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1 Alterations in Immunity and Inflammation (Including Hypersensitivities) Chapter 8.

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Presentation on theme: "1 Alterations in Immunity and Inflammation (Including Hypersensitivities) Chapter 8."— Presentation transcript:

1 1 Alterations in Immunity and Inflammation (Including Hypersensitivities) Chapter 8

2 Mosby items and derived items © 2006 by Mosby, Inc. 2 Hypersensitivity Altered immunologic response to an antigen that results in disease or damage to the host Allergy Deleterious effects of hypersensitivity to environmental (exogenous) antigens Autoimmunity Disturbance in the immunologic tolerance of self- antigens Alloimmunity Immune reaction to tissues of another individual

3 Mosby items and derived items © 2006 by Mosby, Inc. 3 Hypersensitivity Characterized by the immune mechanism Type I IgE mediated Type II Tissue-specific reactions Type III Immune complex mediated Type IV Cell mediated

4 Mosby items and derived items © 2006 by Mosby, Inc. 4 Hypersensitivity Immediate hypersensitivity reactions Anaphylaxis Delayed hypersensitivity reactions

5 Mosby items and derived items © 2006 by Mosby, Inc. 5 Type I Hypersensitivity IgE mediated Against environmental antigens (allergens) IgE binds to Fc receptors on surface of mast cells (cytotropic antibody) Histamine release H 1 and H 2 receptors Antihistamines

6 Mosby items and derived items © 2006 by Mosby, Inc. 6 Type I Hypersensitivity Manifestations Itching Urticaria Conjunctivitis Rhinitis Hypotension Bronchospasm Dysrhythmias GI cramps and malabsorption

7 Mosby items and derived items © 2006 by Mosby, Inc. 7 Type I Hypersensitivity Genetic predisposition Tests Food challenges Skin tests Laboratory tests Desensitization IgG-blocking antibodies

8 Mosby items and derived items © 2006 by Mosby, Inc. 8 Type I Hypersensitivity

9 Mosby items and derived items © 2006 by Mosby, Inc. 9 Type II Hypersensitivity Tissue specific Specific cell or tissue (tissue-specific antigens) is the target of an immune response Five mechanisms Cell is destroyed by antibodies and complement Cell destruction through phagocytosis Soluble antigen may enter the circulation and deposit on tissues Antibody-dependent cell-mediated cytotoxicity Causes target cell malfunction

10 Mosby items and derived items © 2006 by Mosby, Inc. 10 Type II Hypersensitivity

11 Mosby items and derived items © 2006 by Mosby, Inc. 11 Type III Hypersensitivity Immune complex mediated Antigen-antibody complexes are formed in the circulation and are later deposited in vessel walls or extravascular tissues Not organ specific Immune complex clearance Largemacrophages Smallrenal clearance Intermediatedeposit in tissues

12 Mosby items and derived items © 2006 by Mosby, Inc. 12 Type III Hypersensitivity Immune complex disease Serum sickness Arthus reaction

13 Mosby items and derived items © 2006 by Mosby, Inc. 13 Type III Hypersensitivity

14 Mosby items and derived items © 2006 by Mosby, Inc. 14 Type IV Hypersensitivity Does not involve antibody Cytotoxic T lymphocytes or lymphokine producing Th1 cells Direct killing by Tc or recruitment of phagocytic cells by Th1 cells Examples Acute graft rejection, skin test for TB, contact allergic reactions, and some autoimmune diseases

15 Mosby items and derived items © 2006 by Mosby, Inc. 15 Type IV Hypersensitivity

16 Mosby items and derived items © 2006 by Mosby, Inc. 16 Type IV Hypersensitivity

17 Mosby items and derived items © 2006 by Mosby, Inc. 17 Allergy Environmental antigens that cause atypical immunologic responses in genetically predisposed individuals Pollens, molds and fungi, foods, animals, etc. Allergen is contained within a particle too large to be phagocytosed or is protected by a nonallergenic coat Original insult is apparent

18 Mosby items and derived items © 2006 by Mosby, Inc. 18 Autoimmunity Breakdown of tolerance Body recognizes self-antigens as foreign Sequestered antigen Self-antigens not normally seen by the immune system Infectious disease Molecular mimicry Neoantigen Haptens become immunogenic when they bind to host proteins

19 Mosby items and derived items © 2006 by Mosby, Inc. 19 Autoimmunity Forbidden clone During differentiation, lymphocytes produce receptor that react with self-antigens Ineffective peripheral tolerance Defects in regulatory cells Original insult Genetic factors

20 Mosby items and derived items © 2006 by Mosby, Inc. 20 Alloimmunity Immune system reacts with antigens on the tissue of other genetically dissimilar members of the same species Transient neonatal alloimmunity Fetus expresses parental antigens not found in the mother Transplant rejection and transfusion reactions

21 Mosby items and derived items © 2006 by Mosby, Inc. 21 Autoimmune Examples Systemic lupus erythematosus (SLE) Chronic multisystem inflammatory disease Autoantibodies against: Nucleic acids, erythrocytes, coagulation proteins, phospholipids, lymphocytes, platelets, etc. Deposition of circulating immune complexes containing antibody against host DNA More common in females

22 Mosby items and derived items © 2006 by Mosby, Inc. 22 Systemic Lupus Erythematosus Clinical manifestations Arthralgias or arthritis (90% of individuals) Vasculitis and rash (70%-80%) Renal disease (40%-50%) Hematologic changes (50%) Cardiovascular disease (30%-50%)

23 Mosby items and derived items © 2006 by Mosby, Inc. 23 Systemic Lupus Erythematosus Eleven common findings Serial or simultaneous presence of at least four indicates SLE Facial rash (malar rash), discoid rash, photosensitivity, oral or nasopharyngeal ulcers, nonerosive arthritis, serositis, renal disorder, neurologic disorder, hematologic disorders, immunologic disorders, and presence of antinuclear antibodies (ANA)

24 Mosby items and derived items © 2006 by Mosby, Inc. 24 Graft Rejection Transplant rejection is classified according to time Hyperacute Immediate and rare Preexisting antibody to the antigens of the graft Acute Cell-mediated immune response against unmatched HLA antigens Chronic Months or years Inflammatory damage to endothelial cells of vessels due to a weak cell-mediated reaction against minor HLA antigens

25 Mosby items and derived items © 2006 by Mosby, Inc. 25 Graft Rejection

26 Mosby items and derived items © 2006 by Mosby, Inc. 26 Transfusion Reactions Antibodies against blood group antigens ABO system Two major carbohydrate antigens A and B (co-dominant) Individuals have naturally occurring antibodies to the A and B antigens they lack Anti-A and anti-B antibody production is induced by similar antigens on naturally occurring bacteria in the intestinal tract Antibodies are usually of the IgM class O blood type (universal donor) AB blood type (universal recipient)

27 Mosby items and derived items © 2006 by Mosby, Inc. 27 ABO System

28 Mosby items and derived items © 2006 by Mosby, Inc. 28 Immune Deficiencies Failure of immune mechanisms of self- defense Primary (congenital) immunodeficiency Genetic anomaly Secondary (acquired) immunodeficiency Caused by another illness More common

29 Mosby items and derived items © 2006 by Mosby, Inc. 29 Immune Deficiencies Clinical presentation Development of unusual or recurrent, severe infections T cell deficiencies Viral, fungal, yeast, and atypical microorganisms B cell and phagocyte deficiencies Microorganisms requiring opsonization Complement deficiencies

30 Mosby items and derived items © 2006 by Mosby, Inc. 30 Primary Immune Deficiencies Most are the result of a single gene defect Five groups B lymphocyte deficiencies T lymphocyte deficiencies Combined T and B cell deficiencies Complement defects Phagocyte defects

31 Mosby items and derived items © 2006 by Mosby, Inc. 31 B Lymphocyte Deficiencies Hypogammaglobulinemia or agammaglobulinemia Bruton agammaglobulinemia Autosomal agammaglobulinemia X-linked hyper-IgM syndrome IgG subclass deficiency Selective IgA deficiency Common variable immune deficiency

32 Mosby items and derived items © 2006 by Mosby, Inc. 32 T Lymphocyte Deficiencies DiGeorge syndrome Partial or complete absence of T cell immunity Chronic mucocutaneous candidiasis

33 Mosby items and derived items © 2006 by Mosby, Inc. 33 Combined T and B Cell Deficiencies Severe combined immunodeficiency (SCID) Reticular dysgenesis Most severe form Adenosine deaminase (ADA) deficiency X-linked SCID JAK3 deficiency IL-7 receptor deficiency Purine nucleoside phosphorylase deficiency

34 Mosby items and derived items © 2006 by Mosby, Inc. 34 Combined T and B Cell Deficiencies RAG-1 or RAG-2 deficiency Bare lymphocyte deficiency MHC class I and II deficiency Wiskott-Aldrich syndrome Ataxia-telangiectasia (AT)

35 Mosby items and derived items © 2006 by Mosby, Inc. 35 Complement Deficiencies C3 deficiency Mannose-binding lectin (MBL) deficiency Properdin deficiency Factor I and factor H deficiency C9 deficiency

36 Mosby items and derived items © 2006 by Mosby, Inc. 36 Complement Deficiencies

37 Mosby items and derived items © 2006 by Mosby, Inc. 37 Phagocytic Deficiencies Severe congenital neutropenia Cyclic neutropenia Leukocyte adhesion deficiencies (LAD) C3 receptor deficiency Chédiak-Higashi syndrome Myeloperoxidase deficiency Chronic granulomatous disease

38 Mosby items and derived items © 2006 by Mosby, Inc. 38 Secondary Deficiencies Also referred to as acquired deficiencies Far more common than primary deficiencies

39 Mosby items and derived items © 2006 by Mosby, Inc. 39 Secondary Deficiencies Causes Normal physiology conditions Psychological stress Dietary insufficiencies Malignancies Physical trauma Medical treatments Infections Acquired immunodeficiency syndrome (AIDS)

40 Mosby items and derived items © 2006 by Mosby, Inc. 40 Acquired Immunodeficiency Syndrome (AIDS) Syndrome caused by a viral disease Human immunodeficiency virus (HIV) Depletes the bodys Th cells Incidence Worldwide 5 million per year United States About 31,000 cases per year 400,000 currently living with AIDS

41 Mosby items and derived items © 2006 by Mosby, Inc. 41 Acquired Immunodeficiency Syndrome (AIDS) Effective antiviral therapies have made AIDS a chronic disease Epidemiology Blood-borne pathogen Increasing faster in women than men

42 Mosby items and derived items © 2006 by Mosby, Inc. 42 Acquired Immunodeficiency Syndrome (AIDS) Pathogenesis Retrovirus Genetic information is in the form of RNA Contains reverse transcriptase to convert RNA into double-stranded DNA Integrase

43 Mosby items and derived items © 2006 by Mosby, Inc. 43 Human Immunodeficiency Virus (HIV)

44 Mosby items and derived items © 2006 by Mosby, Inc. 44 Human Immunodeficiency Virus (HIV) Structure gp120 protein binds to the CD4 molecule found primarily on the surface of helper T cells CD4 + Th cells Typically 800 to 1000 cells/mm 3 Reverses CD4/CD8 ratio Co-receptors CXCR4 and CCR5 Strains can be selective for these receptors; influences the tropism of the target cells

45 Mosby items and derived items © 2006 by Mosby, Inc. 45 Human Immunodeficiency Virus (HIV)

46 Mosby items and derived items © 2006 by Mosby, Inc. 46 Human Immunodeficiency Virus (HIV)

47 Mosby items and derived items © 2006 by Mosby, Inc. 47 Human Immunodeficiency Virus (HIV) Clinical manifestations Serologically negative, serologically positive but asymptomatic, early stages of HIV, or AIDS Window period Th cells <200 cells/mm 3 Diagnosis of AIDS is made in association with various clinical conditions Atypical or opportunistic infections, and cancer

48 Mosby items and derived items © 2006 by Mosby, Inc. 48 Human Immunodeficiency Virus (HIV)

49 Mosby items and derived items © 2006 by Mosby, Inc. 49 Human Immunodeficiency Virus (HIV) Treatment and prevention Highly active antiretroviral therapy (HAART) Reverse transcriptase inhibitors Protease inhibitors New drugs Entrance inhibitors Integrase inhibitors Vaccine development

50 Mosby items and derived items © 2006 by Mosby, Inc. 50 Graft-vs.-Host Disease (GVHD) Immunocompromised individuals are at risk for graft-vs.-host disease T cells in the graft are mature and capable of cell- mediated destruction tissues within the recipient Not a problem if patient is immunocompetent

51 Mosby items and derived items © 2006 by Mosby, Inc. 51 Evaluation of Immunity Complete blood count (CBC) with a differential Subpopulations of lymphocytes Quantitative determination of immunoglobulins Subpopulations of immunoglobulins Assay for total complement Skin tests

52 Mosby items and derived items © 2006 by Mosby, Inc. 52 Treatment for Immunodeficiencies Gamma-globulin therapy Transplantation or transfusion Treatment with soluble immune mediators Gene therapy


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