autoimmunity final

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    OBJECTIVES

    DEFINITION

    TOLERANCE

    FACTORS OF AUTOIMMUNITY

    MECHANISMS OF AUTOIMMUNITY

    CLASSIFICATION OF

    AUTOIMMUNEDISEASES

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    Autoimmunity

    Basically meansimmunity to self

    A condition thatoccurs when theimmune systemmistakenly attacksand destroyshealthy body tissue.

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    Genes and Autoimmunity

    The concept that a single gene mutationleads to a single autoimmune disease isthe EXCEPTION not the rule.

    Because of this autoimmune diseasesare generally classified as complex

    diseases as there is not a singlepinpoint-able gene

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    Many autoimmune diseases are associated with

    certain HLA types and with gender

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    Hormones

    Females are much more likely to developautoimmune illness

    Rise in hormones associated withpregnancy supports the idea

    Hypothesis: estrogen responseelements (EREs) in several

    genes

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    Estrogens and Autoimmunity

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    Nature Immunology 2, 777 - 780 (2001)

    Sex differences in autoimmunity

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    ENVIRONMENTAL FACTORS

    Environmental factors elicit autoimmune diseasesby:

    1-molecular mimic theory

    2-tissue injury releases intracellular antigens thatelicit immune response

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    Factors influencing autoimmune disease

    Internal triggering

    factors

    genotype / HLA

    cytokines

    apoptosis genes

    ID (IgA, CID, CVID,WA, C1,2,4),

    hormones

    External triggering

    factors

    infections

    UV

    drugs

    chemicals (includingfood)

    stress

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    MOLECULAR MIMICRYALTERATION OF NORMALPROTEINSRELEASE OF SEQUESTERED

    ANTIGENSEPITOPE SPREADING

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    Rheumatic fever

    is a classicexample ofmolecularmimicry

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    Pick an organ, any organ . . .Autoimmunity can affect ANY organ/organ system in the human body

    Pemphigus

    Multiple Sclerosis

    Sjogrens Syndrome

    Rheumatic Fever

    Autoimmune Hepatitis

    Ulcerative Colitis

    Goodpastures Syndrome

    Diabetes

    Autoimmune Uveitis

    Autoimmune hemolytic Anemia

    Addisons Disease

    Rheumatoid Arthritis

    Autoimmune Oophoritis

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    Multiple Sclerosis

    MS patients can have autoantibodies and/or self reactive T cells

    which are responsible for the demyelination of white matter of brain

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    DIABETES :

    Auto destructive T cells destroy the islets

    cells of pancreas

    The main antigen against which t cells

    attack is directed is the islet cell enzyme,Glutamic acid decarboxylase

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    Diabetes

    G di

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    Graves disease(anti-thyroid stimulating hormonereceptor; anti-TSHR)

    In Graves disease, the antibodiesdo not destroy the thyroid but actas if they are TSH (i.e., they bindand activate the TSH receptor)(agonist)

    (compare this to theHashimotos thyroiditis;

    previous slide)

    Normal

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    Autoimmune hemolytic anemia

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    l f i

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    Examples of Systemic

    Autoimmunity

    SLE

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    Autoantibodies are formedagainst igG

    Synovial memb infiltrated

    With t cells,plasmacells,macrophages

    Clinical finding is inflammation ofjoints of hands and feet

    Treatment isNSAIDS,immunosuppressive

    drugs,corticosteroids

    Rheumatoidarthritis

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    GOODPASTEURSSYNDROME

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    Auto antibodies are formed

    against collagen in basementmembranes of kidneys and lungs

    Clinical findings

    Hematurea

    Proteinurea

    Pulmonary hemorrhage

    Cytotoxic antibodies activatecomplement c5a released

    neurtophils enzymes destroy lungand kidney tissue

    Treatment include

    Plasma exchange toremove antibodies

    Immunosuppresive drugs

    Goodpasteurssyndrome

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    REFERENCES

    LEVINSON MEDICAL MICROBIOLOGY ANDIMMUNOLOGY

    ROBBINS AND KUMAR

    WWW.GOOGLE.COM FOR PICTURES

    http://www.google.com/http://www.google.com/
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