k. pa immunodeficiency diseases

8/18/2019 K. PA Immunodeficiency Diseases

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IMMUNODEFICIENCYIMMUNODEFICIENCYDISEASESDISEASES

Defects in one or moreDefects in one or morecomponents of the immunecomponents of the immune

system can lead to serious andsystem can lead to serious and

often fatal disordersoften fatal disorders


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T4

T8

B

T4APC

Granulocytes Plasma Cell

Antibody

Non-Specific

System

Specific

System

Antigen

Presentation

Macrophage

Monocyte

Antigen

RecognitionNeutrophil

Cytokines

Lymphocytes

The Two Immune SystemsThe Two Immune Systems

Communicate and CooperateCommunicate and Cooperate


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ImmunodeficiencyImmunodeficiency

1. Types according to etiology1. Types according to etiology :: 1.1.1.1. PrimaryPrimary Immunodeficiency :Immunodeficiency :

* hereditary genetic diseases* hereditary genetic diseases 1.2.1.2.SecondarySecondary Immunodeficiency :Immunodeficiency :

* resulted from other primary disorder* resulted from other primary disorder

e.g.e.g. infection; cancer;infection; cancer; * resulted from therapy : chemotherapy* resulted from therapy : chemotherapy

(cytostatics), immunosuppresives,(cytostatics), immunosuppresives,radiation ;radiation ;

2. Types according to involved component2. Types according to involved component ::

2.1.2.1. BB lymphocytes immunodeficiencylymphocytes immunodeficiency

2.2.2.2. TT lymphocytes immunodeficiencylymphocytes immunodeficiency

2.3.2.3. BB andand TT lymphocytes combinedlymphocytes combinedimmunodeficiencyimmunodeficiency

2..2.. ComplementComplement ! phagocyte system ! phagocyte systemimmunodeficiencyimmunodeficiency


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Ce-me!i"te! imm#ne $esponse directed against intracellular substances

viruses tumours

!"lymphocytesthymus"derived

%#mo$" imm#ne $esponse

directed against e#tracellular substancesbacteria

$"lymphocytes %&hich mature into plasma cells'bone marro& derived

Specific MechanismsSpecific Mechanisms


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Primary Immunodeficiency %('Primary Immunodeficiency %('

1. Bruton type1. Bruton type Agammaglobulinemia Agammaglobulinemia,, X-linked X-linked * " cells are not developed and depleted in* " cells are not developed and depleted in

peripheral lymphoid organs (tonsil, spleen, lymphperipheral lymphoid organs (tonsil, spleen, lymphnodes)nodes) agammaglobulinemia;agammaglobulinemia;

* cellular immune system is intact;* cellular immune system is intact; 2.2. Common Variable Immunodeficiency (CVI)Common Variable Immunodeficiency (CVI)

* the number of B cells is adequate, differentiation* the number of B cells is adequate, differentiation

defect or its terminal functiondefect or its terminal function incapable toincapable to

produce Immunoglobulin; produce Immunoglobulin; * some due to Ig gene mutation ;* some due to Ig gene mutation ;

* other mechanism due to abnormal helper T cells* other mechanism due to abnormal helper T cells

or elevated suppressor T cellsor elevated suppressor T cells

hypogammaglobulinemiahypogammaglobulinemia


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Primary Immunodeficiency %)'Primary Immunodeficiency %)' 3. Selective Ig !eficiency3. Selective Ig !eficiency

* differentiation defect of #g$* differentiation defect of #g$

producing " cells, %hile the othersproducing " cells, %hile the others

are normalare normal

* immature " cells feature (#g&, #g');* immature " cells feature (#g&, #g');

* other mechanism : antibody against* other mechanism : antibody against

#g$ ( cases)#g$ ( cases) #g$ level#g$ level decreased ;decreased ;

* recurrent respiratory, intestinal and* recurrent respiratory, intestinal and

urogenital infection;urogenital infection;


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Primary Immunodeficiency %*'Primary Immunodeficiency %*'

". !i#eorge syndrome $T%ymus &ypoplasia'". !i#eorge syndrome $T%ymus &ypoplasia'

* hypoplasia ! aplasia of thymus* hypoplasia ! aplasia of thymus cellularcellularimmunodeficiencyimmunodeficiency

* antibody synthesis is normal;* antibody synthesis is normal; * viral and fungal infection* viral and fungal infection severe diseasesevere disease and complication;and complication; * accompanied by tetany due to parathyroid* accompanied by tetany due to parathyroid aplasia;aplasia; * thymus transplantation* thymus transplantation improvement ;improvement ;


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Primary Immunodeficiency %*'Primary Immunodeficiency %*'

(is)ott*ldric%(is)ott*ldric% SyndromeSyndrome

* recessive* recessive x-lined x-lined

* accompanied by thrombocytopenia dan ecema* accompanied by thrombocytopenia dan ecema

* defect in glycosilisation of membrane protein and* defect in glycosilisation of membrane protein and

defect in maturation of hematopoetic stem cells;defect in maturation of hematopoetic stem cells;

** decreased +'3 epression in " and - cells,decreased +'3 epression in " and - cells,

macrophages, netrophils dan thrombocytes;macrophages, netrophils dan thrombocytes;

* -hymus is normal, deminished - cells in the blood* -hymus is normal, deminished - cells in the blood

and paracortical area of lymph nodes;and paracortical area of lymph nodes;

* antibody sysnthesis is normal;* antibody sysnthesis is normal;

* prone to recurrent infections;* prone to recurrent infections;

* susceptible to lymphoid malignancy.* susceptible to lymphoid malignancy.


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Primary Immunodeficiency %+'Primary Immunodeficiency %+'

+. Severe Comined Immunodeficiency !isease $SCI!'+. Severe Comined Immunodeficiency !isease $SCI!'

* combination of cellular and humoral immunodeficiency;* combination of cellular and humoral immunodeficiency; * 2 types: 1) autosomal recessive or* 2 types: 1) autosomal recessive or 2)2) !-lined !-lined recessive;recessive; ** ad 1)ad 1) $'$ (adenosine deaminase) deficiency$'$ (adenosine deaminase) deficiency accumulation of deoy$-/ dan 0adenosilaccumulation of deoy$-/ dan 0adenosil

homocysteinhomocystein toic to immature limfocytestoic to immature limfocytes -- and " cells reduction;and " cells reduction; other form: // ( other form: // ( protein nucleotidephosphorylase protein nucleotidephosphorylase) deficiency) deficiency accumulation of deoyguanosine and deoy -/accumulation of deoyguanosine and deoy -/ toic to - cell " cells;toic to - cell " cells; ne% form: defect in &4+ ## epression on " cells, macrophages ne% form: defect in &4+ ## epression on " cells, macrophages

and dendritic cellsand dendritic cells defect in delayed hypersensitivitydefect in delayed hypersensitivityreaction ('45) and susceptible to viral infection;reaction ('45) and susceptible to viral infection; ** ad 2)ad 2) 6 7) mutation6 7) mutation defect in #82, and 9defect in #82, and 9 activation of activation of - is impaired;- is impaired; patients patients susceptible to infection ( bacteria, fungus, virus);susceptible to infection ( bacteria, fungus, virus); thymus is hypoplastic, limfocytes are depleted in the lymph nodes. thymus is hypoplastic, limfocytes are depleted in the lymph nodes.


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Primary Immunodeficiency %,'Primary Immunodeficiency %,'

-. !eficiency of complement system-. !eficiency of complement system

* deficiency of +3* deficiency of +3 susceptible to infection %ith piogenicsusceptible to infection %ith piogenic

bacteria;bacteria;

* deficiency of +1, 2, * deficiency of +1, 2, susceptible to immunesusceptible to immune

comple disease;comple disease;

* deficiency of +1 esterase enyme* deficiency of +1 esterase enyme activation of +1 isactivation of +1 is

uncontrolleduncontrolled hereditary angioedema;hereditary angioedema;

* deficiency of +6* deficiency of +6 sensitive to infection %ith eisseriasensitive to infection %ith eisseria

(gonococci dan meningococci);(gonococci dan meningococci);

. !eficiency of t%e function of p%agocytes system. !eficiency of t%e function of p%agocytes system * rarely occured;* rarely occured; ** granulomatosal infllamation;granulomatosal infllamation;

* failure to control infection;* failure to control infection;


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-econdary Immunodeficiency %('-econdary Immunodeficiency %(' 11.. #mmunodeficiency as the result of other disease or#mmunodeficiency as the result of other disease or

therapytherapy efficiency of therapy decreased, prone toefficiency of therapy decreased, prone to recurrency and sensitive to opportunistic infection;recurrency and sensitive to opportunistic infection;

2. I!S $2. I!S $ Acquired Immunodeficiency Syndrome Acquired Immunodeficiency Syndrome'' * etiology: retrovirus 4#< (* etiology: retrovirus 4#< (human immunodeficiencyhuman immunodeficiency virusvirus) type 1 ( =0, >urope, >ast $frica) and type 2) type 1 ( =0, >urope, >ast $frica) and type 2 ( ?est $frica);( ?est $frica); * disorders involving organs of the immune system* disorders involving organs of the immune system and central nervous system;and central nervous system;

* complication of opportunistic infection in various* complication of opportunistic infection in various organs;organs; * virus attac@s helper- (+'7) lymphocytes* virus attac@s helper- (+'7) lymphocytes throughthrough gp"#$gp"#$ receptorreceptor internaliation;internaliation;

* infection ! transmission is* infection ! transmission is blood-born type;blood-born type; * transmission% both homosexual and heterosexual * transmission% both homosexual and heterosexual;


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-econdary Immunodeficiency %*'-econdary Immunodeficiency %*' /ervous system disorders in I!S/ervous system disorders in I!S::

* monocytes ! macrophages infected by certain 4#< strain;* monocytes ! macrophages infected by certain 4#< strain;

Clinical course of I!SClinical course of I!S 3 p%ases3 p%ases::

1.1. $cute phase (312 %ee@s):$cute phase (312 %ee@s): viremia and involvement of lymphoidviremia and involvement of lymphoid

tissues;tissues;

* -h cells are reduced* -h cells are reduced antibody and -cantibody and -c acute phase ArecoveryB;acute phase ArecoveryB;

* fever, myalgia, s@in rash, sore throat* fever, myalgia, s@in rash, sore throat self limiting;self limiting;

2. 82. 8atent phase:atent phase: virus replication in lymphoid tissue, may last for years;virus replication in lymphoid tissue, may last for years;

* persisting general lymphadenopathy, fever, s@in rash, fatigue;* persisting general lymphadenopathy, fever, s@in rash, fatigue;

* partly asymptomatic;* partly asymptomatic;

* damage of -h cells continues;* damage of -h cells continues;

3. +3. +risis phase:risis phase: -h!-s ratio decreases; -h (+'7) counts C 2 !u8-h!-s ratio decreases; -h (+'7) counts C 2 !u8

progressivity (diagnostic criteria of +enter for 'isease +ontrolprogressivity (diagnostic criteria of +enter for 'isease +ontrol(+'+);(+'+);

* fever 1 month, fatigue, loss of body %eight , diarrhea;* fever 1 month, fatigue, loss of body %eight , diarrhea;

* opportunistic infection:* opportunistic infection: &andida albicans, 'neumocystis carinii,&andida albicans, 'neumocystis carinii,

&ytomegalovirus. (ycobacteria, &ryptococcus neoformans,&ytomegalovirus. (ycobacteria, &ryptococcus neoformans,

)istoplasma capsulatum, Toxoplasma gondii;)istoplasma capsulatum, Toxoplasma gondii;

* uncommon neoplasma: Daposi sarcoma, malignant lymphoma;* uncommon neoplasma: Daposi sarcoma, malignant lymphoma;


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Terima Terima

kasihkasih


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Development of different types of lymphocytes from a pluripotential

stem cell in the bone marro&.


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k. pa immunodeficiency diseases

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