Antibody responses

As a low molecular weight compound DAS is not significantly immunogenic, ie, it is a hapten and thus requires conjugation to a suitable antigenic carrier in order to eUcit a successfiil antibody response in animals. DAS treated with succinic anhydride results in the D AS—hemisuccinate (DAS—HMS) shown. 

The active immunotherapeutic approach is specific and based on the premise that tumor antigens are immunogenic and the host is sufficientiy immunocompetent to mount an effective immune response to an autologous tumor. Theoretically, a weak or suppressed host immune system that had allowed the formation of a tumor may be overridden by active immunization or immunostimulation. In practice, vaccines composed of so-called autologous tumor extracts have been used to treat patients with malignant melanoma (73), and purified melanoma tumor-associated antigens have been used to ehcit antibody responses in melanoma patients (74). 

T-c fl effector functions Antibody response T-cell effector functions... 

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... 

When amphotericin B or diuretics are administered with ACTH, the potential for hypokalemia is increased. There may be an increased need for insulin or oral antidiabetic drag s in the patient with diabetes who is taking ACTH. There is a decreased effect of ACTH when the agent is administered with the barbiturates. Profound muscular depression is possible when ACTH is administered with the anticholinesterase drugp. Live virus vaccines taken while taking ACTH may potentiate virus replication, increase vaccine adverse reaction, and decrease the patient s antibody response to the vaccine... 

Do not take live virus vaccinations (eg, smallpox) because of the risk of a lack of antibody response This does not include patients receiving the corticosteroids as replacement therapy. 

Plasma digoxin levels may decrease when the drug is administered with bleomycin. When bleomycin is used witii cisplatin, there is an increased risk of bleomycin toxicity Pulmonary toxicity may occur when bleomycin is administered with other antineoplastic drugs. Plicamycin, mitomycin, mitoxantrone, and dactino-mycin have an additive bone marrow depressant effect when administered with other antineoplastic drugs. In addition, mitomycin, mitoxantrone, and dactinomycin decrease antibody response to live virus vaccines. Dactinomycin potentiates or reactivates skin or gastrointestinal reactions of radiation therapy There is an increased risk of bleeding when plicamycin is administered witii aspirin, warfarin, heparin, and the NSAIDs. 

Miller Scott (1985) reported marked reduction in thymus weight in rats fed dioctyltin dichloride for 8 or 12 weeks at a level of 75 mg/kg diet. Numbers of lymphocytes together with T cell subpopulations were reduced in treated rats, but no difference was seen in antibody response to sheep red blood cells in vivo. No evidence was foimd of in vitro cytocidal effects of dioctyltin dichloride on blood lymphocytes. Evans et al. (1986) dosed pregnant and non-pregnant rats for 3 weeks at 75 mg/kg diet and reported severe thymic atrophy and extensive vacuolation of reticuloendothelial cells in pregnant animals only. 

Rat DBTC 4-6 weeks at 0, 50, and 150 mg/kg diet = 0, 2.5, and 7.5 mg/kg body weight Decrease in ceiiuiar and humorai immune response, in haemaggiutination and haemoiysin titres suppression of primary antibody response against sheep red biood ceiis Lowest dose at which effects were reported = 2.5 Seinen et al. (1977b)... 

Ross, P.S., de Swart, R.L., and Reijnders, P.J.H. et al. (1995). Contaminant related suppression of delayed type hypersensitivity and antibody responses in harbor seals from the Baltic Sea. Environmental Health Perspectives 103, 162. 

The terms allergy and atopy are in close proximity of our lives in the new millennium since our lifestyles have enormously changed. Encounters with various new molecules in air, water and diet, living in a more polluted world with less exposure to infections, and infectious agents are supposed to be the major causative factors added to the genetic propensity of developing IgE antibodies responsible for symptoms and... 

Pilette C. Nouri-Aria KT. Jacobson MR. Wilcock LK, Detry B. Walker SM. Francis JN. Durham SR Grass pollen immunotherapy induces an allergen-specific IgA2 antibody response associated with mucosal TGF-P expression. J Immunol 2007 178 4658-4666. 

After antigenic stimulation, the normal antibody response involves the activation of a... 

Tolerance can also be induced in adults, but higher doses ofthe antigen are required where it has been shown that both T and B cells are made unresponsive. As most antibody responses are T-dependent it is likely that it is these cells which are the ones affected. In order to maintain this state of tolerance it is necessary for the antigen to persist in the animal, as in its absence immunocompetent cells which are being produced throughout life are not being rendered tolerant. 

LALLES J p, DREAU D, HUET A, TOULLEC R (1995) Systemic and local gut-specific antibody responses in preruminant calves sensitive to soya. Res Vet Sci. 59 56-60. 

Lactoferrin resembles transferrin in terms of molecular weight, amino-acid sequence homology and number of Fe(lII) binding sites. Lactoferrin is released from activated PMNs upon degranulation and may play a role in myelopoiesis, primary antibody response, lymphocyte proliferation, cytokine production and complement activation. 

Two goats were immunized three times during the first 2 weeks with 1 mg of the antigen emulsified in 1 ml of Freund s complete adjuvant at several subcutaneous sites near regional lymph centers. Booster injections of 3 mg of antigen were administered at monthly intervals. The animals were bled 7 days after each boost. After several months of immunization, the titer and affinity of the antibody response was judged sufficient for use. 

Previously vaccinated Known responder Known non-responder Antibody response unknown No treatment HBIG x 1 and initiate HB revaccination or HBIG x 2 Test exposed person for anti-HBs (1) if adequate, no treatment (2) if inadequate, HBIG x 1 and vaccine booster No treatment No treatment No treatment No treatment If known high-risk source, treat as if source were HBsAg-positive Test exposed person for anti-HBs (1) if adequate, no treatment (2) if inadequate, vaccine booster and recheck titer in 1-2 months... 

Type I reactions occur when the drug or its bound hapten incites an IgE antibody response. IgE binds to high-affinity receptors on mast cells and basophils. When the original antigen cross-links the cell-bound IgE, the effector cell releases enormous amounts of preformed mediators, producing the... 

Type II reactions are produced by IgG (or IgM) antibody. The drug or hapten that elicited the antibody response binds to target cells. When antibody binds the drug, complement activation destroys the cell. Blood dyscrasias such as thrombocytopenia and hemolytic anemia are the most common examples of type II reactions. 

Lymphocyte 20-40% T cells (cell-mediated immunity) B cells (humoral antibody response) Lymphocytosis Viral infections (e.g., mononucleosis) Tuberculosis Fungal infections Lymphopenia human immunodeficiency virus... 

There are two pneumococcal vaccines, a 7-valent conjugated vaccine for children younger than 6 years of age and a 23-purified-capsular polysaccharide antigen vaccine for adults. The 23 capsular types in the vaccine represent at least 85% to 90% of the serotypes that cause invasive pneumococcal infections among children and adults in the United States.41 After vaccination, an antigen-specific antibody response, indicated by a twofold or greater rise in serotype-specific antibody, develops within 2 to 3 weeks in 80% or more of healthy young adults.42... 

Vinuesa CG, Tangye SG, Moser B, Mackay CR. Follicular B helper T cells in antibody responses and autoimmunity. Nat Rev Immunol 2005 5(ll) 853-865. 

Zhang PF, Bouma P, Park EJ, et al. A variable region 3 (V3) mutation determines a global neutralization phenotype and CD4-independent infectivity of a human immunodeficiency virus type 1 envelope associated with a broadly cross-reactive, primary virus-neutralizing antibody response. J Virol 2002 76(2) 644-655. 

Figure 4. Comparison of Freund s Adjuvant to Adjuvax formulations in stimulating antibody response to P55 oligopeptide antigen. Relative antibody titers between adjuvant groups at day 27 were determined by measuring the absorbance at 450 nm of a 1 500 dilution of anti-P55 immune sera by ELISA.

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