Hypersensitivies

Using the blog for notes today. (Why? Because. It's here. I like to try new note taking formats.)

Type I:

antibody: IgE
antigen: foreign
effector mechanism: Activation of mast cells and mediators
skin test is available
Time to onset: seconds to minutes
Examples of the disease: include hay fever and anaphylaxis.

Type II:

antibody: IgG and IgM
antigen: Cell or tissue antigens AND cell surface receptors work as antigens.
Effector mechanisms: Complement activation, which leads to phagocytosis; also, cell signalling altered by antibody.
No skin test available.
Minutes to hours for onset.
Examples of disease: transfusion reactions, autoimmune hemolytic anemia, pemphigus vulgaris, and some drug allergies.
Other diseases include Grave's disease, myasthenia gravis, and type 2 diabetes.

Type III:

antibody: IgG aand IgM
antigen: Immune complexes work as the antigen; they activate complement system and phagocytosis. "Why would phagocytosis or complement activation of immune defenses lead to tissue damage? Why is the pathology of mycoplasma immune-mediated? It's because mycoplasms are bound so tightly to the cells that the immune defense can't differentiate. It's bystander damage."
skin test: Arthus reaction (inject antigen and circulating antibodies bind, forming an immune complex and resulting in 'weal and flare').
Inappropriate immune response to antigen, and also excessive.
How do allergy shots, desensitization, work? Kicks the body into T helper 1 response, with IgG. This moves it away from TH2, where IgE activate mast cells for massive degranulation.
6-8 hours to see reaction.
Examples: rheumatoid arthritis, serum sickness, systemic lupus erythematosus (SLE). What is serum sickness? Let's say someone with hepatitis is discovered to have helped prepare food; everyone who ate some is given a massive dose of anti-serum to mop up the hepatitis. (And yes, I know hepatitis is technically just a word for unhappy livers)
Not all hypersensitivities are auto immune.

Type IV
Antibody: none
antigens: foreign, cell antigen...or cell associated.
Effector mechanism: macrophage activation by TH1, plus inflammation
Or CTL mediated cytotoxicity (and inflammation) (if antigen is cell associated).
Skin test: most certainly. It takes 48-72 hours (though the TB skin test in cattle can be nicely simulated in under an hour by using chicken blood cells. On the other hand, you can also induce anaphylaxis, hypersensitivity type I, with chicken cells...apparently reversible).
Examples: contact dermatitis, tuberculin reaction, type 1 diabetes, multiple sclerosis. CTL mediated: acute graft rejection ("omg alien invasion kill kill kill!" scream the CTLs)

Hemolytic disease in newborns: the mother makes antibodies to the fetal antigens (just think of the fetus as an allograft; this is why pregnant women are immunosuppressed). This is a problem for horses; the mare concentrates antibodies in her colostrum. The foal is born without any problems and nurses, and ingests what is essentially anti-foal colostrum. The complicated bit is that this doesn't happen with the first foal she has by that stallion; it takes that first pregnancy to introduce her immune system to the foreign genetics. By breeding her to a different stallion each time, she never builds up the antibody response. The other option is to feed the foal colostrum from a different mare. HOWEVER, the replacement colostrum should be from a mare on the same farm. Horses develop very localized immunity; the endemic pathogens of one farm are not the same as what may be endemic on a different farm.