multiple sclerosis, myasthenia gravis, pernicious anemia, and
Combination of genetic, environmental, and hormonal factors
play into autoimmunity.
affecting women more strongly
CRITERIA FOR AUTOIMMUNE DISORDER Guidelines for classifying autoimmune disorder cause based on 3 types of evidence 3 TYPES OF EVIDENCE Direct Proof Indirect Evidence Circumstantial Evidence
DIRECT PROOF HOW??? - By transferring of self-reactive lymphocytes to the host. Example – self-reactive lymphocytes are transferred transplacentally from mother to the fetus. INDIRECT EVIDENCE HOW?? - (1) Reproducing the disease in the experimental animal after identify the target antigen and isolated it on animal model. This method has their disadvantage where the human disease cannot be found on experimental animal. (2) study genetically determined animal models (3) isolating T cells from the target organ
CIRCUMSTANTIAL EVIDENCE Autoimmunity is referred based on the clinical clues such as familial tendency, lymphocytes infiltration, MHC association, and others
CAUSES GENETIC FACTOR ENVIRONMENTAL FACTOR TRIGGERS FOR AUTOIMMUNE
Loss of T suppressor
Both immunoglobulin and T cell involve in recognition of antigens and give rise in self reactivity.
MHC (major histocompatibility complex):
Individuals who have inherited a particular (MHC) of genes such as HLA-DR4 have a higher probability of developing an autoimmune skin disease.
Sequestered antigens- protected antigens that not stimulate immune response.
Molecular mimicry- Ab and T cells cross-react with self antigens.
Polyclonal activation- polyclonal activator trigger many T or B cell clones( from superantigens)
Triggers for autoimmunity
Hormone - SLE hormone common in women.
Drugs - alter T cell receptors to render it immunogenic.
Loss of T suppressor- ↓ T suppressor, ↑ cell-mediated n lead to cell-mediated autoimmune.
Mechanisms Anti-idiotypic responses Failure of suppressive mechanisms Release of sequestered/ cryptic antigens Provision of T cell epitopes Cross-reactivity and molecular mimicry
Cross-reactivity and molecular mimicry.
The microorganism express antigens that are structurally similar to self-antigens.
As a result, the immune response to the microorganism also cause damage to the self-proteins.
Provision of T cell epitopes.
Linkage of foreign proteins (e.g.: drugs or chemicals) to self-proteins.
B cells binding to the self-non-self complex have the potential to process and present the non-self component to T cells reactive to the foreign epitopes.
T cells will deliver helper signals to B cells binding the self-component, stimulating an autoimmune reaction.
Mechanisms of autoimmunity.
Mechanisms of autoimmunity.
Release of sequestered/cryptic antigens.
Some self-antigens are not normally exposed to the immune system and said to be sequestered.
Tissue damage can release such antigens.
Cryptic antigens only released during the normal turnover of body proteins by APC.
Because they are not normally expressed, tolerance not develop and their release allow the generation of autoimmune responses.
Mechanisms of autoimmunity.
Failure of suppressive mechanisms.
Involve the ‘suppressor T cell’.
Altering the T cell constitution can result in autoimmune disease.
Therefore, thought that the balance of T cell cytokines secretion in humans may be important in influencing autoimmune responses.
Idiotypes is the antigen-binding sites of antibody.
During normal infection, a ‘second wave’ of anti-idiotype antibodies is generated, directed against idiotypic sites.
In viral infection, because anti-idiotype antibodies may similar to the virus, it is possible that antibody bind to the viral cell-surface receptor, so becoming an autoantibody.
SYSTEMIC LUPUS ERYTHEMATOSUS, SLE
condition characterized by chronic inflammation of body tissues caused by autoimmune disease
abnormal antibodies produced in blood target tissues within own body rather than foreign infectious agents
antibodies & accompanying cells of inflammation can involve tissues anywhere in the body has potential to affect a variety of areas of the body
can cause disease of the skin, heart, lungs, kidneys, joints, and/or nervous system
only the skin involved discoid lupus
internal organs involved SLE
loss of appetite
ulcers of the mouth & nose
facial rash ("butterfly rash")
unusual sensitivity to sunlight (photosensitivity)
poor circulation to the fingers & toes with cold exposure (Raynaud's phenomenon)
shape referred to as the "butterfly rash" of SLE
painless, does not itch
worsened by exposure to sunlight (photosensitivity)
no permanent cure for SLE
goal of treatment - to relieve symptoms & protect organs by decreasing inflammation and/or the level of autoimmune activity in the body
mild symptoms - need no treatment or only intermittent courses of antiinflammatory medications
serious illness (damage to internal organ) - require high doses of corticosteroids with other medications that suppress the body's immune system
Systemic autoimmune disorder that causes the immune system to attack the synovial joints
- causes inflammation and destruction of cartilage and bone
can also damage some organs
diagnosed with blood tests and X-rays
Symptoms are pain, stiffness in the morning, and fatigue
Goal treatment: relieve pain and inflammation, slow down or prevent destruction of joints and restore the use and function of areas that already have been damaged.
described as Type III hypersensitivity
Synovium is closely packed with dendritic cells, macrophages, T, B, NK cells and plasma cells
Mixture of antigen- antibody complexes, complement, polymorphonuclear neutrophils, inflammatory CD4 T cells, CD8 cytotoxic T cells, activated macrophages and NK cells
- release cytokines that destroy integrity of cartilage
Chondrocytes exposed to immune system, release cytokines and growth factor
Synovial accumulate in joints and contain large no. of polymorphonuclear neutrophils
Fibrin is deposited, cartilage is replaced by fibrous tissue and joint fuses
Inflammatory process are initiated by abnormally produced antibody, IgM (rheumatoid factor)
RF- useful marker of disease activity
Hands affected by RA
TREATMENTS IN AUTOIMMUNE DISEASES .
THERAPEUTIC STRATEGIES (TREATMENTS)
Basically, autoimmune disease often chronic, require lifelong care and
monitoring even the person look or feel well.
A few autoimmune diseases can be cured or made to disappear with
treatments. Many people that have it can live normal with appropriate
There are few research conducted on develop the
treatment for autoimmune disease.
Current treatments for autoimmune disease are usually is
immunosuppressive and anti-inflammatory.
The drugs that been used in this treatment are corticosteroid and
However, in some people a limited number of immunosuppressive
medications may result in remission (disappearance of a disease for
particular of time).
INTRAVENOUS IMMUNE GLOBULIN (IVIg)
It is a treatment that used to threat autoimmune neuropathies
which is Chronic Inflammatory Demyelinating Polyneuropathy.
CIDP is chronic progressive and relapsing. It may lasting for months
IVIg considered effective and safe treatment compared to
alternative treatment such as chemotherapy.
Patients frequently given a standard dose and may be followed by
maintenance therapy as needed.
Reaction that may be related with this treatment is anaphylaxis
due to the IgG deficiency. But, it can be controlled by slowing the