Vernal Conjunctivitis

Cancer; an induced disease of twentieth century! Induction of tolerance, increased entropy and ‘Dark Energy’: loss of biorhythms (Anabolism v. Catabolism)

“…In 1980s, we established experimental models of acute and chronic ocular inflammatory diseases using guinea pigs conjunctival-associated lymphoid tissues (CALTs). Systematic analyses of a series of reported data suggested the first and only evidence for direct association between inflammation and time course kinetics of developmental phases of immune dysfunction (acute, intermediate and chronic phases) in the direction of tumorigenesis and angiogenesis (‘accidental’ discoveries) [ 5 – 8 , 26 – 41 ]. Briefly, in the acute phase (immediate hypersensitivity responses), early clinical and histopathological findings included strong or weak type 1 ocular reactions, tearing, activation and degranulation of mast cells (MCs), vascular hyperpermeability reactions and tissue edema.…”

“…The release of histamine and prostaglandins (PGF-1α) were reported as primary and secondary mediators of immune responses in acute phase reactions. Animals with strong acute ocular reactions also demonstrated wheezing suggestive of MCs sensitization and activation in lung airways [ 8 , 26 , 30 , 31 ]. The intermediate phase (down-regulation phenomena) responses were associated with minimum clinical responses, increased degranulated MCs, heavy infiltration of eosinophils in ocular secretions and goblet cells, induction of neovascularization and tissue atrophy [ 27 , 31 ].…”

“…Mixing antigen with tumor-promoting agents shifted the induction of tumorigenesis and angiogenesis to earlier time course, compared with using antigen alone, suggesting involvement of growth promoting kinases. Presence of circulating IgE antibodies did not necessarily correlated with strong acute reactions, suggesting sensitization of local and distal MCs including the lung airways or the fetus tissues [ 8 , 26 , 31 ]. In 2014, further analyses and integration of original data led to the first report on interactions and synergies between host/local immune and non-immune cells (e.g., mast cells, mucus-secreting goblet cells, epithelium, B/plasma cells) and the recruitment and infiltration of activated immune cells (e.g., eosinophils, tumor associated macrophages/TAM-M2) via activation of vasculature toward tumorigenesis and angiogenesis at different stages of immune dysfunction [ 38 ].…”

Cancer; an induced disease of twentieth century! Induction of tolerance, increased entropy and ‘Dark Energy’: loss of biorhythms (Anabolism v. Catabolism)

“…In 1980s, we established experimental models of acute and chronic ocular inflammatory diseases using guinea pigs conjunctival-associated lymphoid tissues (CALTs). Systematic analyses of a series of reported data suggested the first and only evidence for direct association between inflammation and time course kinetics of developmental phases of immune dysfunction (acute, intermediate and chronic phases) in the direction of tumorigenesis and angiogenesis (‘accidental’ discoveries) [ 5 – 8 , 26 – 41 ]. Briefly, in the acute phase (immediate hypersensitivity responses), early clinical and histopathological findings included strong or weak type 1 ocular reactions, tearing, activation and degranulation of mast cells (MCs), vascular hyperpermeability reactions and tissue edema.…”

“…The release of histamine and prostaglandins (PGF-1α) were reported as primary and secondary mediators of immune responses in acute phase reactions. Animals with strong acute ocular reactions also demonstrated wheezing suggestive of MCs sensitization and activation in lung airways [ 8 , 26 , 30 , 31 ]. The intermediate phase (down-regulation phenomena) responses were associated with minimum clinical responses, increased degranulated MCs, heavy infiltration of eosinophils in ocular secretions and goblet cells, induction of neovascularization and tissue atrophy [ 27 , 31 ].…”

“…Mixing antigen with tumor-promoting agents shifted the induction of tumorigenesis and angiogenesis to earlier time course, compared with using antigen alone, suggesting involvement of growth promoting kinases. Presence of circulating IgE antibodies did not necessarily correlated with strong acute reactions, suggesting sensitization of local and distal MCs including the lung airways or the fetus tissues [ 8 , 26 , 31 ]. In 2014, further analyses and integration of original data led to the first report on interactions and synergies between host/local immune and non-immune cells (e.g., mast cells, mucus-secreting goblet cells, epithelium, B/plasma cells) and the recruitment and infiltration of activated immune cells (e.g., eosinophils, tumor associated macrophages/TAM-M2) via activation of vasculature toward tumorigenesis and angiogenesis at different stages of immune dysfunction [ 38 ].…”

Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

“…Activated B cells become transformed to plasma cells and synthesize specific antibodies (e.g., IgGs, IgM, IgD, IgA, IgE) and appropriately sensitize or activate other immune cells. In such cases, HI and expression of specific antibodies seem to principally determine which innate immune cells are required for further response processes and for appropriate induction of memory B and T cells [3,13,14,27,28,30,35,37,39,44,47,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78]. …”

“…For example, in tissues such as the CALTs or perhaps lung airways and GALTs, B and plasma cells are the first line of defense when exposed to stimuli to express specific IgE antibodies for binding and sensitizing MC-IgE-fcε (epsilon) receptor molecules for appropriate responses (e.g., degranulation and release of pre-formed or newly synthesized mediators) during acute hypersensitivity or anaphylactic reactions (see details in Section 8) [3,35,37,59,60,61,62,63,64,65]. …”

Cancer; an induced disease of twentieth century! Induction of tolerance, increased entropy and ‘Dark Energy’: loss of biorhythms (Anabolism v. Catabolism)

“…In 1980s, we established experimental models of acute and chronic ocular inflammatory diseases using guinea pigs conjunctival-associated lymphoid tissues (CALTs). Systematic analyses of a series of reported data suggested the first and only evidence for direct association between inflammation and time course kinetics of developmental phases of immune dysfunction (acute, intermediate and chronic phases) in the direction of tumorigenesis and angiogenesis (‘accidental’ discoveries) [ 5 – 8 , 26 – 41 ]. Briefly, in the acute phase (immediate hypersensitivity responses), early clinical and histopathological findings included strong or weak type 1 ocular reactions, tearing, activation and degranulation of mast cells (MCs), vascular hyperpermeability reactions and tissue edema.…”

“…The release of histamine and prostaglandins (PGF-1α) were reported as primary and secondary mediators of immune responses in acute phase reactions. Animals with strong acute ocular reactions also demonstrated wheezing suggestive of MCs sensitization and activation in lung airways [ 8 , 26 , 30 , 31 ]. The intermediate phase (down-regulation phenomena) responses were associated with minimum clinical responses, increased degranulated MCs, heavy infiltration of eosinophils in ocular secretions and goblet cells, induction of neovascularization and tissue atrophy [ 27 , 31 ].…”

“…Mixing antigen with tumor-promoting agents shifted the induction of tumorigenesis and angiogenesis to earlier time course, compared with using antigen alone, suggesting involvement of growth promoting kinases. Presence of circulating IgE antibodies did not necessarily correlated with strong acute reactions, suggesting sensitization of local and distal MCs including the lung airways or the fetus tissues [ 8 , 26 , 31 ]. In 2014, further analyses and integration of original data led to the first report on interactions and synergies between host/local immune and non-immune cells (e.g., mast cells, mucus-secreting goblet cells, epithelium, B/plasma cells) and the recruitment and infiltration of activated immune cells (e.g., eosinophils, tumor associated macrophages/TAM-M2) via activation of vasculature toward tumorigenesis and angiogenesis at different stages of immune dysfunction [ 38 ].…”

Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

“…Activated B cells become transformed to plasma cells and synthesize specific antibodies (e.g., IgGs, IgM, IgD, IgA, IgE) and appropriately sensitize or activate other immune cells. In such cases, HI and expression of specific antibodies seem to principally determine which innate immune cells are required for further response processes and for appropriate induction of memory B and T cells [3,13,14,27,28,30,35,37,39,44,47,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78]. …”

“…For example, in tissues such as the CALTs or perhaps lung airways and GALTs, B and plasma cells are the first line of defense when exposed to stimuli to express specific IgE antibodies for binding and sensitizing MC-IgE-fcε (epsilon) receptor molecules for appropriate responses (e.g., degranulation and release of pre-formed or newly synthesized mediators) during acute hypersensitivity or anaphylactic reactions (see details in Section 8) [3,35,37,59,60,61,62,63,64,65]. …”

Cancer; an induced disease of twentieth century! Induction of tolerance, increased entropy and ‘Dark Energy’: loss of biorhythms (Anabolism v. Catabolism)

“…In 1980s, we established experimental models of acute and chronic ocular inflammatory diseases using guinea pigs conjunctival-associated lymphoid tissues (CALTs). Systematic analyses of a series of reported data suggested the first and only evidence for direct association between inflammation and time course kinetics of developmental phases of immune dysfunction (acute, intermediate and chronic phases) in the direction of tumorigenesis and angiogenesis (‘accidental’ discoveries) [ 5 – 8 , 26 – 41 ]. Briefly, in the acute phase (immediate hypersensitivity responses), early clinical and histopathological findings included strong or weak type 1 ocular reactions, tearing, activation and degranulation of mast cells (MCs), vascular hyperpermeability reactions and tissue edema.…”

“…The release of histamine and prostaglandins (PGF-1α) were reported as primary and secondary mediators of immune responses in acute phase reactions. Animals with strong acute ocular reactions also demonstrated wheezing suggestive of MCs sensitization and activation in lung airways [ 8 , 26 , 30 , 31 ]. The intermediate phase (down-regulation phenomena) responses were associated with minimum clinical responses, increased degranulated MCs, heavy infiltration of eosinophils in ocular secretions and goblet cells, induction of neovascularization and tissue atrophy [ 27 , 31 ].…”

“…Mixing antigen with tumor-promoting agents shifted the induction of tumorigenesis and angiogenesis to earlier time course, compared with using antigen alone, suggesting involvement of growth promoting kinases. Presence of circulating IgE antibodies did not necessarily correlated with strong acute reactions, suggesting sensitization of local and distal MCs including the lung airways or the fetus tissues [ 8 , 26 , 31 ]. In 2014, further analyses and integration of original data led to the first report on interactions and synergies between host/local immune and non-immune cells (e.g., mast cells, mucus-secreting goblet cells, epithelium, B/plasma cells) and the recruitment and infiltration of activated immune cells (e.g., eosinophils, tumor associated macrophages/TAM-M2) via activation of vasculature toward tumorigenesis and angiogenesis at different stages of immune dysfunction [ 38 ].…”

Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

“…Activated B cells become transformed to plasma cells and synthesize specific antibodies (e.g., IgGs, IgM, IgD, IgA, IgE) and appropriately sensitize or activate other immune cells. In such cases, HI and expression of specific antibodies seem to principally determine which innate immune cells are required for further response processes and for appropriate induction of memory B and T cells [3,13,14,27,28,30,35,37,39,44,47,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78]. …”

“…For example, in tissues such as the CALTs or perhaps lung airways and GALTs, B and plasma cells are the first line of defense when exposed to stimuli to express specific IgE antibodies for binding and sensitizing MC-IgE-fcε (epsilon) receptor molecules for appropriate responses (e.g., degranulation and release of pre-formed or newly synthesized mediators) during acute hypersensitivity or anaphylactic reactions (see details in Section 8) [3,35,37,59,60,61,62,63,64,65]. …”