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Alterations in Immunity and Inflammation Chapter 8 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

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Presentation on theme: "Alterations in Immunity and Inflammation Chapter 8 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc."— Presentation transcript:

1 Alterations in Immunity and Inflammation Chapter 8 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

2 2 Hypersensitivity Altered immunologic response to an antigen; results in disease/damage to host Altered immunologic response to an antigen; results in disease/damage to host Allergy Allergy Deleterious effects of hypersensitivity to environmental (exogenous) antigens Deleterious effects of hypersensitivity to environmental (exogenous) antigens Autoimmunity Autoimmunity Disturbance in immunologic tolerance of self-antigens Disturbance in immunologic tolerance of self-antigens Alloimmunity Alloimmunity Immune reaction to tissues of another individual Immune reaction to tissues of another individual

3 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 3 Hypersensitivity Characterized by the immune mechanism Characterized by the immune mechanism Type I Type I IgE mediated IgE mediated Type II Type II Tissue-specific reactions Tissue-specific reactions Type III Type III Immune complex mediated Immune complex mediated Type IV Type IV Cell mediated Cell mediated

4 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 4 Hypersensitivity Immediate hypersensitivity reactions Immediate hypersensitivity reactions Anaphylaxis Anaphylaxis Delayed hypersensitivity reactions Delayed hypersensitivity reactions

5 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 5 Type I Hypersensitivity IgE mediated IgE mediated Against environmental antigens (allergens) Against environmental antigens (allergens) IgE binds to Fc receptors on surface of mast cells (cytotropic antibody) IgE binds to Fc receptors on surface of mast cells (cytotropic antibody) Histamine release Histamine release H 1 and H 2 receptors H 1 and H 2 receptors Antihistamines Antihistamines

6 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 6 Mast Cell Type I

7 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 7 Type I Hypersensitivity Manifestations Manifestations Itching Itching Urticaria Urticaria Conjunctivitis Conjunctivitis Rhinitis Rhinitis Hypotension Hypotension Bronchospasm Bronchospasm Dysrhythmias Dysrhythmias GI cramps and malabsorption GI cramps and malabsorption

8 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 8 Clinical Symptoms of IgE Type I Reactions

9 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 9 Anaphylaxis Severity depends on level of sensitization Severity depends on level of sensitization Can be very small dose (ordinary skin testing) Can be very small dose (ordinary skin testing) Within minutes after exposure: Within minutes after exposure: Itching Itching Hives Hives Skin erythema Skin erythema Contraction of respiratory bronchioles Contraction of respiratory bronchioles Laryngeal edema results in hoarseness Laryngeal edema results in hoarseness Vomiting, abdominal cramps, diarrhea Vomiting, abdominal cramps, diarrhea Laryngeal obstruction Laryngeal obstruction

10 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 10 Type I Hypersensitivity Genetic predisposition Genetic predisposition Tests Tests Food challenges Food challenges Skin tests Skin tests Laboratory tests Laboratory tests Desensitization Desensitization IgG-blocking antibodies IgG-blocking antibodies

11 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 11 Type II Hypersensitivity Tissue specific Tissue specific Specific cell or tissue (tissue-specific antigens) is the target of an immune response Specific cell or tissue (tissue-specific antigens) is the target of an immune response Five mechanisms Five mechanisms Cell is destroyed by antibodies and complement Cell is destroyed by antibodies and complement Cell destruction through phagocytosis Cell destruction through phagocytosis Soluble antigen may enter the circulation and deposit on tissues Soluble antigen may enter the circulation and deposit on tissues Antibody-dependent cell-mediated cytotoxicity Antibody-dependent cell-mediated cytotoxicity Causes target cell malfunction Causes target cell malfunction

12 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 12 Phagocytosis

13 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 13 Neutrophil-Mediated Damage

14 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 14 Antibody-Dependent Cell-Mediated Cytotoxicity

15 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 15 Induced Cell Malfunction

16 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 16 Type III Hypersensitivity Immune complex mediated Immune complex mediated Antigen-antibody complexes formed in the circulation and later deposited in vessel walls or extravascular tissues Antigen-antibody complexes formed in the circulation and later deposited in vessel walls or extravascular tissues Not organ specific Not organ specific Immune complex clearance Immune complex clearance Largemacrophages Largemacrophages Smallrenal clearance Smallrenal clearance Intermediatedeposit in tissues Intermediatedeposit in tissues

17 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 17 Type III Hypersensitivity

18 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 18 Systemic lupus erythematosus Systemic lupus erythematosus Vasculitis Vasculitis Poststreptococcal glomerulonephritis Poststreptococcal glomerulonephritis Acute glomerulonephritis Acute glomerulonephritis Reactive arthritis Reactive arthritis Examples of Immune Complex– Mediated Diseases: Type III

19 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 19 Type IV Hypersensitivity Mediated by T lymphocytes Mediated by T lymphocytes Destruction of the tissue usually caused by direct killing by toxins from Tc cells Destruction of the tissue usually caused by direct killing by toxins from Tc cells Th1 cells produce cytokines that recruit phagocytes, especially macrophages Th1 cells produce cytokines that recruit phagocytes, especially macrophages Examples Examples Acute graft rejection, skin test for TB, contact allergic reactions, and some autoimmune diseases Acute graft rejection, skin test for TB, contact allergic reactions, and some autoimmune diseases

20 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 20 Type IV Hypersensitivity

21 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 21 Type IV Hypersensitivity

22 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 22 Antigenic Targets of Hypersensitivity Reactions Allergy Allergy Environmental Ags Environmental Ags Autoimmunity Autoimmunity Self Ags, with damage to host tissues Self Ags, with damage to host tissues Alloimmunity Alloimmunity Against foreign tissue Ags Against foreign tissue Ags

23 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 23 Allergy Environmental antigens that cause atypical immunologic responses in genetically predisposed individuals Environmental antigens that cause atypical immunologic responses in genetically predisposed individuals Pollens, molds, fungi, foods, animals, etc. Pollens, molds, fungi, foods, animals, etc. Allergen contained within a particle too large to be phagocytosed or is protected by a nonallergenic coat Allergen contained within a particle too large to be phagocytosed or is protected by a nonallergenic coat Original insult is apparent Original insult is apparent

24 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 24 Autoimmunity Breakdown of tolerance Breakdown of tolerance Body recognizes self-antigens as foreign Body recognizes self-antigens as foreign Sequestered antigen Sequestered antigen Self-antigens not normally seen by the immune system Self-antigens not normally seen by the immune system Infectious disease Infectious disease Molecular mimicry Molecular mimicry Neoantigen Neoantigen Haptens become immunogenic when they bind to host proteins Haptens become immunogenic when they bind to host proteins

25 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 25 Autoimmunity Forbidden clone Forbidden clone During differentiation, lymphocytes produce receptors that react with self-antigens During differentiation, lymphocytes produce receptors that react with self-antigens Ineffective peripheral tolerance Ineffective peripheral tolerance Defects in regulatory cells Defects in regulatory cells Original insult Original insult Genetic factors Genetic factors

26 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 26 Autoimmune Examples Systemic lupus erythematosus (SLE) Systemic lupus erythematosus (SLE) Chronic multisystem inflammatory disease Chronic multisystem inflammatory disease Autoantibodies against: Autoantibodies against: Nucleic acids, erythrocytes, coagulation proteins, phospholipids, lymphocytes, platelets, etc. Nucleic acids, erythrocytes, coagulation proteins, phospholipids, lymphocytes, platelets, etc. Deposition of circulating immune complexes containing antibody against host DNA Deposition of circulating immune complexes containing antibody against host DNA More common in females More common in females

27 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 27 Systemic Lupus Erythematosus Clinical manifestations Clinical manifestations Arthralgias or arthritis (90% of individuals) Arthralgias or arthritis (90% of individuals) Vasculitis and rash (70% – 80%) Vasculitis and rash (70% – 80%) Renal disease (40% – 50%) Renal disease (40% – 50%) Hematologic changes (50%) Hematologic changes (50%) Cardiovascular disease (30% – 50%) Cardiovascular disease (30% – 50%)

28 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 28 Systemic Lupus Erythematosus Eleven common findings Eleven common findings Serial or simultaneous presence of at least four indicates SLE Serial or simultaneous presence of at least four indicates SLE Facial (malar) rash, discoid rash, photosensitivity, oral or nasopharyngeal ulcers, nonerosive arthritis, serositis, renal disorders, neurologic disorders, hematologic disorders, immunologic disorders, and presence of antinuclear antibodies (ANAs) Facial (malar) rash, discoid rash, photosensitivity, oral or nasopharyngeal ulcers, nonerosive arthritis, serositis, renal disorders, neurologic disorders, hematologic disorders, immunologic disorders, and presence of antinuclear antibodies (ANAs)

29 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 29 Alloimmunity Immune system reacts with antigens on the tissue of other genetically dissimilar members of the same species Immune system reacts with antigens on the tissue of other genetically dissimilar members of the same species Transient neonatal alloimmunity Transient neonatal alloimmunity Fetus expresses parental antigens not found in the mother Fetus expresses parental antigens not found in the mother Transplant rejection and transfusion reactions Transplant rejection and transfusion reactions

30 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 30 Graft Rejection Transplant rejection classified according to time Transplant rejection classified according to time Hyperacute Hyperacute Immediate and rare Immediate and rare Preexisting antibody to the antigens of the graft Preexisting antibody to the antigens of the graft Acute Acute Cell-mediated response against unmatched HLA antigens Cell-mediated response against unmatched HLA antigens Chronic Chronic Months or years Months or years Inflammatory damage to endothelial cells of vessels due to a weak cell-mediated reaction against minor HLA antigens Inflammatory damage to endothelial cells of vessels due to a weak cell-mediated reaction against minor HLA antigens

31 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 31 Transfusion Reactions Antibodies against blood group antigens Antibodies against blood group antigens ABO system ABO system Two major carbohydrate antigens Two major carbohydrate antigens A and B (codominant) A and B (codominant) Individuals have naturally occurring antibodies to the A and B antigens they lack 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 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 Antibodies are usually of the IgM class O blood type (universal donor) O blood type (universal donor) AB blood type (universal recipient) AB blood type (universal recipient)

32 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 32 ABO Incompatibility: Alloimmune Reaction Blood type AgAb Incompatible with blood type AAAnti-B B, AB BBAnti-A A, AB AB Universal recipient A+BNoneNone O Universal donor None Anti-A and Anti-B A, B, AB

33 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 33Immunodeficiencies Result of impaired function of T cells, B cells, phagocytes and/or complement Result of impaired function of T cells, B cells, phagocytes and/or complement Primary (genetic) Primary (genetic) Secondary (acquired) Secondary (acquired) Hallmark is recurrent infections often with opportunistic organisms Hallmark is recurrent infections often with opportunistic organisms Type of infection can lead to diagnosis of type of deficiency Type of infection can lead to diagnosis of type of deficiency Gonorrhea suggests complement deficiency Gonorrhea suggests complement deficiency Viral infections suggest T cell deficiency Viral infections suggest T cell deficiency

34 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 34 Immunodeficiencies Clinical presentation Clinical presentation Development of unusual or recurrent, severe infections Development of unusual or recurrent, severe infections T cell deficiencies T cell deficiencies Viral, fungal, yeast, and atypical microorganisms Viral, fungal, yeast, and atypical microorganisms B cell and phagocyte deficiencies B cell and phagocyte deficiencies Microorganisms requiring opsonization Microorganisms requiring opsonization Complement deficiencies Complement deficiencies

35 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 35 Immunodeficiencies Primary (congenital) immunodeficiency Primary (congenital) immunodeficiency Genetic anomaly Genetic anomaly Secondary (acquired) immunodeficiency Secondary (acquired) immunodeficiency Caused by another illness Caused by another illness More common More common

36 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 36 Primary Immunodeficiencies Most are the result of a single gene defect Most are the result of a single gene defect Five groups Five groups B lymphocyte deficiencies B lymphocyte deficiencies T lymphocyte deficiencies T lymphocyte deficiencies Combined T and B cell deficiencies Combined T and B cell deficiencies Complement defects Complement defects Phagocyte defects Phagocyte defects

37 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 37 B Lymphocyte Deficiencies Hypogammaglobulinemia or agammaglobulinemia Hypogammaglobulinemia or agammaglobulinemia Bruton agammaglobulinemia Bruton agammaglobulinemia Autosomal agammaglobulinemia Autosomal agammaglobulinemia X-linked hyper-IgM syndrome X-linked hyper-IgM syndrome IgG subclass deficiency IgG subclass deficiency Selective IgA deficiency Selective IgA deficiency Common variable immunodeficiency Common variable immunodeficiency

38 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 38 T Lymphocyte Deficiencies DiGeorge syndrome DiGeorge syndrome Partial or complete absence of T cell immunity Partial or complete absence of T cell immunity Chronic mucocutaneous candidiasis Chronic mucocutaneous candidiasis

39 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 39 Combined T- and B-Cell Deficiencies Severe combined immunodeficiency (SCID) Severe combined immunodeficiency (SCID) Reticular dysgenesis Reticular dysgenesis Most severe form Most severe form Adenosine deaminase (ADA) deficiency Adenosine deaminase (ADA) deficiency X-linked SCID X-linked SCID JAK3 deficiency JAK3 deficiency IL-7 receptor deficiency IL-7 receptor deficiency Purine nucleoside phosphorylase deficiency Purine nucleoside phosphorylase deficiency

40 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 40 Combined T and B Cell Deficiencies RAG-1 or RAG-2 deficiency RAG-1 or RAG-2 deficiency Bare lymphocyte deficiency Bare lymphocyte deficiency MHC class I and II deficiency MHC class I and II deficiency Wiskott-Aldrich syndrome Wiskott-Aldrich syndrome Ataxia-telangiectasia (AT) Ataxia-telangiectasia (AT)

41 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 41 Complement Deficiencies C3 deficiency C3 deficiency Mannose-binding lectin (MBL) deficiency Mannose-binding lectin (MBL) deficiency Properdin deficiency Properdin deficiency Factor I and factor H deficiency Factor I and factor H deficiency C9 deficiency C9 deficiency

42 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 42 Complement Deficiencies

43 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 43 Phagocytic Deficiencies Severe congenital neutropenia Severe congenital neutropenia Cyclic neutropenia Cyclic neutropenia Leukocyte adhesion deficiency (LAD) Leukocyte adhesion deficiency (LAD) C3 receptor deficiency C3 receptor deficiency Chédiak-Higashi syndrome Chédiak-Higashi syndrome Myeloperoxidase deficiency Myeloperoxidase deficiency Chronic granulomatous disease Chronic granulomatous disease

44 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 44 Secondary Deficiencies Also referred to as acquired deficiencies Also referred to as acquired deficiencies Far more common than primary deficiencies Far more common than primary deficiencies

45 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 45 Secondary Deficiencies Causes Causes Normal physiology conditions Normal physiology conditions Psychologic stress Psychologic stress Dietary insufficiencies Dietary insufficiencies Malignancies Malignancies Physical trauma Physical trauma Medical treatments Medical treatments Infections Infections AIDS AIDS

46 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 46 Graft-Versus-Host (GVH) Disease Graft-Versus-Host (GVH) Disease Immunocompromised individuals are at risk for GVH disease Immunocompromised individuals are at risk for GVH disease T cells in the graft are mature and capable of cell- mediated destruction tissues within the recipient T cells in the graft are mature and capable of cell- mediated destruction tissues within the recipient Not a problem if patient is immunocompetent Not a problem if patient is immunocompetent

47 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 47 Evaluation of Immunity Complete blood count (CBC) with a differential Complete blood count (CBC) with a differential Subpopulations of lymphocytes Subpopulations of lymphocytes Quantitative determination of immunoglobulins Quantitative determination of immunoglobulins Subpopulations of immunoglobulins Subpopulations of immunoglobulins Assay for total complement Assay for total complement Skin tests Skin tests

48 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 48 Treatment for Immunodeficiencies Gamma-globulin therapy Gamma-globulin therapy Transplantation or transfusion Transplantation or transfusion Treatment with soluble immune mediators Treatment with soluble immune mediators Gene therapy Gene therapy


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