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What is the primary purpose of immunologic tolerance?
Which type of T cells is responsible for the education to distinguish self from non-self antigens?
What is anergy in the context of self-tolerance?
Which process involves the deletion of self-reactive lymphocytes in the central lymphoid organs?
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What role do regulatory T cells play in the immune system?
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What condition arises when the maintenance of immune tolerance fails?
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What is the primary mechanism by which self-reactive lymphocytes are deleted in peripheral tissues?
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Which cells are the primary effector cells in autoimmune diseases?
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What is one of the common symptoms associated with xerostomia?
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What manifestation is observed in one-third of patients with Sjogren syndrome?
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What is Mikulicz syndrome characterized by?
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Which condition is associated with Sjogren syndrome?
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What factor is most clearly associated with the development of ankylosing spondylitis?
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What characterizes diffuse systemic sclerosis?
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Which mechanism can lead to autoimmune reactions through molecular mimicry?
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Which of the following is a feature of CREST syndrome?
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What is a proposed cause of tissue damage in systemic sclerosis?
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What is one way infections can trigger autoimmune disorders?
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Which statement best describes the role of environmental factors in autoimmune disease development?
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What represents a common pathological process in systemic sclerosis?
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What is a potential consequence of chemical modifications of self antigens?
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Which statement about gender bias in autoimmune diseases is true?
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Release of sequestered antigens can occur when:
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What is a common feature of most autoimmune diseases?
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What is a common systemic complication associated with pulmonary vasculature involvement in systemic sclerosis?
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Which of the following cellular components is implicated in the pathogenesis of systemic sclerosis?
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In systemic sclerosis, where does the process of fibrosis typically begin?
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What is a typical morphological change seen in the fingers of systemic sclerosis patients in advanced stages?
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How does systemic sclerosis affect the alimentary tract?
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What renal abnormalities are most commonly associated with systemic sclerosis?
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Which of the following organs is least likely to be involved in systemic sclerosis?
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What type of changes occur in the musculoskeletal system during the early stages of systemic sclerosis?
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Which organ systems are primarily affected by Sjögren syndrome?
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What is the characteristic feature of symptoms in Sjögren syndrome?
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What type of immune cells are predominantly involved in the inflammation seen in Sjögren syndrome?
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What role do ribonucleoprotein antigens SS-A (Ro) and SS-B (La) play in Sjögren syndrome?
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What is the earliest histologic finding in the salivary glands affected by Sjögren syndrome?
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In which age group and gender is Sjögren syndrome most commonly diagnosed?
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What is the underlying cause of the tissue damage in Sjögren syndrome?
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Which autoimmune disorder falls under the category of multisystem autoimmune diseases?
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Study Notes
Immunologic Tolerance
- The immune system's ability to differentiate between self and non-self antigens is called immunological tolerance.
- Self-tolerance is crucial for preventing the immune system from attacking the body's own cells and tissues.
- T lymphocytes are capable of recognizing a vast number of antigens.
- T lymphocytes undergo maturation in the thymus, where they learn to distinguish between self and non-self antigens.
- Autoreactive T cells are deleted or inactivated in healthy individuals.
Mechanisms of Self-tolerance
- Central tolerance: Immature lymphocytes that recognize self-antigens in the thymus (T cells) or bone marrow (B cells) undergo apoptosis.
- Peripheral tolerance: Mechanisms that inactivate or delete self-reactive lymphocytes that escape central tolerance in peripheral tissues.
- Anergy: Irreversible inactivation of lymphocytes that recognize self-antigens in peripheral tissues.
- Suppression by regulatory T cells: T cells that prevent immune responses against self-antigens.
- Deletion by apoptosis: Self-reactive T cells can undergo apoptosis when they encounter self-antigens in peripheral tissues.
Autoimmune Diseases
- Autoimmune diseases occur when immune tolerance fails and the immune system attacks self-antigens.
- Immune system attacks self antigens leading to cell and tissue destruction by:
- antigen-specific CD8 cytotoxic T cells
- autoantibodies (antibodies to self-proteins) and accompanying inflammation
- The exact causes of autoimmune diseases are unclear, but both genetic and environmental factors likely contribute.
- Genetics: Autoimmune diseases often have a genetic component, with higher incidence in twins of affected individuals, especially monozygotic twins.
- Environmental factors: Hormonal influences, chemical and physical agents, and certain infections can trigger autoimmune reactions.
Role of Susceptibility Genes
- Most autoimmune diseases are complex multigenic disorders.
- Genetics play a role in the development of autoimmune disorders, evidenced by higher incidence in twins of affected individuals.
- A strong association exists between ankylosing spondylitis and HLA-B27.
Role of Infections and Other Environmental Factors
- Infections can trigger autoimmune reactions through various mechanisms:
- Upregulation of costimulators on antigen-presenting cells (APCs) leading to breakdown of anergy and activation of self-reactive T cells.
- Molecular mimicry: Some microbes express antigens that share amino acid sequences with self-antigens, causing immune responses against self-reactive lymphocytes.
- Microbes induce other abnormalities promoting autoimmune reactions: Some viruses, like EBV and HIV, cause polyclonal B-cell activation, leading to autoantibody production.
- Modification of self-antigens: Smoking can chemically modify self antigens, making them recognized as foreign by T cells.
- Release of sequestered antigens: Self antigens hidden from the immune system during development may be recognized as foreign if exposed later.
- Gender bias: Many autoimmune diseases are more common in women than men, possibly due to hormonal influences.
Examples of Autoimmune Diseases
-
Organ-specific autoimmune disorders:
- Type 1 diabetes mellitus
- Pernicious anemia
- Graves' disease
- Hypothyroidism
- Autoimmune hepatitis and primary biliary cirrhosis
- Sjögren syndrome
-
Multisystem autoimmune diseases:
- Rheumatoid arthritis
- Systemic lupus erythematosus (SLE)
- Polyarteritis nodosa
- Autoimmune hemolytic anemia
- Systemic sclerosis (Scleroderma)
Sjögren Syndrome
- A chronic autoimmune inflammatory disease affecting salivary and lacrimal glands, causing xerostomia (dry mouth) and xerophthalmia (dry eyes).
- Pathogenesis:
- Triggered by viral infection of salivary glands, causing local cell death and release of self antigens.
- CD4+ T cells and B cells specific for these self antigens may have escaped tolerance and react.
- Antibodies against SS-A (Ro) and SS-B (La) are detected in 90% of patients.
- Inflammation, tissue damage, and fibrosis occur.
- Morphology:
- Initial periductal and perivascular lymphocytic infiltration in salivary glands.
- Extensive lymphocytic infiltrate with lymphoid follicles and germinal centers.
- Ductal epithelial hyperplasia, obstruction, and atrophy of acini.
- Fibrosis and hyalinization.
Clinical Features of Sjögren syndrome
- Most common in women between 50 and 60 years of age.
- Symptoms result from the destruction of exocrine glands.
- Keratoconjunctivitis causes blurred vision, burning, itching, and thick secretions.
- Xerostomia leads to difficulty swallowing, taste impairment, cracks in the mouth, and buccal mucosa dryness.
- Parotid gland enlargement occurs in half of patients.
- Dry nasal mucosa, epistaxis, recurrent bronchitis, and pneumonitis may occur.
- Extraglandular manifestations include synovitis, diffuse pulmonary fibrosis, and peripheral neuropathy.
- Mikulicz syndrome: Inflammation of both lacrimal and salivary glands.
- Increased risk of developing marginal zone lymphoma, a B-cell malignancy.
Systemic Sclerosis (Scleroderma)
- An immunologic disorder causing excessive fibrosis in multiple tissues, obliterative vascular disease, and autoimmunity with multiple autoantibodies.
- Two categories:
- Diffuse systemic sclerosis: Widespread skin involvement, rapid progression, and early visceral involvement.
- Limited systemic sclerosis (CREST syndrome): Mild skin involvement, often confined to fingers and face. Visceral involvement occurs late.
- Pathogenesis:
- Autoimmune responses: CD4+ T cells responding to an unknown antigen accumulate in the skin releasing cytokines.
- Vascular damage: Microvascular disease is common, including endothelial activation, injury, and increased platelet activation.
- Fibrosis: Accumulation of alternatively activated macrophages, fibrogenic cytokines produced by leukocytes, fibroblast hyperresponsiveness, and ischemic damage.
Morphology of Systemic Sclerosis
- Most prominent changes in the skin, alimentary tract, musculoskeletal system, and kidney.
- Skin: Diffuse fibrosis and atrophy, starting in fingers and extending proximally, leading to clawlike appearance and limited joint mobility.
- Alimentary tract: Progressive atrophy and fibrous replacement of the muscularis, causing esophageal stricture and malabsorption in the small intestine.
- Musculoskeletal system: Synovitis and fibrosis, resulting in joint inflammation and stiffness.
- Kidneys: Vascular lesions resembling those seen in malignant hypertension, without specific glomerular changes.
- Lungs: Pulmonary hypertension due to pulmonary vascular involvement.
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Description
This quiz explores immunologic tolerance, focusing on the immune system's ability to differentiate between self and non-self antigens. It covers key concepts such as self-tolerance, the role of T lymphocytes, and the mechanisms of central and peripheral tolerance. Test your knowledge about how the immune system prevents autoimmunity.
