WHAT ROUTES DO INFECTIONS FOLLOW? WHAT ARE THE  DIFFERENCES BETWEEN THE DIFFERENT ROUTES?

We reviewed in previous chapters the different immune mechanisms (innate and adaptive responses) and non-immune responses (mechanical-chemical barriers) as well as the differences between primary and secondary responses. In this chapter, we will see the importance of the infection route in the stimulation of each mechanism and the role that the characteristics of the infectious agent can play in the immune activation. Some of the essential questions for knowing which of the different immune mechanisms will be most relevant are: Is the infection extracellular or intracellular?, or is it both extra and intracellular? 

Usually, infectious agents enter the pig through the respiratory and gut epithelium and through the skin. More rarely, they enter via the urogenital system.

The surface epithelium is protected by the innate and adaptive immune processes of the mucosa-associated lymphoid tissue. It consists of lymphatic tissue nodules that have different names depending on their localization: GALT (gut-associated lymphoid tissues) and BALT (bronchial-associated lymphoid tissues). The immunity of the mucosa has several important characteristics that make it different from systemic immunity. This occurs both at the structural level (M cells, the most important of which is: IgA) as well as at a functional level. This allows the induction of both a local and a general response after a local antigenic stimulation.All the characteristics and information on the mucosal immune response were explained in chapter 3.  

Stimulation of the lymphoid tissue of the mucosa. BALT or GALT. This mechanism allows a general immune response even when the antigenic stimulation has taken place only at the local level.

Interferon  plays a role in the innate response by inducing a transitory resistance in the cells. 

Another frequent route of infection in the pig is through the skin: wounds, inoculation by syringes, or parasites. Usually, most infections do not progress thanks to the activation of the mechanisms of the innate response (phagocytosis, activation of NK, alternative pathway of the complement, interferon, etc.). If the infection does progress, antigens are carried to local lymph nodes where they are processed by antigen presenting cells and presented to CD 4+ lymphocytes. Then, antibody production begins and the rest of the humoral defense mechanisms start to work.  

Cytotoxic mechanisms act when the infectious agent is not extracellular and are mediated by ADCC  and CD 8+ 

T cytotoxic lymphocytes 
© James A. Sullivan, Cells Alive! 

The characteristic features of the infectious agent will determine which immune mechanisms are more effective. For example, intracellular stages are attacked by cytotoxicity mechanisms, especially cellular cytotoxicity. These mechanisms will take place either during the innate response (NK cells, activation of the complement by the classical pathway), or during the adaptive response (CD 8+ lymphocytes, macrophage activation, CD4 Th1, complement activation through the classical pathway or antibody-dependent cell-mediated cytotoxicity: ADCC).

Macrophage phagocyting Candida albicans cells
© James A. Sullivan, Cells Alive!

When the infectious agent presents an extracellular cycle the most relevant mechanisms will be humoral. This is mediated by antibodies which are stimulated by Th 2 lymphocytes. Antibodies induce neutralization of the infectious agent and its opsonization in order to facilitate phagocytosis by macrophages (through the Fc receptor). 

Some pathogens, such as some viruses, have both phases during their infection cycle. They appear as extracellular viral particles, and as viral antigens in the membrane of infected cells that will trigger different cytotoxic mechanisms.