Hypersensitivity Flashcards
What are the 4 types of hypersensitivity?
- Type I: Immediate/anaphylactic hypersensitivity mediated mainly by IgE, Th2, mast cells, and eosinophils
- Type II: Antibody-mediated (specifically IgG and IgM). Also called Cytotoxic reaction
- Type III: Immune complex-mediated
- Type IV: T-cell-mediated
Give examples of Type I hypersensitivity
- Anaphylaxis
- Hay fever
- Asthma
- Food allergy
Give examples of Type II hypersensitivity
- Hemolytic transfusion reactions
- Hemolytic disease of fetus and newborn
- Thrombocytopenia
Give examples of Type III hypersensitivity
- Arthus reaction
-Serum sickness
-SLE
Define hypersensitivity
A normal but exaggerated or uncontrolled immune response to an Ag that can produce inflammation, cell destruction, or tissue injury
How do you classify hypersensitivity reactions?
Based on time after exposure to Ag
Give the 2 classifications of hypersensitivity (based on time after Ag exposure)
- Immediate: antibody-mediated
- Delayed: cell-mediated
Define immunization and provide a synonym for this term
Definition: Immunologic reaction dependent on host response to Ag exposure. Initially, small amounts of Ag may restrict amount of Ab formed. Since there’s not enough Ab formed, second exposure can lead to uncontrolled immune response
Synonym: sensitization
Name the most significant property of IgE Ab
They can be specific for hundreds of different Ag (e.g., dander, pollen, foods, mold, dust, metals, drugs, insect stings)
Define atopy and a synonym for this term
Definition: IgE-mediated hypersensitivity reaction
Synonym: Allergy
List the different types of allergens we discussed in class (hint: there’s 5)
- Latex
- Environmental (dust, drugs, metals/chemicals)
- Infectious agents (Flu, strep)
- Self-antigens
- Food
Which types of hypersensitivity reactions are Ab dependent? Which ones are cell-mediated?
Antibody dependent: Types I, I, and III
Cell-mediated: Type IV only
True or False: The 4 types of hypersensitivity have zero overlap
False
Which receptors attach to mast cells (hint: involved in anaphylactic hypersensitivity)
IgE
Where are mast cells usually found?
- Connective tissues
- Lungs
- Uterus
- Around blood vessels
- Kidneys
- Liver
- Spleen
- Heart
Describe the steps of an anaphylactic reaction
- Ag binds IgE Ab receptor found on basophils/mast cells.
- Two IgEs crosslink to initiate mast cell/basophil mediator release
- Mediator release leads to vascular changes, platelet activation, eosinophils, neutrophils, and coagulation cascade
List 4 major mediators of allergies and asthma in Type I
- Histamine
- Leukotriene C4
- IL-4 (leads to Th2 proliferation)
- IL-13
Which cytokine only acts on basophils and causes them to release allergy mediators?
IL-3
Distinguish between an anaphylactic reaction and anaphylactoid reaction
Anaphylactic: Ag-Ab mediated
Anaphylactoid: NOT Ag-Ab mediated. Activate alternative complement pathway and various proteases instead. This means that Ag bind mast cells directly (not Ab receptors)
Define atopic reaction
Exaggerated response to allergens that is not as severe as an anaphylactic reaction. IgE Ab secreted. Th2 cells secrete cytokines (IL-4, IL-5, and IL-13)
Distinguish between anaphylactic and atopic reactions
Anaphylactic reactions are rapid, severe, and life-threatening responses to allergens, while atopic reactions are generally milder, chronic, and often associated with a genetic predisposition to various allergic conditions.
What is the general hallmark of allergic disease?
Th2 infiltration of tissues
What are signs and symptoms of Type I?
Skin redness, sneezing, wheezing within minutes. Localized reaction (e.g., hives) or generalized anaphylactic reaction. Allergy march in atopic children
What’s the medical term for hives?
Urticaria with angioedema
How do you test for Type I?
- Skin (pin prick) testing
- Patch testing (if non-IgE mediated food allergy)
- Food-specific serum IgE testing
- Test if serum tryptase is activated in anaphylactic reaction
What are 2 lab evaluations for Type I?
- ImmunoCAP: measure serum IgE
- Chemiluminescent enzyme immunoassay: Measures IgE too by binding allergens to soluble polymer-ligand matrix
What are treatment options for Type I?
- Epinephrine
- Antihistamines (not useful in asthma though) that block specific histamine receptors and slower than epinephrine
- Corticosteroids
- Desensitization (immunotherapy)
Distinguish Type II and Type III reactions based on where the Ag-Ab complex is formed
Type II: Ag is fixed onto cell or tissues
Type III: Ag is soluble and freely circulating
List the 3 Type II reaction Ab-mediated mechanisms
- Ab-dependent + Complement-mediated cytotoxicity
- Ab-dependenet + cell-mediated cytotoxicitiy
- Anti-receptor Ab
What are the types of transfusion reactions? Which type of hypersensitivity reaction do these fall under?
Type II
- Immediate hemolytic (*intravascular *)
- Delayed hemolytic (extravascular)
- Immediate non-hemolytic
- Delayed non-hemolytic
Most common cause of immediate hemolytic reactions in Type II? Other causes?
Common cause: ABO incompatible blood. Usually Type A because most people are Type A
Other causes: bacteremia + infusion of hemolyzed RBCs
What are some diagnostic/lab evaluations for Type II reactions?
- For HDFN:
- ABO blood grouping, Rh testing, amniocentesis, DAT, peripheral blood smear, flow cytometry - DAT (polyspecific anti-human globulin for screening)
- Rh-IgG can prevent
What causes Type III hypersensitivity?
Repeated exposure to Ag sensitizes the immune system such that insoluble Ag-Ab complexes are deposited in blood vessel walls and tissues. Complement system and innate cells activate
Which disease types are associated with immune complexes?
- Autoimmune (RA, SLE, glomerulonephritis)
- Neoplastic (tumors)
- Infectious diseases (strep, hepatitis, mono, bacterial infective endocarditis
What are 3 mechanisms of injury in Type III reactions?
- Antibodies can interact with soluble antigens in the bloodstream, leading to the formation of immune complexes that can travel and lodge in tissues with extensive filtration, potentially causing immune complex diseases.
- Antibodies can also react with locally secreted or injected antigens in the tissue fluid, exemplified by the Arthus reaction, a model for localized immune complex diseases.
- Antibodies may interact with structural antigens found on cell surfaces or fixed intercellular structures, as seen in systemic immune complex diseases like serum sickness, involving both soluble and tissue-bound antigens.
Is the persistence of immune complexes inherently harmful?
Actually, no. As long as they eventually get successfully cleared from circulation, they are NOT inherently harmful
Describe serum sickness in Type III hypersensitivity (this is one of the clinical manifestations)
Ag excess forms Ag-Ab complexes. Develops 1-2 weeks after initial exposure or repeated exposures by injection of heterologous serum protein. No preexisting Ab (Disease appears as Ab formation starts). Can induce chronic serum sickness if small Ag given daily that is just enough to balance Ab production
What is an autoimmune disorder in Type III hypersensitivity (this is one of the clinical manifestations)?
- SLE is characterized by auto-Ab that form immune complexes with autoantigens that deposit in renal glomeruli. Get glomerulonephritis
How do you test for Type III hypersensitivity reactions?
- Latex agglutination
- Nephelometry
- Chemiluminescence
- Fluorescent staining of tissue biopsy specimens
-Quantify C3 and C4 from complement
How do you treat Type III hypersensitivity reactions?
- Avoid offending Ag
- Corticosteroids: can block some damaged caused by effector cells
- Cyclophosphamide: alkyating agent that impairs DNA synthesis and prevents rapid proliferation of cells
Which immune components mediate Type IV hypersensitivity reactions?
T cells. Specifically the link between T cells and phagocytes (monocytes/macrophages)
List the 3 defining characteristics of Type IV reactions
- Delayed type hypersensitivity (DTH)
- Rejection of foreign tissue grafts, elimination of tumor cells bearing neoantigens
- Formation of chronic granulomas
Describe DTH in detail (in context of Type IV reactions)
Type IV hypersensitivity involves antigen-sensitized T cells or phagocytized particles that are encountered by previously activated T cells for a second or subsequent time. It serves as a major defense mechanism against intracellular pathogens, including mycobacteria, fungi, and certain parasites. Additionally, it is responsible for immunologic mechanisms in contact sensitivity and can occur in response to pathogens that are difficult to clear, such as the hepatitis B virus and Mycobacterium tuberculosis. This immune response can also be triggered by innocuous environmental antigens, autoantigens, and is notably associated with allergic contact dermatitis and pulmonary hypersensitivity caused by various substances.
Describe latex sensitivity in context of Type IV hypersensitivity
Cell-mediated contact dermatitis (Type IV) to latex is not life-threatening, but this allergic reaction is usually due to sensitivity to any chemicals used to make latex products vs actual rubber. Most healthcare facilities use non-latex products (e.g., nitrile gloves), but since 1985, Standard Precautions increased latex glove and condom use.
How do you test for DTH (context: Type IV reactions)
- TB skin test
- Patch testing (used in cases of persistent dermatitis)
- Latex allergy: take patient history and immunologic testing
How do you treat for DTH (in Type IV reaction context)
- Avoid Ag exposure
- Anti-inflammatory drugs or corticosteroids might be useful
