Page 1200 - Veterinary Immunology, 10th Edition

molecules regulate the presentation of processed epitopes. In
VetBooks.ir theory, therefore, they determine resistance or susceptibility to

many diseases. In practice, there is strong selection against genes
that predispose to susceptibility to infectious agents, and MHC

genes have been selected for a strong response to most common
infectious pathogens. In contrast, MHC genes causing autoimmune
diseases in old, post-reproductive animals do not offer a selective
disadvantage, and MHC-linked predispositions have been

identified. Studies of humans have shown that almost all
autoimmune diseases are linked to multiple MHC loci. Presumably
an essential prerequisite for any autoimmune disease is that the
autoantigen is appropriately processed and presented on an MHC

molecule. Thus the structure of the MHC antigen-binding groove
determines whether a specific autoantigen will trigger an immune
response. Some MHC alleles appear to protect against
autoimmunity, and any predisposition to autoimmunity may be the

result of the net effect of both enhancing and protective genes. In
addition, most autoimmune diseases are associated with multiple
MHC alleles. For example, in humans the combination of HLA-A1,
-B8, and -DR3 is associated with increased risk for type I diabetes,

myasthenia gravis, and SLE. One possible reason for the increased
predisposition of females to develop autoimmune diseases may be
attributed to TLR7. This gene is located on the X-chromosome so
that females have two copies while males only have one. TLR7 is

closely linked to the development of systemic lupus (Chapter 38)
(Box 36.1).

Box 36.1

The Effects of Spaying or Neutering on

Autoimmune Diseases in Dogs

Sex hormones have significant effects on immune function, and it is
unsurprising therefore that they affect the development of
autoimmune diseases. In veterinary medicine, we have four

distinct “genders” to assess: intact and neutered males and intact
and spayed females. The relationship between spay/neutering and
the development of autoimmune disease has been investigated in a
population of over 90,000 dogs. Compared to intact dogs, spayed

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