How Do Type IV Hypersensitivity Reactions Occur?
Adaptive immunity, which relies on a variety of responses to work, maybe involved in a variety of issues when it comes to tissue injury and disease. It can protect the body from harmful infections, but it can also be involved in cases where the body's immune system overreacts, causing tissue damage. Hypersensitivity reactions are the collective term for these disorders.
A variety of factors can cause hypersensitivity reactions. For starters, our immune system may respond to the functioning cells in our bodies. The immune system uses a screening mechanism in which self-detecting immune cells are removed from circulation in normal circumstances. However, in some people, this function may be absent.
In the presence of a microbe, hypersensitivity may also be triggered. The attempts to neutralize the microorganism are exaggerated in this case. This can result in the destruction of cells, tissues, and structures near the invasion site. When the microorganism is persistent, this process is most noticeable.
Antigens in the environment can also contribute to tissue degradation as a result of the immune response. In the presence of an allergen from the environment, a specific antibody (immunoglobulin E or IgE) is formed in some people, resulting in an allergic reaction.
This article will study Type IV Hypersensitivity/T Cell-Mediated Hypersensitivity and type 4 hypersensitivity treatment in detail.
Type IV Hypersensitivity/T Cell-Mediated Hypersensitivity
Type 4 Allergic Reaction due to helper T lymphocytes
Type 4 hypersensitivity reactions are also known as type 4 delayed hypersensitivity characterized by a delayed response mediated by either helper or cytotoxic T cells, as the name suggests. The helper T cells are normally involved in the majority of cases of hypersensitivity.
This subset of T lymphocytes does not target pathogens directly. Instead, it develops interleukins and other cytokines that help other immunologically active cells proliferate. The TH1 and TH17 types of helper T cells are involved in type IV hypersensitivity.
When cells that display antigens, such as dendritic cells and macrophages, release certain cytokines, helper T cells become activated. These cytokines cause TH1 or TH17 cells to proliferate. These effector cells enter the circulation after being developed and act as long-term guardians against potential pathogens.
Since damaged interleukins take hours to days to accumulate in the circulation, the effects of this form of the mechanism are delayed. The interleukins that are produced attract cells like neutrophils and macrophages, which can phagocytose or destroy pathogens in the region.
Type 4 Hypersensitivity Reaction Leads to -
Tuberculin reaction
Contact dermatitis
Some drug reactions
Rheumatoid arthritis-RA is a long-term condition that causes inflammation and pain in the joints. Flares or exacerbations are times when these symptoms and signs appear. Periods of remission, on the other hand, are when symptoms fully vanish.
Although RA symptoms can affect a number of organs in the body, the symptoms of RA in the joints include joint pain, joint swelling, joint stiffness and loss of joint function and deformities
Multiple sclerosis-Multiple sclerosis is characterized as the presence of multiple indurations (sclerosis) in the central nervous system (CNS). MS is a chronic, immune-mediated, inflammatory CNS disease that causes physical disabilities by destroying the myelin sheath and nerve cells to varying degrees.
Inflammatory bowel disease-The inflammatory disease ulcerative colitis (UC) affects the mucosal surface of the colon and is idiopathic. It, like Crohn's disease, is an inflammatory bowel disease (IBD). The rectum is often involved, and inflammation will spread through the colon proximally. Diffuse friability, erosions with bleeding, and haustra loss are all evident on endoscopy in ulcerative colitis.
Inflammatory diseases
Type 4 Hypersensitivity Due to Cytotoxic T Cell
Cytotoxic T cells, unlike helper T cells, kill the cells that carry the triggering antigen directly. As a result, this subtype is particularly effective against viral and parasitic infections where the pathogen is present intracellularly.
These cells cause harm to the microbe by releasing molecules and complexes that harm it. Unfortunately, these compounds are not exclusive to offending agents and may damage healthy tissues in the surrounding area. The following are examples of cytotoxic T lymphocyte-mediated hypersensitivity:
Liver damage during viral hepatitis
Organ graft rejection
Did You Know?
Adaptive immunity employs a more complex group of receptors to detect a wider variety of microbes that may cause disease in the body. Lymphocytes and antibodies are the most important components of this group. Humoral immunity and cell-mediated immunity are the two forms of immunity in this group.
The humoral immunity is maintained by antibodies formed by B lymphocytes. These highly specialized proteins bind to target microorganisms and either neutralize, eliminate, or present them to more effective effector mechanisms.
T lymphocytes, on the other hand, are mainly responsible for cell-mediated immunity, which involves phagocytosis and the destruction of microorganisms and infected cells. Since antibodies are ineffective at neutralizing and killing intracellular microorganisms including parasites and viruses, T lymphocytes may be a better option.
FAQs on Type IV Hypersensitivity: Mechanism, Causes & Examples
1. What is Type IV hypersensitivity?
Type IV hypersensitivity, also known as Delayed-Type Hypersensitivity (DTH), is a cell-mediated immune response that, unlike other types, does not involve antibodies. It is driven by T-lymphocytes (T-cells). The reaction is not immediate and typically takes 24 to 72 hours to develop after a sensitised individual is re-exposed to a specific antigen.
2. What are the key differences between Type IV and Type I hypersensitivity reactions?
The primary difference lies in the immune mediator and the timing of the reaction. Here’s a comparison:
- Immune Mediator: Type I reactions are mediated by IgE antibodies that bind to mast cells and basophils. In contrast, Type IV reactions are mediated directly by T-cells (both helper and cytotoxic T-cells).
- Reaction Time: Type I reactions are immediate, occurring within minutes of exposure to an allergen (e.g., pollen allergy). Type IV reactions are delayed, with symptoms appearing 24-72 hours after exposure.
- Mechanism: Type I involves the release of histamine and other pre-formed mediators. Type IV involves the release of cytokines by T-cells, which recruit and activate other immune cells like macrophages.
3. What are some common examples of Type IV hypersensitivity reactions?
Type IV hypersensitivity is responsible for many common clinical conditions. Some key examples include:
- Contact Dermatitis: Skin reactions to substances like nickel in jewellery, chemicals in cosmetics, or the urushiol oil from poison ivy.
- Tuberculin (Mantoux) Skin Test: A diagnostic test for tuberculosis exposure where a localised skin reaction indicates a T-cell memory response.
- Granuloma Formation: A chronic inflammatory response seen in diseases like tuberculosis and leprosy, where macrophages wall off the pathogen.
- Autoimmune Diseases: Conditions like Type 1 diabetes, multiple sclerosis, and rheumatoid arthritis involve T-cell-mediated attacks on the body's own tissues.
- Graft Rejection: The rejection of a transplanted organ is often a Type IV response where the recipient's T-cells attack the foreign tissue.
4. How does the mechanism of Type IV hypersensitivity work?
The mechanism occurs in two distinct phases:
- Sensitisation Phase: Upon first exposure to an antigen (e.g., a chemical from poison ivy), antigen-presenting cells (APCs) process it and present it to naive T-cells. These T-cells then differentiate into memory T-cells specific to that antigen. This phase is asymptomatic.
- Effector Phase: Upon subsequent exposure, the now-sensitised memory T-cells recognise the antigen. They become activated and release cytokines. These chemical messengers attract and activate macrophages and other immune cells to the site, leading to inflammation and tissue damage, which causes the visible symptoms of the reaction.
5. Why is Type IV hypersensitivity called 'delayed'?
The term 'delayed' refers to the time lag between antigen exposure and the appearance of clinical symptoms. This delay of 24 to 72 hours exists because the response relies on the migration and activation of T-cells and macrophages at the site of exposure. This cellular recruitment and activation process is much slower compared to antibody-mediated reactions (like Type I), where pre-formed antibodies and mediators can cause a reaction within minutes.
6. What is the specific role of T-cells in a Type IV hypersensitivity reaction?
T-cells are the central players in Type IV reactions. There are two main types involved:
- CD4+ Helper T-cells: These cells act as coordinators. Upon activation, they release cytokines that recruit other immune cells, primarily macrophages, to the site. The activated macrophages are responsible for much of the inflammation and tissue damage.
- CD8+ Cytotoxic T-cells: In some Type IV reactions, these cells are directly involved. They can recognise antigen-displaying cells (like virus-infected cells or graft cells) and kill them directly, contributing to tissue destruction.
7. How does the tuberculin skin test (Mantoux test) demonstrate a Type IV reaction?
The Mantoux test is a classic example of a Type IV reaction used for diagnosis. When a small amount of tuberculin antigen is injected into the skin of an individual previously exposed to Mycobacterium tuberculosis, their body will have specific memory T-cells. These memory T-cells recognise the antigen, triggering the effector phase. They release cytokines, causing a local influx of immune cells. This results in a hard, red, swollen area (induration) at the injection site after 48-72 hours, indicating a positive, cell-mediated immune memory.
8. Can Type IV hypersensitivity cause autoimmune diseases?
Yes, Type IV hypersensitivity is a key mechanism behind several autoimmune diseases. In these conditions, T-cells mistakenly identify the body's own cells as foreign and attack them. Examples include:
- Type 1 Diabetes: T-cells attack and destroy the insulin-producing beta cells in the pancreas.
- Multiple Sclerosis (MS): T-cells attack the myelin sheath that insulates nerve fibres in the brain and spinal cord.
- Rheumatoid Arthritis: T-cells contribute to the inflammation and destruction of tissues within the joints.
