Skin
Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard in Toxicologic Pathology, 2018
Changes in clinical pathology parameters associated with skin lesions may be reflected in alterations in hematology parameters, such as increased white blood cell counts and neutrophilia in an acute (non-immunologic) inflammatory response. Immunologic skin reactions are often accompanied by changes in lymphocyte subsets and immunoglobulin levels, depending on the type of immune reaction. In atopic dermatitis (type I hypersensitivity reaction), the anaphylactic response is mediated by increased IgE levels, which instigate degranulation of mast cells and basophils with subsequent release of histamine, serotonin, and other mediators of acute inflammation. The Arthus reaction in skin (type III hypersensitivity reaction) is also an antibody-mediated response involving complement-fixing IgG and IgM. In this reaction, antigen and antibody form complexes that precipitate in the bloodstream and become lodged in the microvasculature where they trigger complement activation and consequent release of cytokines, chemokines, and vasoactive factors. In delayed-type reactions (type IV hypersensitivity reaction), small-molecule antigens bound to carrier proteins interact with antigen-presenting cells (e.g., Langerhans cells), which present the modified antigen to T lymphocytes. This reaction is manifested by increased lymphocyte counts. Erythema multiforme and TEN are associated with increased levels of cytotoxic (CD8+) T cells against keratinocytes. The severe cutaneous lesions of TEN are also associated with increased levels of TNF and IL-6.
Effects of Antithrombotic and Results of Drug Screening
Josef Hladovec in Antithrombotic Drugs in Thrombosis Models, 2020
An interesting group of models, quite different from those generally used for testing antithrombotics, were based on the effect of sulfinpyrazone on inflammatory reactions and particularly those associated with the activation of the immune system. This effect is probably related to the contribution of platelets. Butler et al.167, 168 and Butler and White169 studied the inhibition of Arthus reaction in guinea pigs. Sulfinpyrazone at a dose of 50 mg/kg i.v. inhibited the resulting thrombocytopenia. Some other antiplatelet agents were also effective (ASA 10 mg/kg, indomethacin), but dipyridamole was ineffective. In some experiments platelet sequestration in the lungs was quantitatively assessed by radiolabeled platelets. Whereas with some drugs, a correlation of in vivo and in vitro or ex vivo studies with platelet aggregation was present to some extent, with sulfinpyrazone it was not. Of course, immune reaction of Arthus type is a very complex process and sulfinpyrazone might have interfered at various stages (production of mediator effects on various targets except platelets, etc.). A similar complexity has to be accepted in response to the Forssman reagent where sulfinpyrazone was also effective, but in general, high doses were necessary. However, its favorable effect in models of allograft rejection (Sharma et al.,170 in dogs, Vaessen et al.,171 in rats, and Jamiesson,172 in rats) might have some implication for clinical therapy.
Immunopathology
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
Intradermal injection of antigen into a previously immunized animal generates immune complexes at the injection site. These complexes consist of preformed antibody and the injected antigen. Complement activation leads to neutrophil infiltration of the injection site and tissue destruction. The reaction is detectable 1–3 hours post-injection and reaches a peak after 4–10 hours. The injection site becomes edematous, erythematous, and may ulcerate. This is called the Arthus reaction. Histologically, one observes fibrinoid necrosis. Antibody and complement are detectable with immunostaining. A “passive” Arthus reaction may be induced by simultaneous intradermal injection of antigen and antibody.
Understanding Retinal Vasculitis Associated with Brolucizumab: Complex Pathophysiology or Occam’s Razor?
Published in Ocular Immunology and Inflammation, 2022
Ashish Sharma, Nilesh Kumar, Nikulaa Parachuri, Sonali Singh, Francesco Bandello, Carl D. Regillo, David Boyer, Quan Dong Nguyen
It is possible that small size may allow higher molar concentration and incite a strong local immune reaction leading to inflammation. We have highlighted the role of type III hypersensitivity reaction (HSR) in the past.15 The majority of vasculitic diseases involve the deposition of antigen-antibody complex, which is Type III HSR. These deposits have been shown in the capillary bed and vessel walls and can lead to occlusive vasculitis. Arthus reaction, a subtype of Type III HSR has been reported in patients on systemic monoclonal antibody (mAb), including systemic anti-VEGF therapies. Such reactions are assumed to be due to high antigen load, which leads to a subsequent increase of antibodies.16,17 Arthus reaction is more frequent in patients with auto-immune conditions. The higher molar concentration of brolucizumab (11 and 22 times greater than aflibercept and ranibizumab, respectively), if antigenic, may produce a higher rate of antibody formation. Type III HSR is due to the formation of biologic/ADA immune complexes in the circulation. When these complexes are in the correct stoichiometric ratio, they are deposited in tissues and cause inflammation and tissue damage. The requirement of the correct ratio to have tissue deposition might explain why vasculitis is seen in some individual rather than in clusters as each individual having differing amounts of ADAs leading to different stoichiometric ratios.18
The enigmatic nature of the triggering receptor expressed in myeloid cells -1 (TLT- 1)
Published in Platelets, 2021
Siobhan Branfield, A. Valance Washington
Insights to role for TLT-1 in hemostasis came from studies using the reverse Arthus reaction. In the reverse Arthus reaction, immune complexes develop sub dermally and lead to complement deposition and neutrophil infiltration. In normal mice it leaves a bruise, in thrombocytopenic mice it leads to overt bleeding. In these studies, by Goerge et al [44] the β3 mice did not bleed, suggesting that the αIIbβ3/fibrinogen interaction was not important for hemostasis derived from immune triggers. Treml1−/- mice show a distinct petechia when compared to their wild type counterparts [37] suggesting that the TLT-1/fibrinogen interaction may regulate immune functions of platelets.
Keratoconjunctivitis as a Single Entity in X-linked Agammaglobulinemia?
Published in Ocular Immunology and Inflammation, 2023
Stefan Mielke, Bastian Grundel, Sebastian M. Schmidt, Frank Tost
In the current case, a type III allergic reaction (Arthus reaction) was also possible. In this situation, after activating the complement system, the local inflammation reaction is initiated by immune complexes after contact with microbial complements. Both medications could improve the inflammation as seen during the clinical course: the anti-inflammatory medication directly and the antibiotics indirectly by reducing the local microbial flora, given that our repeated conjunctival swabs failed to detect still existing, possibly physiological skin flora.
Related Knowledge Centers
- Antibody
- Immune Complex
- Immunology
- Serous Membrane
- Type III Hypersensitivity
- Hypersensitivity
- Blood Vessel
- Type III Hypersensitivity
- Antigen
- Pulmonary Pleurae
- Pericardium