Hypersensitivity reactions - Type II: Nursing

A hypersensitivity reaction is an overreaction to a foreign antigen which then causes serious damage to the body’s tissues.

There are four types of hypersensitivity reactions: type I is immunoglobulin E, or IgE mediated; type II is mediated by antibodies that activate cellular cytotoxicity, type III is mediated by immune-complexes, and type IV is a delayed T cell mediated hypersensitivity reaction.

A type II, or cytotoxic, hypersensitivity reaction occurs when IgG or IgM antibodies bind to an antigen on the surface of a cell and cause other immune cells and complements to attack it, leading to the cell’s destruction.Let’s start by discussing the physiology of the humoral immune response.

The humoral immune response is the part of the immune system that provides protection against invading pathogens by utilizing antibodies designed to specifically target certain antigens.

It all begins in the bone marrow, where undifferentiated hematopoietic stem cells differentiate into various types of white blood cells, including T and B lymphocytes, or T and B cells, for short.

When a pathogen, like a bacteria or virus enters the body, it runs into antigen-presenting cells, or APCs. APCs like macrophages or dendritic cells, then engulf and digest the pathogen and the fragments are then presented on the APC’s surface via proteins called major histocompatibility complex class II, or MHC II.

Now these fragments serve as antigens which are any thing that could trigger an immune response. So the APCs present these antigens to T helper cells which have T-cell receptors, or TCRs, that recognize the antigen.

These T helper cells will go on to activate specific B cells which causes them to transform into plasma cells that could produce antibodies against the specific antigen.

Antibodies called IgM and IgG are produced and they can attach to the antigens on the bacteria or virus that activates the complement system.

Complements are a group of proteins, named C1 through C9, created by the liver and released into the blood. When these complement proteins encounter an antibody bound to an antigen, they activate the complement cascade where one complement protein helps activate the next one in sequence by helping enzymes cleave them to functional fragments.

So first, C1 attaches to the antibody on the bacteria and activates other complements. Some of these complements attract macrophages and neutrophils to the area where they release enzymes that create oxygen free radicals that are harmful to the bacteria.

Others can attach to the pathogen and mark it as a target for the macrophages to phagocytose. The rest will form membrane attack complexes, or MAC, on the bacteria’s surface which then creates a hole that lets surrounding fluid leak into the cell and intracellular content leak out, causing the cell to die.

Now, to ensure the immune cells do not attack their owner’s tissue, there are processes called central and peripheral tolerance.

Central tolerance causes immature T cells in the thymus and B cells in the bone marrow to self-destruct if they react to any antigens.

In peripheral tolerance, surviving T and B cells are tested again after they leave the thymus and bone marrow and any self reactive immune cells that were missed by central tolerance are destroyed.

Okay, type II hypersensitivity reactions occur when the humoral immune system mistakes the body’s own cells with pathogens and activates the complement system.

Since the complement system is a part of the innate immune system, it doesn’t distinguish between friend and foe, so it's perfectly happy to attack the body’s own cells as well as bacterial ones.

The main risk factor for type II reactions is having a blood transfusion, taking certain medications, or a personal or family history of type II reactionsNow, let’s take a look at the pathology of type II hypersensitivity reactions.

The specific condition caused by a type II reaction depends on what cells in the body are targeted by the autoantibodies.

First, some medications like penicillin can cause autoimmune hemolytic anemia. The medication binds to red blood cells and the immune system sees it as an antigen.

IgG and IgM antibodies against the medication are created and bind to the penicillin and activate the complement system.

As a result the red blood cells are destroyed, causing hemolytic anemia and symptoms like pallor, fatigue, weakness, shortness of breath and dizziness.The pathology is similar in transfusions.

As an example, a person with type A blood will not make antibodies against type A red blood cells; however if they get a transfusion from someone with type B blood, they will make antigens against the foreign cells, causing a type II hypersensitivity reaction.

Common symptoms of a transfusion reaction include fever and chills, hypotension, dyspnea, dark urine, rash, and pruritus, or even renal failure.Sometimes, B cells and T cells start creating autoantibodies against self antigens, which damages cells and tissues.

One example is Goodpasture Syndrome, where autoantibodies are produced against the basement membrane of the glomerulus in the kidney and against the lung alveoli.

Kidney damage causes hematuria, hypertension and anemia, while lung damage causes coughing with bloody sputum, chest pain and dyspnea.

Finally, in some diseases like myasthenia gravis and Graves disease, the autoantibodies target the body’s own cells, but instead of damaging the cells directly, they disrupt their normal function.

In myasthenia gravis, the autoantibodies attack the neuromuscular junction which leads to muscle weakness. Muscles in the eye region are commonly affected, and this causes diplopia, or double vision, and drooping eyelid.

Weakness of the muscles in the mouth and throat could lead to problems eating or speaking, and there’s also weakness of the limbs that impair ADLs.

In Graves disease, the antibodies attach to thyroid stimulating hormone, or TSH, receptors on the thyroid. These antibodies actually mimic the thyroid stimulating hormone and cause the overproduction of thyroid hormone.

The result is hyperthyroidism with symptoms like anxiety, tachycardia and palpitations, weight loss, heat intolerance, and goiter.

All right, as a quick recap... Type II hypersensitivity reactions are mediated by autoantibodies against the body’s own cells, which activate cellular toxicity mechanisms.

The main risk factor is having a blood transfusion, as well as a personal or family history of type II hypersensitivity reactions.

Common types of type II reactions include immune thrombocytic purpura, autoimmune hemolytic anemia, pernicious anemia, rheumatic fever, Goodpasture syndrome, and transfusion reactions.

Type II hypersensitivity begins when the body is exposed to an antigen and IgM or IgG antibodies are produced. These antibodies can be directed against a foreign antigen, like a medication or a red blood cell from a transfusion; or against self antigens.

Autoantibodies can cause damage to self cells, which is the case with Goodpasture syndrome, a condition associated with kidney and lung damage; or disrupt