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  1. 1. Immunity and Diseases Scientific background to autoimmune diseases Dr Michael F. Ofori Noguchi Memorial Institute for Medical Research College of Health Sciences University of Ghana
  2. 2. <ul><li>Autoimmune diseases result when the immune system attacks the body's own organs, tissues and cells. </li></ul><ul><li>Physicians and scientists have identified a number of different autoimmune diseases. </li></ul><ul><ul><li>Some are well known, </li></ul></ul><ul><ul><li>Others are less familiar, </li></ul></ul>
  3. 3. Tolerance and Autoimmunity <ul><li>The Immune system could go awry and instead of reacting only against foreign antigens, could focus its attack on SELF ANTIGENS </li></ul><ul><li>This can result in a number of chronic and acute diseases including </li></ul><ul><ul><ul><li>Rheumatoid Arthritis </li></ul></ul></ul><ul><ul><ul><li>Multiple screlosis </li></ul></ul></ul><ul><ul><ul><li>Lupus Erythematosis </li></ul></ul></ul><ul><ul><ul><li>Certain types of Diabetes </li></ul></ul></ul>
  4. 4. <ul><li>Physicians and scientists have identified more than 80 different autoimmune diseases. </li></ul><ul><ul><li>Some are well known, </li></ul></ul><ul><ul><ul><li>rheumatoid arthritis, </li></ul></ul></ul><ul><ul><ul><li>multiple sclerosis, </li></ul></ul></ul><ul><ul><ul><li>type 1 diabetes </li></ul></ul></ul><ul><ul><ul><li>systemic lupus; </li></ul></ul></ul><ul><ul><li>others are less familiar, </li></ul></ul><ul><ul><ul><li>autoimmune hepatitis, </li></ul></ul></ul><ul><ul><ul><li>Sjögren's syndrome </li></ul></ul></ul><ul><ul><ul><li>pemphigus </li></ul></ul></ul>Types Of Autoimmune diseases
  5. 5. <ul><li>The results of the failure of the host’s humoral and cellular immune system to distinguish SELF from NON-SELF </li></ul><ul><li>This will result in the attack of self cells and organs by Auto-antibodies and self reactive T-cells. </li></ul>WHY THIS?
  6. 6. <ul><li>This is referred to the inappropriate response of the immune system against self components . </li></ul><ul><li>Autoimmune reactions can cause serious damage to cells and organs </li></ul>WHAT IS AUTOIMMUNITY?
  7. 7. Examples
  8. 8. <ul><li>Organ specific Autoimmune Diseases </li></ul><ul><ul><li>Hashimoto’s Thyroiditis </li></ul></ul><ul><ul><ul><li>Frequently seen in middle aged women </li></ul></ul></ul><ul><ul><ul><li>X’terised by infiltration of thyroid gland by lymphocytes, macrophages and plasma cells </li></ul></ul></ul><ul><ul><ul><li>The ensuing inflammatory response causes GOITER or visible enlargement of thyroid gland – a physiological response to hypothyroidism (decreased production of thyroid hormones </li></ul></ul></ul><ul><li>Hypothyroidism is caused when Abs are formed to a number of thyroid proteins including thyroglobulin and thyroid peroxidase – both involved in iodine uptake </li></ul><ul><li>Autoimmune hemolytic anaemia </li></ul>
  9. 9. Systemic Autoimmune Diseases <ul><li>Here the response is directed towards a broad range of targets and antigens and also involve a number of organs and tissues </li></ul><ul><ul><li>Systemic Lupus erythematosus (SLE) </li></ul></ul><ul><ul><ul><li>Appears in women b/n 20 and 40 years of age </li></ul></ul></ul><ul><ul><ul><li>Ratio of females to males is 10:1 </li></ul></ul></ul><ul><ul><ul><li>X’terised by fever, weakness, arthritis, skin rashes and kidney desfunction </li></ul></ul></ul><ul><ul><ul><li>It is more common in African American and Hisponic women than Caucasians </li></ul></ul></ul><ul><ul><ul><li>Reasons? </li></ul></ul></ul>
  10. 10. <ul><ul><li>Multiple sclerosis </li></ul></ul><ul><ul><ul><li>Attacks the CNS and causes neurological disabilities </li></ul></ul></ul><ul><ul><ul><li>IT could be mild such as numbness in limbs or severe such as paralysis or loss of vision </li></ul></ul></ul><ul><ul><ul><li>Genetic influence is important here </li></ul></ul></ul><ul><ul><ul><li>Risk is higher in women than men 2 - 3X higher </li></ul></ul></ul><ul><ul><li>Rhematoid arthritis </li></ul></ul><ul><ul><ul><li>Attacks the joints </li></ul></ul></ul><ul><ul><ul><li>Most often common in women b/n the ages of 40 – 60 </li></ul></ul></ul><ul><ul><ul><li>Main effect being the inflammation of the joints </li></ul></ul></ul><ul><ul><ul><li>But can also cause hemolytic, cardiavascular and respiratory systems </li></ul></ul></ul>
  11. 11. Economic Importance <ul><li>The social and financial burdens imposed by these chronic, debilitating diseases include: </li></ul><ul><ul><li>poor quality of life, </li></ul></ul><ul><ul><li>high health care costs </li></ul></ul><ul><ul><li>substantial loss of productivity </li></ul></ul><ul><li>In addition, the majority of autoimmune diseases disproportionately affect women, </li></ul>
  12. 12. Why are women more susceptible than men to Autoimmunity?
  13. 13. Reasons put forward so far includes; <ul><li>Differences in Antibody production </li></ul><ul><ul><li>Females produces more Ab than males </li></ul></ul><ul><ul><li>They also mount more vigorous immune response than males </li></ul></ul><ul><li>Sex hormones also play important role </li></ul><ul><ul><li>Studies have shown that estrogen can stimulate auto-antibody production </li></ul></ul><ul><ul><ul><li>Demonstrated in SLE-prone mice </li></ul></ul></ul><ul><ul><li>Testosterone seems to be protective against several types of autoimmune diseases, eg.SLE, diabetes,MS etc </li></ul></ul><ul><li>Ability of pregnant women to modify their immune system during pregnancy to keep the fetus </li></ul><ul><li>The presence of fetal cell in maternal circulation for decades – this can also lead to the development of autoimmune diseases </li></ul>
  14. 14. Major research Areas <ul><li>Causes of Autoimmune Diseases </li></ul><ul><li>The Burden of Autoimmune Diseases </li></ul><ul><li>Diagnosis, Treatment and Prevention </li></ul><ul><li>Training, Education and Information </li></ul>
  15. 15. POSSIBLE CAUSES Of Autoimmune diseases <ul><li>Genetic, Environment, Infections etc </li></ul><ul><li>Recent reports have shown a marked association between 2-nonynoic acid , a cosmetic ingredient and primary biliary cirrhosis (PBC), a disease 9 times more likely to occur in women. </li></ul><ul><li>Other suspected triggers of Autoimmune diseases include </li></ul><ul><ul><li>smoking, </li></ul></ul><ul><ul><li>bacterial & retroviral proteins, </li></ul></ul><ul><ul><li>hormone replacement therapy, </li></ul></ul><ul><ul><li>use of nail polish. </li></ul></ul><ul><li>It’s thought that chemical degradation in the liver causes a loss of immune tolerance that predisposes Individuals to autoimmune diseases. </li></ul>
  16. 16. Research In Ghana <ul><li>Study Conducted between 1983 and 1989 - 6yrs Period. </li></ul><ul><li>Korle Bu Teaching Hospital </li></ul><ul><li>They recorded 23 cases of Connective tissue disease during the period out of 4,507 admissions </li></ul><ul><li>Age ranged from 26 – 63 yrs (mean = 44yrs) </li></ul><ul><li>16 ( 70%) were females </li></ul><ul><li>11 had SLE </li></ul><ul><li>8 had R.A </li></ul><ul><ul><li>SLE 2.4 per thousand </li></ul></ul><ul><ul><li>RA. 1.8 per thousand </li></ul></ul><ul><li>They then concluded that SLE and RA are NOT COMMON </li></ul>Affram RK and Neequaye AR, (1991 ). Systemic Lupus erythematosus and Other Rheumatic Disorders: Clinical Experience in Accra:, Ghana Medical Journal Vol 25:299-302
  17. 17. Other studies <ul><li>SLE is most prevalent in women of African Origin – This has been demonstrated in a number of studies </li></ul><ul><li>McCarthy et al 1995 </li></ul><ul><li>Symmons,1995, </li></ul><ul><li>Houcgberg,1985, </li></ul><ul><li>Siegel et al 1970 </li></ul>
  18. 18. SLE IN AFRICANS <ul><li>Population studies unavailable up to date </li></ul><ul><li>Most studies done are on case reports or series of reports of hospitalized patients. </li></ul><ul><li>Some of the countries in which these studies has taken place include: </li></ul><ul><ul><li>South Africa, Zimbabwe, Ghana , Nigeria, Guinea, Cote D’ voire, Gabon, DR Congo, Senegal </li></ul></ul><ul><li>From all these published reports, SLE appears to be RARE in Africa </li></ul>
  19. 19. SLE IN AFRICANS Cont’ <ul><li>Recent Studies from South and Central African suggest SLE to be increased in these regions whilst that in West African remain to be RARE </li></ul><ul><ul><li>This can be explained by the reporting BIAS </li></ul></ul>
  20. 20. Treatment of Auto-immune Diseases <ul><li>Current therapies include </li></ul><ul><ul><li>Treatment with immunosuppressive drugs </li></ul></ul><ul><ul><li>Thymectomy and plasmapherisis for diseases involving immune complexes </li></ul></ul><ul><ul><li>TNF alpha Blockers </li></ul></ul><ul><ul><ul><ul><li>For controlling RA and Crohn’s disease </li></ul></ul></ul></ul><ul><li>Treatment of human autoimmune diseases poses special challenges </li></ul>
  21. 21. Challenges <ul><li>Use of Immunosuppressive drugs does not leave the other immune system Intact </li></ul><ul><li>Immuno suppressive drugs such as: </li></ul><ul><ul><li>Corticosteriods, </li></ul></ul><ul><ul><li>Azathioprine </li></ul></ul><ul><ul><li>Crclophosphamide </li></ul></ul><ul><li>are capable of depressing the immune response but also puts the patient at a greater risk of infection and development of cancers </li></ul><ul><li>Most current Therapies are not for cure but only reduces symptoms </li></ul>