Basic Immunology

International audienceImmune system provides the mechanisms for attacking foreign invaders, eliminating autologous toxic substances and offering self-tolerance. A reductionist approach of the immune system components and their interactions as provided in this chapter will offer knowledge important to better understand the core mechanisms of autoimmune diseases and design therapies targeting their pathogenic mechanisms. Immunity is divided into (a) innate (or natural), implemented by macrophages, dendritic cells, granulocytes (neutrophils, basophils, and eosinophils), natural killer cells, the complement system, and the acutephase proteins, and (b) adaptive, implemented by B and T cells. Immune cells express sensors on cytoplasmic or endosomal membranes or in the cytoplasm, called “pathogen-associated molecular pattern receptors” (PAMPRs), also called pattern recognition receptors (PRRs), and damage-associated molecular pattern receptors (DAMPRs) to sense foreign invaders or damaged tissues and provide defense against them. Natural immunity cells provide the fjrst line of defense, usually successful in eliminating pathogens, but also they limber up the adaptive immune system to take action in case of any failure of defense. The sensors of B and T cells are their antigen receptors (membrane immunoglobulins and T-cell receptors, respectively) which are dissimilar to each other in terms of specificity; each receptor recognizes very specifically one antigen and especially a few peptide residues on it (epitope). However, by taking as a whole the pool of lymphocytes, their receptors offer a vast array of specificities exceeding 1011 that is more than the genes of the human body. This implies that not particular genes but rather gene fragments are spontaneously rearranged to make an immunoglobulin or a T-cell receptor gene. One such rearrangement for each peptide chain of the receptor is allowed, so the cells will retain their antigenic specificity as long as they live. Immune cells communicate with each other and approach their targets, either by cell-to-cell contact using adhesion molecules or by soluble mediators known as cytokines or chemokines, respectively. Mechanisms like central (taking place in bone marrow and thymus) and peripheral (taking place in the lymph nodes) tolerance ensure that the immune system will not attack self. Braking of tolerance initiates autoimmune reactivity which may be subclinical but, under certain circumstances, may obtain a clinical phenotype