Page 66 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Autoimmune Diseases
When the immune system continuously forms ance or anergy of the T cells, but rather an im-
autoantibodies (AAB) or activates T cells munological ignorance; this is transformed into
against endogenous antigens, this may cause destruction of myelin when (e.g., with an in-
damage to tissues or organs (autoimmune dis- fection) MBP-specific, inflammatory T H1 cells
ease [AID]). (The occurrence of AAB is by itself are activated elsewhere and then penetrate
no proof of AID, because AAB can be demon- into the brain. In a similar fashion proteins
strated as a transient response to tissue dam- may be released in an injury to the eye and
age). the immune response to it can endanger the
AID is normally prevented, because other, intact, eye (sympathetic ophthalmia).
– immature T cells, which recognize the most Infertility due to sperm-AABs is another exam-
common, ubiquitous autoantigens (AAG), ple. Normally the embryo or fetus with its nu-
are subject to clonal deletion in the thymus merous foreign antigens (inherited from the
(→ p. 42); father) is immunologically tolerated, since the
– mature T cells are clonally inactivated (aner- placenta induces anergy (→ p. 45) of maternal
gy; → p. 45). The reason for this is that cells lymphocytes. Inability of the placenta to do so
in tissue do not give off any costimulation leads to abortion.
signals (e.g., B7-protein; → p. 46, B1); 4. Infections may be involved in the devel-
– AAG-specific T cells are not activated in cer- opment of AID. For example, MBP-specific T
Blood tain circumstances, despite recognition (im- cells (see above) are activated when certain
munological ignorance; see below, point 3).
bacteria are present (experimentally, for ex-
3 The etiology and pathogenesis of AID has not ample, by mycobacteria in Freund’s adjuvant).
been adequately clarified, yet the formation of These pathogens may elicit the missing co-
AAB and T cell activation are based on the stimulation signal (see above). In addition, an-
same mechanisms that operate in immune re- tibodies against certain pathogen antigens or T
actions to foreign bodies (→ p. 42ff. and 52ff.). cells may cross-react with AAG (molecular
The following causes may be fully or in part re- mimicry), such as antibodies against A strepto-
sponsible for the development of AID (→ A): cocci with AAG in the heart (endocarditis),
1. Genetic predisposition is due to certain joints (rheumatoid arthritis), and kidney (glo-
HLA-II alleles: carriers of the HLA-II allele merulonephritis).
DR3 + DR4 are, for example, 500 times more 5. Faulty regulation of the immune system
likely than carriers of DR2 + DR2 to develop of an unknown kind (absence of suppressive
type I diabetes mellitus (→ p. 286). CD8 cells that kill antigen-presenting CD4
2. A sex linkage that is especially marked in cells?) may also be involved.
puberty points to hormonal influences. For ex- The immune mechanisms of AID corre-
ample, the female to male ratio in systemic lu- spond to type II–V hypersensitivity reactions
pus erythematodes is 10:1, while in ankylosing (→ p. 52ff.). One also distinguishes systemic
spondylitis it is 1:3. AID (e.g., systemic lupus erythematodes [type
3. AAG from immunologically privileged re- III reaction]) from organ-specific and tissue-
gions (brain, eye, testis, uterus) may leave specific AID (→ B). Examples of type II reactions
these (via blood vessels, but not via lymphat- are autoimmune hemolytic anaemia and
ics) and interact with T cells, but this does Goodpasture’s syndrome; rheumatoid arthri-
usually not trigger AID, because AAGs are ac- tis, multiple sclerosis (?) and type I diabetes
companied by TGFβ. This is probably responsi- mellitus (in which CD8-T cells destroy the
ble for T H2 cells being activated (instead of the own pancreatic B cells; → p. 286) are examples
destructive T H1 cells). None the less, it is pre- of type IV reactions. Examples of type V reac-
cisely from these regions that AAGs cause AID, tions are hormone receptor–activating
for example, myelin base protein (MBP) of the (Graves’ disease) or hormone receptor–block-
brain causing multiple sclerosis, one of the ing (myasthenia gravis) AAD.
56 most common AIDs. It has been shown in ani-
mal experiments that MBP produces no toler-
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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