Models for Th1 differentiation. (Part a of the Figure 1). Source: Weaver, 2007.

The Th1-Th2 paradigm provides a framework for understanding T cell biology and the interplay of innate and adaptive immunity.

The roles and interactions of Th1, Th2 and Th17 immunity is a fascinating piece of physiological literacy with implications in the treatment of viral infections, allergies and autoimmune disorders. Weaver and colleagues, 2007 (1), produced a quality review on the topic. In the article below, we shared our notes and several curated citation from the review by Weaver and colleagues (1) as well as from other sources.

Fig. 1. Eicosanoid biosynthesis from arachidonic acid [ARA]. In response to various stimuli, ARA is released from cell membranes by phospholipase A2 [PLA2]. Free ARA can be metabolized to eicosanoids through the epoxygenase P-450, cyclooxygenase [COX 1 and 2], or lipoxygenases [5-LOX, 12-LOX and 15-LOX] pathways. In epoxygenase P-450, ARA is metabolized to epoxyeicosatrienoic acids [EETs]. The COX enzymes catalyze the conversion of ARA into intermediate prostaglandin G2 [PGG2] and then into prostaglandin H2 [PGH2]. PGH2 acts as a substrate for the generation of biologically active products such as prostaglandins [PGD2, PGE2, PGF2α], thromboxanes [TXA2 and TXB2] and the prostacyclin [PGI2], together these metabolites are called prostanoids. In the presence of aspirin, COX-2 is acetylated [indicated by‘Ac'], which enhances the COX-2-catalyzed formation of 15-R-hydroxyeicosatetraenoic acid [15R -HETE] which can be converted by 5- LOX into the called aspirin-triggered lipoxins [LXA4 and LXB4]. LOX converts ARAfirst to the respective hydroperoxy-eicosatetraenoic acids [5, 12, and 15 - HpETEs] to produce the corresponding hydroxy-eicosatetraenoic acid [5, 12 and 15 - HETEs]. 5-HpETE is also further metabolized to form leukotriene [LT] A4 by 5-LOX. LTA4 is later converted to LTB4, LTC4, LTD4, and LTE4. The 15-HETE lead to the formation of lipoxins by 15-LOX. Based in Dennis & Norris [2015] and Harizi et al., [2008]. Source: Rogero, 2020.

Eicosanoid biosynthesis from arachidonic acid (20:4n-6).

Our notes and several illustrations on pro-inflammatory and anti-inflammatory lipid mediators generated from arachidonic acid.

Long walks to heal the joints and ligaments. Carrying something in your hand, for example, a bag, can be a way to also engage muscles and ligaments of the upper body. The weight of the bag or other object that you decide to use for this purpose should be selected intelligently.

Long walks to heal joints and ligaments. Tools.

Insufficient blood supply may be the reason why your joints and ligaments do not recover between workouts.

Figure 4 |Three modes of adaptation and maintenance of tissue homeostasis. The state of a tissue can range from basal, to stressed or malfunctioning, to damaged or infected, and each state is graded (as indicated by shading). The state affects the mode of maintenance of tissue homeostasis or adaptive responsethat is engaged by tissue-resident macrophages and, in some tissues, by other types of leukocyte. Blue arrows indicate signals that report the tissue state to macrophages; red arrows indicate macrophage-derived signals thatcontrol tissue adaptation. At one extreme of the range of responses is inflammation, which follows infection or tissue damage. By contrast, tissue stress or malfunction induces parainflammation, which helps a tissue to adapt to the noxious conditions and restore tissue functionality. Dysregulated para-inflammation might be responsible for the chronic inflammatory states that are associated with many modern human diseases, such as type 2 diabetes and atherosclerosis. Source: Medzhitov, 2008.

Physiological and pathological outcomes of inflammation.

Depending on the trigger, the inflammatory response has a different physiological purpose and pathological consequences. Of the three possible initiating stimuli, only infection-induced inflammation is coupled with the induction of an immune response.