Congenital and Acquired Immunodeficiency

Immunology

1. Mother Patern College of Health Sciences Immunology Group Presentation Topic: Congenital and Acquire Immunodeficiency Group 3 Members: A. Sylnice Urey Ciatta Gogbeh Giftee J. Roumi Arnold Flahn

2. Objective Know what are Primary and secondary Immunodeficiencies Differentiate between both of them Know some primary and secondary immunodeficiency and diseases they cause.

3. Overview Congenital IMDs are deficiencies present at birth while, Acquired IMDs are developed. 1 ° IMD is caused by genetic defects while, 2 ° IMD is developed due to abnormalities. X-linked agammaglobulinemia and HIV infections are egs : of 1 ° and 2 ° IMD Different 1 ° and 2 ° IMDs may differ considerably in clinical and pathologic manifestations.

4. Defects in Lymphocytes maturation These are types of congenital IMD. Many are the result of genetic abnormalities that block maturation of B, T or both lymphocytes. SCID , caused by several genetic abnormalities but about half of them are X-linked. X- linked SCID: caused by mutations in a signaling of a receptor for cytokines It is called the common yc chain because it is a component of the receptors for numerals cytokines. When yc chain is not functional, immature lymphocytes, pro-T cells cannot proliferate in response to major growth factor. Reduced survival and maturation of lymphocytes precursors are caused by defective IL-7 Consequence of this block is due to decrease in mature T-cells

5. Cont’d Natural killer cells : are also deficient because the receptor for IL-15 also uses the yc chain. Receptors for this is a major cytokin involved in NK cell proliferation and maturation. Autosomal SCID: about half of the cases are caused by mutation in an enzyme called adenosine deaminase , involved in the break down of purine. Lymphocytes that actively proliferate durong their maturation are injured by these accumulating toxic metabolites. ADA deficiency results in a block in T cell maturation more than B cell Rare cases of A-SCID is caused by mutations in the RAG- 1 and RAG- 2 genes that encode the lymphocytes specific components of VDJ recombinase .

6. Cont’d X- linked and Autosomal cases : appox . 50 % of the caused is known. Most common clinical syndrome is X- linked agammaglobulinemia . B cells fail to mature beyond pre B cells stage resulting in decrease or absense of mature B cells and serum immuniglobulins . It’s caused by mutation in the gene encoding a Kinase called Btk Selective defects affecting T cell maturation : the most common is the DiGeorge Syndrome. Patience with this disease tend to improve with age probably because the small amount of thymic tissue that does develop id able to support some T cell maturation.

7. Cont’d Selective B celldefects patients may be given pooled Ig from healthy donors to provide passive immunity.

8. Defects in lymphocytes activation and function

9. Defects in Innate Immunity Being the first line of defense, it is also susceptible to deficiencies. Innate immunity operates through two major aspects: Recognition- via receptors(killer activation receptors, killer inhibition receptors, complement receptors,etc .) Response- phagocytosis and inflammation Defect in any of those aspects may lead to immunodeficiency.(eg. Abnormalities in phagocytes and the complement system)

10. Defects in Innate Immunity Chronic granulomatous disease Mutations in phagocyte oxidase leads to low ROS in lysosomes. Immune system tries to compensate by calling in more macrophages and activating T-cells which stimulate the recruitment and activation of even more phagocytes. Collections of phagocytes accumulate and resemble granulomas, giving rise to the name of this disease

11. Defects in Innate Immunity Leukocyte adhesion deficiency Mutations in genes encoding integrins or in enzymes required for the expression of ligands for selectins ; Integrins and selectin ligands are involved in the adhesion of leukocytes to other cells As a result, blood leukocytes do not bind firmly to vascular endothelium and are not recruited normally to sites of infection.

12. Defects in Innate Immunity Cystic Fibrosis Gene defect in ion-gated chloride channel leading to accumulation of abnormally thick secretions in airways. Factor I Deficiency Uncontrolled complement activation, leading to complement protein depletion

13. Congenital Immunodeficiencies caused by defects in Innate immunity

14. Lymphocyte Abnormalities Associated With Other Diseases DiGeorge’s syndrome Most understood T-cell deficiency Associated with hypoparathyroidism, congenital heart disease, Wiskott-Aldrich syndrome A n X-linked disease characterized by eczema, reduced blood platelets, and immunodeficiency(B&T-cells defect) IgM & IgG levels are low Impaired functions of both B&T-cells leads to pyogenic bacteria and opportunistic viruses

15. Acquired (Secondary) Immunodeficiencies Later in life Resultsfrom infection, malnutrition, or treatments that cause loss or inadequate funtion of various components of the immune system. Most common is aquired immunodeficiency syndrome or AIDS.

16. ACQUIRED IMMUNODEFICIENCIES

17. Causes of Acquired Immunodeficiencies

18. Acquired immunodeficiency syndrome( AIDS) The first case of AIDS was reported in the 1980s and the disease is characterized by a susceptibility to infections. AIDS is caused by infection with the Human immunodeficiency virus (HIV). It is estimated that there are more than 42 million HIV-infected people in the world. HIV is a retrovirus that infects cells of the immune system , mainly CD4+ T lymphocytes. Two types: HIV-1 HIV-2

19. HIV….. HIV infects cells by virtue of its major envelope glycoprotein, called gp120 Binds to CD4 and particular chemokine receptors on T cells and macrophages

20. HIV establishes a latent infection in cells of the immune system and may be reactivated to produce infectious virus . The depletion of CD4+ T cells after HIV infection is due to a cytopathic effect of the virus .

21. Clinical features of HIV and AIDS The clinical course of HIV infection leads to immune deficiency. AIDS are primarily the result of increased susceptibility to infections and some cancers Some pathogen that cause infection are: Pneumocystis jiroveci Cytomegalovirus Some viruses that cause cancer are: Epstein-Barr virus Human Herpesvirus - 8

22. Therapy and Vaccination strategies The current treatment for AIDS is aimed at controlling replication of HIV and the infectious complications. Therapy: HAART or cART Antiretroviral Drugs: Nevirapine & Efavirenz Prevention: Use protection The control of HIV worldwide will require the development of effective vaccines

23. THANK YOU!!