The pathophysiology of atopic dermatitis is complex and multifactorial, involving elements of barrier dysfunction, alterations in cell mediated immune responses, IgE mediated hypersensitivity, and environmental factors. Loss of function mutations in filaggrin have been implicated in severe atopic dermatitis due to a potential increase in trans-epidermal water loss, pH alterations, and dehydration. Other genetic changes have also been identified which may alter the skin's barrier function, resulting in an atopic dermatitis phenotype. The imbalance of Th2 to Th1 cytokines observed in atopic dermatitis can create alterations in the cell mediated immune responses and can promote IgE mediated hypersensitivity, both of which appear to play a role in the development of atopic dermatitis. One must additionally take into consideration the role of the environment on the causation of atopic dermatitis and the impact of chemicals such as airborne formaldehyde, harsh detergents, fragrances, and preservatives. Use of harsh alkaline detergents in skin care products may also unfavorably alter the skin's pH causing downstream changes in enzyme activity and triggering inflammation. Environmental pollutants can trigger responses from both the innate and adaptive immune pathways. This chapter will discuss the multifaceted etiology of atopic dermatitis which will help us to elucidate potential therapeutic targets. We will also review existing treatment options and their interaction with the complex inflammatory and molecular triggers of atopic dermatitis.

Purpose Autoimmune diseases are thought to be caused by a loss of self-tolerance of the immune system. One candidate marker of immune dysregulation in autoimmune disease is the presence of increased double negative T cells (DNTs) in the periphery. DNTs are characteristically elevated in autoimmune lymphoproliferative syndrome, a systemic autoimmune disease caused by defective lymphocyte apoptosis due to Fas pathway defects. DNTs have also been found in the peripheral blood of adult patients with systemic lupus erythematosus (SLE), where they may be pathogenic. DNTs in children with autoimmune disease have not been investigated. Methods We evaluated DNTs in pediatric patients with SLE, mixed connective tissue disease (MCTD), juvenile idiopathic arthritis (JIA), or elevated antinuclear antibody (ANA) but no systemic disease. DNTs (CD3+CD56−TCRαβ+CD4−CD8−) from peripheral blood mononuclear cells were analyzed by flow cytometry from 54 pediatric patients including: 23 SLE, 15 JIA, 11 ANA and 5 MCTD compared to 28 healthy controls. Results Sixteen cases (29.6%) had elevated DNTs (≥ 2.5% of CD3+CD56−TCRαβ+ cells) compared to 1 (3.6%) control. Medication usage including cytotoxic drugs and absolute lymphocyte count were not associated with DNT levels, and percentages of DNTs were stable over time. Analysis of multiple phenotypic and activation markers showed increased CD45RA expression on DNTs from patients with autoimmune disease compared to controls. Conclusion DNTs are elevated in a subset of pediatric patients with autoimmune disease and additional investigations are required to determine their precise role in autoimmunity.

Simian virus 40 (SV40) contains an essential protein, large tumor antigen (Tag), which assists in viral replication and causes cell transformation and immortalization. Our laboratory has examined plasmid DNA, expressing SV40 Tag under two different promoters, for use in potential cancer vaccination strategies. One plasmid, pSV3-neo, failed to induce SV40 Tag antibody, produced a weak cell-mediated response, and only partial protection in murine experimental tumor challenge systems. The second plasmid, pCMV-Tag, induced antibodies to SV40 Tag, produced a robust cell-mediated response, and invoked complete tumor immunity in vivo. The induction of CD4+ and CD8+ T cell responses following plasmid DNA immunization and tumor cell challenge reflected a type 1 cytokine secretion profile. Our hypothesis for this differential immune response is that pCMV-Tag exhibits a higher level of transgene expression due to a more efficient promoter. We determined that pCMV-Tag levels of SV40 Tag mRNA and protein expression were higher when compared to pSV3-neo. A threshold amount of SV40 Tag may be required to stimulate antibody production and provide complete systemic tumor immunity.

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Aspirin intolerance is the hallmark of aspirin-exacerbated respiratory disease (AERD). Overproduction of cysteinyl-leukotrienes (Cys-LTs) has been implicated as major mediators of AERD; however, the LT receptor antagonist montelukast is only partially effective in inhibiting aspirin responses. Several studies have documented the importance of cytokine production by T lymphocytes in asthma. Peripheral blood lymphocyte (PBL) cytokine expression and its relation to aspirin desensitization in aspirin-sensitive patients with asthma have not been studied. This study was performed to examine PBL cytokine expression in aspirin-sensitive patients who have asthma before and after aspirin desensitization. A 42-year-old white woman with a history of severe asthma, nasal polyps, aspirin sensitivity, and chronic sinusitis was treated with aspirin desensitization. Blood was taken before and after aspirin desensitization, and PBL cytokine expression was studied by flow cytometry. Aspirin desensitization differentially affects interferon (IFN) gamma expression. This effect results in an increase in IFN-gamma expression by CD4(+) lymphocytes and a decrease in IFN-gamma expression by CD8(+) lymphocytes. Aspirin desensitization in an aspirin-sensitive patient with asthma resulted in an increase in IFN-gamma expression by CD4(+) lymphocytes and a decrease in IFN-gamma expression by CD8(+) lymphocytes, the significance of which needs additional investigation.

Angioedema is swelling caused by fluid leakage from blood vessels into the surrounding skin and tissue. Angioedema can involve any part of the body but is usually more pronounced around the eyes, lips, mouth, tongue, extremities, and genitalia. The swelling may be accompanied by hives, which are more superficial, while angioedema affects the deeper layers of skin.

To review the current knowledge of biomolecular factors surrounding otorhinolaryngeal illnesses and analyze their presence in COVID-19 virulence. Emphasis was placed on cytokines and vitamin D for determining susceptibility of illness.

Background: Since the Severe Acute Respiratory Syndrome Coronavirus-2 was discovered in December 2019, there have been tireless efforts by the medical and scientific community to understand its pathophysiology, treatment, and prevention. Discussion: In the last several months, several therapeutic treatments, including a corticosteroid, antiviral drugs, convalescent plasma, and several others, have been tried in the treatment of SARS-CoV-2 with varying results. Pfizer and Moderna COVID-19 vaccines recently received approval for Emergency Use Authorization. Although COVID-19 vaccine is the first hurdle in an attempt to control the pandemic, the following challenges still remain: adequate vaccine doses, issues with mass distribution, global access, proper storage, and sufficient vaccine compliance. Summary: Vaccination, in addition to social distancing and wearing facemasks, will likely provide the best way to control the COVID pandemic. Healthcare professionals and government officials will need to address any concern or hesitancy the community has with the COVID vaccine to promote compliance. Keywords: coronavirus therapeutics, herd immunity, coronavirus vaccine, vaccine targets, clinical trials