Type I Hypersensitivity (MT2)

Type I Hypersensitivity

Immediate hypersensitivity, allergies and anaphylaxis

Damage caused by IgE + eosinophils

Can be local or systemic response

Type I: Major cells

• Th2 lymphocytes: Activate B cells

• B cells: Produce IgE

• Mast cells, eosinophils, basophils: Cause inflammation

Type I: Major cytokines

IL-4 and IL-13

Mast cell of the blood

Basophils

Th1 pathway

Fights intracellular pathogens

IFN gamma

Th2 pathway

Fights extracellular pathogens

IL-4 and IL-13

Th2 paradigm/Atopy

Genetic predisposition to allergies

Th2 pathway dominates during immune system development

Hygiene Hypothesis

Reduced exposure to extracellular pathogens prevent lymphocyte education

Robust Th2 response against Ag

Allergic Conjunctivitis

• Itching (pruritus): Caused by histamine

• Watery eyes

• Swelling: Conj balloons away from sclera (chemosis)

• Papillae: Small red bumps with red centers on palp conj

Other examples of local allergies

• Allergic Rhinitis (hay fever)

• Allergic asthma

• Atopic dermatitis: Type of chronic eczema, dry itchy rash seen in elbow, knees, or ears

• Episodic uriticaria/hives: Wheal and flare, raised itchy red welts

• Food allergies: Vomiting, diarrhea

Anaphylaxis

Type I response that affects whole body at once

Life-threatening, involves circulating basophils

Anaphylaxis clinical presentations

• Systemic inflammation: Swelling of mouth, throat, eyes, hives

• Broncospasm: Clamp down → Can’t breathe

• Anaphylactic shock: Blood vessels dilate → Hypotension

Anaphylaxis treatment

Bronchodilation

EpiPen, steroids, avoid Ag

Sensitization

Must occur prior to allergic reaction

Production of IgE which binds to IgE dependent mast cells

Type I: Immediate Phase

Exposure to Ag and sensitizes mast cells + basophils

Characterized by vasodilation and increased vascular permeability

Type I: Late Phase

Characterized by eosinophil activation

Causes tissue destruction

Sensitization of IgE dependent mast cells

1. Ag exposure

2. APC presentation + secrete IL-4

3. Th2 cells overactivated + produce IL-13

4. B cell primed + activated

5. Th2 secretes IL-4 + IL-13 causing isotype switching to IgE

6. IgE binds receptor on IgE dependent mast cell and basophils in blood

7. Mast cells and basophils now sensitized

Allergic reaction pathogenesis: Immediate phase

Mast cells and/or basophils (15s - 30min)

1. Ag exposure

2. Ag binds IgE on sensitized cell and crosslinks IgEs triggering activation

3. Cell degranulation + synthesis + secretion

4. Vasodilation, increased vascular permeability, mucus, and pruritus

5. Eosinophil recruitment for delayed phase

Allergic response pathogenesis: Late phase

Eosinophils amplify and sustain inflammation, occurs in 2 waves, 4-8hrs

1st wave: Degranulate cytotoxins, MBP, ECP → Cell death and increase mucus

2nd wave: Synthesis of SRS-A + eotaxin

If basophils were part of the immediate phase…

Eosinophils flood plasma and cause systemic damage (anaphylaxis)

Degranulation molecules in immediate phase

Histamine, heparin, eosinophil, chemotactic factor

Synthesized molecules in immediate phase

PAF, PGD2, PGE2, slow reaction substances of anaphylaxis (SRS-A)

SRS-A

LTC4, LTD4, LTE4

Synthesized via the LOX pathway

Released molecules in immediate phase

IL-1 and TNF alpha

Diagnosis of allergic conjunctivitis

Relies on eye exam

Scratch or blood test

Identifies assorted allergens

Has negative and positive controls

Treatment for allergic conjunctivitis

Non-pharmacological: Avoid Ag, cold compress, non-preservative artificial tears

Pharmacological:

• Anti-histamines: Short acting

• Mast cell stabilizers: Cromolyn, don’t allow degranulation

• Dual action antihistamine/mast cell stabilizers

• Topical corticosteroids

Allergy shots to desensitize body

EpiPen

Treat patient during anaphylaxis, contains epinephrine to open airways

Does not treat allergic response