Normal Immune Response

The normal immune response is modeled using antibodies A, B cells, helpers H, suppressors S and antigens, or viruses, V. Each of these concentrations can be either high (= 1) or low 0). The dynamics is defined as follows  

We can interpret these equations in the following way. The first line assures us that antibodies will be present only when B cells, helper cells and antigens are all present. The second line states that B cells will grow if antigens and/or B cells are present and if helped by helper cells. The third line indicates that helper cells arise either if other helper cells ai e present or, if no suppressor cells are present, if there are any antigens. The fourth line yields suppressor cells if suppressor cells are already present and/or there are any helper cells. The last line implies that the antigen remains if there are no antibodies or vani.shes if antibodies are present. Since concentrations cannot exceed 1, it is understood that, in the above equations, 1 + 1 = 1. 

Consider, for example, the case where a virus is present in an otherwise untouched virgin system (ABHSV = 00000). Application of the above rules results in the destruction of the virus in two iterations  

Notice that the system is left with high concentrations of B, H and S cells. Thus, if a virus is reintroduced into the same system after the original infection has been eliminated, it is immediately destroyed  

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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. 

A requirement for a better understanding of how cancer cells evade the normal immune response. 

Vorderstrasse, B.A., et. al., Aryl hydrocarbon receptor-deficient mice generate normal immune responses to model antigens and are resistant to TCDD-induced immune suppression, Toxicol. Appl. Pharmacol., 171, 157, 2001. 

Vaccinations Do not give live vaccines concurrently with anakinra. No data are available on the secondary transmission of infections by live vaccines in patients receiving anakinra. Because anakinra interferes with normal immune response mechanisms to new antigens such as vaccines, vaccination may not be effective in... 

ELEMENTS OF THE IMMUNE SYSTEM NORMAL IMMUNE RESPONSES... 

Nitschke, L., Kosco, M.H., Kohler, G., Lamers, M.C. (1993). Immunoglobulin D-deficient mice can mount normal immune responses to thymus-independent and -dependent antigens. Proc. Natl. Acad. Sci. USA 90, 1887-1891. 

High-dose IL-2 is approved for the treatment of metastatic renal cell carcinoma. The tumor is intrinsically immunogenic, and can elicit a host immune response that infrequently results in spontaneous remission of disease administration of IL-2 is believed to augment the normal immune response [53]. In a Phase II study that supported the approval of high-dose IL-2 for this indication, 15% of patients achieved objective responses (8% were partial responses and 7% complete responses). In this trial, patients received IL-2 at 600 000 or 720 000 U/kg per dose. The cumulative dose and the efficacy were similar between dose groups patients receiving the higher dose tolerated fewer cycles of therapy due to toxicity. 

The difference between a normal immune response and a type I hypersensitive response is that in the latter, plasma cells secrete IgE. This class of antibody binds to Ec receptors on the surface of tissue mast cells and blood basophUs. Mast cells and basophUs coated by IgE are sensitised . Later exposure to the same allergen cross-links the bound IgE on sensitised cells, resulting in degranulation and the secretion of pharmacologically active mediators such as histamine, leukotrienes and prostaglandins. The principal effects of these products are vasodilation and smooth-muscle contraction (Table 15.6). 

Inflammation it an essential part of the normal immune response, but if uncontrolled and persistent, it leads to disease. 

While the immune system is highly regulated by complex interactions, both between components of the system and between immune and nonimmune organ systems, xenobiotics can modulate the immune system effecting either up - or down -regulation of the process. Inhaled chemicals may provoke a variety of different responses, including (1) reduction of normal immune response - immunosuppression resulting in an increased incidence of... 

Inhibition of the normal immune response results from a gradual destruction of lymphoid tissue, followed by a decline in antibody production and a decrease in the numbers of eosinophils, basophils, and lymphocytes. The reduction in T-lymphocyte counts by glucocorticoids can occur acutely as a result of the redistribution of these cells from the intravascular space to the spleen, lymph nodes, and bone marrow. Thus an increase in the neutrophil count is commonly observed after glucocorticoid administration. The major suppressive effects of glucocorticoids on the inflamniatory response and the immune system appear to be through the modulation of cytokine production via an inhibition of nuclear factor kappa B (NF-kB) expression and nuclear translocation. Cytoldnes released from immunocompetent cells mediate both the acute and chronic phases of inflammation and participate in the control of the immune response (see Chapter 22). 

The amount of total fat consumed, rather than the specific type of fat, has been positively associated with cancer risk (Dupont et al. 1990). However, animal studies suggested that linoleic acid promotes carcinogenesis under special circumstances (Sundram et al. 1989 Dupont et al. 1990), and that linolenic acid has a potential anticarcinogenic effect (Fritsche and Johnson 1988). Involvement of linolenic acid in carcinogenesis has not been found in humans. The amount of fat and its unsaturation significantly influence normal immune response and expression of inflammatory diseases (Connor 2000). 

Exposure to pesticides can provoke a variety of immune reactions. These reactions can be classified into (a) modulation of normal immune responses (immune dysfunction), characteristically manifested as immunosuppression, and (b) pathological enhancement of the immune response, most often manifested as hypersensitivity or autoimmunity. The number of reviews on this subject underscores the interest in and concern for the potential of pesticides to alter immune function (8-15). The two general categories of immune alterations induced by pesticides are discussed below. 

Leukocyte recruitment and plasma fluid efflux represent physiological changes that are critical in the normal immune response to invading and noxious stimuli. Therefore, mechanisms that allow transvascular passage of the blood constituents while at the same time preventing irreversible loss of barrier... 

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