Immunotherapy Generalized immunosupperssor therapies Disease specific therapies Hodgkin

Immunotherapy • Generalized immunosupperssor therapies • Disease specific therapies • Hodgkin lymphoma • Breast cancer • Psoriasis • Naeglreia fowleri • CNS tumors • Myasthenia graves

Conventional immunosuppressive drugs in clinical use.

• Anti-inflammatory effects of corticosteroid therapy. Corticosteroids regulate the expression of many genes, with a net anti-inflammatory effect. First, they reduce the production of inflammatory mediators, including cytokines, prostaglandins, and nitric oxide (NO). Second, they inhibit inflammatory cell migration to sites of inflammation by inhibiting the expression of adhesion molecules. Third, corticosteroids promote the death by apoptosis of leukocytes and lymphocytes. The layers of complexity are illustrated by the actions of annexin-1 (originally identified as a factor induced by corticosteroids and named lipocortin), which has now been shown to participate in all of the effects of corticosteroids listed on the right. NOS, NO synthase.

Fig. 16. 3 Cyclosporin A and tacrolimus inhibit lymphocyte and some granulocyte responses.

Hodgkin’s Lymphoma : IMMUNO THERAPY Monoclonal Antibodies ØAnti-CD 52 alumtuzumab depletes survival of HL cells. Alumtuzumab Ø Anti-CD 52 binds to CD 52 receptors present on Immune cells and facilitates their removal by activating APC’s & complement cascade.

Trastuzumab for breast cancer • Trastuzumab (trade names Herclon, Herceptin) is a monoclonal antibody that interferes with the HER 2/neu receptor • The combination of trastuzumab with chemotherapy has been shown to increase both survival and response rate, in comparison to trastuzumab alone • One of the significant complications of trastuzumab is its effect on the heart, associated with cardiac dysfunction in 27% of cases • Trastuzumab is given intravenously once every two to three weeks for one year in total

Psoriasis treatments can be divided into three main types: Topical Treatments Light Therapy Systemic Medications

Systemic medications Immunomodulator drugs: These drugs are given by intravenous infusion, intramuscular injection or subcutaneous injection and are usually used for people who have failed to respond to traditional therapy. These work by blocking interactions between certain immune system cells and particular inflammatory pathways. Retinoids: Related to vitamin A, this group of drugs may reduce the production of skin cells.

IMMUNOPATHOLOGY AND SEROLOGY of Naeglreia fowleri: • However, Seidelet al. (1982) documented a specific antibody response to N. fowleriin a • In mice study, evoked ig. G response Californian patient who recovered from Sera contained antibody titer level in this disease. wild and domesticated animal • Based on immunoblot studies conductedat • Sera posessed ameobacidal activity Centers for Disease Control and Prevention that was lost upon heating: (CDC), Ig. M was the principal class of antibody complements (rakoons, rats, frogs, generated by this patient as well as by three squirrels etc) others who contracted PAM. • Patients die soon after infection with • These antibodies are particularly well PAM: hard to collect data regarding developed to N. fowleri antigens of c. 190, 66, serological test and antibody titre 30 and 14 k. Da. Whether these antibodies have any protective activity is not clear at this time

Neagleria fowleri strategies to resist complement damage 1) expression of complement-regulatory proteins and 2) shedding of the MAC (C 5 b-C 9) on vesicles • Toney & Marciano- Cabral (1992) reported that proteins on the surface of highly pathogenic N. fowleri played an important role in trophozoite resistance to complement lysis. CD 59. Serine/threonine and tyrosine protein kinase, interacts with CD 59 to shed the lytic complex (C 5 -C 9). undergo a process of vesiculation as a means of removal of the lytic MAC of complement.

STRATEGIES FOR THE IMMUNOTHERAPY OF CNS TUMORS • Glioma-associated antigens recognizable by the immune system have been identified and shown to protect against intracranial tumor formation in pre-clinical studies • Scrutanization of amino acid sequences to stabilize MHC expression to enhance immune system response against tumors

Treatment- Myasthenia graves ANTICHOLINESTERASE MEDICINES • These medicines delay the breakdown of acetylcholine when it is released from the nerve endings. More acetylcholine is then available to compete with autoantibodies. The most commonly prescribed anticholinesterase medicine is called Pyridostigmine. THYMECTOMY • This is an option in some cases. A thymectomy can improve symptoms in more than 7 in 10 people with Myasthenia Gravis and may even cure some. STEROID MEDICATION • Steroids suppress the immune system and prevent the abnormal antibodies from being made. A low dose, often on alternate days, is usually enough for people where symptoms only affect muscles around the eye. Example would be Prednisolone IMMUNOSUPPRESSANT MEDICINES • An immunosuppressant medicine such as Azothiaprine may be advised in addition to steroid medication. These medicines work by suppressing the immune system.