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Questions and Answers
What is the definition of hypersensitivity (allergy)?
What is the definition of hypersensitivity (allergy)?
an amplified state of immune response to a harmless antigen that results in injury to the tissue, disease, or even death
What type of hypersensitivity reactions are classified into 4 subtypes based on the mechanism and nature of the triggering antigen?
What type of hypersensitivity reactions are classified into 4 subtypes based on the mechanism and nature of the triggering antigen?
Localized hypersensitivity reactions are more pronounced in respiratory passages, intestinal walls, or the skin.
Localized hypersensitivity reactions are more pronounced in respiratory passages, intestinal walls, or the skin.
True
Type I hypersensitivity reactions always involve ____ mediated degranulation of basophils or mast cells.
Type I hypersensitivity reactions always involve ____ mediated degranulation of basophils or mast cells.
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What is the main purpose of conducting a Western blot test in relation to HIV diagnosis?
What is the main purpose of conducting a Western blot test in relation to HIV diagnosis?
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Which test detects the RNA of HIV rather than antibodies to HIV?
Which test detects the RNA of HIV rather than antibodies to HIV?
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Autoimmune diseases result from the immune system attacking foreign antigens.
Autoimmune diseases result from the immune system attacking foreign antigens.
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What is self-tolerance in the context of autoimmunity?
What is self-tolerance in the context of autoimmunity?
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Autoimmunity represents a breakdown or failure of the mechanisms of ______
Autoimmunity represents a breakdown or failure of the mechanisms of ______
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Match the following mechanisms contributing to autoimmune emergence with their descriptions:
Match the following mechanisms contributing to autoimmune emergence with their descriptions:
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What antibodies are most specific for Systemic Lupus Erythematosus (SLE)?
What antibodies are most specific for Systemic Lupus Erythematosus (SLE)?
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Which antibody is specific for lupus and produces a coarsely speckled pattern of nuclear fluorescence on indirect immunofluorescence?
Which antibody is specific for lupus and produces a coarsely speckled pattern of nuclear fluorescence on indirect immunofluorescence?
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RF antibody is specific only for Rheumatoid Arthritis (RA).
RF antibody is specific only for Rheumatoid Arthritis (RA).
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Patients with Hashimoto's thyroiditis develop a goiter and ___.
Patients with Hashimoto's thyroiditis develop a goiter and ___.
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Match the autoimmune disease with the antibody test used for diagnosis:
Match the autoimmune disease with the antibody test used for diagnosis:
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What are the two types of immunodeficiencies mentioned in the text?
What are the two types of immunodeficiencies mentioned in the text?
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Which cells are mediated by TH1 cells and CD8 cytotoxic T cells?
Which cells are mediated by TH1 cells and CD8 cytotoxic T cells?
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Delayed-type hypersensitivity reactions typically occur ___ days after T cells interact with antigen.
Delayed-type hypersensitivity reactions typically occur ___ days after T cells interact with antigen.
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Immunodeficiencies are disorders where the body's immune system is overactive.
Immunodeficiencies are disorders where the body's immune system is overactive.
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Match the following categories of primary immunodeficiencies with their features:
Match the following categories of primary immunodeficiencies with their features:
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Study Notes
Hypersensitivity
- Hypersensitivity (allergy): an amplified state of immune response to a harmless antigen, resulting in tissue injury, disease, or even death.
- Allergen: a type of antigen that can cause an allergic reaction.
- Hypersensitivity reactions are classified into four subtypes based on the mechanism (immune mediators) and the nature of the triggering antigen:
- Type I: Immediate hypersensitivity, involving IgE-mediated degranulation of basophils or mast cells.
- Type II: Antibody-mediated hypersensitivity, involving the interaction of antibodies with cell membrane or the extracellular matrix.
- Type III: Immune complex-mediated hypersensitivity, involving the interaction of antibodies with soluble molecules to form immune complexes that deposit in tissues.
- Type IV: Cell-mediated hypersensitivity, involving the direct attack of host cells by immune cells in the absence of antibody.
Type I Hypersensitivity
- Occurs within seconds to minutes of exposure to an antigen.
- Involves IgE-mediated degranulation of basophils or mast cells.
- Causes the release of vasoactive amines (e.g., histamine) and other inflammatory mediators.
- Examples: hay fever, asthma, food allergies, bee stings, and atopic dermatitis.
Type II Hypersensitivity
- Involves the interaction of antibodies with cell membrane or the extracellular matrix.
- Cell destruction is mediated by:
- Complement-mediated cell lysis
- Antibody-dependent cell-mediated cytotoxicity
- Opsonization
- Examples: hemolytic anemia, transfusion reaction, and autoimmune diseases.
Type III Hypersensitivity
- Involves the interaction of antibodies with soluble molecules to form immune complexes that deposit in tissues.
- Examples: Arthus reaction, serum sickness, and autoimmune diseases.
Type IV Hypersensitivity
- Involves the direct attack of host cells by immune cells in the absence of antibody.
- Examples: contact dermatitis, delayed-type hypersensitivity, and autoimmune diseases.
Laboratory Diagnosis
- Type I hypersensitivity: skin testing, RAST, and IgE ImmunoCAP test.
- Type II and III hypersensitivity: complement activation by complement fixation test.
- Type IV hypersensitivity: application of the antigen to the surface of the skin or injected intradermally.
Immunodeficiency
- Primary immunodeficiency: genetic or developmental defects of the immune system, present at birth.
- Secondary immunodeficiency: loss of immune function due to exposure to various agents, such as infections, malignancies, or immunosuppressive drugs.
- Examples of primary immunodeficiency: X-linked agammaglobulinemia, DiGeorge syndrome, and severe combined immunodeficiency (SCID).
- Examples of secondary immunodeficiency: AIDS, chemotherapy, and radiation therapy.### Primary Immunodeficiencies (PIDs)
- Classified into nine categories based on clinical features, immunologic defects, and genetic abnormalities:
- Category 1: Combined Immunodeficiencies
- Category 2: Combined Immunodeficiencies with Associated or Syndromic Features
- Category 3: Predominantly Antibody Deficiencies (most common, representing 50% of PIDs)
- Category 4: Diseases of Immune Dysregulation
- Category 5: Congenital Defects of Phagocyte Number, Function, or Both
- Category 6: Defects in Innate Immunity
- Category 7: Autoinflammatory Disorders
- Category 8: Complement Deficiencies
- Category 9: Phenocopies of Primary Immunodeficiencies
Laboratory Evaluation of Immune Dysfunction
- Three important stages:
- Clinical diagnostics
- Laboratory diagnostics
- Genetic diagnostic
- Screening tests:
- Used for initial evaluation of suspected immunodeficiency
- Can be performed in any hospital laboratory
- Include patient history, complete blood count (CBC), and white blood cell (WBC) differential
- May reveal reduced lymphocyte count, thrombocytopenia, and small platelets
Secondary Immunodeficiencies
- Caused by external factors, such as:
- Acquired hypogammaglobulinemia (e.g., corticosteroid or immunosuppressant drug use, nutritional disorders, infections, chemotherapy, malignancy, nephrotic syndrome, other metabolic diseases, and hazardous environmental conditions)
- Agent-induced immunodeficiency (e.g., environmental agents, such as immunosuppressive drugs and accidental radiation exposure)
- Extremes of age (e.g., young and elderly)
- Severe malnutrition affecting both innate and adaptive immunity
- Human immunodeficiency virus (HIV)
HIV Laboratory Testing
- Enzyme-linked immunosorbent assay (ELISA)
- Western blot
- Indirect fluorescent antibody (IFA)
- Polymerase Chain Reaction (PCR)
Treatment of Immune Deficiencies
- Depends on the causative agent
- Examples:
- Enzyme replacement therapy
- Gene therapy
- Interferon
- Hematopoietic stem cell transplant
- Bone marrow transplantation
- Protective isolation
- Immunoglobulin replacement therapy
- Prophylactic treatment for fungus and viruses
Autoimmunity
- Autoimmune diseases:
- Conditions in which damage to organs or tissues results from the presence of autoantibody or autoreactive cells
- Examples: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA)
- Mechanisms of self-tolerance:
- Clonal deletion
- Receptor editing
- Clonal anergy
- Peripheral tolerance
- Regulatory T cells (Tregs)
Autoimmune Diseases
- Systemic lupus erythematosus (SLE):
- Chronic systemic inflammatory disease
- Alternating exacerbations and remissions
- Peak age of onset: 20-40 years
- Affects women more than men
- More common in African Americans and Hispanics
- Signs and symptoms: fatigue, weight loss, malaise, fever, anorexia, joint involvement, skin manifestations
- Diagnosed with antinuclear antibodies (ANA) and anti-double-stranded DNA (anti-ds-DNA) antibodies
- Rheumatoid arthritis (RA):
- Systemic autoimmune disorder
- Characterized by symmetric, erosive arthritis of the peripheral joints
- Can also affect multiple organs
- Women are three times as likely to be affected as men
- May occur at any age, but typically strikes between 35-50 years
- Progress of the disease varies, with spontaneous remissions or active disease
- Complications: heart attack, stroke, anemia, formation of subcutaneous nodules, pericarditis, lymphadenopathy, splenomegaly, interstitial lung disease, or vasculitis### Rheumatoid Arthritis (RA)
- IgM antibodies combine with IgG, forming immune complexes that deposit in joints, leading to a type III hypersensitivity reaction and activation of the classical complement cascade.
- C3a and C5a are generated, acting as chemotactic factors for neutrophils and macrophages.
- Chronic inflammation damages the synovium.
- Anti-citrullinated protein (anti-CCP) antibodies are a more specific marker for RA detection than RF.
- The earliest lesions in rheumatoid joints show:
- Increased cells lining the synovium.
- Infiltration of mononuclear cells, mostly CD4 T lymphocytes.
- Scattered CD8 T cells, B cells, and antibody-producing plasma cells.
- Macrophages and neutrophils attracting to the area, forming a pannus that grows into the joint space and invades the cartilage.
Diagnosis of Rheumatoid Arthritis (RA)
- Diagnosis is based on a combination of clinical manifestations, radiographic findings, and laboratory testing.
- RF is often tested for to aid in making the initial diagnosis, but a negative result does not rule out RA, and a positive result is not specific for RA.
- Anti-CCP EIA assays have better sensitivity and specificity, making it a more reliable indicator of RA.
Treatment of Rheumatoid Arthritis (RA)
- Traditional therapy includes anti-inflammatory drugs like salicylates and ibuprofen to control local swelling and pain.
- Disease-modifying antirheumatic drugs (DMARDs) like hydroxychloroquine and sulfasalazine are used.
- Biological agents that block the activity of TNF-α, such as infliximab and adalimumab, are used to halt joint damage.
Autoimmune Thyroid Diseases (AITDs)
- AITDs encompass conditions like Hashimoto's thyroiditis and Graves' disease.
- Both conditions have distinct symptoms but share some common antibodies that interfere with thyroid function.
- Antibodies present in AITDs include:
- Antibodies to thyroglobulin.
- Thyroid peroxidase.
- TSH receptors.
Diagnosis of Autoimmune Thyroid Diseases (AITDs)
- Diagnosis is based on the presence of the above antibodies, tested by indirect immunofluorescent assays, passive agglutination, and EIA.
Type I Diabetes Mellitus
- Characterized by insufficient insulin production caused by selective destruction of beta cells in the pancreas.
- Diagnosis is typically made by hyperglycemia.
- Immunoassays for antibodies to:
- Insulinoma antigen 2 (IA-2 or ICA 512).
- IA-2β (phogrin).
- Anti-insulin antibodies.
- Antibodies to the enzyme GAD.
- Islet cell antibodies (ICAs).
Multiple Sclerosis (MS)
- Characterized by the formation of lesions called plaques in the white matter of the brain and spinal cord, leading to progressive destruction of the myelin sheath of axons.
- A combination of genetic and environmental factors contributes to the development of MS.
- Patients with MS have a higher concentration of antibody to EBV than the control population.
- Other viruses implicated in MS include measles, herpes simplex, varicella, rubella, influenza C, human herpes virus-6, and some parainfluenza viruses.
- Diagnosis of MS is supported by:
- Antibody production against a myelin basic protein peptide.
- Magnetic resonance imaging (MRI).
- There is no single laboratory test that can confirm an MS diagnosis.
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Description
This quiz covers the mechanisms and types of hypersensitivity reactions, including Type I, II, III, and IV. It's a key concept in clinical immunology, helping you understand immune reactions and diseases.
