X-linked Agammaglobulinema

Brilly WinsenMelinda Ong

Michella JulianaRico Antonio

Yoel Tanuwijaya

Immune system The immune system : collection of cells,

tissues and molecules that protects the body from numerous pathogenic microbes and toxins in our environment

divided into two general types of reactions:

-innate immunity -adaptive immunity

Innate imunity innate immune system : cells and proteins that are

always present and ready to mobilize and fight microbes at the site of infection

Characteristic: - nonspecific defense mechanisms- active immediately or within hours of an antigen's

appearance in the body (fast response)- activated by chemical properties of the antigen.- These mechanisms include: physical barriers

(skin,mucus), chemicals in the blood, and immune system cells

1. Physical epithelial barrierEpitelial of the skin, respiratory tract, GI tract Mechanism:- antimicrobial enzyme lyzozime digest cell

wall- Antimicrobial peptide defensin, cathelicidin,

hisatatins cell membrane - Tight junction between cell - Mucus secretion - Stomach acid acidic ph- Peristaltic

Physical barrier

2. Phagocytes: macrophage, neutrophilPass trough the physical barrierPhagocyte ingest mo into

vesicle destroy Produce antimicrobial protein

cytokine Machropage cyokine that

stimulate inflammation causing: capillary dilation, increase blood flowMacrophage n DC APC

activate adaptive

3. Dendritic cells Phagositing microbe that passs through the

epitelial barrierExpress receptor (TLR) that recognize

microbe (PAMP) produce cytokine Major cell type that capture and display

antigens to T-cell Link between innate & adaptive

4.Plasma protein Many circulating protein bind microbes and

help to eliminate them Mechanism: this complement protein bind to

microbe’s surface receptor recruit more phagocyte for phagocytosis

5. Natural Killer Cells (NKcells)Came from the same lineage of

lymphocite precursorBut express the receptor that bind

to general bacterial/viral antigen. Than spesific peptide sequence

Activating receptor to detect stressed/infected cell with DNA damage kill them

Produce: macrophage-activating cytokine IFN-γ

Adaptive immunity adaptive immune system, on the other hand, is

called into action against pathogens that are able to evade or overcome innate immune defenses. 

Chareacteristic:- Antigen-Spesific immune respons- Slow response- More complex- Include “memory” future response againts the

same spesific antigen more efficient

1. T-LymphocyeThymus-derived lymphocyteMajor population in spleen & peripheral lymp nodesT cell are only able to recognize peptide fragment

that displayed by specialized molecule (MHC) on the surface of APC

Can recognize antigen that might be floating in the cytosol or contained within ingested vesicle of various cells

T cell: CD4+ T-helper & CD8+ T-cytotoxic, T memory

B-lymphocyteBone marrow-derived lymphocyte 10-20%- peripheral lymphocytes , bone

marrow, other lymphoid tissueCapable recognizing chemical structure

(protein, lipid, polysaccaride,small chemicals)When stimulated by antigen, B cell plasma

cell antibody recognize antigen via membrane bound antibody

After response: B-memory

ADAPTIVE IMMUNE SYSTEM:B CELL

HUMORAL IMMUNITY

ANTIGEN PRESENTING

CELL

BONE MARROWB CELL

RECEPTOR (BCR)

POSITIVE SELECTION

AND NEGATIVE SELECTION

SYNTHESIS OF B CELL

B CELL DEVELOPMENT

B CELL DEVELOPMENT

• BCR enables the cell to bind and, if additional signals are presents, to be activated by and respond to an epitope on molecules of a soluble antigen.

• B cells bind to toxins and digest them to smaller pieces, where the response ends with descendants of B cell secreting antibodies (via plasma cells).

B CELL SELECTION

POSITIVENEGATIVE

B CELL ACTIVATION

MEMORY B CELL ACTIVATION

T-CELL INDEPENDENT

ACTIVATION

T-CELL DEPENDENT ACTIVATION

B CELL ACTIVATION (DEPENDENT)

• B cells are activated when antigen binds to receptor on B cells surface, followed by a co-stimulatory signal, usually provided by T-helper cells.

• Antigens that require co-stimulation by a T-cell to activate B cell are T-dependent antigens and are usually protein.

• In order for T-helper cells to stimulate the B cells, both must be activated. Requires that the B cell internalize the antigen, process it, and the present it on the cell surface bound to a class II HLA molecule.

• The HLA-antigen complex is recognized by a receptor on the surface of the T cell (TCR)

B CELL ACTIVATION (DEPENDENT)

• The B cell expresses an activation on its surface (CD40) that binds to a complementary ligand (CD154) on the surface of T-helper cells. B cells then will proliferate.

• In addition, the T-helper cells will secrete interleukins that will promote growth and antibody production by the activated B cells.

• T-helper cells normally have been activated by interaction with a macrophage or DC, but B cells can act as APC as well.

• The B cell can express B7 proteins on its surface which will bind to CD28 on T-helper cell’s surface.

• Combination of TCR-HLA/antigen binding and B7-CD28 binding will activate the T cells.

MEMORY B CELL ACTIVATION

Perkembangan T-Cell di dalam TimusT-Cell berasal dari multipotent hematopoietic

stem cell yang terdapat di sumsum tulang.Sel prekursor T-Cell bergerak dari sumsum

tulang menuju timus, dan mengalami pematangan menjadi T-Cell

Terdapat dua garis keturunan pada proses pembentukan T-Cell, yaitu α:β (alfa:beta) dan γ:δ (gamma:delta).

Timosit (T-Cell yang sedang berkembang) juga mengalami seleksi berdasarkan interaksi dengan sel timus.

Proses Perkembangan T-Cell2A

1B

2B

1A

Proses Perkembangan T-Cell3A

3B

4B

4A

Tahap Perkembangan Timosit di TimusTimus terdiri dari dua bagian, yaitu korteks

dan medula. Bagian luar medula adalah cortico-medullary junction, sedangkan bagian luar korteks adalah daerah subkapsular.

Proses perkembangan T-Cell terjadi di korteks, sedangkan hanya timosit single-positive matang yang terdapat di medula.

Proses Pematangan Timosit

X-linked Agammaglobulinaemia (XLA)Disebut juga Bruton’s Disease, recurrent

pyogenic infectionsTidak ada circulating mature B cells, T cells

normalTidak ada plasma cells di Bone marrow,

lymph node, atau GI tractGen Btk termutasi Very low serum levels all isotypes

immunoglobulin

TREATMENTIntravenous Infusion (IVIg)Muscle Injections (IMIg)Subcutaneous (SCIg)AntibioticsGene Therapy

Kesimpulan

Daftar PustakaMurphy, K. 2012. Janeway’s Immunobiology.

London: Garland Science.Cunningham-Rundles, C. & Ponda, P. P. 2005.

Molecular Defects In T- and B-Cell Primary Immunodeficiency Diseases. Nature Reviews, 5: 880-892.