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.

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.

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.

• 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)

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)

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

• 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)

• Hemolytic anemia

• Thrombocytopenic purpura

• Goodpasture's syndrome

Treatments:

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

• Immunosuppressive therapy

• Corticosteroids

• Serum sickness

• Systemic lupus erythematosus (SLE)

• Polyarteritis nodosa

Treatments:

• Removal of the antigen

• Immunosuppressive therapy

• Corticosteroids

• 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)