Strategies of avoidance, resistance, and tolerance represent different ways to deal with pathogens. Anatomic barriers and various chemical barriers such as complement and antimicrobial proteins may be considered a primitive form of avoidance, and they are the first line of defense against entry of both commensal organisms and pathogens into host tissues. If these barriers are breached, the vertebrate immune response becomes largely focused on resistance. Inflammatory inducers, which may be either chemical structures unique to microbes (PAMPs) or the chemical signals of tissue damage, act on receptors expressed by sensor cells to inform the immune system of infection. Sensor cells are typically innate immune cells such as macrophages or dendritic cells. Sensor cells can either directly respond with effector activity or produce inflammatory mediators, typically cytokines and chemokines that act on other immune cells, such as the innate NK cells and ILCs. These cells then are recruited into target tissues to provide specific types of immune-response effector activities, such as cell killing or production of cytokines that have direct antiviral activity, all aimed to reduce or eliminate infection by pathogens. Responses by mediators in target tissues can induce several types of inflammatory cells that are specially suited for eliminating viruses, intracellular bacteria, extracellular pathogens, or parasites.
Principles of adaptive immunity.
these are large, granular, lymphoid-like cells with important functions in innate immunity, especially against intracellular infections, being able to kill other cells. unlike lymphocytes, they lack antigen-specific receptors. Photograph courtesy of B. Smith.
We come now to the components of adaptive immunity, the antigen-specific lymphocytes. Unless indicated otherwise, we shall use the term lymphocyte to refer only to the antigen-specific lymphocytes. Lymphocytes allow responses against a vast array of antigens from various pathogens encountered during a person’s lifetime and confer the important feature of immunological memory. Lymphocytes make this possible through the highly variable antigen receptors
Fig. 1.12 Lymphocytes are mostly small and inactive cells. the left panel shows a light micrograph of a small lymphocyte in which the nucleus has been stained purple by hematoxylin and eosin dye, surrounded by red blood cells (which have no nuclei). note the darker purple patches of condensed chromatin of the lymphocyte nucleus, indicating little transcriptional activity and the relative absence of cytoplasm. the right panel shows a transmission electron micrograph of a small lymphocyte. Again, note the evidence of functional inactivity: the condensed chromatin, the scanty cytoplasm, and the absence of rough endoplasmic reticulum. Photographs courtesy of n. rooney.
on their surface, by which they recognize and bind antigens. Each lymphocyte matures bearing a unique variant of a prototype antigen receptor, so that the population of lymphocytes expresses a huge repertoire of receptors that are highly diverse in their antigen-binding sites. Among the billion or so lymphocytes circulating in the body at any one time there will always be some that can recognize a given foreign antigen.
A unique feature of the adaptive immune system is that it is capable of generating immunological memory, so that having been exposed once to an infectious agent, a person will make an immediate and stronger response against any subsequent exposure to it; that is, the individual will have protective immunity against it. Finding ways of generating long-lasting immunity to pathogens that do not naturally provoke it is one of the greatest challenges facing immunologists today.
1-8 The interaction of antigens with antigen receptors induces lymphocytes to acquire effector and memory activity.