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.

Antigen presenting cells process proteins into peptides for binding by either Major Histocompatibility Class I (MHC-I) or Class II (MHC-II) molecules which are then displayed at the cell surface as peptide/MHC complexes, where they are recognized by T cell receptors leading to T cell activation. MHC-I molecules also serve as indispensable ligands for a variety of NK cell receptors. Cell biological, biochemical, and structural details of these processes as we now understand them will be discussed as well as recent data on strategies for human NK cell activation for cancer immunotherapy.

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 demonstrated impressive response rates in certain cancers that were historically challenging to treat by harnessing the body’s own immune system to detect and destroy tumor cells. In this presentation, we will explore the current landscape of immunotherapy, highlighting key approaches such as cytokine therapies, cancer vaccines, adoptive cell therapies, and immunomodulation strategies.

Bispecific antibodies (bispecifics) and antibody-drug conjugates (ADCs) are among the most advanced targeted therapies, offering significant potential for treating complex diseases such as cancer. Despite their high efficacy, understanding and addressing their safety profiles is crucial for improving patient outcomes and ensuring successful integration into clinical practice. The presentation will provide a high-level review with case studies of the safety concerns associated with these therapies and the strategies employed to improve them.

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.

Biopharmaceuticals represent a diverse class of therapeutics, contributing significantly to advancing treatment of serious diseases, including chronic inflammatory and autoimmune diseases, genetic deficiencies, and cancer. Unfortunately, unwanted immunogenic responses against some of these products can occur, often reducing efficacy and sometimes causing safety consequences, such as hypersensitivity, immune complex disease, and autoimmune syndromes. In this overview, factors that affect the degree to which the immune system responds, and the degree to which the response affects the efficacy and safety, are discussed.

While it has been long appreciated that liver-derived systemic complement guards the vascular space, it has been more recently recognized that cell intrinsic and/or intracellularly derived complement components play pivotal roles in tissue immunity through the regulation of normal cell physiology, metabolism, survival, and effector functions in a plethora of cell types in the human body. Our lab studies the role of cell-autonomous complement in immune and non-immune cells and its role in homeostasis and disease (infection, cancer and autoimmunity) to further our understanding of how this system can be targeted therapeutically.