Allergy and Hypersensitivity

Question 1

With examples, give the different types of hypersensitivity reactions.

Answer 1

• TYPE 1 - IgE mediated. EXAMPLE - ANAPHYLAXIS
• TYPE II - Antibody dependant eg IgG or IgM. EXAMPLE - Haemolytic anaemia
• TYPE III - Immune complex mediated. EXAMPLE - SLE
• TYPE IV - T-Cell mediated. EXAMPLE - Rash

Question 2

Describe what occurs in Type 1 hypersensitivity reactions. PART 1

Answer 2

• CD4+ T helper cells activate B cells - produce IgE antibodies specific to antigen
• Antibodies bind to Fc receptors on surface of mast cells and basophils
• Cells become sensitised. Immediate response on re-exposure to same allergen.

Question 3

Describe what occurs in Type 1 hypersensitivity reactions. PART 2

Answer 3

• Allergen cross links bound IgE on sensitised cells - causes anaphylactic degranulation.
• Chemical mediators e.g histamines and cytokines released
• Vasodilation and smooth muscle contraction occurs

Question 4

What mast cell mediators cause vasodilation and increased permeability, and smooth uscle spasms?

Answer 4

• Histamines/PAF/ Prostaglandin D2/ Leukotriene C4/D4/E4

Question 5

What causes leuocycte extravasation?

Answer 5

• Cytokines
• Chemotactic factors for neutrophils and eosinophils

Question 6

Describe bronchial asthma

Answer 6

• Chronic inflammation with intermittent/reversible airway obstruction
• Dominated by presence of eosinophils, CD4+ cells and CD4+ NK cells expressing invariant TCR - recognises antigens

Question 7

What causes the following and what are the responses?
- WHEAL AND FLARE
- ALLERGIC RHINITIS
- FOOD ALLERGY

Answer 7

• WHEAL AND FLARE - Insect bites. Route of entry is subcutaenous and causes local increase in blood flow.
• ALLERGIC RHINITIS - Caused by pollens when inhaled causing inflammation of nasal mucosa.
• FOOD ALLERGY - Orally. Causes vomiting but progresses to anaphylaxis

Question 8

What are some treatments for Type 1 hypersensitivity reactions?

Answer 8

• IMMUNOTHERAPY - Allergy shots/ ANTIHISTIAMINES AND ANTI-INFLAMMATORIES

Question 9

Describe anaphylaxis.

Answer 9

• Severe reaction to allergens causing body wide degranulation of mast cells. Causes vasodilation and shock
• Evoked by direct exposure or being in presence of allergen

Question 10

What are some risk factors of anaphylaxis?

Answer 10

• Age-related factors
• Co-existing diseases
• Concurrent medications
• Emotional stress and acute infections

Question 11

How can anaphylaxis be identified?

Answer 11

• Sudden reductions in BP
• Sudden skin, GI and respiratory symptoms
• Itching, generalised hives and swollen tongue, lips etc.

Question 12

How can anaphylaxis be treated? PART 1

Answer 12

• Remove exposure to trigger
• Assess airway, breathing and circulation
• Call for help
• Inject epinephrine intramuscularly into mid-anterolateral aspect of thigh
• Place patient on back or position of comfort if respiratory distress and/or vomiting

Question 13

How can anaphylaxis be treated? PART 2

Answer 13

• Elevate lower extremities - can be fatal if patient sits/stands suddenly
• When indicated, give high-flow supplemental oxygen by face mask
• Establish IV access using needles and give 1-2 litres of saline rapidly
• Perform CPR and continuously check patient vitals

Question 14

Describe Type II hypersensitivity reactions.

Answer 14

• IgG and IgM antibodies directed against antigens on host cells
• Leads to cell lysis or tissue damage through complement (in)dependent mechanisms
• Results in opsonisation, cell lysis by MAC and RBC agglutination

Question 15

Describe complement dependent Type II hypersensitivity reactions.

Answer 15

• Antibody targets antigens on host cells
• Ab-Ag complexes activate complement causing cell lysis by MAC or opsonisation with C4 causing other immune cells to phagocytose opsonised material
• Caused by incompatible blood transfusions, autoimmune haemolytic anaemia and Goodpasture’s syndrome

Question 16

Describe antibody dependent cell mediated cytotoxicity in Type II hypersensitivity reactions.

Answer 16

• Low concentrations of IgG coat target cells
• Inflammatory cells e.g NK cells and granulocytes bind to IgG via Fc receptors and lyse target cells using perforins.
• Occurs during transplant rejection, immune reactions against neoplasms/parasites

Question 17

Describe HDN.

Answer 17

• Occurs when immune system develop antibodies against baby’s RBCs causing haemolysis
• If mother is Rh- and carries Rh+ fetus, anti-Rh antibodies produced i.e IgG antibodies (anti-D antibodies)
• Cross placenta into fetal circulation and lead to haemolysis
• Treated with antibodies to the Rh antigen - no anti-D antibody production

Question 18

Describe Type III hypersensitivity reactions.

Answer 18

• Generation of Ab-Ag immune complexes inducing inflammation
• Antigens bind to antibodies and form immune complexes which deposit in tissues
• Activates complement clasical pathway and recruits neutrophils and macrophages causing inflammation
• Causes inflammation and tissue injury

Question 19

Describe serum sickness.

Answer 19

• Occurs when patients administered serum from healthy people (containing antibodies beneficial to patients)
• Antibodies produced against antigens in donor’s serum
• Deposition of Ab-Ag complexes in kidneys and joints
• Can cause glomerulonephritis and arthritis

Question 20

Describe the characteristics of Type IV hypersensitivity.

Answer 20

• T-cell mediated NOT ANTIBODY MEDIATED
• Reaction takes several days to develop

Question 21

What is the mechanism of Type IV hypersensitivity reactions?

Answer 21

• CD4+ T helper cells recognise antigens in complex with MHC Class II on surface of APCs
• CD4+ T cells secrete IL-2 inducing further cytokine release
• Activated CD8+ T cells destroy target cells and activated macrophages produce hydrolytic enzymes.
• Overreaction of cells and overproduction of cytokines causes inflammation and cell death.

Question 22

Describe the tuberculin skin test. PART 1

Answer 22

• Determines if patient infected with Mycobacterium tuberculosis
• Antigen injected subcutaenously and processed by APCs
• Th1 cell recognises antigen and releases cytokines - act on vascular endothelium

Question 23

Describe the tuberculin skin test. PART 2

Answer 23

• Recruitment of phagocytes and plasma to site of injection
• Produces pale elevation of skin