Innate Responses

Neuropeptide S (NPS) is a recently discovered bioactive peptide that has emerged as a new signaling molecule in the complex circuitry that modulates sleep-wakefulness and anxiety-like behavior. The peptide precursor is expressed most prominently in a novel nucleus located in the perilocus coeruleus, a brain structure with well-defined functions in arousal, stress, and anxiety. NPS was also found to induce anxiolytic-like behavior in a battery of four different tests of innate responses to stress. Infusion of NPS potently increases wakefulness and suppresses non-REM (NREM) and REM sleep (Xu et al, 2004). NPS binds to a G-protein-coupled receptor, the NPS receptor, with nanomolar affinity activation of the receptor mobilizes intracellular calcium. The NPS receptor is expressed throughout the brain, particularly in regions relevant to the modulation of sleep and waking, in the tuberomammillary region, lateral hypothalamus, and medial thalamic nuclei. 

Several comprehensive reviews of the immunotoxicity of TCDD have been published.13 Therefore, the goal of this chapter is to highlight the most recent developments in the field, with particular attention given to studies that provide new insight into the possible cellular and molecular mechanisms of PHAH immunotoxicity. New data that address three less-studied aspects of TCDD immunotoxicity will also be reviewed, including altered innate responses, toxicity to the developing immune system, and deregulation of anamnestic immune responses. 

Talaat KR, Bonawitz RE, Domenech P, Nutman TB Preexposure to live Brugia malayi microfilariae alters the innate response of human dendritic cells to Mycobacterium tuberculosis. J Infect Dis 2006 193 196-204. 

In this book, discussion is limited to their significance in coordination of the responses to an infection or in trauma. Although it is an oversimplihcation from the biochemical and clinical points of view, the cytokines can be separated into two classes those that are involved in the innate response (secreted by the macrophages, particularly during inflammation), and those involved in the responses of the adaptive system (secreted by the T-helper cells). Some of those secreted by T-lymphocytes and their effects are shown in Figure 17.20. Those secreted by macrophages and their effects are described in Figure 17.21. 

Innate responses of the parasitoids Cotesia glomerata and C. rubecula (Hymenoptera Braconidae) to volatiles from different plant-herbivore complexes. Journal of Insect Behavior 9 525-538. 

These cells are crucial in fighting viral infections as part of the early innate response. Severe systemic viral infections, specifically herpes virus, may result from a lack or malfunction of NK cells. Patients infected with human immunodeficiency virus (HIV) have low numbers of NK cells. These cells also play a role in killing tumors. Patients with Chediak-Higashi syndrome have an increased risk of lymphomas, and this disease is associated with impaired NK cells, macrophages and neutrophils. A number of cytokines including IL-2, IL-12, IL-15, IL-21, IFN-a and IFN-(3 induce NK cells, which results in their proliferation, margination, cytokine production and cytotoxicity. 

When the innate immune response is inadequate to cope with infection, the adaptive immune system is mobilized by cues from the innate response. The adaptive immune system has a number of characteristics that contribute to its success in eliminating pathogens. These include the ability (1) to respond to a variety of antigens, each in a specific manner (2) to discriminate between... 

Londei M, Ciacci C, Ricciardelli I, Vacca L, Quaratino S, Maiuri L. Gliadin as a stimulator of innate responses in celiac disease. Mol Immunol 2005 42 913-918. 

Immune responses are divided into innate responses directed nonspecifically against foreign substances and acquired responses directed against specific antigens (see Table 32.2 for important definitions). Innate immunity is generally viewed as the... 

Other components of the innate response include natural killer (NK) cells and a number of cytokines. NK cells lyse certain types of tumor cells and virally infected cells and are a rich source of immune interferon (interferon-y), which stimulates macrophages and T cells hence they are thought to play an important role in host resistance to both neoplastic and viral disease. Type I interferons (interferon a and interferon P) are produced by a number of different cell types and appear very rapidly after viral infection. Type I interferons inhibit viral replication, inhibit cell proliferation, and increase the lytic potential of NK cells and therefore play a role in controlling viral and neoplastic disease. Several cytokines are important in the initiation of inflammatory responses. Those that have received the most attention include tumor necrosis factor alpha (TNFa), interleukin (IL)-1, and IL-6. There are also a number of chemotactic cytokines (including IL-8), called chemokines, which help to mobilize immune cells to the site of injury. 

Parroche P, Lauw FN, Goutagny N, Latz E, Monks BG, Vis-intin A, Halmen KA, Lamphier M, Olivier M, Bartholomeu DC, GazzinelU RT, Golenbock DT. Malaria hemozoin is immunolog-ically inert but radically enhances innate responses by presenting malaria DNA to Toll-Uke receptor 9. Proc. Natl. Acad. Sci. U.S.A. 2007 104 1919-1924. 

Chu WM, Ostertag D, Li ZW, Chang L, Chen Y, Hn Y, Williams B, Perrault J, Karin M. JNK2 and IKKbeta are reqnired for activating the innate response to viral infection. Immunity. 1999 11 721-731. 

Adaptive Immunity Is Needed to Control Local Innate Response in the CNS... 

In early experiments aimed at boosting of the innate response in the injured CNS to facilitate better phagocytosis of myelin debris, it was found that implantation of homologous macrophages in the completely transected spinal cords of adult rats, it was demonstrated partial recovery of motor function (manifested by locomotor activity scored in an open field) and electrophysio-logical activity (assessed by motor-evoked potential responses) (Rapalino et al., 1998). These behavioral manifestations were also reflected in the electrophysiological recovery of motor-evoked potential responses in the implanted rats. 

A. Overview The innate immune system initiates the defense against pathogens and antigenic insult. It involves the concerted actions of complement components, lysozyme, macrophages, and neutrophils. If the innate response is inadequate, the adaptive immune response is mobilized. This culminates in the activation of T lymphocytes, the effectors of cell-mediated immunity and the production of antibodies, by activated B lymphocytes, the effectors of humoral immunity. The cell types involved in immune responses can be identified by specific cell surface components or clusters of differentiation (CDs). For example, T helper cells bear the CD4 protein complex, whereas cytotoxic T lymphocytes express the CDS protein complex. Clusters of differentiation also can be used to characterize other types of hematopoietic cells, including precursors of granulocytes, megakaryocytes, and erythrocytes (Chapter 33). 

Animals show both innate and learned responses to odors in their environment. Examples of innate responses include the anemotactlc behavior of those male moths that fly upwind towards a pheromone-emitting female or the defensive responses of honeybees to their alarm pheromone.Many animals also learn to associate odor with important events such as the presence of food. The... 

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