AUTOIMMUNITY &
HYPERSENSITIVITY REACTION
,AUTOIMMUNITY
,• This occurs when the immune system attacks self-molecules as a result of a br
of immunologic tolerance to autoreactive immune cells.
• Many autoimmune disorders have been strongly associated with genetic, infec
and/or environmental predisposing factors.
• Comprising multiple disorders and symptoms ranging from organ-specific to sy
autoimmune diseases include;
• Insulin-dependent diabetes mellitus,
• Rheumatoid arthritis (RA),
• Systemic lupus erythematosus (SLE),
• Scleroderma,
• Thyroiditis, and
• Multiple sclerosis (MS).
• There are also implications of autoimmune pathology in such common health
as;
• arteriosclerosis,
• inflammatory bowel disease,
• schizophrenia, and
• certain types of infertility.
,• Autoimmune reactions also reflect an imbalance between effector and
regulatory immune responses, typically developing through stages;
• Initiation and propagation, and
• Frequent phases of resolution (indicated by clinical remissions) and
• Exacerbations (indicated by symptomatic flares).
• Internationally, it is now estimated that cases of autoimmune diseases a
rising by between 3% and 9% a year, with this increased associated with
western diet.
• Autoimmune diseases are also more common in women, suggesting a
hormonal or sex-linked influence.
• Collectively, 75% of autoimmune disease is found in women and most
commonly arises during the childbearing years.
• The most striking gender bias is seen in SLE where, during this time of t
women are approximately 10 times more likely to develop this disease t
men. However, this drops to only a 2.5‐fold excess following the menop
,• There is a suggestion that higher oestrogen levels are found in patients
compared with controls.
• In glomerulonephritis, knocking out the oestrogen receptor α chain in t
× NZW mouse model lowers autoantibody levels, decreases the severity
glomerulonephritis, and increases survival.
• Pregnancy is often associated with amelioration/improvement of autoim
disease severity.
• For example in rheumatoid arthritis (RA), and there is sometimes a strik
relapse after giving birth, a time at which there are drastic changes in
hormones such as prolactin, not forgetting the loss of the placenta.
• Autoimmune attacks follow a variety of routes:
• Circulating antibodies bind to cells and either assist in destroying them or interf
their functions.
• Antibody-antigen combinations circulate in the blood and lymph systems, lodge
various tissues, and cause cell destruction.
• Cell-killing lymphocytes launch a direct attack on healthy tissues.
,
,• Autoimmune diseases can be either organ-specific or systemic.
• In organ-specific autoimmunity, an immune response is directed toward
antigens in a single organ.
• Examples are;
• Addison disease, in which autoantibodies attack the adrenal cortex, and
• myasthenia gravis, in which they attack neuromuscular cells.
• In systemic autoimmunity the immune system attacks self antigens in se
organs.
• For example, systemic lupus erythematosus (SLE), is characterized by
inflammation of the skin, joints, and kidneys, among other organs.
• Because the cause of immune system failure is unknown, treatment of
autoimmune diseases centres on alleviating symptoms such as inflamm
• Current therapies, such as cytokine antagonists, have shown great prom
treating many of these diseases.
,• TNF-α antagonists have changed the course of rheumatoid arthritis, an
cytokine antagonists are showing impressive efficacy in various other di
• In organ-specific disorders, attempts are made to correct the specific de
• Drugs that suppress the production of antibodies must be used carefull
avoid lowering the body’s resistance to infection.
• In most cases, this necessitates continued and sometimes life-long ther
resulting in an increased risk of malignant and infectious complications.
• Tackling these diseases at their source will require an understanding of
the abnormal immune reactions arise, how they are sustained, and the
intrinsic mechanisms used to suppress these responses in healthy indiv
• Augmenting regulatory mechanisms and establishing robust and long-li
disease resolution is a goal of new therapeutic strategies.
,• Autoimmune diseases, like GENETIC SUSCEPTIBILITY, ENVIRONMENTAL STIMULI, AND
REGULATION ARE RESPONSIBLE FOR INITIATING AUTOIMMUNI
many other complex disorders,
are believed to arise from a
combination of genetic and
environmental factors.
• One hypothesis on their origin
is that polymorphisms in
various genes result in
defective regulation, or
reduced threshold for
lymphocyte activation,
additionally, environmental
factors initiate or augment
activation of self-reactive
lymphocytes that have escaped
control, and are poised to react
against self-constituents.
, • Genetic polymorphisms in immune-related genes (including HLA (MHC)
cytokines/receptors, and those involved in central tolerance) may lower
threshold for the activation of autoreactive T cells.
• Environmental triggers such as infection, the microbiome, and tissue inj
generate a proinflammatory environment that supports the activation o
autoreactive lymphocytes.
• Tregs normally function to suppress autoreactive T cells, but defects in
development, stability, or function may render these cells dysfunctiona
unable to control autoreactive T cell responses.
• Alone or in combination, these factors can contribute to the escape, act
and proliferation of autoreactive lymphocytes that result in tissue injury
clinical disease.
• Numerous genetic polymorphisms have been tied to different autoimm
diseases.
