Chapter 3 Disorders of the Immune System The Nature of Disease: Pathophysiology for the Health Professions, 2nd ed. Thomas H. McConnell Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.1 Self and nonself Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins NONIMMUNE DEFENSE MECHANISMS • Physical and chemical barriers – Skin and sclerae – Respiratory, GI, and GU mucosae Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.2 Nonimmune defense mechanisms Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins LYMPHOID ORGANS AND THE LYMPHATIC SYSTEM • Lymphatic system: lymph vessels and nodes • Mucosa-associated lymphoid tissue (MALT) • Spleen Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.3 Lymphoid organs and the lymphatic system Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins INNATE AND ADAPTIVE IMMUNITY • Innate (native): present from birth, capable of attacking any nonself substance. Rapid and broad (shotgun) • Adaptive (acquired, specific): intercepts nonself, learns, programs, produces specific response (rifle) • “Immune response” always refers to adaptive Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.4 The types and sequences of immune reactions Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins CELLS OF THE IMMUNE SYSTEM • Macrophages, dendritic cells (antigen-presenters) • Lymphocytes: – natural killer (NK) cells (innate system) – B and T lymphocytes (adaptive system) Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins B LYMPHOCYTE-MEDIATED (ANTIBODY) IMMUNITY • Plasma cell: AB-secreting B-cell • Antibodies (“gamma globulins,” immunoglobulins, Ig) – Ig G, A, M, D, E Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 7.19 Protein electrophoresis in plasma cell disease Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.5 Antibody response to antigen exposure Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 1. Fab region 2. Fc region 3.Heavy chain 4.Light chain 5. Antigen binding site 6. Hinge regions Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins T LYMPHOCYTE-MEDIATED (DELAYED) IMMUNITY • Cytotoxic cells: the effector T cell • Helper T cells help both B and T cell response • Supressor T cells • Memory T cells Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins HYPERSENSITIVITY REACTIONS • Type I immune reaction: immediate hypersensitivity • Type II immune reaction: cytotoxic hypersensitivity • Type III immune reaction: immune-complex hypersensitivity • Type IV immune reaction: cellular hypersensitivity Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.6 Type I immune reaction: immediate hypersensitivity Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.7 Type II immune reaction: cytotoxic hypersensitivity Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.8 Type III immune reaction: immune-complex hypersensitivity Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.9 Type IV immune reaction: cellular hypersensitivity Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins ALLERGIC DISORDERS AND ATOPY • Allergy is exaggerated immune sensitivity. • Allergen: the inciting nonself substance • Atopy is allergy due to type I hypersensitivity. • Anaphylaxis: Type I, acute, potentially fatal, IgEmediated; requires prior sensitization Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins AUTOIMMUNE DISORDERS • Self antigens become immune target. • Various mechanisms, e.g., molecular mimicry, hidden self antigen, inflammation, failure of tolerance Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.10 Molecular mimicry Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Table 3.1 Selected Autoimmune Diseases Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.11 Malar “butterfly” rash of systemic lupus erythematosus (SLE) Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Systemic lupus erythematosus (SLE) • Characterized malnor bufferfly rash • Presence antinuclear antibodies (ANA) – Ab’s dsDNA • Fairly common ds: 1/2500 people • 90% of patients are female (15-30 y) • Etiology – Genetic factor (one twin has SLE the other most likely) – Sex hormones influences since ds seen mostly in females – Medication: procainamide (a antirarhythmic drug) – Hydrazine (an antihypertensive drug). Removal of drug – remissionCopyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins SLE…..continue • Autoimmune – loss of self-tolerance. Considered as overactive help T cells that stimulate B cell production of antis self Ab’s. • Very sensitive test – Ab ds DNA in the blood. • Not highly specific test. – I.e every SLE would have ANA Ab’s. – But positive ANA Ab’s may be seen in other autoimmune ds • Note: Ab’s against not only DNA and RNA but also, RBC’s, platelets, lymphocytes and other cells. • RISK: Ab-Ag complexes – Vasculitis (inflammation and necrosis) – Hypercoagulatable -> venous and arterial thromboses, thrombocytopenia, and spontaneous abortion. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.12 Clinical findings in SLE Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Other Autoimmune Diseases Systemic Diseases Systemic lupus erythematosus Rheumatic fever Rheumatoid arthritis Systemic sclerosis (scleroderma) Polyarteritis nodosa Organ-Specific Diseases Multiple sclerosis (brain) Hashimoto thyroiditis (thyroid) Autoimmune hemolytic anemia Glomerulonephritis (kidney) Primary biliary cirrhosis (liver) Dermatomyositis (skin) Myasthenia gravis (skeletal muscle) Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.13 Systemic sclerosis (scleroderma) Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins AMYLOIDOSIS • Dysfunction associated with systemic deposition of amyloid protein; local amyloid deposits in some organs usually innocuous • Amyloid protein: misfolded mutant or normal proteins • Light chain amyloidosis • Chronic inflammatory amyloidosis • Hereditary amyloidosis Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.14 Amyloidosis Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins IMMUNITY IN TISSUE TRANSPLANTATION AND BLOOD TRANSFUSION • Transplant rejection is an immune phenomenon. • Blood transfusion is temporary liquid tissue transplantation. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.15 Common blood groups Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.16 The major crossmatch Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins IMMUNODEFICIENCY DISORDERS • Inherited immunodeficiency diseases • Acquired immunodeficiency syndrome (AIDS) Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Immunodeficiency Disorders • May be primary or acquired • Primary immunodeficiencies are usually genetic • Acquired immunodeficiencies are secondary to another ds (leukemia) and are more common • AIDS is the most common of all immunodeficiency ds • Immunodeficiencies: – Entire immune system – Only B cells – Only T cells – Characteristic: Pt with persistent infections and develop opportunistic infection eg Staphylococcus and streptococcus. T cell defect: virus and fugal infection. May develop neoplasm (failure of immune surveillance) Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Five types of inherited Immunodeficiency Disorders • X-linked agammaglobinemia (Bruton Disease) – Defect B cell development and inability to make normal Ab’s. First six month ok. Because ?. Very noticeable after this. – Pt with recurrent infections: bronchitis, pneumonia, sinusitis, pharygengitis, ear and GI infections. – Bacteria: staphylococcus, streptococcus, and haemophilus • Isolated immunoglobulin A (IgA) deficiency. – Second most common immunodefiency – Caused by autosomal recessive defect – Low IgA Ab’s: Pts have recurrent GI, sinus and pulmonary infections Five types of inherited Immunodeficiency Disorders • Common variable immunodeficiency (CVID) – A type characterized B cell malfunction associated with low plasma antibodies. (most Pt: 20-30 yo) – Very common: pneumonia but other as well. sinus and ear infection, inflammation of GI (diarrhea, weight loss) – Most common immune disorders associated with this is thrombocytopenia purpura and autoimmune hemolytic anemia • Thymic hypoplasia (DiGeorge syndrome) – Failure to partially develop thymus – Different from Athymic – T cell function is deficient but B cell function is normal – Associated with hypoparathyroidism – Suffer from viral, fugal and protozoan infections Five types of inherited Immunodeficiency Disorders – Severe combined immunodeficiency (SCID) – Inherited ds • Affecting both B and T cell function • Many different genetic defects • some are X linked and affect males only • Lymphoid tissues and thymus are underdeveloped • NOTE: infections usually appear before 6 months of age • Pts: suffer wide range of infection. • Pneumocystis, Candida, and other opportunistic infections. Acquired Immunodeficiency Syndrome (AIDS) Risk groups • Men who have sex with men • Intravenous drug abusers • Males with hemophilia • Recipients of transfusions of human blood or blood components • Heterosexual contacts of the above Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.17 HIV infection of a T lymphocyte Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.18 Phases of HIV infection and AIDS Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.19 Clinical and pathologic features of AIDS Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Figure 3.20 Pneumocystis jirovecii pneumonia Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
