HYPERSENSITIVITY Flashcards
• Normal but exaggerated or uncontrolled immune response to an antigen that can produce inflammation, cell destruction, or tissue injury
HYPERSENSITIVITY
antigen can persist, and the immune response can cause damage to the host
Hypersensitivity
Time of exposure
Immediate
Delayed
• Time of exposure
• Immediate-
Delayed-
antibody mediated
IgE, IgG, IgM
cell mediated
T-helper cells
48-72 hours
TYPES OF ANTIGENS AND REACTIONS
Latex allergies
Environmental substances
Infectious agents
Food allergies
Latex Allergies
• High-risk group:
- Latex:
children with frequent medical treatment or lengthy surgeries
natural rubber product
Reactions:
• IgE-mediated allergic reactions
• Cell-mediated contact dermatitis
• Irritant dermatitis
Latex
Environmental Substances
Allergens
Haptens
Toxin and irritants
Drug administration
• Influenza virus
• Damage epithelial cells in the respiratory tract
• Cytokine storm
Infectious Agents
• Cow’s milk, soy, chicken eggs, peanuts, tree nuts, wheat, fish, and crustaceans
• No current treatment available
Food Allergies
TYPE I HYPERSENSITIVITY
Aka
(Anaphylactic Hypersensitivity)
•______ derived from the Greek word atopos (meaning “out of place”): an inherited tendency to develop classic allergic responses to naturally occurring inhaled or ingested allergens
Atopy
• passive cutaneous anaphylaxis
Carl Wilhelm Prausnitz and Heinz Küstner (1921):
• Triggered by allergens (peanuts, eggs, and pollen)
• Immediate allergic reactions
TYPE I HYPERSENSITIVITY
(Anaphylactic Hypersensitivity)
TYPE I HYPERSENSITIVITY
IMMUNOLOGIC MECHANISM
-
Sensitization Phase
Activation phase
Late phase
- Sensitization Phase
- First exposure leads to\____ production and mast cell sensitization.
• Th2 cells release cytokines (3)
• These cytokines prompt B cells to turn into plasma cells, which produce IgE antibodies specific to that allergen.
• The IgE antibodies attach to mast cells and basophils, preparing them for future encounters with the allergen.
IgE
like IL-4, IL-5, and IL-13.
• Re-exposure triggers the immediate release of histamine and other mediators, causing rapid allergic symptoms.
Activation Phase
Inflammatory mediators:
histamine, heparin and tryptase
- Chronic inflammation results from the recruitment of immune cells, leading to prolonged symptoms.
- Late Phase
TYPE I HYPERSENSITIVITY
CLINICAL MANIFESTATIONS
Allergic rhinitis
Asthma
Urticaria
Angioedema
Anaphylaxis
Food allergies
Drug allergies
Eosinophilic esophagitis
: Sneezing, nasal congestion, and itchy eyes.
: Wheezing, shortness of breath, and coughing.
: Red, itchy, raised hives on the skin.
: Swelling of deeper tissues, especially in the face and throat.
- Allergic Rhinitis
- Asthma
- Urticaria
- Angioedema
: Severe, systemic reaction with rapid onset of symptoms, including difficulty breathing and hypotension.
: Oral, gastrointestinal, skin, and
respiratory symptoms after ingesting allergenic foods.
: Skin reactions, respiratory symptoms, and anaphylaxis.
: Swallowing difficulties and chest pain due to allergic inflammation in the esophagus.
- Anaphylaxis
• Food Allergies
• Drug Allergies
- Eosinophilic Esophagitis
TYPE I HYPERSENSITIVITY
TREATMENT
- Pharmacological
• Antihistamines
- Corticosteroids
• Leukotriene Receptor Antagonist
• Beta-2-Adrenergic Agonists
• Mast cell stabilizers
• Epinephrine
TYPE I HYPERSENSITIVITY
TREATMENT
(Allergen-specific)
• Immunotherapy
TYPE I HYPERSENSITIVITY
TREATMENT
• Emergency treatment of anaphylaxis
• Epinephrine
• Oxygen
• Intravenous fluids
• Antihistamine and corticosteroids
TYPE I HYPERSENSITIVITY
DETECTION/TESTS
Skin testing
Serological tests
Challenge testing
Others
Nasal smear
Exhaled Nitric Oxide (FeNO)
- Skin testing (3)
- Serological tests (2)
- Skin Prick Test (SPT)
• Intradermal test - Patch test
• Total Serum IgE
- Allergen-Specific (RAST)
TYPE II HYPERSENSITIVITY
Aka
(Antibody-Mediated Cytotoxic Hypersensitivity)
• Involves IgG and IgM antibodies directed against antigens found on cell surfaces.
• antigens may be altered self-antigens or heteroantigens
TYPE II HYPERSENSITIVITY
(Antibody-Mediated Cytotoxic Hypersensitivity)
TYPE II HYPERSENSITIVITY
(Antibody-Mediated Cytotoxic Hypersensitivity)
• Binding of the antibody to a cell can have one of three major effects
• cell can be destroyed
• function of the cell can be inhibited
- function of the cell can be increased above normal
TYPE II HYPERSENSITIVITY
MAJOR EFFECTS: Cell Damage
Cytotoxicity
Mechanism:
Examples:
• Complement activation
• Opsonization
- Antibody-Dependent Cellular Cytotoxicity (ADCC)
- Blood Transfusion reactions
• Hemolytic Disease of the Newborn (HDN)
• Autoimmune Hemolytic Anemia
TYPE II HYPERSENSITIVITY
MAJOR EFFECTS: Inhibition/Stimulation of Cell Function
• Dysfunction of the affected tissue or organ
• Enhance activity beyond normal levels
• Functional Impairment
• Overactivation
TYPE II HYPERSENSITIVITY
MAJOR EFFECTS: Inhibition/Stimulation of Cell Function
• Autoantibody binds to ACH receptor= MUSCLE WEAKNESS
• TSI bind to TSH receptor on thyroid cells=excessive thyroid hormone production= HYPERTHYROIDISM
- Myasthenia Gravis
• Grave’s Disease
TYPE II HYPERSENSITIVITY
CLINICAL EXAMPLES
- Transfusion Reactions
• Mechanism
- Mismatched blood transfusion
• Antibody-Antigen binding - Complement activation
• Hemolysis and tissue damage
TYPE II HYPERSENSITIVITY
CLINICAL EXAMPLES
- Clinical Manifestation
• Immediate Symptoms: Fever, chills, back pain, tachycardia, and hypotension
• Hemoglobinuria
• Jaundice
TYPE II HYPERSENSITIVITY
CLINICAL EXAMPLES
• Mechanism
• Rh incompatibility
• Sensitization of the Mother
• Subsequent pregnancy
• Destruction of fetal RBCs
• Hemolytic Disease of the Newborn
- Clinical Manifestation
• Anemia - Hydrops Fetalis
• Jaundice - Enlarged Liver and Spleen
• Hemolytic Disease of the Newborn
TYPE II HYPERSENSITIVITY
CLINICAL EXAMPLES
- Autoimmune hemolytic Anemia (AIHA)
• Goodpasture Syndrome - Grave’s Disease
• Myasthenia Gravis
• Pernicious Anemia
TYPE II HYPERSENSITIVITY
DETECTION/TESTS
• Direct Antiglobulin Test (DAT) or
Direct Coombs Test
• Indirect Antiglobulin Tests (IAT) or Indirect Coombs Test
TYPE II HYPERSENSITIVITY
DETECTION/TESTS
• Detects Abs/complement on the surface of RBCs
• Detects free Abs in the serum that can bind to RBC Ags
• Direct Antiglobulin Test (DAT) or
Direct Coombs Test
• Indirect Antiglobulin Tests (IAT) or Indirect Coombs Test
TYPE II HYPERSENSITIVITY
DETECTION/TESTS
- Measure specific autoantibodies
• Quantifies surface-bound antibodies on cells
• Detects Abs deposition in tissues
• Enzyme-Linked Immunosorbent Assay (ELISA)
• Flow Cytometry
• Tissue Biopsy with Immunofluorescence
TYPE III HYPERSENSITIVITY
Aka
(Immune Complex-Mediated)
Mechanism
• Immune complex formation
• Ag-Ab complex in circulation
• Immune complex deposition
• Blood vessel walls, kidneys, joints and lungs
- Activation of complement
• Release of C3a and C5a (inflammatory mediators)
- Inflammatory response
• Release lysosomal enzymes and reactive oxygen species
- Tissue injury
• Vasculitis, glomerulonephritis, arthritis
TYPE III HYPERSENSITIVITY
(Immune Complex-Mediated)
TYPE III HYPERSENSITIVITY
CLINICAL EXAMPLES
• autoantibodies form against nuclear components
• Immune complexes deposit in kidneys, skin, joints and other organs
- Systemic Lupus Erythematosus (SLE)
TYPE III HYPERSENSITIVITY
CLINICAL EXAMPLES
• autoantibodies form immune complexes with IgG
• deposit in the synovial joints, leading to chronic inflammation and joint damage.
Rheumatoid Arthritis (RA)
TYPE III HYPERSENSITIVITY
CLINICAL EXAMPLES
Serum sickness
Post-streptococcal Glomerulonephritis
Arthus reaction
TYPE III HYPERSENSITIVITY
CLINICAL EXAMPLES
• foreign proteins are introduced into the body
• formation of immune complexes that deposit in blood vessels.
• formation of immune complexes
• deposit in the kidneys, leading to glomerular inflammation
- Ag is injected into an individual with high levels of circulating Abs
• Immune complexes form at the site of injection, leading to localized inflammation.
• Serum Sickness
• Post-Streptococcal Glomerulonephritis
- Arthus Reaction
TYPE III HYPERSENSITIVITY
DETECTION/TESTS
• Immune Complex Detection
• Complement Levels (C3, C4).
• Tissue Biopsy with Immunofluorescence
- ANA and Anti-dsDNA Tests.
• Rheumatoid Factor Test
• Cryoglobulin Test
TYPE IV HYPERSENSITIVITY
Aka
(Delayed-Type Hypersensitivity)
TYPE IV HYPERSENSITIVITY
(Delayed-Type Hypersensitivity)
- Described by_____
-______ to develop after antigen exposure
• driven by________
Robert Koch (1890)
48 to 72 hours
T cells and macrophages
TYPE IV HYPERSENSITIVITY
Mechanisms:
• Sensitization Phase
- Effector Phase (Subsequent Exposure)
- Inflammation and Tissue Damage
TYPE IV HYPERSENSITIVITY
(Delayed-Type Hypersensitivity)
1-2 weeks after the first contact with Ag
APCs process the Ag and present it to CD4+ helper (Th1) cells
- Th1 cells become sensitized to the antigen and proliferate, generating a population of memory T cells that are specific to the antigen.
Sensitization Phase
TYPE IV HYPERSENSITIVITY
(Delayed-Type Hypersensitivity)
• Upon re-exposure to the same antigen, these sensitized Th1 cells recognize the antigen and become activated.
• Activated Th1 cells==IFN-y
and TNF==macrophages to site of antigen exposure
• Macrophages==lysosomal enzymes, ROS, pro-inflammatory cytokines==tissue damage
Effector Phase (Subsequent Exposure)
Inflammation and Tissue Damage
• The influx of immune cells
leads to inflammation and tissue damage at the site of antigen exposure, which manifests clinically as a delayed hypersensitivity reaction.
TYPE IV HYPERSENSITIVITY
(Delayed-Type Hypersensitivity)
TYPE IV HYPERSENSITIVITY
(Delayed-Type Hypersensitivity)
• Development of granulomas that release large amounts of lytic enzymes that can destroy surrounding tissue and promote fibrin deposition
Chronic Type
TYPE IV HYPERSENSITIVITY
(Delayed-Type Hypersensitivity)
Chronic Type
Triggers:
: M. tuberculosis, M. leprae, P. carinii, Leishmania spp and herpes simplex virus
: poison ivy, poison oa, metals, hair dyes and cosmetics
Intracellular
Contact Ag
TYPE IV HYPERSENSITIVITY
CLINICAL EXAMPLES
• Contact Dermatitis
• Common Cause:_______
• poison ivy, poison oak, and poison sumac
• Signs:
• erythema, swelling, and the formation of papules that appears from 6 hours to several days after the exposure
• Duration:_____
URUSHIOL
3-4 weeks
TYPE IV HYPERSENSITIVITY
CLINICAL EXAMPLES
• inflammation of the alveoli and interstitial spaces.
• Common Cause
- Bacterial and fungal spores
• Symptoms
• a dry cough, shortness of breath, fever, chills, weight loss, and general malaise
• Hypersensitivity Pneumonitis
TYPE IV HYPERSENSITIVITY
DETECTION/TESTS
- Patch Testing
• Tuberculin Skin Test (Mantoux Test) - Candida and Other Skin
Antigens
• Granuloma Formation (via Biopsy)
