Welcome to Current Understanding of Immune Mechanisms. The immune system is poised to distinguish self from foreign substances or non-self as a first line of defense. This session will examine areas of biology and medicine of the human immune system's structure, cell involvement, and function, all of which impact on states of health and disease.

Novel therapeutics based on modified scaffold protein structures are being developed as alternative, more potent means to target disease-producing immunologic pathways than currently utilized mAbs. Such scaffold proteins including ankyrin repeat domains (DARPins), lipocalins (Anticalins), and Adnectins all have endogenous human counterparts raising the spectacle that immune responses to the therapeutic could cross-reactively bind to and disrupt the function of these critical structural endogenous proteins.

This presentation will focus on what we have learned from immune responses to traditional protein therapeutics that cross-react to endogenous proteins with non-redundant function as now applied to the development of this novel class of therapeutic with otherwise potentially greater efficacy in targeting multiple disease pathways. The factors affecting the status of immune tolerance to endogenous proteins will be emphasized.

This presentation will overview the four areas of hypersensitivity: immediate Type I IgE-mediated, Type II antibody-dependent cytotoxicity, Type III immune-complex-mediated, and delayed-Type hypersensitivity. Type I human allergic disease will then be examined, covering its pathophysiology, current diagnostic strategies, four modes of disease management, and special caveats relating to food, drug, venom, and respiratory allergic disease. Finally, the new discipline of molecular allergology will be highlighted with an emphasis on ten cross-reactive allergen families and how allergenic molecules have improved the accuracy of allergy diagnosis.

The field of innate lymphoid cell (ILC) biology has progressed rapidly, highlighting these cells’ roles in immunity, barrier tissue integrity, and homeostasis. ILCs can be classified based on cytokine production, mirroring patterns in CD4 T helper (Th) cell analogs. Unlike Th cells, ILCs respond promptly to pathogens without needing antigen-specific receptor recognition. Understanding ILC differentiation and immunoregulation is key to developing new treatments for autoimmunity, infection, and cancer.

Immunotherapy has shown remarkable response rates in some previously hard-to-treat cancers by redirecting the body’s own immune system to recognize and eliminate tumor cells. Here, we will discuss the current state of immunotherapy by briefly covering cytokine therapy, cancer vaccines, adoptive immunotherapy, and immunomodulation therapy.

Antibody-based therapeutics have provided great therapeutic benefit to many patients across various disease states. Multispecific antibodies afford therapeutic opportunities not feasible with single-target antibodies or combinations, while drug conjugates provide opportunity to extend therapeutic benefit through combining the targeting specificity of an antibody with a "payload." Examples of these advances will be summarized in the context of molecule design, target selection, biological characterization, and clinical benefit.

Our lab investigates tissue inflammation, injury, and repair, focusing on gene expression influenced by micro-environmental signals and transcription factors using functional genomics approaches. An important aspect of our work centers around complement components produced by cells in tissues. In this talk, we will discuss the mechanisms and roles of locally produced complement in inflammation, how this influences tissue biology, and the key transcriptional regulators involved.

Since the beginning of immunotherapy using monoclonal antibodies, we have pushed the limits for higher efficiency of this therapeutic modality. This shift did not come without trade-offs for safety and immunogenicity. In this presentation, I will talk about several examples of drug-enhancing approaches that also can have a profound impact on immunogenicity. Understanding the underlying mechanisms could help us to stay away as far as possible from this immunogenic transformation and lead to the development of better drugs for patients.