Immune response infection

Mankertz J, Tavalali S, Schmitz H, Mankertz A, Riecken EO, Fromm M, Schulzke JD (2000) Expression from the human occludin promoter is affected by tumor necrosis factor alpha and interferon gamma. J Cell Sci 113 2085-2090 Marinaro M, Fasano A, De Magistris MT (2003) Zonula occludens toxin acts as an adjuvant through different mucosal routes and induces protective immune responses. Infect Immun 71 1897-1902... 

Yasselon T, Detmers PA (2002) Toll receptors a central element in innate immune responses. Infect Immun 70 1033-1041... 

Targowski, S.P., W.Klucinski, S.Babiker, and B.J.Nonnecke. 1984. Effect of ammonia on in vivo and in vitro immune responses. Infect. Immun. 43(l) 289-293. 

Childers, N. K.,Tong, G Mitchell, S Kirk, K Russel, M. W., and Michalek, S. M. (1999), A controlled clinical study of the effect of nasal immunization with a Streptococcus mutans antigen alone or incorporated into liposomes on induction of immune responses, Infect. Immun., 67, 618-623. 

Kanistanon D, Powell DA, Hajjar AM et al (2012) Role of Francisella lipid A phosphate modification in virulence and long-term protective immune responses. Infect Immim 80 943-951... 

Dainkhi T, Maekawa Y, Ishii K et aL Nippocystatin, a cysteine protease inhibitor from nippostrongylus brasilknsis, inhibits antigen processing and modulates am en-spcdfic immune response. Infect Immun 2001 69 7380-7386. 

Nanomaterials controlling Immune responses, infection, or cancer growth... 

Interferons (lENs) (52,53), a family of species-specific vertebrate proteins, confer nonspecific resistance to a broad range of viral infections, affect cell proliferation, and modulate immune responses. AH three principal interferons, a-interferon (lEN-a) produced by blood leucocytes, P-interferon (lEN-P) by fibroblasts, and y-interferon (lEN-y) by lymphocytes, also have antiviral activity. The abiUty of interferons to inhibit growth of transplantable and carcinogen-induced tumor led to research showing the direct antiproliferative and indirect immune-mediated antitumor activities (see Chemotherapeutics, anticancer). IENs have been found to be efficacious in certain malignancies and viral infections, eg, hairy cell leukemia (85% response) and basal cell carcinoma (86% response). However, the interferons do have adverse side effects (54). 

Hydroxymethyl-6-methyluracil (1043) was prepared many years ago from 6-methyl-uracil and formaldehyde, or in other ways. Since 1956 it has received much attention in the USSR under the (transliterated) name pentoxyl or pentoxil. It is used in several anaemic and disease conditions. For example, a mixture of folic acid and pentoxyl quickly reduces the anaemia resulting from lead poisoning pentoxyl stimulates the supply of serum protein after massive blood loss it stimulates wound healing it stimulates the immune response in typhus infection and it potentiates the action of sulfonamides in pneumococcus infections (70MI21300). 

Chemical-mediated immune suppression has been identified from the experimental study of several wildlife species. Harbour seals fed either chemically contaminated fish from the Wadden Sea or imcontaminated fish were found to have differing immune responses, with the exposed group showing lowered immune response to microbial infections and certain types of cancer. "" Mink fed fish taken from below a discharge point for bleached Kraft pulp mill effluent have also shown impaired immune function, " showing that the non-accnmillative chemicals in this effluent can actively disrupt endocrine associated functions. 

The consequence of ADA deficiency is accumulation of adenosine and 2 -deoxyadenosine, substances toxic to lymphocytes, important cells in the immune response. 2 -Deoxyadenosine is particularly toxic because its presence leads to accumulation of its nucleotide form, dATP, an essential substrate in DNA synthesis. Elevated levels of dATP actually block DNA replication and cell division by inhibiting synthesis of the other deoxynncleoside 5 -triphosphates (see Chapter 27). Accumulation of dATP also leads to selective depletion of cellular ATP, robbing cells of energy. Children with ADA SCID fail to develop normal immune responses and are susceptible to fatal infections, unless kept in protective isolation. 

There are a number of practical problems involved with using polysaccharides as vaccines as there are frequently too many different chemotypes for it to be practicable to prepare a vaccine. In some cases a limited number of serotypes are the dominant cause of infection and it may then be possible to produce vaccines. A major problem is the poor immune response elicited by polysaccharide antigens, which may in some cases be improved by chemical modification. This is (fie case for vaccines for Haemophilus influenzae type b (a causative agent of meningitis), where the antigenicity of the polysaccharide can be increased by coupling to proteins. 

A number of chimerized, humanized, and one human mAb have now been approved for therapeutic use in humans in the treatment of autoimmunity, malignancy, infection and cardiovascular disease (Table 1). Some of the currently licensed mAb will be discussed here. A much larger number of mAb are currently being evaluated in Phase I, II and III trials. In general, chimeric, humanized and human mAb are very well tolerated with few side effects. Chimeric or humanized mAb still have the potential to evoke host immune response to the variable domains or CDRs of the antibody so-called HACA (human anti-chimeric antibody) or HAHA (human anti-human antibody) responses, although these responses are uncommon. Short-lived and occasionally severe infusion-related acute hypersensitivity reactions such as fever, skin itching, shivering, respiratory compromise and low blood pressure sometimes occur-. Such effects may... 

Several cytokines are in clinical use that support immune responses, such as IL-2, DFNs, or colony-stimulating factors. IL-2 supports the proliferation and effector ftmction of T-lymphocytes in immune compromised patients such as after prolonged dialysis or HIV infection. IFNs support antiviral responses or antitumoral activities of phagocytes, NK cells, and cytotoxic T-lymphocytes. Colony-stimulatory factors enforce the formation of mature blood cells from progenitor cells, e.g., after chemo- or radiotherapy (G-CSF to generate neutrophils, TPO to generate platelets, EPO to generate erythrocytes). 

Hepatitis B Hepatitis B vaccines provide another illustration of how drug products have advanced vdth increasing technical capability. Vaccination against hepatitis B is common pradice for health workers, travellers and others who may be at risk of exposure to the virus. The initial vaccines contained inactivated virus to promote the immune response necessary to proted against future infection by the live virus. However, there was always some concern in case there was not complete inactivation of the virus used for vaccination. Further research into the virus identified the surface proteins against which the immune response is raised. The genetic... 

Apart from offering a new and highly specific approach to the inhibition of herpesviruses, this new mechanism of action could potentially also have beneficial immunological consequences. During treatment with BAY 38-4766, viral protein synthesis continues, but due to the lack of monomeric genomic length DNA, only empty particles (dense bodies) can be formed. It is conceivable that these non-infections viral particles could aid the establishment of an antiviral immune response, leading to better control of the virus by the host. This mechanism appears... 

Gough DJ, Sabapathy K, Ko EY, Arthur HA, Schreiber RD, Trapani JA, Clarke CJ, Johnstone RW (2007) A novel c-Jun-dependent signal transduction pathway necessary for the transcriptional activation of interferon gamma response genes. J Biol Chem 282 938-946 Guidotti LG, Chisari EV (2001) Noncytolytic control of viral infections by the innate and adaptive immune response. Annu Rev Immunol 19 65-91... 

The clinical relevance of this finding was suggested by the observation that mice were more susceptible to sepsis following infection with Streptococcus pneumoniae when basophils were depleted before the second vaccination with pneumoccocal antigen [22]. Antigen-specific IgG antibodies produced after the second vaccination were significantly lower in the basophil-depleted mice than in control mice. Thus, basophils are important contributors to humoral memory immune responses. 

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