Immune Diseases

1. Immune Diseases Dr ROOPA Premed 2 Pathophysiology

2. IMMUNITY • The term immunity refers to the resistance exhibited by the host towards injury caused by microorganisms and their products..

3. Natural or Non-specific Immunity • Respone is antigen-independent • There is immediate maximal response • Not antigen-specific • Exposure results in no immunologic memory

4. Acquired or Specific Immunity • Response is antigen-dependent • There is a lag time between exposure and maximal response • Antigen-specific Exposure results in no immunologic memory • Exposure results in immunologic memory

5. The key primary lymphoid organs of the immune system are thymus and bone marrow, and secondary lymphatic tissues such as spleen, tonsils, lymph vessels, lymph nodes, adenoids, and skin.

6. Normal Immune System • Primary Lymphoid organs • Secondary Lymphoid organs • Cells • Cytokines • Complement system • HLA system

7. The complement system is a biochemical cascade that helps clear pathogens from an organism.

8. The diseases caused by disorders of the immune system fall into two broad categories: immunodefeciency, in which parts of the immune system fail to provide an adequate response (examples include chronic granulomatous disease), • and autoimmunity, in which the immune system attacks its own host's body (examples include systemic lupus erythematosus, rheumatoid arthritis, Hashimoto's disease and myasthenia gravis). Other immune system disorders include different hypersensitivities, in which the system responds inappropriately to harmless compounds (asthma and other allergies) .

9. Hypersensitivity refers to excessive, undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system. Hypersensitivity reactions require a pre-sensitized (immune) state of the host. Hypersensitivity reactions can be divided into four types: type I, type II, type III and type IV, based on the mechanisms involved and time taken for the reaction. Frequently, a particular clinical condition (disease) may involve more than one type of reaction.

10. Hypersensitivities • Type I : immediate, anaphylactic • 1st exposure to an antigen: stimulates IgE to bind to mast cells, basophils • 2nd exposure: IgE causes lysis of the cells, release of histamine • Allergic asthma, atopic dermatitis, seasonal rhinitis, systemic anaphylaxis

12. Type II: antibody-mediated or cytotoxic • Antigens are bounded to human basement membranes in tissues • Or to blood cell membranes • Antibodies, COMPLEMENT react to the antigens, • NK cells may add on to the injury

13. Type II hypersensitivity • Hemolytic disease of the newborn • Blood transfusion reactions • Goodpastures syndrome: kidney and lung abnormalities

14. Type III: immune complex mediated • Antigen is NOT part of the cell, or basement membrane • Immune complex: antigen+ antibody • Very insoluble, not removed by macrophages • Deposited on vessel walls, extravascular sites

15. Type III • Systemic lupus erythematosus (SLE) • Serum sickness • Arthus reaction • Poststreptococcal glomerulonephritis

16. Type IV: delayed hypersensitivity, cell-mediated • CD4 cells react to MHC Class II • Memory cells • 2nd exposure to antigen: stronger reaction • CD cells may also be involved

17. Type IV • Tuberculin test • Contact dermatitis

18. Transplant reactions • Matching ABO blood group • Matching HLA antigens • Organs that can be transplanted: liver kidney lungs bone marrow skin

19. Histocompatibility antigen test • histocompatibility antigen blood test looks at proteins called human leukocyte antigens (HLAs), which are found on the surface of nearly every cell in the human body. HLAs are found in large amounts on the surface of white blood cells. They help the immune system tell the difference between body tissue and foreign substances.

20. Types of transplant rejection • Hyperacute: OCCURS IN MINUTES -due to preexisting antibodies to donor antigens • Acute: OCCURS DAYS TO WEEKS -due to T cells • Chronic: OCCURS MONTHS TO YEARS - antibodies will form to the antigens in the donor cells

21. Graft-versus-host disease (GVHD) is a complication that can occur after a bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body.

22. Graft-versus-host disease • Common in bone marrow transplant • Immunocompetent cells in the transplant (graft) • Host cells are damaged by: CD8+ cells cytokines macrophages • Organs damaged: liver, skin, GIT • Fever, rash, large liver, jaundice

23. Primary Immunodeficiency diseases • X-linked agammaglobulinemia • Or Bruton’s agammaglobulinemia • Male babies, more than 6 months old • Absent plasma cells absent germinal centers absent IG • Prone to bacterial infections

25. IgA deficiency • Most common B cell defect • 1 in 700 persons, Caucasians • May be with no symptoms (asymptomatic) • Recurrent Upper respiratory tract infection (URTI) and frequent diarrhea

26. Severe Combined Immunodeficiency Disease (SCID) • Low B cells and T cells • Absence of ADA (adenosine deaminase) or PNP ( purine nucleotide phosphorylase): enzymes which remove metabolites in lymphocytes • Severe infections • Treatment: gene therapy

27. Systemic Lupus Erythematosus (SLE) • Antibodies against nucleic acids in the connective tissues (antinuclear antibodies or ANA) • Women • Immune complex deposits: kidneys joints skin lungs serous membranes

28. SLE • Wire-loop lesions in the kidneys (subendothelial layer) • Eye lesions • Fever, body pains, joint pains • Pericarditis/pleuritis • Raynaud phenomenon • Endocarditis • Libman-Sacks vegetations on mitral valve