Figure 1-1 Immunity and Defense against PathogensPathogens that manage to penetrate the body’s physical barriers (skin, mucous membranes, enzymes, etc.) are first met by cells of the innate immune system. Using broadly specific control mechanisms, these cells attempt to limit the pathogen’s spread. If the innate immune system cells are unable to eradicate the threat, immune system cells called lymphocytes (which recognize unique antigens) generate humoral and cell-mediated adaptive responses to pathogens. The interplay between innate and adaptive immunity occurs via chemical messengers and through direct contact between cells of the innate and adaptive responses. By cooperating in this way, innate and adaptive immunity mount optimum defense against pathogens.

Figure 1-3 The Three Phases of Host DefenseThe three phases of host defense are defined on the basis of whether the elements involved in protecting the host are continually ready to act or need to be called into action (induced) by a pathogen, and the degree to which a pathogen is treated as a unique entity relative to other pathogens. During each phase, a new defense tactic takes action against the pathogen and continues to function throughout the infection. Phase 1 represents the pre-existing body barriers that work in a constant but passive way to prevent invaders from gaining a foothold within the body. It is during phase 2 that the innate immune system cells first begin the active fight against the infection by employing mechanisms such as inflammation, phagocytosis and complement activation. These induced and broadly specific defenses kill pathogens and recruit other immune system cells to the site of damage. After 4 days, B and T lymphocytes that uniquely recognize a particular pathogen are called into action for the adaptive response. At this point it is a “primary” response because the host has not encountered the particular invader before. Effector T cells and specific antibodies (Ab) are produced and aggressively work to eliminate the pathogen. Upon future infection with the same pathogen, memory B and memory T lymphocytes remaining in the body after the primary response are induced to respond as early as 24–72 hours after the second infection.

Figure 2-1 Antigens Recognized by the Receptors of the Innate and Adaptive Responses Unique antigens found on pathogens are bound by the adaptive antigen receptors. In general, these types of antigens are rarely found on more than one type of pathogen. In contrast, common surface antigens may be found on many different pathogens and are bound by recognition molecules of the innate immune system.

Figure 1-6 The Immune Response Mediates Health and Disease The way in which the immune system mounts a response can maintain a healthy body or lead to disease. In a healthy individual, the immune system mounts an appropriate response that leads to the death of infectious organisms or cancerous cells. States of disease can occur, however, when the immune system mounts an inappropriate response, such as an unwanted attack leading to transplant rejection, an attack on self tissues during autoimmune disease, an overzealous attack resulting in allergy and hypersensitivity, or a weak or absent attack resulting from immunodeficiency.

Figure 1-2 Establishment of Infection(A) Extracellular pathogens (e.g., Staphylococcus aureus, Streptococcus pyogenes) that are not stopped by epithelial barriers will gain access to the underlying tissues and replicate to cause a local infection. Further spread may result in the pathogen entering the bloodstream to cause a systemic infection. (B) After gaining entrance into the host, intracellular pathogens (e.g., Hepatitis C virus, Mycobacterium tuberculosis) must penetrate a host cell in order to establish an infection. Replication within the host cell leads to the death of that cell and spread of the pathogen to new host cells and/or to the bloodstream.

Figure 2-3 B and T Lymphocyte Division of Labor Lymphocyte subsets have evolved unique effector functions that are particularly suited to ridding the body of different pathogens. Helper T cells act indirectly to rid the body of both extracellular and intracellular threats by secreting cytokines that activate cytotoxic T cells and help B cells to make antibody. By secreting antibodies, B cells are able to mark the surface of extracellular pathogens and soluble toxins for destruction by innate system mechanisms. The spread of infection and disease symptoms caused by toxins are thus blocked. Cytotoxic T lymphocytes clear intracellular pathogens by lysing infected host cells that harbor pathogens.

Figure 2-10 Antigen Processing and Presentation:(A) Cells infected with a virus (1) produce endogenous viral peptides (2), which associate with MHC class I in the endoplasmic reticulum (ER) (3). The class I–viral peptide complex is transported through the ER and released from the Golgi apparatus in an exocytic vesicle (4), which is transported to the cell surface (5) and presented as a unit to CD8+ cytolytic T cells (Tc) (6). (B) Exogenous antigens are phagocytosed into the cell (1) and upon entering the endocytic pathway (2) antigen is broken down by acidic granules in endosomes (3a) and lysosomes (3b). Meanwhile, MHC class II molecules are synthesized in the ER and then processed through the Golgi apparatus (4). Peptides associate with MHC class II molecules in an endosome (5) and the two are transported to the cell surface as a unit (6), where they are presented to CD4+ helper T cells (Th) (7).

Figure 2-8 T Cell Receptor Antigen Recognition T cell receptors (TCRs) recognize the overall shape of a processed peptide combined with an MHC molecule. The TCR on a helper cell (Th) binds to peptide associated with MHC class II on the surface of an antigen-presenting cell (APC). The TCR on a cytolytic T cell (Tc) binds to peptide associated with MHC class I on the surface of a nucleated host cell (HC).

Figure 2-13 T Cell Effector Functions Circulating CD4+ and CD8+ T cells bind to specific peptide–MHC complexes and undergo clonal selection, expansion, and differentiation into daughter Th cells and cytotoxic T lymphocytes (CTLs), respectively. Effector Th cells secrete cytokines that activate macrophages, B cells, and Tc cells. CTLs lyse infected host cells and tumor cells.