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X-linked Agammaglobulinema

Brilly Winsen
Melinda Ong
Michella Juliana
Rico 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
barrier
Epitelial 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, neutrophil


Pass trough the physical barrier
Phagocyte ingest mo into vesicle

destroy
Produce antimicrobial protein
cytokine
Machropage cyokine that
stimulate inflammation
causing: capillary dilation,
increase blood flow
Macrophage n DC APC
activate adaptive

3. Dendritic cells
Phagositing microbe that passs through the

epitelial barrier
Express 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
microbes surface receptor recruit more
phagocyte for phagocytosis

5. Natural Killer Cells


(NKcells)
Came from the same lineage of

lymphocite precursor
But 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-

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-Lymphocye
Thymus-derived lymphocyte
Major population in spleen & peripheral lymp nodes
T 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-lymphocyte
Bone marrow-derived lymphocyte
10-20%- peripheral lymphocytes , bone

marrow, other lymphoid tissue


Capable 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
HUMORAL
IMMUNITY
IMMUNITY

POSITIVE
POSITIVE
SELECTION
SELECTION
AND
AND NEGATIVE
NEGATIVE
SELECTION
SELECTION

B
B CELL
CELL
RECEPTOR
(BCR)
(BCR)

ANTIGEN
ANTIGEN
PRESENTING
PRESENTING
CELL
CELL

BONE
BONE MARROW

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
POSITIVE

NEGATIVE

B CELL ACTIVATION

T-CELL
T-CELL
INDEPENDENT
INDEPENDENT
ACTIVATION
ACTIVATION

MEMORY B CELL
ACTIVATION
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 cells 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 Timus


T-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 : (alfa:beta) dan :
(gamma:delta).
Timosit (T-Cell yang sedang berkembang) juga
mengalami seleksi berdasarkan interaksi dengan
sel timus.

Proses Perkembangan TCell


1
A

1
B

2
A

2
B

Proses Perkembangan TCell


3
A

3
B

4
A

4
B

Tahap Perkembangan Timosit di Timus


Timus 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 Brutons Disease, recurrent

pyogenic infections
Tidak ada circulating mature B cells, T cells
normal
Tidak ada plasma cells di Bone marrow, lymph
node, atau GI tract
Gen Btk termutasi
Very low serum levels all isotypes
immunoglobulin

TREATMENT
Intravenous Infusion (IVIg)
Muscle Injections (IMIg)
Subcutaneous (SCIg)
Antibiotics
Gene Therapy

Kesimpulan

Daftar Pustaka
Murphy, K. 2012. Janeways 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.