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The initiator is a specific antigen

Immune system recognizes it as harmful but does not involve antibodies for its action

Upon first exposure to this antigen, the antigen is captured and processed by APCs

The processed antigen is then presented on (MHC) class II molecules by APCs to CD4+ T helper cells in lymph node

The CD4+ T helper cells recognize the antigen-MHC class II complex and become activated.

This process leads to the proliferation and differentiation of these T cells into antigen-specific Th1 cells.

Upon subsequent exposure to the same antigen, the previously sensitized CD4+ T cells recognize the antigen again. This recognition leads to the release of cytokines

recruitment and activation of these immune cells result in an inflammatory response, which is characteristic of cell-mediated hypersensitivity reactions.

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Components of the Immune System Involved

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Components of the Immune System Involved

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1) Antigen Presenting Cells

i) Dendritic Cells

primary APCs that capture antigens from the environment, process them, and present them to T cells

ii) Macrophages

involved in both the presentation of antigens and the execution of the immune response. They can act as APCs by presenting antigens to T helper cells and by phagocytosing pathogens

iii) B Cells

primary role is in antibody production, B cells can also act as APCs, especially in specific contexts

2) T cells

i) Helper T Cells (CD4+T cells)

recognize antigens presented by APCs MHC class II molecules. Upon recognition, they become activated and release cytokines that help coordinate the immune response.

ii) Cytotoxic T Cells (CD8+ T Cells)

Involved in some scenarios, such as direct killing of antigen-presenting cells or infected cells.

3) Cytokines

i) Interleukin-2 (IL-2)

Produced by activated T cells, IL-2 stimulates T cell proliferation and supports the expansion of the immune response.

ii) Interferon-gamma (IFN-γ)

Produced mainly by CD4+ T helper 1 (Th1) cells, IFN-γ activates macrophages and enhances their ability to phagocytose and kill pathogens.

iii)Tumor Necrosis Factor-alpha (TNF-α)

Produced by macrophages and T cells, TNF-α is involved in mediating inflammation and promoting the recruitment of other immune cells to the site of antigen exposure.

IV) Interleukin-12 (IL-12)

Secreted by APCs, IL-12 promotes the differentiation of naive T cells into Th1 cells, which are crucial for cell-mediated responses.

4) Effector Cells

i) Activated Macrophages

After receiving signals from Th1 cells (especially IFN-γ), macrophages become more effective at phagocytosing pathogens and producing inflammatory cytokine

ii) Inflammatory Cells

recruited to the site of antigen exposure, contributing to the inflammatory response.

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Type II hypersensitivity initiators are typically antibodies (lgG or lgM) directed against cell surface or matrix-associated antigens. Antigens can be part of the host's cells or extracellular matrix, which have been altered or recognized as foreign due to various factors, including drug-induced modifications or molecular mimicry

Examples of Antigens of Type II hypersensitivity:

1. Antigens Blood Group Antigens:

Incompatible blood transfusions (eg. A, B, AB, or O antigens)

2. Rh Antigens:

Rh factor incompatibility (e.g., Rh-positive blood given to an Rh-negative person)

Reference:

Bajwa, Shammas F. “Type II Hypersensitivity Reaction.” StatPearls [Internet]., U.S. National Library of Medicine, 4 July 2023, www.ncbi.nlm.nih.gov/books/NBK563264/#:~:text=Type%20II%20hypersensitivity%20reaction%20refers,loss%2C%20or%20damage%20to%20tissues. Accessed 29 July 2024.

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Components of the immune system involved 

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Components of the immune system involved 

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1. Antibodies:

lgG and lgM -> These antibodies bind to antigens on the surface of the cells, such as red blood cells, leading to their destruction

2. Complement system

The complement pathway can be activated by the antigen-antibody complexes. This activation leads to the formation of complement components such as C3b, which act as opsonins and promote phagocytosis, and the membrane attack complex (C5b-9), which can directly lyse target cells

3. Macrophages: These cells can be activated through the Fc receptors on their surface, leading to the phagocytosis of antibody-coated target cells.

4. Natural Killer (NK) Cells: NK cells can mediate antibody-dependent cellular cytotoxicity (ADCC) by binding to the Fc portion of antibodies on target cells and causing cell lysis through the release of perforins and granzymes.

5. Neutrophils: In some cases, antibodies can activate the complement system and generate complement components such as C3a and C5a, which act as chemotactic factors for neutrophils, leading to their recruitment and activation. Neutrophils then release enzymes and reactive oxygen species that can damage tissues.

Reference:

Bajwa, Shammas F. “Type II Hypersensitivity Reaction.” StatPearls [Internet]., U.S. National Library of Medicine, 4 July 2023, www.ncbi.nlm.nih.gov/books/NBK563264/#:~:text=Type%20II%20hypersensitivity%20reaction%20refers,loss%2C%20or%20damage%20to%20tissues. Accessed 29 July 2024.

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YouTube video link: https://www.youtube.com/watch?v=0T_SAXyMs_c&t=10s

The initiator is the formation of an immune complex consisting of a specific allergen (antigen) with the antigen-specific antibody.

These immune complexes are deposited in various tissues, triggering the complement system and recruiting various immune cells, resulting in inflammation and leading to tissue damage.

Examples of type III hypersensitivity:

Serum sickness - Occurs when a foreign serum (containing specific antigens) is administered [1].

Systemic lupus erythematosus (SLE) - An autoimmune disease where autoantibodies bind to self-antigens. The immune complexes are deposited in various organs leading to inflammation [1].

Post-streptococcal glomerulonephritis - Occurs after a streptococcal infection when the immune system mistakenly targets parts of the glomeruli as it resembles certain components of streptococcal bacteria. This leads to inflammation and damage to the glomeruli [2].

References:

1. Type III hypersensitivity. (n.d.). Osmosis from ELSEVIER. https://www.osmosis.org/learn/Type_III_hypersensitivity (Accessed: 29th July 2024)

2. Rawla, P., & Ludhwani, D. (2019, June 26). Poststreptococcal Glomerulonephritis. Nih.gov; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK538255/ (Accessed: 29th July 2024)

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Type III hypersensitivity (immune complex mediated) - causes, symptoms & pathology

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Components of the Immune System Involved (Ganden)

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Components of the Immune System Involved (Ganden)

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1. Antibodies

IgG and IgM bind to soluble antigens to form immune complexes. Immune complexes are deposited in various tissues and organs [1].

2. Complement system

The complement system clears the immune complexes deposited through various mechanisms.

(1) Opsonisation: Complement proteins such as C3b bind to the immune complexes, marking them for phagocytosis by phagocytic cells such as macrophages and neutrophils.

(2) Anaphylatoxin/inflammatory mediators: C3a and C5a recruit more phagocytes to the site of immune complex deposition, leading to more inflammation [1].

3. Inflammatory cells

Inflammatory cells such as neutrophils are recruited to the site where the immune complexes are deposited by anaphylatoxins (C3a and C5a), cytokines and histamines. Cytokines are primarily secreted by mast cells and histamines are secreted by various immune cells such as macrophages and mast cells [1].

Recruited neutrophils release destructive enzymes that cause tissue damage. Inflammation and neutrophils result in inflammatory reactions and tissue damage [2].

4. Phagocytes

Some inflammatory cells recruited to the site of immune complex deposition such as neutrophils and macrophages are also phagocytes. Phagocytes engulf and destroy the immune complexes. They contribute to the inflammatory response [1].

References:

1. Usman, N., & Annamaraju, P. (2020). Type III Hypersensitivity Reaction. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK559122/ (Accessed: 29th July 2024)

2. Snyder, P. W. (2017). Diseases of Immunity1. Pathologic Basis of Veterinary Disease, 242-285.e5. https://doi.org/10.1016/b978-0-323-35775-3.00005-9 (Accessed: 29th July 2024)

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The initiator of Type I hypersensitivity is primarily allergens. It is almost always mediated through IgE antibodies that are bound to the surface of mast cells. Interaction of this IgE with antigens result in activation of mast cells and their rapid degranulation with the release of histamine and other inflammatory mediators.

Examples of Type I Hypersensitivity:

1. Allergic Rhintis

Symptoms: Sneezing, Runny and/or Itchy nose

2. Asthma

Symptoms: Wheezing, Shortness of breath, Coughing

3. Atopic Dermatitis (Eczema)

Itchy, Red and Dry skin

References:

https://www.sciencedirect.com/topics/immunology-and-microbiology/type-i-hypersensitivity

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Components of the Immune System involved 

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Components of the Immune System involved 

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1. B cells

allergens are first phagocytosed by B cells which act as Antigen Presenting Cells to present allergen peptides to naive T cells to activate them.

2. Th2 Cells

activated T helper 2 cells help the activated B cells undergo class switching to produce antigen-specific IgE molecules.

3. IgE

allergen specific IgE molecules will bind to Fc receptors on mast cell surfaces to sensitise it.

4. Mast cells

each antigen binds to 2 IgE on mast cell surfaces to activate mast cells to release inflammatory mediators.

5. Inflammatory mediators

inflammatory mediators such as histamine are released upon the activation of mast cells.

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Rapid onset (minutes to hours)

Allergic rhinitis (hay fever)

Asthma

Atopic dermatitis (eczema)

Food allergies

Anaphylaxis (severe, potentially life-threatening reaction)

Treatments:

Avoidance of allergens

Antihistamines

Corticosteroids

Epinephrine (for anaphylaxis)

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Symptoms & treatments for type II(Edith)

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Symptoms & treatments for type II(Edith)

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Symptoms:

Hemolytic anemia

Thrombocytopenic purpura

Goodpasture's syndrome

Treatments:

Elimination of the offending antigen (e.g., blood transfusion)

Immunosuppressive therapy

Corticosteroids

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Symptoms & treatments for type III(Edith)

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Symptoms & treatments for type III(Edith)

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Symptoms:

Serum sickness

Systemic lupus erythematosus (SLE)

Polyarteritis nodosa

Treatments:

Removal of the antigen

Immunosuppressive therapy

Corticosteroids

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Symptoms & treatments for type IV(Edith)

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Symptoms & treatments for type IV(Edith)

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Symptoms:

Contact dermatitis (e.g., poison ivy)

Allergic contact dermatitis

Tuberculin skin test reaction

Graft-versus-host disease

Treatments:

Avoidance of the allergen

Topical corticosteroids

Antihistamines (may offer some relief)

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https://www.youtube.com/watch?v=jXTW4F-8jd4

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Hypersensitivity, Overview of the 4 Types, Animation.