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Resources used for this section:

https://youtu.be/mzC9NgY2Rj0?si=vqDFAoDZd7rNdMKP

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

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Type I or immediate-type hypersensitivity is an allergic reaction stimulated by the binding of pre-formed IgE to high affinity Fc receptor for IgE on mast cells or basophils.

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.

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Type I hypersensitivity (IgE-mediated hypersensitivity) - causes, symptoms, pathology

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Immune complexes which consists of:

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

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Complement system (activated by the immune complexes as C1, C2, C3, C4 can bind to the Fc region of antibodies in the complex)

Phagocytic cells (neutrophils and macrophages which phagocytose immune complexes)

Antibodies (Primarily IgG and IgM are the ones binding to the soluble antigens forming immune complexes)

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Rash

Arthritis (joint pain)

Fever

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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)

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Short video showing how reaction occurs. (Obtained from Hack Dentistry on YouTube)

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Two types of initiators are involved in this reaction - Antigen-presenting cells (APCs - dendritic cells and macrophages) and T Helper 1 (TH1) cells.

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)

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Fig 1 Showing how response works. (Obtained from SCORM Package)

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It is also known as delayed-type hypersensitivity and is one of the forms of immune response that does NOT involved antibodies. It uses T cells instead!

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

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Contact dermatitis - Redness, itchiness, swelling.

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

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

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1. Topical Corticosteroids / Antihistamines

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.

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figure above is a summary of the overview of how type I hypersensitivity occurs. 

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Sensitisation

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.

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From mast cell activation and granule release it affects

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.

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Treatments are classified into which step of the response the treatment is targetting.

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

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Also known as cytotoxic hypersensitivity, are mediated by IgG and IgM antibodies binding to cell-surface antigens or matrix-associated antigens on basement membranes.

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Hypersensitivity Type II is initiated by Ig G and Ig M release by plasma cells (B cells)

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Ig G and Ig M will bind to antigen of allergen, forming immune complex. C1 complementary proteins will bind to immune complex forming C1 complex, activating classical pathway.

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chronic inflammation can damage healthy cells, tissues and organs, and may cause internal scarring, tissue death and damage to the DNA in previously healthy cells

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C3b protein from classical pathway and antibodies (Ig G and Ig M) will act as opsonin, binding to allergen. Triggering phagocytosis

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Ig G and Ig M will bind to antigen of allergen. NK cell CD 16 Fc receptors will recognise Fc region of antibodies. NK cells will bind to target cell and triggering degranulation. Resulting in cell lysis and apoptosis.

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Formation of membrane attack complex (MAC)

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Formation of membrane attack complex (MAC)

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Formation of MAC complex on the target cell will form pore on the membrane, draining the cell.

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Perforin and granzymes will be secreted.

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

Granzymes act as protease to cleave molecules within target cell.

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Bajwa, S.F. and Mohammed, R.H. (2023). Type II Hypersensitivity Reaction. [online] PubMed. Available at: https://www.ncbi.nlm.nih.gov/books/NBK563264/ [Accessed 3 Aug. 2024].

Biosciences, iQ (2015). ADCC: The Antibody Awakens…the Immune System (Part 1). [online] iQ Biosciences. Available at: https://iqbiosciences.com/blog/adcc-the-antibody-awakens-the-immune-system-part-1/ [Accessed 2 Aug. 2024].

courses.lumenlearning.com. (n.d.). Hypersensitivities | Microbiology. [online] Available at: https://courses.lumenlearning.com/suny-microbiology/chapter/hypersensitivities/ [Accessed 3 Aug. 2024].

HealthEngine Blog. (2005). Type II hypersensitivity reaction information | myVMC. [online] Available at: https://healthinfo.healthengine.com.au/hypersensitivity-reaction-type-ii [Accessed 3 Aug. 2024].

Karki, G. (2018). Type II hypersensitivity reaction: Mechanism and examples - Online Biology Notes. [online] Online Biology Notes. Available at: https://www.onlinebiologynotes.com/type-ii-hypersensitivity-reaction-mechanism-and-examples/ [Accessed 3 Aug. 2024].

Thau, L., Asuka, E. and Mahajan, K. (2022). Physiology, Opsonization. [online] PubMed. Available at: https://www.ncbi.nlm.nih.gov/books/NBK534215/#:~:text=Opsonization%20of%20a%20pathogen%20can%20occur%20by%20antibodies%20or%20the%20complement%20system.&text=Classical%20pathway%3A%20The%20formation%20of [Accessed 3 Aug. 2024].

Wilson, D.R. and Millar, H. (2021). What are the different types of hypersensitivity reactions? [online] www.medicalnewstoday.com. Available at: https://www.medicalnewstoday.com/articles/hypersensitivity-reactions#type-2 [Accessed 3 Aug. 2024].

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1. Hemolytic anemia and damage

weakness

paleness

jaundice

heart murmur

kidney failure

2. Cytopenias - reduction in numbers of mature blood cells

thrombocytopenia, reduce in platelet; difficulties in blood clotting

neutropenia, reduced in neutrophil; recurring infections

3. Autoimmunity disease

joint paint and swelling

recurring fever

skin rashes

4. Drug toxicity

5. neuromuscular disorders

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1. Prevention

Avoid source of hypersensitivity

clarify blood type before blood transfusion

avoid drugs that may cause allergy reactions like penicillin, thiazides, cephalosporins, methyldopa

2. Immunosuppressant drugs

Like systemic glucocorticoids, cyclophosphamide and cyclosporin agents, intravenous immunoglobulin infusions, plasmapheresis

To prevent actions of unusual antibodies.

3. intragam infusion

infusing the body with antibodies

many potentially severe side effects due to this; must be administered under specialist supervision

4. plasmaphoresis

removing the blood autoantibodies.

5. other drugs

interferon

cyclophosphamide

cyclosporin