Immunological Diseases

1. Navid Jubaer Lecturer The University of Asia Pacific Immunological disorders 1

2. 2 An  immune disorder  is a dysfunction of the immune system. These disorders can be characterized in several different ways: By the component(s) of the immune system affected By whether the immune system is overactive or underactive By whether the condition is congenital or acquired Immunological Disorder

3. 3 Definition: A state of altered reactivity in which the body reacts with an exaggerated immune response to what is perceived as a foreign substance. Immune response that results in tissue injury or other physiological changes are called hypersensitivity (allergic) reactions”.  Hypersensitivity (allergy)

4. 4 Hypersensitivity reactions are classified into four types: Type I: Anaphylactic hypersensitivity Type II: C ytotoxic hypersensitivity Type III: Immune complex hypersensitivity Type IV: Cell mediated hypersensitivity Types of hypersensitivity reactions

5. 5 It is an immediate reaction beginning within minutes of exposure to an antigen . It is mediated by antibodies . It requires previous exposure to specific antigen . It usually affects on skin, lungs and gastrointestinal tract . Examples: Asthma Allergic rhinitis Systemic anaphylaxis. Atopic dermatitis Type I: Anaphylactic hypersensitivity:

6. 6 Anaphylactic (type I) Hypersensitivity

7. 7 It occurs when the system mistakenly identifies a normal constituent of the body as foreign . This reaction may be a result of cross-reacting antibody, possibly leading to cell and tissue damage It involves activation of complement by IgG or IgM antibody binding to an antigenic cell . Examples: Myasthenia gravis Thrombocytopenia Type II: Cytotoxic hypersensitivity

8. Pathogenesis of type II hypersensitivity 8 Cytotoxic (type Il) Hypersensitivity

9. 9 It involves in the formation of immune complexes when antigen binds to antibodies . These type III complexes deposit in tissues or vascular endothelium and leads to injury with the help of vasoactive amines and the increase number of circulating complexes. The joints and kidneys are particularly susceptible . Examples: Systemic lupus erythematous Rheumatoid arthritis Serum sickness Type III: Immune complex hypersensitivity

10. 10 Immune complex (type III) hypersensitivity Pathogenesis of type III hypersensitivity

11. 11 Also known as cellular hypersensitivity It occurs 24-72 hrs after exposure to an allergen The reaction is mediated by sensitized T cells and macrophages . The reaction results In tissue damage by releasing lymphokines , macrophages and lysozymes . Examples : Contact dermatitis Tuberculin test. Type IV: Cell mediated hypersensitivity

12. 12 Cell mediated (type IV) HYPERSENSITIVITY Pathogenesis of type IV hypersensitivity

13. 13 It is also called as Hay Fever Definition: It is an inflammation of the nasal mucosa by an allergen. Allergic Rhinitis

14. Pathogenesis: Allergic Rhinitis 14 Inhalation of an antigen (sensitization) Re-exposure Nasal mucosa reacts (histamine is mediator) Slowing of ciliary action, edema formation and leukocyte infiltration Tissue edema and increase capillary permeability (vasodilatation).

15. 15 Clinical manifestations : Nasal congestion Clear to greenish rhinorrhea Intermittent sneezing and nasal itching Headache Epistaxis Fatigue, loss of sleep and poor coordination . Medical management: Oral anti histamines (blocks the action of histamine ) N asal decongestant Mast cell stabilizers . Analgesics and antipyretics.

16. Atopic dermatitis (eczema) 16 Definition : Inflammation of the skin Incidences/Causes: Familial tendency It is highest in infants and children 1% population is suffering from this disease Aggravated in low humidity and in winter.

17. Pathophysiology: Atopic dermatitis 17 Allergen /Sensitizing antigen Affect the skin (changes in lipid content, sebaceous gland activity and sweating) R educed water-binding capacity of the skin Higher trans epidermal water loss and decreased water content Dry skin Itching, rubbing leads to infection

18. 18 Clinical manifestations: Atopic dermatitis Red oozing crusting rash (in childhood ) Dry thick brownish – grey and scaly skin (later stage ) Pruritus Lesion are mostly found on hand, foot, back of the knees, neck, face, eyelids and elbow bands . Medical Management: Atopic dermatitis Moisturizers Antibiotics Antihistamines

19. 19 Anaphylaxis Definition : It is an immediate life threatening systemic reaction that can occur on exposure to particular substances It is an immediate (type I hypersensitivity) immunologic reaction, results from IgE antibody This reaction affects many tissues and organs. Death may occur due to respiratory tract spasm and constriction or collapse . Causes Food ( peanuts, fish, milk, eggs, wheat and chocolate). Medications (penicillin, NSAID’s) Insects stings (bees, ants)

20. 20 Pathophysiology: Anaphylaxis Interaction of foreign antigen with IgE antibodies Release of histamine Activation of platelets, eosinophils and neutrophils smooth muscle spasm, bronchospasm, mucosal edema and inflammation.

21. Mild Moderate Severe Occurs within first 2hrs of exposure Same Same Peripheral tingling Flushing Bronchospasm Sensation of warmth Itching Laryngeal edema Fullness in mouth and throat Bronchospasm Severe Dyspnea, cyanosis Nasal congestion Edema of larynx Hypotension Periorbital swelling Dyspnea Cardiac arrest and coma may follow. Pruiritus Cough   Sneezing wheezing   21 Clinical manifestations: Anaphylaxis

22. 22 Medical management: Anaphylaxis If cardiac arrest then cardiopulmonary resuscitation initiated. Antihistamine to prevent recurrence reaction Start intravenous fluids to maintain hemodynamics . Give aminophylline for bronchospasm

23. 23 Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplantation can be : autologous (own) homologous ( alogenic ) - human tissue heterologous - animal tissue (pig skin, ovine pericardium) Transplantation Rejection

24. 24 hyperacute ( Ab mediated) - widespread arteriolitis , arteritis , ischemic necrosis (minutes-hours) acute (cell mediated) - vasculitis , tubulitis , edema (days-months ) chronic - vascular changes - sclerosis, intimal fibrosis (months-years) Rejection Reactions

25. 25 GVHD happens when particular types of white blood cell (T cells) in the donated bone marrow or stem cells attack host body cells. This happens because the donated cells (the graft) see the body cells (the host) as foreign and attack them. It is difficult to say who will develop GVHD after a transplant. We don’t know exactly, but somewhere between 1 and 4 out of every 5 people (20 to 80%) having a donor transplant will develop some degree of GVHD. Some people have a very mild form which doesn’t last long. For others, GVHD can be severe. It may even be life threatening in a few cases. Some people may have GVHD over many months, or even years. Graft Versus Host Disease

26. 26 GVHD happens because the transplant affects your immune system. The donor's bone marrow or stem cells will contain some T cells. T cells are a type of white blood cell that help us fight infections. T cells attack and destroy cells they see as foreign, and potentially harmful, such as bacteria and viruses. Normally T cells don’t attack our own body cells, because they recognize proteins on the cells called HLA (human leukocyte antigens). We inherit our HLA from our parents. Apart from identical twins HLA is unique to each person. Before a bone marrow or stem cell transplant, you and your donor have blood tests to check how closely your HLA matches. This test is called tissue typing. If you and your donor have very similar HLA this lowers the chance of GVHD. The more differences there are between your HLA and your donor's, the more likely you are to get GVHD. After a transplant your bone marrow starts making new blood cells from the donor stem cells. These new blood cells have the donor's HLA pattern. They recognize the HLA pattern on your body cells as different (foreign) and may begin to attack some of them. The GVHD may affect different areas of your body. Most commonly it affects the Skin Digestive system (including the bowel and stomach) Liver How GVHD Develops

27. 27  Thank you 