The innate immune response

Recent studies have shown that pathogens share molecular patterns that activate the innate immune response and influence the later adaptive reaction. For example, many Gram-negative bacteria express lipopolysaccharides on their outer membranes. Lipopoly-saccharides interact with Toll-like receptors (TLR) on dendritic cells, macrophages, and neutrophils to induce production of TNF-a and other cytokines. 

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The innate immune response is initiated once the host detects the presence of foreign pathogens. This recognition step is performed by specialized cells of... 

There is only one known type II IFN, IFN-y, discovered in 1965 (Wheelock and Sibley 1965). IFN-y is exclusively produced by immune cells, such as activated thymus-derived T cells and natural killer (NK) cells, after stimulation by foreign antigens or mitogens in the early stages of the innate immune response (Boehm etal. 1997). The human IFN-y gene maps to chromosome 12. IFN-y is a noncovalent... 

Following tissue injury, the innate immune response is the first line of defense against possible pathogen infections. Through evolutionary pressures, the body automatically assumes infection which will be present post injury. Innate immunity... 

Aderem, A. and Ulevitch, R. J., Toll-like receptors in the induction of the innate immune response, Nature, 406, 782, 2000. 

Thus, together these studies suggest that the oxidative burst machinery has evolved before the crown diversification of eukaryotes (Baldauf 2003) to provide marine algal lineages with natural and induced innate immunity mechanisms. These play a role similar to the HR in terrestrial plants infected by incompatible pathogens and they share important common traits with the innate immunity response of mammalian phagocytes. 

While this technique has its appeal, there are several challenges. Delivery of the siRNA to the cells has to be devised. One method is the use of plasmid as a delivery vehicle. Another challenge is to overcome the possibility of invoking the innate immune response. To alleviate this problem, the use of microRNA rather than siRNA has been proposed. 

Numerous experiments have suggested that LDL oxidation generates determinants that lead to a specific immune response that, together with the innate immune response, acts as an oxLDL clearance mechanism (Fignre lA) (Horkko etal, 2000 Shaw etal, 2000). 

Fehniger T-A, Shah MH, Turner MJ, VanDeusen JB, Whitman SP, Cooper MA, Suzuki K, Wechser M, Goodsaid F, Caligiuri MA Differential cytokine and chemokine gene expression by human NK cells following activation with IL-18 or lL-15 in combination with lL-12 implications for the innate immune response. J Immunol 1999 162 4511-4520. 

The MAPK cascade in the plant s defense against bacterial pathogens is remarkably similar to the innate immune response triggered by bacterial lipopolysac-charide and mediated by the Toll-like receptors in mammals (Fig. 12-30b). Other membrane receptors use similar mechanisms to activate a MAPK cascade, ultimately activating transcription factors and turning on the genes essential to the defense response. 

T lymphocytes are major mediators of the innate immune response they are under control of the dendritic cells (DCs), which are found in "immature" forms in tissues throughout the body.9/22 26a... 

IFN-y production is regulated by IL-12 and IL-18, both cytokines secreted by APCs. In the innate immune response, a link is established between infection and IFN-y by these cytokines. IL-12 and chemokines including macrophage inflammatory protein-la (MIP-la) are secreted as macrophages recognize pathogens, and NK cells are attracted to the site of inflammation by the chemokines. This is followed by the induction of IFN-y production and secretion by IL-12. IL-12 and IL-18 further stimulate the production of IFN-y from macrophages. The production of IFN-y is inhibited by IL-4, IL-10 and TGF-(3. 

Hogg, K.G., Kumkate, S., Anderson, S. and Mountford, A.P. (2003) lnterleukin-12 p40 secretion by cutaneous CD11 c+ and F4/80t- cells is a major feature of the innate immune response in mice that develop Th1 -mediated protective immunity to Schistosoma mansoni. Infection and Immunity 71, 3563-3571. 

Zaccone, P., Lehervari, Z., Jones, L.M., Sidobre, S., Kronenberg, M., Dunne, D.W. and Cooke, A. (2003) Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes. European Journal of Immunology 33, 1439-1449. 

Smith PL, Lombardi G, Foster GR. Type I interferons and the innate immune response—more than just antiviral cytokines. Mol Immunol. 2005 42 869-877. 

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... 

The CNS also contains resident cells that are responsible for the innate immune response. The main cell types responsible for this function are microglia and astrocytes. 

Pashine, A., Valiante, N.M., and Ulmer, J.B. (2005) Targeting the innate immune response with improved vaccine adjuvants. Nat. Med. 11(4 Suppl), S63-68. 

Cosseau, C., Devine, D.A., Dullaghan, E. et al. 2008. The commensal Streptococcus salivarius K12 downregulates the innate immune responses of human epithelial cells and promotes host-microbe homeostasis. Infect Immun 76 4163-4175. 

In addition to the plant defensins mentioned in Section 4, defensins are also widespread in vertebrates. These antimicrobial peptides are involved in the innate immune response, and are classified into three subfamilies that present... 

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