Hypersensitivity Flashcards
Type 1 Hypersensitivity
- description
- mechanism
- examples
Description- anaphylactic, immediate-type sensitivity
Mechanism- Ag binding directly to IgE on mast/basophil causing degranulation of mast/basophil leads to the release of histamine, prostaglandins, and leukotrienes. *Response is IgE dependent
Examples-
- anaphylaxis
- angioedema
- bronchospasm
- urticaria
- allergic rhinitis
Type 2 Hypersensitivity
- description
- mechanism
- examples
- description: Aby-dependent cytotoxicity
- mechanism: Ag/hapten binds aby leading to cell/tissue injury
- examples:
- hemolytic anemia
- interstitial nephritis
- blood transfusion run
Type 3 Hypersensitivity
- description
- mechanism
- examples
- description: immune complex disease
- mechanism: deposition of ag-aby complex in vessel/tissue leading to damage
- examples:
- serum sickness
- lupus
- glomerular nephritis
- rheumatoid arthritis
Type 4 hypersensitivity
- description
- mechanism
- examples
- description: cell-mediated or delayed hypersensitivity
- mechanism: ag exposure sensitized T cell which then mediate tissue injury
- examples: contact dermatitis
Allergic rxns manifest on a wide spectrum, true or false?
True
What is the function of histamine?
potent vasodilator, increases capillary permeability, stimulates smooth muscle contraction
Type 1 IgE mediators of allergic rxns include…
- histamine
- complement (inflamm and release of histamine)
- Ach (bronchial smooth muscle contraction)
- leukotrienes (delayed and more prolonged; similar to histamine), prostaglandins
- kinins (vasodilation, smooth muscle contraction)
- eosinophils
2 subgroups of IgE mediated Allergy
- atopy
- anaphylaxis
Atopy
- what signs/symptoms are presented?
- triggers
- allergy kids; allergic salute, allergic shiners,
- eczema
- allergic rhinitis
- allergic asthma
- allergic gastroenteropathy
triggers:
pollon, mold, animal dander, dust mites
Anaphylaxis
- what signs/symptoms?
- triggers?
-atopy + respiratory issues
(MASSIVE atopy to millionth degree)*
-systemic response, bronchioconstriction, vasodilation (volume decreases, cardiogenic shock), bronchospasm, GI and uterine muscle contraction, urticaria, angioedema, allergy that affects airway
Trigges:
drugs like penicillin, latex, insect venom, certain foods
What is urticaria?
How would this present?
Time for development and cessation
hives- may be few mm to cm in diameter
-immune mediated skin eruption of well circumscribed, blanching wheals on an erythematous base
often have central pallor, may be raised or flat
-can develop in minutes to hours, may only last 12-24hrs
what is Angioedema?
How would this present?
*drugs that may cause this?
Time for development and cessation
-rapid swelling of the dermis, sub Q tissue, mucosa, and submucosal
- facial, throat, and tongue swelling
- non-pitting(not like memory foam)
- lisinopril (ACE inhibitor)
- can develop in minutes to hours, may only last 12-24hrs
Urticaria and Angioedema caused by?
mast cell release of inflamm mediators (primarily histamine)
- chronic urticaria thought to be cause by autoimmune process
- food and drug induced- tend to be brief
Physical Urticarias
dermatographism- gentle stroking of skin
pressure urticaria- pressure to skin
cold- eruptions following application of cold
cholinergic urticaria- triggered by exercise or hot shower
aquagenic urticaria- hives after contact with water
solar urticaria- hives develop after UV light exposure
Urticaria and ANgioe edema management
- avoid etologic agents
- ASA, NSAIDS, ETOH, *ACE inhibitors
-prescribe epipen for anyone w/ sever bout of angioedema or anaphylaxis
Differences between Anaphylaxis and Anaphylactoid
anaphylaxis- allergic IgE mediated rxn
anaphylactoid- not IgE mediated rxn
*Presentation and management are identical
What is a late stage anaphylactic response and how would you treat it?
- an anaphylactic response occuring at least 60minutes to several hours after exposure.
- you treat w/ prednisolone
- this is why you dont send someone home directly after treatment/immunization of anything, you need to monitor them to make sure they dont develop anaphylaxic response.
Anaphylactic pt manifestation
pruiritus (itching), flushing, sense of impending doom, urticaria (hives), angioedema, respiratory tract involvment (50%)
anaphylactic shock (30%)- caradiovascular collapse resulting from hypovolemia (d/t increased vascular permeability and up to 50% blood volume loss), myocardial depression
Anaphylactic Management
depends upon severity
- stabilization (intubation, large bore IV w/ fluids)
- O2
- *****Epinephrine
- anti-histamine
- bronchodilators (Beta agonist)
- corticosteroids
*dont forget to prescribe epipen!
Common drug culprits of Type 1 IgE mediated hypersensitivity
- beta-lactam abx (penicillins, cephalosporins)
- sulfonamides (most common for causing steven johnsons)
- phenytoin
- carbamazepine (Tegretol)
- allopurinol
- NSAIDS (ibuprofen, aleve)
How long will it take to mainfest symptoms in a patient that takes a drug they are allergic to?
depends on whether or not they have been sensitized.
- previously sensitized? Rapid development of symptoms
- not previously sensitized? May take days for symptoms to develop, or may not appear until subsequent exposure
Drug Allergy Rxn Pattern
Type 1 Hypersensitivity
- urticaria
- angioedema
- anaphylaxis
- drug induced exanthems (eruptive skin rash associated w/ fever)
- hypersesitivity vasculitis
- exfoliative dermatitis/erythroderma
- steven johnsons
- erythema multiforme
- photosensitivity
What is generally the treatment of choice for Type 1 hypersensitivity rxns?
ANTI-HISTAMINES
Type II Hypersensitivity Mechanism
Antibody-dependent cytotoxicity
Mechanism- either IgG or IgM is made against normal self antigens (immune tolerance failure) or a foreign antigen resembling some molecule on the surface of host cells enters the body and IgG or IgM are made against that antigen
the binding of these antibodies to the surface of host cells leads to:
- opsonization of host cell
- activation of classical complement
- ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY (ADCC) destruction of the host cells
Examples of type II hypersensitivity
- AB and Rh blood group rxns
- Autoimmune diseases like: Idiopathic Thrombocytopenia Purpura (ITP), Hashimoto’s thyroiditis, Graves Disease, Myasthenia Gravis, Goodpasture’s syndrome, MS
- Some drug rxns
What is the most common adverse reaction to a blood transfusion?
Febrile non-hemolytic transfusion reastion
symtoms- fever, dyspnea
This is clinically benign, causing no long lasting side effects.
Acute hemolytic transfusion reaction What type of hypersensitivity? When does it occur? Presentation? Mechanism?
- Type II
- within 24 hours of the transfusion
- sense of impending doom, burning at site of infusion, chills, fever, and pain (back and flanks)
- results from rapid destruction of the donor RBCs by host antibodies. Factor P then binds to C3 in the donor blood facilitating the reaction through the alternate pathway.
Severity of acute hemolytic transfusion reaction depends upon:
- How much incompatible antigen was transfused.
- the nature of the antigen
- the nature of the recipients antibodies
Delayed hemolytic transfusion reaction What type of hypersensitivity? When does it occur? Presentation? Mechanism?
Type II
Occurs 1-14 days after blood transfusion
Clinical outcomes depend of the rate at which the patient can produce antibodies and destroy donor RBCs. Usually much less severe than acute hemolytic rxns.
Recipient formed antibodies during a previous sensitization. During the blood transfusion the ab levels are too low to cause acute transfusion reaction. As the blood infuses, the antigen is re-encountered and the immune system is stimulated to rapidly produce more antibodies. Over days, the abs bind to the donor RBCs, which are removed.
Immune Thrombocytopenic Purpura
What type of hypersensitivity?
cause?
Stimulus?
Type II
- idopathic or autoimmune (antibodies are against platelet membrane glycoproteins Ilb-Illa (IgG type). Platelets coated with IgG renders them more susceptible to opsonization and phagocytosis (increase in C3 and C4 adherence on platelets).
- abnormal T-cell activity
Hashimoto’s Thyroiditis
What type of hypersensitivity?
Patient has antibodies to:
Result:
TypeII
chronic autoimmune thyroiditis- eventually hypothyroidism and/or goiter
antibodies to:
- Thyroglobulin (Tg)
- Thyroid peroxidase (TPO)
- TSH receptor (TSHR)
- —> B cells in thyroid are a major site of ab secretion—> T cells become activated and secrete cytokines—> cytokines have a role in antibody production and activate Tc cells which destroy thyroid cell
Grave’s Disease
What type of hypersensitivity?
Causes
Manifestation
Type II
Auto antibodies to TSHR causing:
- Activation of the recpetor
- stimulating thyroid synthesis, secretion, and thyroid growth (over production/activation of T3 and T4)
hyperthyroidism, goiter, bulging eye and anxiety
Myasthenia Gravis
What type of hypersensitivity?
Cause
What is one of the first symptoms?
Type II
Nicotinic Acetylcholine Receptor (AChR) is the target antigen. ACh released from the nerve causes muscle to contract and over time, the receptor is blocked. the muscle fatigues and become paralyzed.
Eyelid droop
Type III Hypersensitivity Mechanism
Antigen-antibody complexes form and enter the circulation forming circulating immune complexes.
Immune complexes are deposited in vessel walls (between the endothelial cells and the basement membrane) and induce inflammation directly or by activating compliment
Neutrophils and mfgs are recruited and produce tissure damage
Glomerulonephritis
What type of hypersensitivity?
Mechanism
Type III
ab-ag complexes can target GBM, bowmans space, endothelium. Results in destruction of glomeruli and prgression to renal compromise and renal failure.
If secondary to infection, treating infection can halt progress but immunosuppressive drug is best hope
Rheumatoid Arthritis
What type of hypersensitivity?
Mechanism
Extra-articular diseases? (outside the joint)
Type III
Immune complexes get deposited in the synovial lining and the cascade of leukocyte migration, phagocytosis, edema, and inflammation occurs, resulting in cartilage and joint injury
Extra-articular disease (outside the joint)- cariopulmonary, renal, skin, vasculitis, ocular, rheumatiod nodules
Systemic Lupus Erythematosus (SLE)
What type of hypersensitivity?
Mechanism
Environmental influences
Type III
- involves many organ systems, wide clinical spectrum with variable course
- presence of antinuclear-antibodies (ANA)
- persistence of pathogenic B cells:
- — polyclonal hyperactivity
- —pathogenic, auto-antibody IgG has high affinity from encoded mutated Ig genes
- failure of regulatory networks to interrupt the process.
- antibodies form the immune complexes with antigens to cause the disease
environmental: sex hormones, sun exposure, drugs, dietary factors, infections, stress
Type IV Hypersensitivity Mechanism
CELL-MEDIATED rather then antibody-mediated
Initiated by antigen activated (sensitized) T lymphocytes
Type 1- delayed type hypersensitivity reactions mediated by CD4+ T cells that secrete cytokines which recruit leukocytes and stimulate inflammation and phagocytosis
Type 2- direct cell cytotoxicity mediated by CD8+ T cells that directly kill tissue cells
*both lead to lymphocyte infiltrates and granuloma formation
Contact Dermatitis What type of hypersensitivity? Mechanism How many exposures to get reaction? Lesion appearance
Type IV
Lymphocytes and monocytes infiltrate upper dermis first. T cells activated by antigen. Once Induced, the CD4+ T cells start releasing cytokines
It only takes one exposure because the first exposure sensitizes, then a small amount remains to elicit the contact dermatitis.
Lesions vary from mild erythema to edematous papules, can be vesicular, itching is hallmark
Temporal Arteritis
What type of hypersensitivity?
Symptoms
Mechanism
Type IV
headache, visual distrubances, tender or enlarged temporal artery, elevated ESR –can cause blindness
T cell mediated. CD4+ and CD8+ T cells infiltrate vessel wall
Celiac Sprue (Gluten-Sensitive Enteropathy) What type of hypersensitivity? Mechanism
Type IV
hypersensitivity to cereal grain proteins (gluten or gliadin)
lymphocitic inflitrate in the lamina propria beneath the epithelial layer. Causes tissue swelling—> villous atrophy of small intestine resulting in malabsorption, steatorrhea (lipid poop), and weight loss.
