It is T cell mediated and no antibodies are involved.

Some examples of antigens are listed below [1].

• Intracellular bacteria: Mycobacteria um tuberculosis, M. leprae, Listeria monocytogenes, Brucella abortus

• Intracellular fungi: Pneumocystis carinii, Candida albican, Histoplasma capsulatum, Cryptococcus neoformans

• Intracellular parasites Leishmania sp.

• Intracellular viruses: Herpes simplex virus, Variola (smallpox), Measles virus

• Contact antigens: Picrylchloride, hair dyes, nickel salts, poison ivy, and poison oak

References:

1. Khanal, S., & Khanal, S. (2024b, June 13). Hypersensitivity type IV: mechanism and clinical manifestation. Microbe Online. https://microbeonline.com/hypersensitivity-type-iv/

Cytokines: Interferon gamma, Interleukins, tumor necrosis factor-alpha, and beta

T cells: CD4 helper T cells and CD8 cytotoxic T cells

Phagocytic Cells: Macrophages, neutrophils, monocytes

Encyclopædia Britannica, inc. (n.d.-a). Encyclopædia Britannica. https://www.britannica.com/science/immune-system-disorder/Type-III-hypersensitivity

example: serum sickness

• occurs when the body is exposed to a foreign serum protein

• takes roughly 6-10 days for antibody development and antigen-antibody complex formation

• host antibody binds to the foreign serum and forms immune complexes.

• immune complexes were the deposited into the joints

• this triggers the activation of the classical complement pathway

• complement proteins C3a and C5a will be released and attract neutrophils and macrophages to the joint (site of deposit) (ncbi, 2023)

• neutrophils will secrete lysosomes and free radicals that will damage the joints

• this will result in arthritis, hence presented as a symptom.

Rixe, N. (2023, August 28). Serum sickness. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK538312/

Usman, N. (2023, May 22). Type III hypersensitivity reaction. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK559122/

Mousa, H. M., Saban, D. R., Foster, C. S., Coma, M. C., & Streilein, J. W. (1970, January 1). Allergy and immune-mediated tissue injury. SpringerLink. https://link.springer.com/10.1007/978-3-319-90495-5_333-1

VP;, K. (n.d.). Aspergillus antigens: Which are important?. Medical mycology. https://pubmed.ncbi.nlm.nih.gov/16110811/

• fever

• rash/ itch --> caused by histamine

• arthritis --> inflammation in the joints

• swelling in areas like eyes

Usman, N. (2023, May 22). Type III hypersensitivity reaction. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK559122/

1. use of antihistamine

   • histamines will be secreted by mast cells due to the trigger by anaphylatoxins

   • this will lead to allergic symptoms like sneezing, swelling etc

   • using antihistamine drugs will help relieve the discomfort of the allergic reactions

2. steroid

   • one example of steroid treatment include corticosteroids, that helps treat rheumatoid arthritis and lupus as it reduces inflammation as it decreases the number of inflammatory cells via apoptosis, and this will eventually reduce tissue damage.

the drugs mentioned can be used for most types of type III hypersensitivity reaction, as well as the example mentioned, serum sickness.

professional, C. C. medical. (n.d.). What is serum sickness?. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/serum-sickness

Common Allergens for these diseases related to Type 1 hypersensitivity:

• Certain medications such as penicillin

• Insect bites such as venom from fire ants

• Food Allergies such as peanuts, nuts, fish and shellfish

Citation :

Mayo Foundation for Medical Education and Research. (n.d.). Anaphylaxis. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/anaphylaxis/symptoms-causes/syc-20351468

• Food Allergies

• Bee or wasp stings

• Allergy testing, such as skin prick test

Citation:

Acute urticaria: Causes, features, and treatment - dermnet. DermNet®. (2024, May 23). https://dermnetnz.org/topics/acute-urticaria

• Indoor Allergens, such as dust mites

• Outdoor Allergens, such as pollens from trees

Citation :

de Groot, H., Brand, P. L. P., Fokkens, W. F., & Berger, M. Y. (2007, November 10). Allergic rhinoconjunctivitis in children. BMJ (Clinical research ed.). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2072026/#:~:text=The%20most%20important%20allergens%20involved,do%20not%20cause%20allergic%20rhinoconjunctivitis.

• Pet dander, such as pet fur, pee or saliva

• Pollen, from trees or weeds

• Molds

• Dust mites

Citation:

professional, C. C. medical. (n.d.). What is allergic asthma?. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/21461-allergic-asthma

• Rash, inflamed and bumpy red skin

• Flushing, warmth sensation

• Hives, raised red bumps / splotches on the skin

• Itching sensation

• Edema, swelling of the tissues when blood vessels leak fluid

• Wheezing, high pitched whistling sound when breathing

• rhinitis, nasal congestion, runny nose

• stomach cramps

Citations :

MediLexicon International. (n.d.). What are the different types of hypersensitivity reactions?. Medical News Today. https://www.medicalnewstoday.com/articles/hypersensitivity-reactions#type-1

--> Increases Vasodilation and peripheral vascular resistance

= decreases airway/mucosal edema

Bronchodilators

-->Relaxes and smooth the muscles in the airways

= improve overall airflow in the lungs

Antihistamines

--> Prevents histamine from binding to the antigen receptors

= reducing many symptoms of allergies

Glucocorticoids

--> Suppresses Inflammation due to anti-inflammatory effect

= increased production of inflammatory mediators

Citations :

Abbas, M. (2023, July 17). Type I hypersensitivity reaction. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK560561/

• exposing the patient to small doses of allergens

  --> this helps patients build up tolerance to eliminate symptoms

Lifestyle Adjustments:

• For Food allergies, have dietary restrictions on food that are harmful for the body

• For environmental allergens, have frequent habits to elimate pet dander / use purifiers in houses

Citation for Allergen Immunotherapy

Immunotherapy for allergies. Allergy & Asthma Network. (2024, May 16). https://allergyasthmanetwork.org/health-a-z/immunotherapy/

--> IgE binds to their surface via the Fc recptors, triggering mast cells, releasing inflammatory mediators

--> leads to allergic symptoms, contributing to the symptoms experienced by the patient

Mast cells also release cytokines and chemokines:

--> Recruits and activate other cells, amplifying inflammatory response

--> Amplifying overall reactions to the allergens

• Hence it serves as a amplification of immune response

• Cell surface antigens

  • Such as those found on RBC (ABO blood group antigens)

• Tissue Antigens

• Drug-induced antigens on cells

Components of immune system involved:

• IgG and IgM

• Activation of classical complement pathway

• NK cells, Neutrophils, Eosinophils and macrophages

Symptoms:

• Fever, Fatigue, chills

• Hemolytic anemia (fatigue, shortness of breath, jaundice, dark urine due to destruction of RBC)

• Hyperacute transplant rejection (rapid graft loss, pain, swelling, inflammation at site of transplant/graft)

Possible Treatments:

• Immunosuppressive therapy

• Monoclonal Antibodies (such as rituximab which targets B cells can be used in some conditions)

• Intravenous immunoglobulin (to modulate the immune response)

• Avoidance (avoid known triggers)

Libretexts. (2022, December 24). 12.4C: Type II (Cytotoxic) reactions. Biology LibreTexts. https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Boundless)/12%3A_Immunology_Applications/12.04%3A_Immunity_Disorders-_Hypersensitivity/12.4C%3A_Type_II_(Cytotoxic)_Reactions

1. Antigen enters the body and the APC engulfs the pathogen via phagocytosis, enclosing the pathogen in a phagosome. The phagosome fuses with the lysosome, forming a phagolysosome.

2. Antigen Processing and Presentation.

   The antigen is processed by digesting the antigen into smaller antigenic peptides, by hydrolytic enzymes in the lysosome.

   MHC receptors are synthesised by ribosomes on the rough endoplasmic reticulum, and modified in the Golgi apparatus.

   A transport vesicle from the Golgi apparatus containing the MHC receptor fuses with the phagolysosome. The antigenic peptides will then bind to the MHC receptor, forming a antigenic peptide:MHC complex.

   The vesicle containing the antigenic peptide:MHC complex is transported to the cell surface membrane. It then fuses with the cell surface membrane, embedding the antigenic peptide:MHC complex in the cell surface membrane. The antigenic peptide can now be presented to naïve T cells to activate these cells.

3. T cell activation.

   During antigen presentation, antigen-presenting cells (APCs) present the antigenic peptide to mature naïve T cells. Naïve T cells with specific T cell receptors (TCRs) will recognise and bind to the antigenic peptide:MHC complex on APCs.

    Activation of naïve T cells require the following signals:

   – Signal 1: Binding of antigenic peptide:MHC complex with TCR

   – Signal 2: Binding of co-stimulatory molecules

   – Signal 3: Secretion of cytokines by APC

4. Clonal Expansion and memory T cell formation.

   The naïve T cell will be activated to proliferate, producing large numbers of genetically identical daughter cells, via clonal selection and expansion. These cells then undergo differentiation to form effector T cells:

   – Helper T cells (TH), which contain CD4 co-receptors

   – Cytotoxic T cells (TC), which contain CD8 co-receptors

   – Memory T cells (either TH or TC cells)

References:

1. Gaudino, S. J., & Kumar, P. (2019). Cross-Talk Between Antigen Presenting Cells and T Cells Impacts Intestinal Homeostasis, Bacterial Infections, and Tumorigenesis. Frontiers in immunology, 10, 360. https://doi.org/10.3389/fimmu.2019.00360

References:

1. MacLeod, M. K., Clambey, E. T., Kappler, J. W., & Marrack, P. (2009). CD4 memory T cells: what are they and what can they do?. Seminars in immunology, 21(2), 53–61. https://doi.org/10.1016/j.smim.2009.02.006

2. Khanal, S., & Khanal, S. (2024c, June 13). Hypersensitivity type IV: mechanism and clinical manifestation. Microbe Online. https://microbeonline.com/hypersensitivity-type-iv/

3. Arango Duque, G., & Descoteaux, A. (2014). Macrophage cytokines: involvement in immunity and infectious diseases. Frontiers in immunology, 5, 491. https://doi.org/10.3389/fimmu.2014.00491

4. Sokol, C. L., & Luster, A. D. (2015). The chemokine system in innate immunity. Cold Spring Harbor perspectives in biology, 7(5), a016303. https://doi.org/10.1101/cshperspect.a016303

Treated with Topical Steriods and Oral corticosteroids

Mantoux Tuberculin Skin test --> results in induration of the skin.

Treatment for Tuberculosis.

Granulomus type --> Sarcoidosis, granuloma

Treated with Anti-TNF antibodies.

Resources:

1. Marwa K, Kondamudi NP. Type IV Hypersensitivity Reaction. [Updated 2023 Aug 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK562228/

Granuloma

Rashes (Contact dermatitis)