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

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

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

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 Hypersensitivity Characterized by the immune mechanism Type I Type II
IgE mediated Type II Tissue-specific reactions Type III Immune complex mediated Type IV Cell mediated

4 Hypersensitivity Immediate hypersensitivity reactions Anaphylaxis
Delayed hypersensitivity reactions

5 Type I Hypersensitivity
IgE mediated Against environmental antigens (allergens) IgE binds to Fc receptors on surface of mast cells (cytotropic antibody) Histamine release H1 and H2 receptors Antihistamines

6 Type I Hypersensitivity
Manifestations Itching Urticaria Conjunctivitis Rhinitis Hypotension Bronchospasm Dysrhythmias GI cramps and malabsorption

7 Type I Hypersensitivity
Genetic predisposition Tests Food challenges Skin tests Laboratory tests Desensitization IgG-blocking antibodies

8 Type I Hypersensitivity

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 Type II Hypersensitivity

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 Large—macrophages Small—renal clearance Intermediate—deposit in tissues

12 Type III Hypersensitivity
Immune complex disease Serum sickness Arthus reaction

13 Type III Hypersensitivity

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 Type IV Hypersensitivity

16 Type IV Hypersensitivity

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 Autoimmunity Breakdown of tolerance Sequestered antigen
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 Autoimmunity Forbidden clone Ineffective peripheral tolerance
During differentiation, lymphocytes produce receptor that react with self-antigens Ineffective peripheral tolerance Defects in regulatory cells Original insult Genetic factors

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 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 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 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 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 Graft Rejection

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 ABO System

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 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 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 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 T Lymphocyte Deficiencies
DiGeorge syndrome Partial or complete absence of T cell immunity Chronic mucocutaneous candidiasis

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 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 Complement Deficiencies
C3 deficiency Mannose-binding lectin (MBL) deficiency Properdin deficiency Factor I and factor H deficiency C9 deficiency

36 Complement Deficiencies

37 Phagocytic Deficiencies
Severe congenital neutropenia Cyclic neutropenia Leukocyte adhesion deficiencies (LAD) C3 receptor deficiency Chédiak-Higashi syndrome Myeloperoxidase deficiency Chronic granulomatous disease

38 Secondary Deficiencies
Also referred to as acquired deficiencies Far more common than primary deficiencies

39 Secondary Deficiencies
Causes Normal physiology conditions Psychological stress Dietary insufficiencies Malignancies Physical trauma Medical treatments Infections Acquired immunodeficiency syndrome (AIDS)

40 Acquired Immunodeficiency Syndrome (AIDS)
Syndrome caused by a viral disease Human immunodeficiency virus (HIV) Depletes the body’s Th cells Incidence Worldwide 5 million per year United States About 31,000 cases per year 400,000 currently living with AIDS

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 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 Human Immunodeficiency Virus (HIV)

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/mm3 Reverses CD4/CD8 ratio Co-receptors CXCR4 and CCR5 Strains can be selective for these receptors; influences the tropism of the target cells

45 Human Immunodeficiency Virus (HIV)

46 Human Immunodeficiency Virus (HIV)

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/mm3 Diagnosis of AIDS is made in association with various clinical conditions Atypical or opportunistic infections, and cancer

48 Human Immunodeficiency Virus (HIV)

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 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 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 Treatment for Immunodeficiencies
Gamma-globulin therapy Transplantation or transfusion Treatment with soluble immune mediators Gene therapy

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