Auto Immune Disease

An antigen (Ag) is defined as a substance, usually protein in nature,

which when introduced into the tissues stimulates antibody
production.
Hapten is a non-protein substance which has no antigenic properties,
but on combining with a protein can form a new antigen capable of
forming antibodies.
An antibody (Ab) is a protein substance produced as a result of
antigenic stimulation. Circulating antibodies are immunoglobulins(Igs)
of which there are 5 classes: IgG, IgA, IgM, Ig E and Ig D.

TYPES OF IMMUNITY
. Broadly speaking, immunity or body defense mechanism is divided into
2 types, each with humoral and cellular components:
Natural or innate immunity is non-specific and is considered as the first
line of defense without antigenic specificity. It has 2 major components:
a) Humoral:comprised by complement.
b) Cellular: consists of neutrophils, macrophages, and natural killer (NK)
cells.
Specific or adaptive immunity is specific and is characterized by antigenic
specificity.
It has 2 main components:
a) Humoral: consisting of antibodies formed by B cells.
b) Cellular: mediated by T cells.

Types of Immunity
Active Immunity
- Naturally-Acquired Active Immunity
- Artificially-Acquired Active Immunity
Passive Immunity
- Naturally-Acquired Passive Immunity
- Artificially-Acquired Passive Immunity

STRUCTURE OF IMMUNE SYSTEM

ORGANS OF IMMUNE SYSTEM
Although functioning as a system, the organs of immunesystem are
distributed at different places in the body. These are as under:
a) Primary lymphoid organs:
i) Thymus
ii) Bone marrow
b) Secondary lymphoid organs:
i) Lymph nodes
ii) Spleen
iii) MALT (Mucosa-Associated Lymphoid Tissue located inthe
respiratory tract and GIT).

CELLS OF IMMUNE SYSTEM

i) Lymphocytes
ii) Monocytes and macrophages
iii) Mast cells and basophils
iv) Neutrophils
v) Eosinophils

Cells of the Immune System and their

Functions.

HLA SYSTEM AND

MAJORHISTOCOMPATIBILITY COMPLEX
HLA system is described here as it is considered important in the
regulation of the immune system.
HLA stands for Human Leucocyte Antigens because these antigens or
genetic proteins in the body which determine ones own tissue from
non-self(histocompatibility) were first discovered on the surface of
leucocytes.

 Subsequently, it was found that HLA are actually

gene complexes of proteins on the surface of all nucleated
cells of the body and platelets.
Since these complexes are of immense importance in matching
donor and recipient for organ transplant,
they are called major histocompatibilitycomplex (MHC) or
HLAcomplex.

Depending upon the characteristics of MHC, they

havebeen divided into 3 classes
Class I MHC antigens have loci as HLA-A, HLA-B and HLA-C. CD8+(i.e. T
suppressor) lymphocytes carry receptors for class I MHC and these
cells are used to identify class I antigen on them.
Class II MHC antigens have single locus as HLA-D. These antigens have
further 3 loci: DR, DQ and DP. Class II MHC is identified by B cells and
CD4+ (i.e. T helper) cells.
Class III MHC antigens are some components of the complement
system (C2 and C4) coded on HLA complex but are not associated
with HLA expression and are not used in antigen identification.

ROLE OF HLA COMPLEX

The HLA complex is significant in a number of ways:
1. Organ transplantation. Historically, the major importance of HLA
system is in matching donor and recipient for tissue transplantation.
The recipients immune system can recognize the histocompatibility
antigens on the donor organ and accordingly accept it or reject it.
Both humoral as well as cell-mediated immune responses are
involved in case of genetically non-identical transplants.

 2. Regulation of the immune system.

Class I and II histocompatibility antigens play a role in regulating
both cellular and humoral immunity:
Class I MHC antigens regulate the function of cytotoxic T cells (CD8+
e.g. in virus infections. Class II MHC antigens regulate the function of
helper T cells (CD4+)

AUTOIMMUNE DISEASES

Autoimmunity is a state in which the bodys immune system fails to

distinguish between self and non-self and reacts by formation of
autoantibodies against ones own tissue antigens.
In other words,there is loss of tolerance to ones own tissues
autoimmunity is the opposite of immune tolerance.

 Immune tolerance is a normal phenomenon present since foetal life

and is defined as the ability of an individual to recognize self tissue
and antigens.
Normally, the immune system of the body is able to distinguish self
from non-self antigens by the following mechanisms:

 1. Clonal elimination. According to this theory, during embryonic

development, T cells maturing in the thymus acquire the ability to
distinguish self from non-self.

These T cells are then eliminated by apoptosis for the tolerant

individual.

2. Concept of clonal anergy. According to this mechanism, T

lymphocytes which have acquired the ability to distinguish self from
non-self are not eliminated but instead become non-responsive and
inactive.

3. Suppressor T cells. According to this mechanism, the tolerance is

achieved by a population of specific suppressor T cells which do not
allow the antigen-responsive cells to proliferate and differentiate.

PATHOGENESIS (THEORIES) OF
AUTOIMMUNITY
The mechanisms by which the immune tolerance of the body is
broken causes autoimmunity. These mechanisms or theories of
autoimmunity may be immunological, genetic, and microbial, all of
which may be interacting.
1. Immunological factors. Failure of immunological mechanisms of
tolerance initiates autoimmunity. These mechanisms are 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 auto-antibody production by B cells contributing
to auto-immunity.

2. Genetic factors. There is evidence in support of genetic

factors in the pathogenesis of autoimmunity as under:
i) There is increased expression of Class II HLA antigens on
tissues involved in autoimmunity.
ii) There is increased familial incidence of some of the
autoimmune disorders.

3. Microbial factors. Infection with microorganisms,

particularly viruses (e.g. EBV infection), and less often
bacteria (e.g. streptococci, Klebsiella) and mycoplasma, has
been implicated in the pathogenesis of autoimmune diseases.

TYPES AND EXAMPLES OF AUTOIMMUNE

DISEASES
Depending upon the type of autoantibody formation, the
autoimmune diseases are broadly classified into 2 groups:
1. Organ specific diseases. In these, the autoantibodies formed react
specifically against an organ or target tissue component and cause its
chronic inflammatory destruction. The tissues affected 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
These are diseases in which a number of autoantibodies are formed
which react with antigens in many tissues and thus cause systemic
lesions.
The examples of this group are various systemic collagen diseases.
However, a few autoimmune diseases overlap between these two
main categories.

AMYLOIDOSIS
Amyloidosis is the term used for a group of diseases characterised by
extracellular deposition of fibrillar proteinaceous substance called
amyloid having common morphological appearance, staining
properties
and physical structure but with variable protein (or biochemical)
composition.

 First described by Rokitansky in 1842, the substance was

subsequently named by Virchow as amyloid under the mistaken
belief that the material was starch-like (amylon =starch). This
property was demonstrable grossly on the cut surface of an organ
containing amyloid which stained brown