Conditions in which a person’s immune system attacks the body’s own cells, causing tissue destruction.

INTRODUCTION

Organ-specific autoimmune diseases, in fact almost all autoimmune diseases affect more than one system in the body. rheumatoid arthritis, systemic lupus erythematosis (lupus), multiple sclerosis, myasthenia gravis, pernicious anemia, and Scleroderma.

Combination of genetic, environmental, and hormonal factors play into autoimmunity.

affecting women more strongly

CRITERIA FOR CRITERIA FOR AUTOIMMUNE AUTOIMMUNE

DISORDERDISORDERGuidelines for classifying autoimmune disorder cause based on 3 types of evidence

3 TYPES OF EVIDENCE

Direct Proof

Indirect Evidence

Circumstantial

Evidence

DIRECT PROOFDIRECT PROOFHOW??? - By transferring of self-reactive lymphocytes to the host.

Example – self-reactive lymphocytes are transferred

transplacentally from mother to the fetus.

INDIRECT EVIDENCEHOW?? - (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 CIRCUMSTANTIAL EVIDENCEEVIDENCE

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

•Immunoglobulin•T-cells receptors•MHC

•Sequestered antigens•Molecular mimicry•Polyclonal activation

•Hormone•Drugs•Loss of T suppressor

Genetic factorsGenetic factors Both Both immunoglobulinimmunoglobulin and and T cellT cell involve in recognition involve in recognition

of antigens and give rise in self reactivity.of antigens and give rise in self reactivity.

MHCMHC (major histocompatibility complex): (major histocompatibility complex):

Individuals who have inherited a particular (MHC) of Individuals who have inherited a particular (MHC) of genes such as genes such as HLA-DR4HLA-DR4 have a higher probability of have a higher probability of developing an developing an autoimmune skin disease.autoimmune skin disease.

Environmental factorsEnvironmental factors Sequestered antigens-Sequestered antigens- protected antigensprotected antigens that not that not

stimulate immune response.stimulate immune response.

Molecular mimicry-Molecular mimicry- Ab and T cells Ab and T cells cross-reactcross-react with self with self antigens.antigens.

Polyclonal activation- Polyclonal activation- polyclonal activatorpolyclonal activator trigger many trigger many T or B cell clones( from superantigens)T or B cell clones( from superantigens)

Triggers for Triggers for autoimmunity autoimmunity

HormoneHormone- - SLE hormoneSLE hormone common in women. common in women.

DrugsDrugs- - alter T cell receptorsalter T cell receptors to render it immunogenic. to render it immunogenic.

Loss of T suppressor-Loss of T suppressor- ↓ T suppressor, ↓ T suppressor, ↑ cell-mediated↑ cell-mediated n lead to n lead to cell-mediated autoimmune.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.

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.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.

Anti-idiotypic 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 SYSTEMIC LUPUS ERYTHEMATOSUS, ERYTHEMATOSUS, SLESLE

LUPUSLUPUS

condition characterized by chronic condition characterized by chronic inflammation of body tissues caused by inflammation of body tissues caused by autoimmune disease autoimmune disease

abnormal antibodies produced in blood abnormal antibodies produced in blood target tissues within own body rather than target tissues within own body rather than foreign infectious agentsforeign infectious agents

antibodies & accompanying cells of antibodies & accompanying cells of inflammation can involve tissues anywhere in inflammation can involve tissues anywhere in the body the body has potential to affect a variety of has potential to affect a variety of areas of the bodyareas of the body

can cause disease of the skin, heart, lungs, can cause disease of the skin, heart, lungs, kidneys, joints, and/or nervous systemkidneys, joints, and/or nervous system

only the skin involved only the skin involved discoid lupus discoid lupus

internal organs involved internal organs involved SLE SLE

SYMPTOMSSYMPTOMS

fatiguefatigue

loss of appetiteloss of appetite

muscle aches muscle aches

ulcers of the ulcers of the mouth & nosemouth & nose

facial rash facial rash ("butterfly rash")("butterfly rash")

unusual unusual sensitivity to sensitivity to sunlight sunlight (photosensitivity)(photosensitivity)

poor circulation to poor circulation to the fingers & toes the fingers & toes with cold with cold exposure exposure (Raynaud's (Raynaud's phenomenon)phenomenon)

shape shape referred to as the "butterfly rash" of SLE referred to as the "butterfly rash" of SLE

painless, does not itchpainless, does not itch

worsened by exposure to sunlight (photosensitivity) worsened by exposure to sunlight (photosensitivity)

TREATMENTSTREATMENTS

no permanent cure for SLEno permanent cure for SLE

goal of treatment - to relieve symptoms & protect goal of treatment - to relieve symptoms & protect organs by decreasing inflammation and/or the organs by decreasing inflammation and/or the level of autoimmune activity in the bodylevel of autoimmune activity in the body

mild symptoms - need no treatment or only mild symptoms - need no treatment or only intermittent courses of antiinflammatory intermittent courses of antiinflammatory medicationsmedications

serious illness (damage to internal organ) - serious illness (damage to internal organ) - require high doses of corticosteroids with other require high doses of corticosteroids with other medications that suppress the body's immune medications that suppress the body's immune systemsystem

Rheumatoid ArthritisRheumatoid Arthritis

Systemic autoimmune disorder that causes the Systemic autoimmune disorder that causes the immune system to attack theimmune system to attack the synovial jointssynovial joints- - causes inflammation and destruction of causes inflammation and destruction of cartilage and bonecartilage and bone

can also damage some organscan also damage some organs diagnosed with blood tests and X-raysdiagnosed with blood tests and X-rays Symptoms are pain, stiffness in the morning, and Symptoms are pain, stiffness in the morning, and

fatiguefatigue Goal treatment: relieve pain and inflammation, Goal treatment: relieve pain and inflammation,

slow down or prevent destruction of joints and slow down or prevent destruction of joints and restore the use and function of areas that already restore the use and function of areas that already have been damaged. have been damaged.

PathophysiologyPathophysiology described as Type III hypersensitivitydescribed as Type III hypersensitivity Synovium is closely packed with dendritic Synovium is closely packed with dendritic

cells, macrophages, T, B, NK cells and cells, macrophages, T, B, NK cells and plasma cellsplasma cells

Mixture of antigen- antibody complexes, Mixture of antigen- antibody complexes, complement, polymorphonuclear complement, polymorphonuclear neutrophils, inflammatory CD4 T cells, CD8 neutrophils, inflammatory CD4 T cells, CD8 cytotoxic T cells, activated macrophages cytotoxic T cells, activated macrophages and NK cells and NK cells - release cytokines that destroy integrity - release cytokines that destroy integrity of cartilageof cartilage

Chondrocytes exposed to immune Chondrocytes exposed to immune system, release cytokines and growth system, release cytokines and growth factorfactor

Synovial accumulate in joints and contain Synovial accumulate in joints and contain large no. of polymorphonuclear large no. of polymorphonuclear neutrophilsneutrophils

Fibrin is deposited, cartilage is replaced Fibrin is deposited, cartilage is replaced by fibrous tissue and joint fusesby fibrous tissue and joint fuses

Inflammatory process are initiated by Inflammatory process are initiated by abnormally produced antibody, abnormally produced antibody, IgMIgM (rheumatoid factor)(rheumatoid factor)

RF- useful marker of disease activity RF- useful marker of disease activity

Hands affected by RAHands affected by RA

TREATMENTS IN

AUTOIMMUNE

DISEASES.

AUTOIMMUNE DISEASESTHERAPEUTIC 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 medical care.

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 azathioprine.

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)

CIDP is chronic progressive and relapsing. It may lasting for months years.

 

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 rate of infusion.