The following points highlight the top four types of hypersensitivity in human body. The types are: 1. Anaphylactic Reactions (Anaphylaxis) – Type I 2. Cytotoxic or Cytolytic Reactions- Type II 3. Toxic Complex Syndrome- Type III 4. Delayed Hypersensitivity.
Hypersensitivity: Type # 1. Anaphylactic Reactions (Anaphylaxis) – Type I:
If a guinea pig is injected with a small dose of a foreign antigen (egg albumin), no adverse effects are observed.
When a second injection of egg albumin is given intravenously after an interval of ten days, a condition known as “anaphylactic shock” develops – the guinea pig becomes restless, starts to chew and rubs its nose with its own front paws. Its respiration is labored; the animal becomes cyanosed, may develop convulsions and, ultimately, die.
The initial injection of antigen is termed “sensitizing dose” and the second dose is known as “shocking dose.” During the interval between the two injections, the animal has formed antibody which gets attached on the surface of cells; later, there will be interaction of shocking dose of antigen with the newly formed antibody on the surface of cells—ultimately leading to “anaphylaxis.”
In anaphylactic reaction, four pharmacologically active substances have been implicated— the most important is histamine. The release of histamine can be demonstrated in vitro by exposing antibody sensitized piece of tissue to the contact of antigen.
(Sensitisation may be induced by prior injection of antigen into the animal supplying the tissue which makes antibody as described above or tissue may be sensitized passively by the addition of antibody produced in other animal). The typical contractions induced in isolated strips of uterus and intestine are called Schultz-Dale reactions—after the discoverers.
In man, there are two types of reactions, systemic and local, which are related to the mode of entry of the shocking dose of antigen into the body.
If the antigen is injected parenterally as in the case of serum (e.g. horse anti-tetanus serum), drug (penicillin) or perhaps by the bite of an insect, the systemic form of anaphylaxis is likely to develop, which is characterised by dyspnoea with bronchospasm, sometime skin rashes, a fall in blood pressure, and, occasionally, death.
On the other hand, if the antigen comes primarily in contact with the respiratory mucous membrane then, in a sensitized individual, the local form of anaphylaxis may develop i.e. hay fever, asthma.
When the appropriate antigen (e.g. nuts, fish, strawberries) come in contact with the intestinal mucous membrane of a sensitized individual a mixed form of reactions may develop with the intestinal symptoms, urticaria, skin rashes and, sometimes, symptoms of asthma.
Antibodies in Anaphylactic reactions:
In man, reaginic antibody is responsible for the sensitisation of the tissues for anaphylactic reactions. This antibody has an affinity for tissues and can readily be detected in the serum of a sensitized individual by injecting a small quantity of this serum into the skin of a normal recipient, which is followed by introduction of the appropriate antigen into the same site of injection, after an interval of 24-48 hours.
A wheal and flare erythematous reaction develops within about 20 minutes at the site of injection, just like a response to an injection of histamine. This reaction is known as Prausnitz-Kustner (PK) test according to its originators.
Hypersensitivity: Type # 2. Cytotoxic or Cytolytic Reactions- Type II:
The antibody directed against a cell which is associated with an antigen brings about cytotoxic or cytolytic effect which involves participation of complement.
(a) In incompatible blood transfusion, the cytolytic effect of antibody on foreign red blood cells was observed.
(b) Haemolytic disease of newborn has a similar mechanism.
(c) Sedormid purpura is a cytotoxic reaction which is due to the union of the drug sedormid with platelets, as a result an antibody response against the platelet-absorbed drug brings about destruction of the platelets and thus cause purpura. Therefore, the drug sedormid was withdrawn from the market.
A variety of infectious diseases due to Salmonella and Mycobacteria are associated with haemolytic anaemia. Studies of salmonella infections revealed that the haemolysis is apparently due to an autoimmune reaction against a lipopolysaccharide endotoxin which becomes coated on the erythrocytes. A detailed study has been conducted in Salmonella gallinarum infections in chickens.
Hypersensitivity: Type # 3. Toxic Complex Syndrome- Type III:
This reaction is due to the combination of antigen with circulating antibody leading to formation of micro precipitates in and around small blood vessels with consequent inflammation and subsequent mechanical blockage of the vessels causing interference with the blood supply to surrounding tissues.
There are two types of reactions:
(a) Systemic form – Serum sickness;
(b) Local form – Arthus phenomenon.
(a) Serum Sickness:
Develops in individuals given injection of foreign serum and it is described soon after the parenteral administration of horse anti-tetanus serum (ATS). Symptoms are asthma or laryngeal oedema. The organs affected are kidney, heart, and joints. Now-a-days the most likely causes of serum sickness are drugs (penicillin) which form drug-protein complexes in the host.
(b) Arthus Phenomenon:
Like serum sickness, Arthus phenomenon is brought about by the formation of antibody-antigen complexes, but, in this case, the phenomenon is local at the site of injection. Arthus reaction occurs in the walls of small blood vessels in the presence of large quantities of IgG antibody, which forms micro precipitates with antigen.
This reaction may occur in diabetes patients who have received many injections of insulin and have developed high levels of IgG antibody to antigenic constituents in the insulin preparation. Similar reaction is also noted in case of anti-Rabies vaccination.
Hypersensitivity: Type # 4. Delayed Hypersensitivity:
Cell mediated hypersensitivity:
This type of reaction occurs after 24-48 hours after injection of antigen.
The classical example of this type of reaction is tuberculin response which occurs when an individual previously or currently infected with tubercle bacilli is given an intradermal injection of 0.1 ml of 1: 1,000 dilution of a protein extract of tubercle bacilli (purified protein derivative, PPD), 48-72 hours later an indurated inflammatory reaction of variable size can be seen on the skin.
The injection site is infiltrated with large number of mononuclear cells-lymphocytes. The mechanism is not yet well understood.
Macrophages in delayed hypersensitivity reaction sites may contribute lysosomal enzymes from their intracellular granules and, thus, further inflammatory changes.
When macrophages come in contact with antigen, the sensitized lymphocytes release a number of non-antibody factors (i.e. lymphokines) which are
(a) A factor inhibiting macrophages migration;
(b) A chemotactic factor; and
(c) A cytotoxic factor. The role of these substances in delayed hypersensitivity is not clear.
Delayed hypersensitivity reactions are observed in brucella, salmonella, mycobacterium, pathogenic fungi and a wide range of viruses (herpes simplex, measles, small pox, vaccinia) infections. It can develop after sensitisation to a variety of metal (nickel and chromium) and dyes (hair dyes).
Skin sensitisation to penicillin is common after topical application of the antibiotic ointment or cream—clinical signs are redness, swelling, vesicles, scaling and exudation of fluid.