymph nodes once activated by antigens and within the lymph nodes they interact with T cells and B cells to initiate and orchestrate the adaptive immune response. Thus, dendritic cells act as messengers between the innate and the adaptive immune systems [48].

Upon virus exposure, dendritic cells in the lungs mature and traffic to the local draining lymph nodes (cervical and mediastinal lymph nodes), where they display peptide antigen to naïve CD4 T cells. After being exposed to antigen, the antigenspecific T cells then become activated and initiate a program of proliferation and differentiation, resulting in the production of effector cells that have the capacity to migrate to the lung and terminate the infection [46]. T cells mediate viral clearance via cytokine production or direct cytolytic mechanisms which may be either perforin or Fas mediated pathways [49].

During the course of a respiratory virus infection, pools of memory T cells are established that persist for the life of the individual. These CD4 T cells differ significantly from their naive precursors in that they persist at a high frequency, generate rapid effector functions in response to antigen exposure, have distinct cytokine production profiles, have low requirements for co-stimulation, and have reduced susceptibility to apoptosis. Many memory cells can be found in secondary lymphoid organs, such as the draining lymph nodes and the spleen [46, 50, 51].

### **7. Conclusion**

The respiratory system will continue to attract attention in terms of research particularly during and in the post covid-19 era. Thus, understanding the functional anatomy and immunology of the respiratory tract will be cardinal. Respiratory diseases will undoubtedly continue to be major public health problems worldwide, with unpredictable morbidities and mortalities. To date, although considerable progress had been in understanding the functional anatomy and immunology of the respiratory tract, there was need to put the subject in the context of the covid-19 pandemic in order to complement the prevailing research efforts in combating covid-19. Much remains to be done in terms of predicting respiratory disease prior to symptoms and also in the development of novel and new treatments in a more personalized manner [52, 53].

#### **Acknowledgements**

The author is grateful to the University of Zambia for providing unlimited internet access and library facilities and to Biotechnology Kiosk and Intech for publishing the work.

#### **Conflict of interest**

The author declares no conflict of interest.

*Refocusing Functional Anatomy and Immunology of the Respiratory Mucosa in the Advent… DOI: http://dx.doi.org/10.5772/intechopen.96251*
