Okay, this is it.
If anyone has time, please take a read over it an tell me if and where it is incorrect or needs more detail.
I really struggled to find information specific to
C. tetani when it came to the immune response, so I just based most of it off of how it would respond to bacteria in general.
TETANUSTetanus is a disease caused by the pathogen Clostridium tetani, a Gram-Positive obligate anaerobic rod shaped bacterium. The organism lives in the soil as spores where oxygen levels are very low, or in the intestinal tract of animals, particularly humans. The incubation period for a tetanus infection in humans can vary between days and months, depending on the proximity of the infection to the nervous system. Generally though, symptoms will begin to appear 8 days after infection.
INFECTIONClostridium tetani infects humans by entering through wounds in the skin. Deep cuts are most likely to lead to infection, as conditions further beneath the skin are the most favourable for the bacterium to survive and reproduce. Deep skin punctures by rusted nails can often cause tetanus, however the rust itself is not the cause of infection. The rough metal surface merely provides a suitable habitat for the bacterial spores to reside. It is the depth of the wound which can lead to infection. Deeper wounds provide the optimal conditions for C. tetani to invade, as this is where oxygen levels are lowest. Once spores germinate, they produce two toxins called tetanolysin and tetanospasmin. These are coded for on the DNA plasmid in the cytosol. The role of tetanolysin is unknown in C. tetani. It is the tetanospasmin which causes harm to humans. It is released into the bloodstream and lymphatic system, where it then travels to parts of the CNS and inhibits some nerve impulses.
SYMPTOMSThe tetanospasmin toxin is responsible for the adverse effects caused by C. Tetani. It is highly potent and can be lethal at concentrations as low as 2.5 nanograms per kilogram of body weight. The toxin reaches the nervous system by first travelling through the circulatory and lymphatic systems. It is there where it acts as an inhibitor and binds to nerve endings on neurons attached to the brain and spinal cord, as well as at some nerve terminals in the PNS. This results in the oppression of inhibitory responses, causing uncontrollable muscle spasms in infected patients. The toxin also effects muscle control by interfering with the release of inhibitory neurotransmitters GABA (gamma-aminobutyric acid) and glycine. In addition to voluntary muscles, the toxin can also cause involuntary muscles such as the lungs and heart to spasm uncontrollably. Breathing can then become restricted and heart rate can also change beyond regulatory limits. Insufficient blood oxygen levels or heart attack could result.
IMMUNE RESPONSE
Non specificThe innate immune system plays a significant role in ensuring bacteria do not enter the body. Mucous in exposed tissues such as the throat and trachea can trap bacterial cells, and then use cilla to sweep them away. Lysozymes in are also present in some areas to destroy bacteria by digesting their cell walls. As C. tetani infection is usually transmitted via wounds in the skin, an intact skin is critical in providing protection against C. tetani, as bacteria are unable to penetrate skin. If the pathogen manages to bypass the innate immune system, then non-specific cellular defences proceed to attempt to destroy the bacterium. Mast cells secrete histamine to induce an inflammatory response when the skin becomes broken. Blood vessels surrounding broken skin tissue become leaky, allowing for increased leukocyte transport to the vicinity. Several leukocytes then act to defend against infection.
Platelets and fibrin in the blood cause clotting at the site of the wound, which prevents excess blood loss, and re seals the skin to prevent other pathogens from entering. Other cells act by recognising foreign membrane surface glycoproteins in order to distinguish between self and non-self, and then respond accordingly. Cells infected by C. tetani will display altered cell surface carbohydrates, and are consequently destroyed by Natural Killer cells. Complement proteins also act against the bacterium. They can directly interfere with its cell wall and cause it to lyse, or attach to its membrane, making it more easily identifiable to phagocytes. There are several forms of phagocytes in the immune system which are responsible for engulfing (phagocytising) pathogens and destroying them. The tetanospasmin toxin responsible for tetanus can act as both an exotoxin and an endotoxin depending on the strain of C. tetani present, as some release the toxin for the duration of their life whilst others only secrete it when they lyse. The immune response against the bacterium can therefore cause the release of the toxin in some cases. This is ineffective in supressing the harmful effects of the infection. Specific immunity is required to neutralise the tetanospasmin. Although a part of the second line of defence, macrophages and dendritic cells are important in initiating adaptive immunity.
SpecificDendritic cells and macrophages are antigen presenting cells (APC), which after engulfing a pathogen such as C. tetani, present its antigens and toxins on their own cell membrane. These then travel to the lymph nodes, where they eventually encounter individual B and T lymphocytes with complementary antibodies and antitoxins. This then initiates the primary adaptive response. Clonal selection results in B-cells rapidly reproducing to form plasma cells, which produce hundreds of thousands of tetanus antibodies (type: IgG) and antitoxins against the bacterium. B-memory cells are also formed, which in the case of future exposure to the bacterium and toxin, will cause the hosts immune system to mount a quick response against the infection. Helper T cells evolve, and have a receptor which also binds to the antigen, and activates cytokines which in turn activate B-cells. Cytotoxic T-cells are also produced, and specifically target and destroy cells which have been infected by C. tetani. Although the third line of defence is able to provide some degree of long term immunity, it is insufficient in being able to completely neutralise the toxin. After first infection, a patient will likely die if left untreated, as the immune response against C. tetani and tetanospasmin, which is one of the most potent toxins in existence, is far too slow to neutralise its detrimental effects in the nervous system.
TREATMENTDepending on the severity and stage of the infection, there are several causes of action which can be taken to neutralise the effects of tetanospasmin. In mild cases, tetanus immunoglobulin is injected into the blood to bind to the toxin, preventing it from inhibiting nerve impulses. The antibiotic metronidazole is also administered, as it weakens the bacterium’s cell wall and interferes with the genetic transcription process, preventing protein synthesis. In severe cases, patients are admitted into intensive care. In addition to the treatments above, they have human tetanus immunoglobulin injected directly into the spinal cord, require mechanical ventilation to aid breathing, and must take muscle relaxants in order to control spasms.
Prevention against tetanus is the best cure. A tetanus vaccine is available against tetanospasmin, which gives immunity against the toxin. It is called tetanus toxoid, and is made from an attenuated version of the toxin, which is harmless to humans. Upon exposure to the inactive form of the toxin, the primary adaptive immune response is initiated, producing B and T memory cells with the appropriate antibodies against the toxin. Should a secondary, ‘real’ infection occur, the immune system will quickly respond by destroying the C. tetani bacterium, well before tetanospasmin concentrations reach lethal levels. The initial course requires three doses of the vaccine, preferably during infanthood, followed by two booster vaccines in adolescence, to ensure that memory against C. tetani and tetanospasmin remains active.
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