Immunopathology Flashcards
Seasonal conjunctivitis is typically caused by allergies to pollens; Allergic rhinitis (hay fever) is the most common type I hypersensitivity disease in adult caused by pollen, house dust, animal dandruff and many other allergens. Antigens inhaled react with IgE attached to basophils in the nasal mucosa, triggering release of vasoactive substances stored in cytoplasmic granules, Histamine, the main mediator released from mast cells, increases the permeability of mucosal vessels, causing edema and sneezing. Type I or immediate type hypersensitivity is manifested by a localized or generalized reaction that occurs within minutes of exposure to an antigen or “allergen” to which the person has previously been sensitized.
Conjunctivitis, hypersensitivity reaction, type I hypersensitivity
Characterized by immune complex deposition, complement fixation, and localized inflammation. Antibody directed against either a circulating antigen or an antigen in a tissue can give rise to a type III response. Diseases that seem to be most clearly attributable to the deposition of immune complexes are systemic lupus erythematosus, rheumatoid arthritis, and varieties of glomerulonephritis.
Type III hypersensitivity reactions
An autoimmune, inflammatory disease that may involve almost any organ, but characteristically affects the kidneys, joints, serous membranes and skin. Autoantibodies are formed against a variety of self-antigens. The most important diagnostic autoantibodies are those against nuclear antigens- in particular antibody to double stranded DNA and to a soluble nuclear antigen complex that is part of the spliceosome and is termed Sm (smith) antigen. High titers for these two autoantibodies (termed antinuclear antibodies) are nearly pathognomic for SLE. Antibodies to rheumatoid factor are seen in patients with rheumatoid arthritis. Antineutrophil cytoplasmic antibodies are seen in patients with small vessel vasculitis. Antigen-antibody complexes deposit in tissues, leading to the characteristic vasculitis, synovitis, and glomerulonephritis. SLE is a prototype of type III hypersensitivity reactions.
Systemic lupus erythematosus
Acquired deficiencies of early complement components occur in patients with autoimmune diseases, especially those associated with circulating immune complexes (e.g., systemic lupus erythematosus (SLE). Antigen-antibody complexes formed in the circulation during the active stage of these diseases lead to a marked reduction in circulating levels of complement proteins (hypocomplementemia)
Binding of complement to immune complexes
An autoimmune disease of connective tissue. Characterized by vasculopathy and excessive collagen deposition in the skin and internal organs, such as the lungs, GI tract, heart and kidneys. Circulating male fetal cells have been demonstrated in blood and blood vessel walls of many women with scleroderma who bore male children many years before the disease began. This disease is similar to graft-verse-host disease. Antinuclear antibodies are common but are usually present in a lower titer than in patients with SLE. Antibodies virtually specific for this disease include (1) nucleolar autoantibodies (primarily against RNA polymerase); (2) antibodies to Scl - 70, a nonhistone nuclear protein topoisomerase; and (3) anticentromere antibodies, which are associated with the “CREST” variant of the disease. Autoantibodies to dsDNA are seen in patients with SLE. Autoantibodies to SS-A/SS-B are seen in patients with Sjogren syndrome.
Scleroderma
Defined as a tissue reaction involving lymphocytes and mononuclear phagocytes, which occurs in response to a soluble protein antigen and reaches greatest intensity 24-48 hours after initiation. In the initial phase, foreign protein antigens or chemical ligands interact with accessory cells bearing class II HLA molecules. Protein antigens are actively processed into short peptides within phagolysosomes and are presented on the cell surface in conjunction with class II HLA molecules. The latter are recognized by CD4 T cells which become activated to synthesize an array of cytokines. The cytokines recruit and activate lymphocytes, monocytes, fibroblasts, and other inflammatory cells.
Delayed type hypersensitivity
These reactions are mediated by antibodies directed against fixed antigens. In this case, preformed antibodies in the patient’s blood attached to foreign antigens (oligosaccharides) on the membranes of the transfused erythrocytes. At sufficient density, bound immunoglobulins fix complement. Once activated, the complement cascade leads to the destruction of the target cell through formation of the membrane attack complex. This type of complement-mediated cell lysis occurs in autoimmune hemolytic anemia. OTHER ANSWERS Antibody-dependent cell mediated cytotoxicity involves cytolytic leukocytes that attack antibody-coated target cells. ADCC may be involved in the pathogenesis of some autoimmune diseases (autoimmune thyroiditis). Delayed-type hypersensitivity occurs over a per. of days and does not involve preformed antibodies.
Type II hypersensitivity reactions
An autoimmune disorder characterized by keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth) in the absence of other connective tissue disease. Targets salivary and lacrimal glands. The production of autoantibodies, particularly antinuclear antibodies directed against DNA or nonhistone proteins, typically occurs in patients with SS. Autoantibodies to soluble nuclear nonhistone proteins, especially the antigens SS-A and SS-B are found in half of patients with primary SS and are associated with more severe glandular and extraglandular manifestations. Autoantibodies to DNA or histones are rare. Organ-specific autoantibodies, such as those directed against salivary gland antigens, are distinctively uncommon. OTHER ANSWERS antibodies to centromere proteins are seen in the CREST variant of progressive systemic sclerosis
Sjogren Syndrome
Appears in male infants at 5-8 months of age, the period during with maternal antibody levels begin to decline. The infant suffers from recurrent pyogenic infections and severe hypogammaglobulinemia. There is an absence of both mature B cells in peripheral blood and plasma cells in lymphoid tissues. The genetic defect, located on the long arm of the X chromosome, is an inactivating mutation of the gene for B-cell tyrosine kinase, an enzyme critical to B-lymphocyte maturation OTHER ANSWERS Wiskott-Aldrich syndrome is also an X-linked genetic disease, but is characterized by defects in both B-cell and T-cell functions (i.e. humeral and cellular immunity). DiGeorge syndrome is a developmental disorder characterized by thymic and parathyroid aplasia.
X-linked agammaglobulinemia of Bruton
Occurs within minutes to hours after transplantation. Manifested clinically as a sudden cessation of urine output, along with fever and pain in the area of the graft site. This immediate rejection is mediated by preformed antibodies and complement activation products. OTHER ANSWERS Lymphocyes and macrophages are associated with acute and chronic graft rejection
Hyperacute graft rejection
A type II hypersensitivity disorder caused by antibodies that bind to the acetylcholine receptor. These antibodies interfere with the transmission of neural impulses at the neuromuscular junction, causing muscle weakness and easy fatigability. External ocular and eyelid muscles are most often affected, but the disease is often progressive and may cause death by respiratory muscle paralysis. OTHER ANSWERS Autoantibodies to desmoglein-3 are found in patients with pemphigus vulgaris, an autoimmune blistering skin disorder. Antibodies to the TSH receptor are seen in patients wtih Graves hyperthyroidism. Antibodies to calcium channels are found in patients with Eaton-Lambert syndrome. This paraneoplastic syndrome also manifests as muscle weakness, but is usually associated with small cell carcinoma of the lung. Rheumatoid factor represents multiple antibodies directed against the Fc portion of IgG and is seen in patients with rheumatoid arthritis and many other collagen vascular diseases.
Myasthenia gravis
The progression of this disease is recognized as a continuum that extends from the initial asymptomatic state to the immune depletion that characterizes patients with this overt disease. The fundamental lesion is infection of CD4+ helper (helper) T lymphocytes. Patients with this disease usually die of opportunistic infections.
AIDS
This disease is a type II hypersensitivity disorder caused by antibodies to the TSH receptor on follicular cells of the thyroid. Antibody binding to the TSH receptor stimulates release of tetraiodothrynine (T4) and triiodothyronine (T3) from the thyroid into the circulation. Circulating T4 and T3 suppress TSH production in the pituitary, Sweating weight loss and tachycardia are evidence of the hypermetabolism typical of hyperthyroidism. This disease also causes exophthalmos. OTHER ANSWERS Delayed type hypersensitivity is seen in patients with poison ivy and graft rejection. Immune complex disease is caused by deposition of immune complexes and complement activation.
Graves disease
A rare syndrome characterized by (1) recurrent infections, (2) hemorrhages secondary to thrombocytopenia, and (3) eczemia. It typically manifests in boys within the first few months of life as petechiae and recurrent infections (e.g. diarrhea), It is caused by numerous distinct mutations in a gene on the X chromosome that encodes a protein called WASP (Wiskott-Aldrich syndrome protein) which is expressed at high levels in lymphocytes and megakaryocytes. WASP binds members of the Rho family of GTPases. WASP itself controls the assembly of actin filaments that are required to form microvesicles. OTHER ANSWERS X-linked agammaglobulinemia of Bruton is not associated with thrombocytopenia and eczemia. DiGeorge syndrome, Isolated IgA deficiency and severe combined immunodeficiency are not X-linked diseases.
Wiskott-Aldrich syndrome
Occurs when lymphocytes in the grafted tissue recognize the recipient . This disease can also occur when an immunodeficient patient is transfused with blood containing HLA-incompatible lymphocytes. The major organs affected in this disease include skin, GI tract and liver. Clinically, this disease manifests as rash, diarrhea, abdominal gramps, anemia, and liver dysfunction.
Graft Versus Host Disease
