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Type IV Hypersensitivity Reaction | Concise Medical Knowledge (lecturio.com)

Initiators of the reactions are allergens which are usually harmless substances but can trigger an allergic reaction in susceptible individuals. Some examples of this would be peanuts, pollen, seafood, etc. 

https://www.youtube.com/watch?v=2tmw9x2Ot_Q video from osmosis explaining hypersensitivity type I. 

• Antibodies (IgG, and less commonly IgM)

• Soluble Antigens (found dissolved in the blood)

The antigens of the allergens are bound to the Fab region of the Antibody forming an immune complex

Purpose of immune complex:

• Accumulates in various tissues to trigger an inflammatory response (Fc region of antibody is exposed and would bind to be able to bind to immune cells with FC receptors on their surface)

• Activating the complement system

1. Avoidance

- Avoiding hypersensitivity triggers (e.g: Drugs, environmental antigens etc.)

2. Anti-inflammatory medication

- Non-Steroidal inflammatory drugs (NSAIDs): Ibuprofen, Naproxen can reduce inflammation, pain and fever

- Corticosteroids (mainly in conditions like lupus or rheumatoid arthritis)

3. Plasmapheresis

- The removal and replacement of plasma from the blood (Helps to remove circulating immune complexes and antibodies from the bloodstream, sometimes used in severe autoimmune cases of lupuis)

Function of the APC is to process and present antigens to the T cells. This will activate the T cells in the presence of the Histocompatibility complex (MHC) molecules.

Function of TH1 cells is to release cytokines once activated by the APCs which will then activate the other immune cells (macrophages). The cytokines will also activate an inflammatory response at site of exposure to attract other immune cells at the site which will then cause the allergic reaction.

Reaction:

1. Person exposed to allergen.

2. Delayed reaction which occurs 24-48 hours after exposure.

3. APCs process and present antigens specific to antigens to the TH1 cells

4. TH1 cells release cytokines (cause inflammatory response)

Examples: Contact dermatitis, allograft rejection and autoimmune diseases such as Type 1 diabetes.

Allergic reactions - Persistent itching, inflammation and thickened skin around site of exposure.

(Develops around 24-48 hours after exposure to allergen)

This is an anti-inflammatory treatment which will help to reduce the redness, swelling and itching for allergic reactions like contact dermatitis.

2. Oral Corticosteroids / Immunosuppressive agents

For more severe reactions such as allergic reactions that spreads from the site of exposure to other parts, this will help to control the inflammation and the immune response from over expressing itself. (Localizes allergic reaction)

3. Phototherapy

This treatment uses UV light therapy to calm chronic dermatitis which reduces inflammation and the other responses to the allergen.

When allergen is first detected, they are phagocytosed by B cells which act as antigen presenting cells (APCs) to present allergen peptides to naive T cells to activate them. After, activated Th2 cells then help activated B cells undergo class switching to produce IgEs specific to the allergen. IgEs will bind toFc receptors on mast cell surface to sensitise it. 

Trigger

During subsequent exposures, an allergen binds to two IgE receptors on mast cell surface to cross link them which activates mast cells, which results in the release of histamine and inflammatory mediators. 

The immediate release of mediators induces vasodilation, vascular permeability, smooth-muscle contractions, mucus secretions and edema formation. This can occur quickly within seconds to minutes. 

Gastrointestinal tract 

- increased fluid secretion

- increased peristalsis

→ leads to expulsion of gastrointestinal tract contents which result in symptoms such as diarrhea and vomitting

Eyes, nasal passages, and airways

- decreased diameter

- increased mucus secretion

→ leads to congestion and blockage of airways which results in symptoms such as wheezing, coughing, phlegm

→ swelling and mucus secretion in nasal passages

Blood vessels

- increased blood flow

- increased permeability 

→increased fluid in tissues causing increased flow of lymph to lymph nodes, increased cells and protein in tissues, which increases effector response in tissues. Hypotension potentially leading to anaphylactic shock. 

Mediator action → Antihistamines medication block histamine action from activated mast cells

The mechanism of action is that it inhibits effects of mediators on specific receptors which inhibit synthesis of specific mediators.

Chronic inflammatory reactions → anti-inflammatory medication (general anti-inflammatory effects)

Th2 response → desensitisation therapy by injections of specific antigen

The mechanism of action is induction of regulatory T cells

Binding of IgE to mast cell → Anti-IgE antibodies (omalizumab → type of monoclonal Ab)

Binds to IgE Fc region and prevents IgE binding to Fc receptors on mast cells

Perforin will create hold on the membrane of the target cell.

Granzymes act as protease to cleave molecules within target cell.