Defects in one or more

components of the immune

system can lead to serious and
often fatal disorders

IMMUNODEFICIENCY
DISEASES

The Two Immune Systems

Communicate and Cooperate
Antigen
Presentation
Antigen
Recognition

Neutrophil

Lymphocytes

T4

APC
Monocyte

Granulocytes

T4

Antibody

Macrophage

Specific
System

Non-Specific
System
Cytokines

Plasma Cell

T8

Immunodeficiency

1. Types according to etiology :

1.1. Primary Immunodeficiency :
* hereditary genetic diseases 1.2.
Secondary Immunodeficiency :
* resulted from other primary disorder
e.g. infection; cancer;
* resulted from therapy : chemotherapy
(cytostatics), immunosuppresives,
radiation ;
2. Types according to involved component :
2.1. B lymphocytes immunodeficiency
2.2. T lymphocytes immunodeficiency
2.3. B and T lymphocytes combined
immunodeficiency
2.4. Complement / phagocyte system
immunodeficiency

Specific Mechanisms
Cell-mediated immune response

directed against intracellular substances

viruses, tumours

T-lymphocytes
thymus-derived

Humoral immune response

directed against extracellular substances

bacteria

B-lymphocytes (which mature into plasma cells)

bone marrow derived

Primary Immunodeficiency (1)

1. Bruton type Agammaglobulinemia, X-linked

* B cells are not developed and depleted in
peripheral lymphoid organs (tonsil, spleen, lymph
nodes) agammaglobulinemia;
* cellular immune system is intact;
2. Common Variable Immunodeficiency (CVI)
* the number of B cells is adequate, differentiation
defect or its terminal function incapable to
produce Immunoglobulin;
* some due to Ig gene mutation ;
* other mechanism due to abnormal helper T cells
or elevated suppressor T cells
hypogammaglobulinemia

Primary Immunodeficiency (2)

3. Selective IgA Deficiency

* differentiation defect of IgA
producing B cells, while the others
are normal
* immature B cells feature (IgM, IgD);
* other mechanism : antibody against
IgA (40 % cases) IgA level
decreased ;
* recurrent respiratory, intestinal and
urogenital infection;

Primary Immunodeficiency (3)

4. DiGeorge syndrome (Thymus Hypoplasia)

* hypoplasia / aplasia of thymus cellular
immunodeficiency
* antibody synthesis is normal;
* viral and fungal infection severe disease
and complication;
* accompanied by tetany due to parathyroid
aplasia;
* thymus transplantation improvement ;

Primary Immunodeficiency (3)

Wiskott-Aldrich Syndrome
* recessive x-linked
* accompanied by thrombocytopenia dan eczema
* defect in glycosilisation of membrane protein and
defect in maturation of hematopoetic stem cells;
* decreased CD43 expression in B and T cells,
macrophages, netrophils dan thrombocytes;
* Thymus is normal, deminished T cells in the blood
and paracortical area of lymph nodes;
* antibody sysnthesis is normal;
* prone to recurrent infections;
* susceptible to lymphoid malignancy.

Primary Immunodeficiency (4)

6. Severe Combined Immunodeficiency Disease (SCID)

* combination of cellular and humoral immunodeficiency;
* 2 types: 1) autosomal recessive or
2) X-linked recessive;
* ad 1) ADA (adenosine deaminase) deficiency
accumulation of deoxy-ATP dan S-adenosil
homocystein toxic to immature limfocytes T
and B cells reduction;
- other form: PNP (protein nucleotidephosphorylase) deficiency
accumulation of deoxyguanosine and deoxy- GTP
toxic to T cell > B cells;
- new form: defect in MHC II expression on B cells, macrophages
and dendritic cells defect in delayed hypersensitivity
reaction (DHR) and susceptible to viral infection;
* ad 2) 50 % +) mutation defect in IL-2,4 and 7 activation of
T is impaired;
- patients susceptible to infection ( bacteria, fungus, virus);
- thymus is hypoplastic, limfocytes are depleted in the lymph nodes.

Primary Immunodeficiency (5)

7. Deficiency of complement system

* deficiency of C3 susceptible to infection with piogenic
bacteria;
* deficiency of C1q, 2, 4 susceptible to immune
complex disease;
* deficiency of C1 esterase enzyme activation of C1 is
uncontrolled hereditary angioedema;
* deficiency of C5-8 sensitive to infection with Neisseria
(gonococci dan meningococci);

8. Deficiency of the function of phagocytes system

* rarely occured;
* granulomatosal infllamation;
* failure to control infection;

Secondary Immunodeficiency (1)

1. Immunodeficiency as the result of other disease or

therapy efficiency of therapy decreased, prone to
recurrency and sensitive to opportunistic infection;
2. AIDS (Acquired Immunodeficiency Syndrome)
* etiology: retrovirus HIV (human immunodeficiency
virus) type 1 ( US, Europe, East Africa) and type 2
( West Africa);
* disorders involving organs of the immune system
and central nervous system;
* complication of opportunistic infection in various
organs;
* virus attacks helper-T (CD4+) lymphocytes
through gp120 receptor internalization;
* infection / transmission is blood-born type;
* transmission: both homosexual and heterosexual;

Secondary Immunodeficiency (3)

Nervous system disorders in AIDS:

* monocytes / macrophages infected by certain HIV strain;
Clinical course of AIDS 3 phases:
1. Acute phase (3-12 weeks): viremia and involvement of lymphoid
tissues;
* Th cells are reduced antibody and Tc acute phase recovery;
* fever, myalgia, skin rash, sore throat self limiting;
2. Latent phase: virus replication in lymphoid tissue, may last for years;
* persisting general lymphadenopathy, fever, skin rash, fatigue;
* partly asymptomatic;
* damage of Th cells continues;
3. Crisis phase: Th/Ts ratio decreases; Th (CD4+) counts < 200 /uL
progressivity (diagnostic criteria of Center for Disease Control
(CDC);
* fever > 1 month, fatigue, loss of body weight , diarrhea;
* opportunistic infection: Candida albicans, Pneumocystis carinii,
Cytomegalovirus. Mycobacteria, Cryptococcus neoformans,
Histoplasma capsulatum, Toxoplasma gondii;
* uncommon neoplasma: Kaposi sarcoma, malignant lymphoma;

Terima
kasih

Development of different types of lymphocytes from a pluripotential

stem cell in the bone marrow.