This document discusses several primary immunodeficiencies including SCID, XLA, DiGeorge's syndrome, Ataxia-teleangiectasia, Wiskott-Aldrich syndrome, and CGD. It defines primary immunodeficiencies as genetically determined disorders characterized by an impaired ability to produce a normal immune response. For each deficiency, it describes the genetic cause, key clinical manifestations like infections, and available treatments such as IVIG, bone marrow transplantation, or gene therapy.

1. Primary Immunodeficiency
Dr.Henock Hailu R1

2. Objectives
• Immunodeficiencies:
Definition ,cause and types
• Primary immunodeficiencies:
Definition ,types , diagnosis and therapy
• Examples; SCID,XLA, Digeorge’s syndrome , Ataxia-teleangectasia,
Wiskott-Aldrich syndrome ,CGD

3. Immunodeficiency
• Immune system’s ability to fight infectious disease is completely
absent or compromised.
• Types:
Primary immunodeficiency
Secodary immunodeficiency

4. Immunodeficiency
• Cause for Immunodeficiency
Human Immune system:
Very Specific
Dependent on memory cells and lymphocytes that recognise foreign
antigen and infected cells respectively.
• Any alteration in these functions will lead to Immunodeficiency.

5. classificatio
Primary
Immunodeficiency
Secodary
Immunodeficiency
• Most are genetically
determined
• May arise as complications of
cancers , infestations ,
malnutrition , or side effects
of immunosuppression ,
irradiation and
chemotherapy.

6. Primary Immunodeficiencies
• A group of disorders characterized by an impaired ability to produce
normal immune response .
• Cause : mutations in genes involved in the developmet and function
of immnue organs , cells and molecules.
• Gentically determined .
• usually disease of infacy & childhood .

7. Primary Immunodeficiency
• Most important feature;
• High incidece in Males
• 6 X- linked ID’s have been described
• 5 -Affect lymphocytes
• 1 -Affect phagocytes

9. Severe combined immuodeficiecy (SCID)
• Synonyms; Glazzman-Riker sydrome ,Bubble Boy Disease ,Thymic
Alymphoplasia
• Genetic disorder characterized by absence of T-lymphocytes.
• Impairment of both cellular & humoral response.
• Specific defects in antigen presentation & functional immune
molecules .
• Patients with this group of disorders have the most severe
immunodeficiency.

12. Features of SCID
• Absent tonsils
• Small or absent lymph nodes
• Absent thymic shadow
• Lymphopenias
• Decreased Number of T cells
• Severe agammaglobulinemia (Swiss type of agammaglouliemia )
• No IG’s usually preset

13. Clinical Manifestations
Infection: the most common presentation
Graft Versus Host Disease:
• Failure to reject foreign tissue
• Rash, hepatosplenomegaly and diarrhea
Omenn syndrome
• Few cells generated in the infant expand and cause a clinical
picture similar to GVHD
Almost all patients will have a low lymphocyte count

14. Laboratory Diagnosis
• CBC: lymphocytopenia
• Flow cytometer: to quantitate T, B & NK cells
• CD45RA and CD45RO markers
• To distinguish maternal engraftment and Omenn syndrome
Treatment
• HSCT
• 95% survival rate
• Gene therapy

16. Bruton’s X-linked Agammaglobulinemia
• Primary B- cell defect.
• Boys are more affected
• Severe reduction in gamma globulins
• Decresed IG’s ,circulating and marrow B-cells
• Probable cause ; Molecular defect at xq22. Mutation of bruton
tyrosine kinase .
• Therapy : IV IG’S.

21. Ataxia telagiectasia
• Autosomal recessive
• Incidence ; 25:10,000,000
• Characterstics : progressive cerebellar ataxia , ocular and cutaeous
telagiectasias , severe sinopulmonary infections , progeric changes ,
scelerodermoid changes .
• Thymus: fetal like histologic pattern .
• Traslocation between 14 and 7 .

24. Wiskott-Aldrich Syndrome
• X-linked condition
• Incidence : 4 : 10,000,000
• Severe eczema , recurrent infections , Bloody diarrhea , chronic otitis
media
• T cells appear bald
• Platelets : Decreased in number , small
• Failure to recognise polyscacchride antiges
• Defect : Failure in expression of sialophorin.

26. Clinical feature
• Circumcision site prolonged bleeding
• Bloody diarrhea during infancy
• Atopic dermatitis
• Recurrent infections .
• major causes of death
• Infections
• Bleeding
• EBV-associated malignancies

27. Chronic Granulomatous Disease
• Incidece : 1:10,000,000
• Defect: inability of pahagocytes to produce superoxide leading to
ineffective reduction of O2.
• Failure to express respiratory burst associated with phagocytosis.
• Cetral necrosis and granulomatoid response in lung , liver , bone , skin
and lymph nodes.
• Presence of numerous pigmented macrophages.
• Common organisms:
• Catalase positive bacteria & fungi.

28. Laboratory Findings
• Normal numbers of WBC
• Elevated ESR
• Dihydrohodamine flow cytometry test
• Absence superoxide production
Treatment
• Antibiotics and antifungals
• Interferon gamma.
• Bone marrow trasplantation.

30. Chediak-Higashi Syndrome
• Rare autosomal disorder.
• Abnormally large granules in leucocytes leading to :
hypopigmetation / partial albinism
severe immunodeficiency
neurologic abormalities
mild bleeding tendencies.
• Defective gene ; CHS 1

32. Leukocyte -Adhesion Deficiencies
• Autosomal recessive disorder.
• Inability of phagocytic cells to adhere to endothelial cells and migrate
to infected sites.
• Characterstics : Delayed cord dehiscece and scar formation , recurret
diarrhea and respiratory symptoms , leucocytosis
• Defect in CD 18 gene.
• Treatment : Bone Marrow Transplantion.

35. Selective IgA Deficiency
• Isolated absence or near absence (<5 mg/dL) of serum and secretory
IgA
• The most common well-defined immunodeficiency disorder.
• Disease frequency as high as 0.33% in some populations
• Asymptomatic or may develop sinopulmonary or GI infections
(especially Giardia )

36. • The basic defect is unknown
• Normal blood B cells are present
• The diagnosis cannot be made until about 4 yr of age, when IgA levels
should be matured to adult levels
• IgA deficiency may evolve into CVID

37. Clinical Manifestations
• Infections in the respiratory, GI, and GUT
• Bacterial infections
• Intestinal giardiasis is common.
• Normal Serum concentrations of other Immunoglobulin
• A normal antibody response to vaccination.

38. Common Variable Immunodeficiency
• Characterized by hypogammaglobulinemia
• Serum IgG must be <2 standard deviations below the age-adjusted
value, with low IgA and or IgM levels
• Clinically similar to those with XLA (except that enterovirus
meningoencephalitis is rare)
• A variable degree of T-cell dysfunction with T cell signaling to B- cells is
defective in CVID.

39. • Normal number of B – cells .
• Normal sized or enlarged tonsils ,lymph nodes
• CVID is the most common of the antibody defects
• Responses to protein and polysaccharide vaccines are poor.

40. Clinical Features
• Recurrent sinopulmonary infections, Bronchiectasis.
• Sepsis and meningitis (encapsulated bacteria)
• Increased risk of lymphomas.
• Splenomegaly (25%)
• Other autoimmune diseases include:Alopecia areata,Hemolytic
anemia,Thrombocytopenia, Gastric atrophy, achlorhydria, and
pernicious anemia

43. THANK YOU.