21.1 INTRODUCTION TO THE IMMUNE SYSTEM
One feature that is common to all organisms is the ability to defend themselves against challenges in the environment in which they live. Mammals have a complex phalanx of defenses against bacteria, viruses, and parasites, which comprise the immune system. The immune system can be characterized broadly as having 2 major arms: innate immunity and adaptive immunity. The innate immune system is the “first line of defense” against pathogens and includes macrophages and dendritic cells that function in part to present antigens to the cells in the adaptive immune system. The adaptive arm of the immune system is mediated by lymphocytes and responds with higher specificity to pathogens. Key cells of the adaptive immune system are helper T cells (TH) that express a marker known as CD4, cytotoxic T lymphocytes (CTL) that are distinguished by the CD8 marker, and B cells that produce antibodies. The molecular components of pathogens that are recognized by T and B cells are referred to broadly as antigens.
The adaptive immune system has evolved to respond to an initial encounter with a variety of foreign pathogens as well as a potential secondary encounter with the same pathogen. These challenges have shaped the development of the immune system to have the properties of diversity, specificity, and memory. Diversity enables an individual to respond to a broad array of possible pathogens, while at the same time generating exquisite specificity to elements of specific pathogens, ensuring a focused response to a given pathogen while minimizing collateral damage to the host tissues. Memory is the ability of the immune system to respond rapidly to a pathogen that has been encountered previously thus quickly clearing the offending organism.
Another feature of the immune system is that it generally does not attack the host’s own tissues. This recognition of “self” vs “non-self” and the ability to avoid attacking self-tissues is referred to as self-tolerance. Although these mechanisms of tolerance are critical to avoid autoimmunity, they are impediments that need to be overcome in antitumor immunity.
21.2.1 Antigen Presentation
One of the main functions of the innate immune system is to present antigens to the adaptive immune system to orchestrate a functional immune response. Dendritic cells (DCs) are highly specialized and efficient antigen-presenting cells (APCs). One key function that differentiates DCs from other “professional” APCs, such as macrophages and B cells, is their ability to activate naïve T cells. Antigens are presented to T cells by major histocompatibility complex (MHC) molecules. The MHC consists of a series of proteins encoded by highly polymorphic codominantly expressed genes. As a result, each individual expresses a particular combination of MHC alleles that is different between individuals, and a huge diversity exists in populations. There are 2 main types of MHC molecules. MHC class I molecules ...