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Pharmacology: Pharmacodynamics: Intradermally injected tuberculin PPD causes a delayed (cellular) hypersensitivity reaction in individual sensitised by mycobacterial infection. Following infection with mycobacteria, sensitisation of T-cell occurs primarily in the regional lymph nodes. Natural infection with M. tuberculosis usually initiates a cell mediated immune response against mycobacterial antigens. T-cells proliferate in response to the infection and give rise to T-cells specifically sensitised to mycobacterial antigens. After several weeks, these T-lymphocytes enter the bloodstream and circulate for a long period of time. Subsequent restimulation of these T-lymphocytes with intradermal injection of tuberculin PPD evokes a local reaction mediated by these cells.
The reaction to intradermal injected tuberculin is a delayed (cellular) hypersensitivity reaction. The reaction which characteristically shows a delayed course, reaching its peak more than 24 hours after administration, consists of induration due to cell infiltration. Clinically, a delayed hypersensitivity reaction to tuberculin is a manifestation of previous infection with M. tuberculosis or a variety of non-tuberculosis bacteria. In most cases sensitisation is induced by a natural mycobacterial infection or by vaccination with BCG Vaccine. The sensitisation following infection with mycobacteria occurs primarily in the regional lymph nodes. Small lymphocytes (T lymphocytes) proliferate in response to the antigenic stimulus to give rise to specifically sensitised lymphocytes.
After several weeks, these lymphocytes enter the bloodstream and circulate for long periods of time. Subsequent restimulation of these sensitised lymphocytes with the same or a similar antigen, such as the intradermal injection of tuberculin, evokes a local reaction mediated by these cells.
Pharmacokinetics: The tuberculin injected into the skin is mostly removed within a few hours via the lymphatics. The remainder is engulfed at the site by macrophages and there is soon a mild inflammatory reaction with the appearance of polymorphs and some mononuclear cell into both the non-sensitive and sensitive subjects. In non-sensitive subjects the inflammatory response soon stops. In sensitive subjects oedema and hyperaemia continue to increase and three is intense perivascular infiltration with mononuclear cells.
The product has been widely tested in animal models, not as much in the form of preclinical safety tests, as in the form of testing performed in relation to the control of potency and comparison of potencies between different preparations.
The documentation for this testing is provided as part of the clinical and pharmaceutical documentation.
The tuberculin reaction is characterised by the early predominance of mononuclear cells (small and medium sized lymphocytes and monocytes). Only a small proportion of these cells appear to be lymphocytes sensitised to tuberculin. Most cells are brought into the reaction through the release of biologically active substances by sensitised lymphocytes. An increase in vascular permeability leading to erythema and oedema also occurs in tuberculin reactions. Characteristically, delayed hypersensitivity reactions to tuberculin begin at 5 to 6 hours, are maximal at 48 to 72 hours and subside over a period of days. In those who are elderly or those who are being tested for the first time reactions may develop slowly and may not peak until after 72 hours. Immediate hypersensitivity reactions to tuberculin or to constituents of the diluent can also occur.
