Disorders of Immune respones Lecturer: Dr.Zainab Sajid Al-Shimmari

1. Disorders of Immune respones Lecturer: Dr.Zainab Sajid Al-Shimmari

4. Hypersensitivity. Normal immune responses are vital in protecting the host against invasion by foreign organisms, tissues and substances. These usually protective responses can have a deleterious effect on the host.-These responses called allergies or hypersensitivities. There are 4 types (Type 1 to 4) where in the hosts immune system damages its own tissues.

5. I-Type 1 hypersensitivity (Anaphylaxis) : 1- These are caused by chemical substances released from basophiles or mast cells. The substances include histamine, slow reacting substance of anaphylaxis, bradykinin and eosinophile chemotaxis factor of anaphylaxis.(E C F). 2- The release of chemical mediators by mast cells when antigen (allergen) binds to specific antibody (reagins) that are present on the mast cell membrane.

7. 3- Reaginic (or cytotropic ) antibodies of man and animals are of the immunoglobulin. E (IgE). These antibodies are also called homocytotropic because of their propensity bind to mast cells and basophiles. 4- The nature of clinical disorder that occurs following the interaction of allergen and cell-bound IgE varies with the dose of allergen, the route by which the allergen enters the body and location of the IgE coated mast cells. Anaphylactic reactions may affect the respiratory system (bronchial spasms and laryngeal edema), gastro intestinal tract (vomiting, diarrhea), cardiovascular system (intestinal and hepatic vasodilatation) or skin(hives,urticaria.

8. II-Type 2 hypersensitivity (Antibody mediated cytotoxicity): Mechanism a-Cytotoxic reactions occur as a result of the binding of IgG , IgM or IgA antibodies to antigenic substances on the surface of body cells. b-complement also associated with the reaction . c- Many types of body cells can be damaged, but blood cells appear to be specific susceptible to immune mediated lysis and phagocytosis.

9. III-Type 3 hypersensitivity ( Immune- complex diseases) a-These reactions occur as a result of the localization of Ag-Ab complexes in tissues, usually vessel walls. When continuous source of circulating Ag, and a continuous production of Ab. When the level of circulating Ag and Ab reach critical concentration, Ag-Ab complexes of intermediate size are produced. b-Smaller complexes are soluble and pass through the vessel walls, while larger complexes are removed by the reticuloendothelial system.

10. C-Inter mediate sized complexes have a tendency to pass through endothelial cell spaces, but become trapped around the basement membrane. d- Complement that is bound to the complexes chemotactically draws polymorphonuclear cells into the area, e- the complexes are ingested by these cells and as a result the neutrophils release their lysosomal enzymes. This process damages the surrounding tissues.

11. IV-Type 4 reaction Cell- mediated immune reaction, Delayed hypersensitivity. This reaction occurs as a result of the interaction of sensitized T Lymphocytes with the sensitizing Ag. The tissue reaction is a result of lymphokines released by the sensitized T Lymphocytes. Lymphokines canbe, 1-Cytotoxic. . 2-Inhibit the movement of macrophages out of the area. 3- Cause small lymphocytes to be transformed into large basophilic blast cells.This type of immunity seen ini)- Tuberculin reaction.ii)- It is important in the destruction of some tumors.iii) - It is important in the destruction of foreign- tissue grafts.

13. Immunodeficiency Disease A-Immunodeficiency can be defined as an abnormality in one or more branches of the immune system that renders a person susceptible to diseases normally prevented by an intact immune system. B-Four major categories of immune mechanisms defend the body against infectious or neoplastic disease: humoral or antibody-mediated immunity (i.e., B lymphocytes), cell-mediated immunity (i.e., T lymphocytes), the complement system, and phagocytosis (i.e., neutrophils and macrophages).

14. I-HUMORAL (B-CELL) IMMUNODEFICIENCIES. i)-Humoral immunodeficiencies involve B-cell function and immunoglobulin or antibody production. Defects in humoral immunity increase the risk for recurrent pyogenic infections, including those caused by Streptococcus pneumoniae,Haemophilus influenzae, Staphylococcus aureus, and gram-negative organisms such as Pseudomonas species.

15. II-CELL-MEDIATED (T-CELL) IMMUNODEFICIENCIES. i)-Mature T lymphocytes are composed of distinct subpopulations whose immunologic assignments are diverse. T cells can be functionally divided into two subtypes (CD4+ helper and CD8+cytotoxic T cells). ii)-Collectively, T lymphocytes protect against fungal, protozoan, viral, and intracellular bacterial infections; control malignant cell proliferation; and are responsible for coordinating the overall immune response.

16. III-DISORDERS OF THE COMPLEMENT SYSTEM. i)-The complement system is an integral part of the innate or nonspecific immune response . The activation of the complement network through the classic, lectinmediated,or alternative pathways promotes chemotaxis, opsonization, and phagocytosis of invasive pathogens, bacteriolysis,and anaphylactic reactions. ii)-Thus, alterations in normal levels of complement or the absence of a particular complement component can lead to enhanced susceptibility to infectious diseases and immune-mediated disorders such as hemolytic anemia and collagen vascular disorders.

17. IV-DISORDERS OF PHAGOCYTOSIS. i)-The phagocytic system is composed primarily of polymorphonuclear leukocytes (i.e., neutrophils and eosinophils)and mononuclear phagocytes (i.e., circulating monocytes and tissue and fixed [spleen] macrophages). ii)-The primary purpose of phagocytic cells is to migrate to the site of infection(i.e., chemotaxis), aggregate around the affected tissue (i.e., adherence), envelope invading microorganisms or foreign substances (i.e., phagocytosis), and generate microbicidal substances (e.g., enzymes or byproducts of metabolism) to kill the ingested pathogens.

18. Transplantation Immunopathology. A-In many years ago, transplantation of solid organs (e.g., liver, kidney, heart) and bone marrow was considered experimental and reserved for persons for whom alternative methods of therapy were exhausted and survival was unlikely. B-However, with a greater understanding of humoral and cellular immune regulation, the development of immunosuppressive drugs such as cyclosporine,and an appreciation of the role of the major histocompatibility complex (MHC) antigens, transplantation has become nearly routine and the subsequent success rate has been greatly enhanced.

19. C-The cell surface antigens that determine whether transplanted tissue is recognized as foreign are the MHC or human leukocyte antigens (HLA). Transplanted tissue can be categorized as allogeneic if the donor and recipient are related or unrelated but share similar HLA types, syngeneic if the donor and recipient are identical twins, and autologous if donor and recipient are the same person.

20. D-Donors of solid organ transplants can be living or dead and related or unrelated (heterologous).When cells bearing foreign MHC antigens are transplanted, the recipient’s immune system can attempt to eliminate the donor cells, a process referred to as host versus-graft disease (HVGD). E-Conversely, the cellular immune system of the transplanted tissue can attack unrelated recipient tissue, causing graft-versus-host disease (GVHD) . The likelihood of rejection varies indirectly with the degree of MHC or HLA relatedness between donor and recipient.

27. Autoimmune Disease. Autoimmune diseases represent a group of disorders that are caused by a breakdown in the ability of the immune system to differentiate between self and non self antigens. Autoimmune diseases can affect almost any cell or tissue in the body. Some autoimmune disorders, such as Hashimoto’s thyroiditis, are tissue specific; others, such as SLE, affect multiple organs and systems.

29. Why an patient produces autoantibodies that react against its own tissues. 1- In some autoimmune disorders there appears to be a deficiency of suppressor T lymphocytes are important in the regulation of the normal immune response and one of their functions may be to suppress auto antibody production.

31. 2- Some tissue antigens are hidden deep in the cell membrane or in other areas inaccessible to the host lymphoid cells. Because of their nature, the host immune system does not recognize them as self in embryonic development if these Ags released during post- embryonic life, the host recognizes them as foreign and makes antibodies against them.

32. 3- Cross- reacting antibodies may also damage host tissues.Certain microbial proteins and drugs are antigenically similar to host antigens e.g. streptococcal Ags that produce antibodies that cross-react with normal glomerular basement membrane. The Ab combine with the Ag the first component of complement is bound to the complex (Ag+ Ab). The host cells are then destroyed by complement mediated lysis or phagocytosis .

33. 1- Auto immune hemolytic anemia. The clinical features of disease depend on the acuteness and severity of the anemia. Acute hemolytic anemia characterized by fever, pallor of the M.M and icterus bilirubin urea . 2 - Thrompocytopenia (decrease number of platlets ) . Characterized by petechial and ecchymotic hemorrhages of the skin and mucous membranes, epistaxis or hematurea. Excessive capillary bleeding can lead to anemia.