Hypersensitivity is when an otherwise healthy immune system has an undesirable exaggerated response to a foreign substance (or perceived foreign substance) that damages the body’s own cells. These are the same immune processes that are necessary to prevent infection, but they create problems when they are hyperactive or misguided. The way I remember the four different types of hypersensitivity is my ABCD mnemonic.
* Types I, II and III all can involve antibodies. Therefore, having antibody in the mnemonic for type II may be confusing. However, the “classic” role of antibody involving complement activation, NK cell activation and opsonization are part of Type II which is why I feel that is the simplest way to remember it.
Type I Hypersensitivity is triggered by an innocuous foreign substance (like dust, pollen or animal dander) that would cause no problems in the majority of people. The antigen simultaneously binds more than one membrane bound IgE on a mast cell (or basophil). This process, called Crosslinking, triggers the release of mast cell granules full of histamine. Histamine then goes on to signal the various changes associated with allergies similar to how it functions during acute inflammation. This allergic reaction happens almost instantly and the symptoms can become evident within minutes. This is possible because the mast cells are Pre-Sensitized to the innocuous substance which means they have pre-formed membrane bound IgE that recognizes the particular innocuous antigen. To be pre-sensitized the immune system must have seen the antigen previously, because antibody (IgE) formation takes time. Histamine’s role in Type I Hypersensitivity is why Anti-Histamines (Histamine Antagonists) like Diphenhydramine or Loratidine can control some allergy symptoms.
Type I Hypersensitivity is the process that leads to various different “allergies”. A more mild form would include Allergic Rhinitis (seasonal allergies) that cause things like coughing, sneezing, watery eyes and nasal congestion. Some individuals with these allergies also experience an atopic rash referred to as Urticaria (Hives) or Atopic Dermatitis (Eczema). This red rash is raised and pruritic (itchy). Through a similar mechanism Type I Hypersensitivity can lead to exacerbation of Allergic Asthma by environmental triggers. This type of hypersensitivity is also the mechanism behind more serious conditions like peanut or bee sting allergies that can lead to swelling of the lips/tongue/throat, shortness of breath, stridor, and anaphylactic shock. Anaphylatic shock is a life threatening condition in which systemic histamine directed inflammation causes hypotension via global vasodilation, an increase in vascular permeability and significant fluid movement into the tissue. It is treated with epinephrine, often in the form of an “Epi Pen” when outside of a medical setting. Epinephrine activates Alpha-1 Adrenergic Receptors to raise blood pressure via vasoconstriction and increased contractility of the heart.
Type II Hypersensitivity is the process by which IgG or IgM binds to a cell to cause injury or death (Antibody Dependent Cytotoxicity). This process has the same mechanism of action as normal humoral immunity except it is targeted at the body’s own cells instead of pathogens. The variable region of the antibody binds to the host cell while the constant portion interacts with NK cells, complement and macrophages. Examples of this reaction can be seen in Rheumatic Fever (body’s own cell look similar to Strep Pyo), Goodpasture Syndrome (Anti-Glomerular Basement Membrane Antibodies) and Hemolytic Disease of Newborns/Erythroblastosis Fetalis (when a Rh- mother has a second Rh+ child and the maternal IgG targets fetal RBCs).
Type III Hypersensitivity is tissue damage created by immune complexes. Immune Complexes are aggregations of antigen and antibodies. Usually, there are far more antibodies than antigen. However, if there is a large amount of antigen or antigen is not being cleared properly by the immune system the antigen:antibody ratio increases. When the amount of antigen and antibody is comparable immune complexes can form. In this scenario a single antibody can simultaneously bind to multiple antigens which are themselves bound to multiple antibodies. This “clump” of antigens and antibody deposits in tissues (most often the vessel, kidneys or joints) and causes inflammation by activating complement and attracting neutrophils. Examples include Lupus, Post Strep Glomerulonephritis & Rheumatoid Arthritis.
Type IV Hypersensitivity is referred to as delayed hypersensitivity and involves Th1 T-Cells attracting and activating Macrophages. It is called delayed because it takes a few days to kick in. This type of hypersensitivity is Cell-Mediated and Antibody Independent. Type IV Hypersensitivity is the only type of hypersensitivity that doesn’t involve antibodies. Examples include Contact Dermatitis (poison ivy and cheap nickel jewelry), PPD (TB skin test) & Multiple Sclerosis (T-Cells attack myelin).
Atopic conditions should not be confused with contact dermatitis. Both conditions involve dermatologic problems as a result of hypersensitivity. However, they act via different mechanisms. The key to differentiate the two is the timeline. Atopic problems form within minutes, while contact dermatitis takes days to form. Any mention of being in the woods is also a big hint suggesting poison ivy exposure which is contact dermatitis.