2. DEFINITION
• AUTOIMMUNE DISEASES Autoimmunity is a state
in which the body’s immune system fails to distinguish
between ‘self’ and ‘non-self’ and reacts by formation
of autoantibodies against one’s own tissue antigens. In
other words, there is loss of tolerance to one’s own
tissues; autoimmunity is the opposite of immune
tolerance.
3. Immune tolerance
• PATHOGENESIS (THEORIES) OF AUTOIMMUNITY
• Normally, the body’s response to self antigens (autoimmunity) is
prevented by three major processes:
• 1. Sequestration of autoantigens and thus their unavailablity for
autoimmune response.
• 2. Generation and maintenance of tolerance or anergy(absence of the
normal immune response to a particular antigen or allergen) by T and
B lymphocytes in the body.
• 3. Regulatory mechanisms limiting response by the immune system.
4. Pathogenesis of autoimmunity
• Normally, the body’s response to self antigens (autoimmunity) is
prevented by three major processes:
• 1. Sequestration(action of taking forcible possession of something) of
autoantigens and thus their unavailablity for autoimmune response.
• 2. Generation and maintenance of tolerance or anergy(absence of the
normal immune response to a particular antigen or allergen) by T and
B lymphocytes in the body.
• 3. Regulatory mechanisms limiting response by the immune system.
5. • The mechanisms by which the immune tolerance of the body is broken causes autoimmunity. These
mechanisms or theories of autoimmunity may be exogenous or endogenous, and include immunological,
genetic, and microbial factors, which may be interacting:
• 1. Immunological factors Failure of immunological mechanisms of tolerance initiates autoimmunity as
follows:
i) Polyclonal activation of B cells B cells may be directly activated by stimuli such as infection with
microorganisms and their products leading to bypassing of T cell tolerance.
ii) Generation of self-reacting B cell clones may also lead to bypassing of T cell tolerance.
iii) Decreased T suppressor and increased T helper cell activity. Loss of T suppressor cell and increase in T
helper cell activities may lead to high levels of autoantibody production by B cells contributing to autoimmunity.
iv) Fluctuation of anti-idiotype network control may cause failure of mechanisms of immune tolerance.
v) Sequestered antigen released from tissues ‘Self-antigen’ which is completely sequestered may act as ‘foreign-
antigen’ if introduced into the circulation later. For example, in trauma to the testis, there is formation of anti-
sperm antibodies against spermatozoa; similar is the formation of autoantibodies against lens crystallin.
2. Genetic factors Th ere is evidence in support of genetic factors in the pathogenesis of autoimmunity as under
• There is increased familial incidence of some forms of the autoimmune disorders.
• There is higher incidence of autoimmune diseases in twins favouring genetic basis.
3. Microbial factors Infection with microorganisms, particularly viruses (e.g. EBV infection), and less often
bacteria (e.g. streptococci, Klebsiella) and mycoplasma, has be
6. TYPES AND EXAMPLES OF AUTOIMMUNE DISEASES
• Autoimmune diseases are a growing number of such diseases in which
autoimmunity is either mediated by formation of immune complexes or they
are mediated by T cells. In order to classify a disease as autoimmune, it is
necessary to demonstrate that immune response in the body is elicited by self
antigen and has caused the specific pathologic change
• Depending upon the type of autoantibody formation, the autoimmune diseases
are broadly classified into 2 groups:
• 1. Organ specific (Localised) diseases In these, the autoantibodies formed
react specifi cally against an organ or target tissue component and cause its
chronic infl ammatory destruction. Th e tissues aff ected are endocrine glands
(e.g. thyroid, pancreatic islets of Langerhans, adrenal cortex), alimentary tract,
blood cells and various other tissues and organs.
• 2. Organ non-specific (Systemic) diseases Th ese are diseases in which a
number of autoantibodies are formed which react with antigens in many tissues
and thus cause systemic lesions. Th e examples of this group are various syste
mic collagen diseases.
8. ALLOGRAFT REJECTION
• MECHANISMS OF GRAFT REJECTION Except for autografts and
isografts, an immune response against allografts is inevitable. Th e
development of immunosuppressive drugs has made the survival of
allografts in recipients possible. Rejection of allografts involves both
cellmediated and humoral immunity.
• 1. CELL-MEDIATED IMMUNE REACTIONS Th ese are mainly
responsible for graft rejection and are mediated by T cells. Th e
lymphocytes of the recipient on coming in contact with HLA antigens of the
donor are sensitised in case of incompatibility. Sensitised T cells in the form
of cytotoxic T cells (CD8+) as well as by hypersensitivity reactions initiated
by T helper cells (CD4+) attack the graft and destroy it. 2. HUMORAL
IMMUNE REACTIONS In addition to the cell-mediated immune reactions,
a role for humoral antibodies in certain rejection reactions has been
suggested. Th ese include: preformed circulating antibodies due to pre-
sensitisation of the recipient before trans plantation e.g. by blood
transfusions and previous pregnancies, or in non-sensitised individuals by
comple ment dependent cytotoxicity, antibody-dependent cell-mediated
cytotoxicity (ADCC) and antigen-antibody complexes.
9. TYPES OF REJECTIONS
• Based on the underlying mechanism and time period, rejection reactions are
classifi ed into 3 types: hyperacute, acute and chronic.
• 1. HYPERACUTE REJECTION Hyperacute rejection appears within
minutes to hours of placing the transplant and destroys it. It is mediated by
preformed humoral antibody against donor-antigen. Cross-matching of the
donor’s lymphocytes with those of the recipient before transplantation has
diminished the frequency of hyperacute rejection.
• 2. ACUTE REJECTION Th is usually becomes evident within a few days to
a few months of transplantation. Acute graft rejection may be mediated by
cellular or humoral mechanisms. Acute cellular rejection is more common
than acute humoral rejection.
• 3. CHRONIC REJECTION Chronic rejection may follow repeated attacks
of acute rejection or may develop slowly over a period of months to a year
or so. Th e underlying mechanisms of chronic rejection may be
immunologic or ischaemic. Patients with chronic rejection of renal
transplant show progressive deteri oration in renal function as seen by rising
serum creatinine levels
