Some tumor cells also release products that inhibit the immune response; for example by secreting the cytokine TGF-β, which suppresses the activity of macrophages and lymphocytes. In addition, immunological tolerance may develop against tumor antigens, so the immune system no longer attacks the tumor cells.Paradoxically, macrophages can promote tumor growth when tumor cells send out cytokines that attract macrophages, which then generate cytokines and growth factors such as tumor-necrosis factor alpha that nurture tumor development or promote stem-cell-like plasticity. In addition, a combination of hypoxia in the tumor and a cytokine produced by macrophages induces tumor cells to decrease production of a protein that blocks metastasis and thereby assists spread of cancer cells. Anti-tumor M1 macrophages are recruited in early phases to tumor development but are progressively differentiated to M2 with pro-tumor effect, an immunosuppressor switch. The hypoxia reduces the cytokine production for the anti-tumor response and progressively macrophages acquire pro-tumor M2 functions driven by the tumor microenvironment, including IL-4 and IL-10. Cancer immunotherapy covers the medical ways to stimulate the immune system to attack cancer tumors. Predicting immunogenicity
Some drugs can cause a neutralizing immune response, meaning that the immune system produces neutralizing antibodies that counteract the action of the drugs, particularly if the drugs are administered repeatedly, or in larger doses. This limits the effectiveness of drugs based on larger peptides and proteins (which are typically larger than 6000 Da). In some cases, the drug itself is not immunogenic, but may be co-administered with an immunogenic compound, as is sometimes the case for Taxol.
Mites penetrate the skin and feed on skin cells that are broken down by an enzyme they secrete from their mouthparts, but they do not lay eggs in the host as T. penetrans does. Moreover, in mites, the adult and the larval forms both feed on other animals. This is not the case with T. penetrans, as only the adults feed on mammals and it is only the female that stays attached to the host. Tunga penetrans is also known by the following names: chigoe flea, sand flea, nigua, chigger flea, jigger flea, bicho de pé, pico, sikka, kuti, and piqui, among many others. Signs and symptoms
The symptoms of this disease include:
Severe pruritus
Pain
Inflammation and swelling
Lesions and ulcerations, with black dots in the centerIf a Tunga infection is left untreated, secondary infections, such as bacteremia, tetanus, necrosis and gangrene, may be expected. In all cases, tungiasis by itself only caused morbidity, though secondary infection may lead to mortality. The life cycle section presents the Fortaleza stages from the fleas developmental perspective. The discussion is specific to symptoms of human infection. The clinical presentation in humans follows the Fortaleza Classification as the stage of infection will determine the symptoms present. The following discussion will give an overview of the symptoms beginning in stage 2 because patients are not likely to present themselves at the early stages of infection, mostly because the fleas burrowing is usually not felt.