Pengaruh Siklus Haid Terhadap Imunitas Mukosa Saluran Reproduksi

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    The Immune System inReproductive Tract Throughout

    Menstrual Cycle

    Budi Wiweko

    Reproductive ImmunoendocrinologyDivisionDepartment of Obstetrics and Gynecology

    Faculty of Medicine niversity ofIndonesia

    Dr! "ipto Mangunkusumo General

    #ospital

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    Outline of this talk

    %! Introduction

    &! Immune system in female

    reproductive tract

    '! Menstrual cycle and femaleimmune system

    (! )ake *ome messages

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    Basic concept of mucosal immunity

    +iyono et al! ,dv Drug Deliver Rev- %../

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    )*e mucous membranes are one of t*elargest organs of t*e body

    )*ey cover a surface area of more t*an

    (00m&1e2uivalent to one and a *alf tenniscourts3

    "omprise t*e linings of t*e gastrointestinal-

    urogenital and respiratory tracts

    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    Brandt4aeg! $ Reprod Immunol- %..5

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    )*e mucous membranes produce a special type of

    antibody called secretory Ig, or sIg,

    )*is antibody is secreted as a dimer- 6oined at t*e non7

    antigen binding end by a protein known as t*e $ c*ain

    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    Brandt4aeg! $ Reprod Immunol- %..5

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    )*e mucosal surfaces of t*e body are particularly

    vulnerable to infection

    )*ey are t*in and permeable barriers to t*einterior

    of t*e body because of t*eir p*ysiological

    activities gas e8c*ange 1t*e lungs3

    food absorption 1t*e gut3

    sensory activities 1eyes- nose- mout*- and t*roat3

    reproduction 1uterus and vagina3

    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

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    Immune system of female reproductive tract ist*e 9rst line of defense against se8uallytransmitted

    diseases 1:)Ds3

    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    Bacteria

    ;iruses

    :perm Fetus

    ,

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    )*e female reproductive tract is a uni2ue

    immunological site t*at is re2uired to protect t*e

    mucosa from a variety of pat*ogens wit*out

    compromising t*e development of an allogenically

    distinct fetus

    #ickey et al! $ Reprod Immunol- &0%%

    There are more than 30 diferent types oparasites, bacteria and viruses that inect the emalereproductive tract

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    "omponents of t*e *umoral and cellular immune

    system are present t*roug*out t*e female genital

    tract w*ic* is bot* an inductive and an e>ector site

    for immune response

    ?*ongmin! "lin Immunol- &00%

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    )*e mucosal immune system in genital tractconsist of

    resident population of monocytes and ) cells in t*esubmucosa of t*e vagina and cervi8

    )*ey are in

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    )*e upper female reproductive tract- consisting of t*eFallopian tubes- uterine endometrium and endocervi8 islined by a single layer of columnar epit*elial cells linked bytig*t 6unctions

    Overlying t*e cells is a protective mucus layer! :ecretion isgenerally preferential towards t*e apical@luminalcompartment wit* a gradient across t*e epit*elial layer

    from lumen to tissue! nderlying t*e epit*elial cells areinnate and adaptive immune cells#ickey et al! $ Reprod Immunol- &0%%

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    )*e lower female reproductive tract- consisting of t*eectocervi8 and vaginais covered by a layer of strati9ed

    s2uamous epit*elial cells

    :imilar to t*e upper female reproductive tract- epit*elialcells are protected by a mucus layer! )*e lower femalereproductive tract *as a resident commensal bacterialpopulation t*at produces lactic acid t*us lowering vaginal

    p#! Below t*e epit*elial layer are innate and adaptiveimmune cells

    #ickey et al! $ Reprod Immunol- &0%%

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    )*e mucosa of vaginaand ectocervi8consist of keratini4ed- strati9ed s2uamousepit*elium and underlying vascularsubmucosa

    Andocervi8consist of a simple columnarepit*elium covering a vascular submucosa

    +iyono et al! ,dv Drug Deliver Rev- %../

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    )*e innate immune responseof upper female reproductivetract epit*elial cells to an

    invading pat*ogen! Apit*elialcells e8press a panel of)oll7likereceptors 1)Rs3 and RIG7likereceptors 1RRs3 t*at allowt*em to recogni4e and respondto bacteria or viruses

    )*e )ype I interferon 1IFC3response 1green arrows- middlesection of panel "3 is a potentdefense system in femalereproductive tract cells!

    ,dditionally- in response topat*ogens and se8 *ormones-antimicrobials andcytokines@c*emokines aresecreted to confer broadspectrum protection#ickey et al! $ Reprod Immunol- &0%%

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    Innate immune system competence is ofcritical importance in preventing microbial

    penetration

    In t*is conte8t- it is important to consider t*edi>erences in t*e microenvironments of t*e

    sterileE upper and non7sterile

    #orne et al! Reproduction- &00=

    :I:ecretory leucocyte protease in*ibit

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    TH !"#CTIO# $#% %ISTRIB"TIO# O! C&&S I# TH "''R!M$& R'RO%"CTI( TR$CT )!$&&O'I$# T"BS* "TRI#

    $#% #%OCR(IC$& M"COS$+ $#% TH &O,R !M$&R'RO%"CTI( TR$CT )CTOCR(IC$& $#% ($-I#$&M"COS$+

    #ickey et al! $ Reprod Immunol- &0%%

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    Reproductive *ormones *ave been s*own to playkey

    roles in t*e regulation of mucosal immunity of t*e

    female genital tract

    Astrogenincreasing selective transport of Ig,

    into t*e cervical mucus

    Franklin! $ Reprod Immunol- %...

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    ,dult women are moresusceptible to :)Isduring menses andt*e follicular p*ase-

    and less likely to beinfected during t*eluteal p*ase

    )*e concentration of genital tractimmunoglobulins in adult women are varyt*roug* t*e menstrual cycleand relatedto ovarian *ormone concentrations

    :*rier et al! $ ,dolescent #ealt* Brief- &00'

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    Mucosal Immunity of The

    $dolescent!emale -enital Tract

    ydia , :*rier- Frederick Bowman

    $ournal of ,dolescent #ealt*- &00'

    )*is study soug*t to c*aracteri4e mucosalimmunity of t*e adolescent genital tractsduring t*e cycle and determine ifadolescent *ave more suppressedimmunoglobulin level in t*e follicular p*aset*an adults

    ,dolescent *ad a greater drop in IgG in t*efollicular p*ase and may be more sensitive

    to estradiol t*an adults

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    :e8ually transmitted infections 1:)Is3

    disproportionately a>ect female adolescents

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    B cell numbers and activity mig*t increase in t*e peri7

    ovulatory period!

    Monocyte numbers increase during t*e luteal p*ase-

    w*ile t*eir I7% and )CFH production develop in opposing

    fas*ion

    Results on C+ cell number and activity *ave been

    con

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    In t*e case of autoimmune conditions- :A and M:appear to worsen premenstrually- w*ile R, worsensduring menstruation

    rigione! ,utoimmune reviews- &0%&

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    Characteri.ation of

    immunoglobulins and cytokinesin human cervical mucus/

    in0uence of e1ogenous andendogenous hormone

    RD Franklin- W# +utte*

    $ournal of Reproductive Immunology- %...

    )*is study soug*t to determine t*e e>ect ofe8ogenous *ormoneson reproductive tractimmunity in women on O" and tocompare t*e results wit* respects tonaturally cycling women

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    )*e peak concentration of Ig, and IgG occurred

    appro8imately one day before t*e estradiol peak6ust

    before ovulation

    Franklin! $ Reprod Immunol- %...

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    Distribution of ) cells at di>erent sites of t*e lowerreproductive tract during various stages of menstrualcycle

    Ma et al! "lin Immunol- &00%

    Cormal

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    Introduction

    Immunesystem infemalereproductive

    tract

    Menstrualcycle andfemale

    immunesystem

    )ake *omemessages

    %! Immune response in t*e female reproductivetract must deal wit* potential bacterial andviral pat*ogens- allogeneic spermato4oa andimmunologically distinct fetus

    &! Immunoglobulins in t*e cervical mucusreac*ed peak levels before ovulation

    '! "*anges in t*e concentration ofimmunoglobulin in cervicovaginal secretions

    are not due to c*anges of t*e immune cellspopulation in t*e genital tract at di>erenttime of cycles

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    TH$#2 3O"

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    TH$#2 3O