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What is the primary purpose of immunologic tolerance?
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?
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?
What is anergy in the context of self-tolerance?
Which process involves the deletion of self-reactive lymphocytes in the central lymphoid organs?
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?
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?
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?
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?
Which cells are the primary effector cells in autoimmune diseases?
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What is one of the common symptoms associated with xerostomia?
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?
What manifestation is observed in one-third of patients with Sjogren syndrome?
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What is Mikulicz syndrome characterized by?
What is Mikulicz syndrome characterized by?
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Which condition is associated with Sjogren syndrome?
Which condition is associated with Sjogren syndrome?
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What factor is most clearly associated with the development of ankylosing spondylitis?
What factor is most clearly associated with the development of ankylosing spondylitis?
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What characterizes diffuse systemic sclerosis?
What characterizes diffuse systemic sclerosis?
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Which mechanism can lead to autoimmune reactions through molecular mimicry?
Which mechanism can lead to autoimmune reactions through molecular mimicry?
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Which of the following is a feature of CREST syndrome?
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?
What is a proposed cause of tissue damage in systemic sclerosis?
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What is one way infections can trigger autoimmune disorders?
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?
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?
What represents a common pathological process in systemic sclerosis?
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What is a potential consequence of chemical modifications of self antigens?
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?
Which statement about gender bias in autoimmune diseases is true?
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Release of sequestered antigens can occur when:
Release of sequestered antigens can occur when:
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What is a common feature of most autoimmune diseases?
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?
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?
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?
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?
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?
How does systemic sclerosis affect the alimentary tract?
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What renal abnormalities are most commonly associated with systemic sclerosis?
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?
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?
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?
Which organ systems are primarily affected by Sjögren syndrome?
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What is the characteristic feature of symptoms in Sjögren syndrome?
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?
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?
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?
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?
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?
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?
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.
