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1. Primary Immunodeficiency
Nishitha A
4TH Term

2. Objectives
WHAT WILL
I LEARN
TODAY?
Immunodeficiencies:
Definition, cause and types
Primary
Immunodeficiencies:
Definition, types, diagnosis
and therapy
Examples:SCID, XLA,
DiGeorge’s syndrome, Ataxia-
teleangectesia, Wiskott-
Aldrich syndrome, CGD

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

4. Immunodeficiency
• Cause for Immunodeficiency:
Human Immune system:
Very specific
Dependent on memory of cells and
lymphocytes that recognise foreign antigen
and infected cells respectively.
• Any alterations in these functions
Immunodeficiency.

5. Classification
•Most are genetically
determined
•Less common
•May arise as complications
of cancers, infestations,
malnutrition, or side effects
of immunosuppression,
Irradiation and
chemotherapy.
•More common
Primary
Immunodeficiency
Secondary
Immunodeficiency

6. Primary Immunodeficiencies
• A group of disorders characterized by an
impaired ability to produce normal immune
response.
• Cause: mutations in genes involved in the
development and function of immune organs,
cells, and molecules.
• Genetically determined.
• Usually diseases of infancy & childhood.

7. Primary Immunodeficiency
• Most important feature:
• High Incidence in Males: Why ?
• 6 X-linked ID’s have been
described:
5 - Affect
Lymphocytes
1- Affect
Phagocyte

9. Table 1. Characteristic infections of the primary immunodeficiencies
component primary pathogen primary site clinical example
T-cells
intracellular, bacteria
viruses, protozoa, fungi,
non-specific SCID, DiGeorge
B-cells
pneumococcus,
streptococcus,
haemophilus
lung, skin, CNS
IgG, IgM deficiency
IgG, IgM deficiency
enteric bacteria and
viruses
GI, nasal, eye IgA deficiency
phagocytes
Staphylococcal,
Klebsiella
Pseudomonas,
lung, skin,
regional lymph
node
Chronic
granulomatous
disease (CGD)
complement
neisseria, Haemophilus,
pneumococcus,
streptococcus
CNS
lung
skin
C3, Factors I and H,
late C omponents

10. Severe Combined
Immunodeficiency(SCID)
• Synonyms: Glanzzman-Rinker syndrome,
Bubble Boy Disease, Thymic Alymphoplasia
• Genetic disorder characterised by absence of
T-lymphocytes.
• Impairment of both cellular & humoral
response
• Specific defects in antigen presentation &
functional immune molecules.

11. Bubble Boy

12. SCID-Types
• Main Types:
Autosomal recessive (-ve T & B cells)
X-linked recessive(+ve B cells)
• Other important types:
Nezelof Syndrome
SCID associated with ADA & PNP deficiency.

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

14. Thymic
Dysplasia

15. .
Cell-Mediated/T cell Immunity

16. Bruton’s X-linked Agammaglobuinemia
• Primarily B-cell defect
• Boys-more affected
• Severe reduction in γ-globulins
• IG’s, circulating and marrow B-cells.
• Probable cause: Molecular defect at
Xq22.Mutation of bruton tyrosine kinase.
• Therapy: IV IG’s.

17. DiGeorge’s syndrome
• Also called thymic hypoplasia
• Congenital disorder
• Abnormalities in structure derived from 3rd
and 4th pharyngeal pouches
• Predominantly T cell defect
• Charactersitics: Neonatal tetany(absence of
parathyroid)
• Therapy: Thymic transplants

18. • Cleft palate
• Antimongoloid eyes
• Short philtrum with
fish-mouth appearance ,
• Micrognathia
• Low set pixie-like ears
• Short palpebral fissures
Facial features of children with DiGeorge syndrome

19. DiGeorge Syndrome

20. DiGeorge syndrome

21. Ataxia-telangiectasia
• Autosomal recessive
• Incidence: 25:10,00,000
• Characteristics: Progressive cerebellar ataxia,
ocular and cutaneous telangiectasias, severe
sino-pulmonary infections, progeric changes,
sclerodermoid changes
• Thymus: fetal-like histological pattern.
• Translocation between 14 and 7

22. Ataxia

23. telangiectasia

24. Wiskott-Aldrich Syndrome
• X-linked condition
• Incidence: 4:10,00,000
• Severe eczema, recurrent infections, Bloody
diarrhea, chronic otitis
• T cells appear bald :?
• Platelets: Decreased in number, small
• Failure to recognise polysaccharide antigens.
• Defect: Failure in expression of sialophorin.

25. Eczema
Histological
Pictutre:

26. Chronic Granulomatous Disease
• Incidence:1:10,00,000
• Defect: Inability of phagocytes to produce
superoxide ineffective reduction of O2.
• Failure to express respiratory burst associated
with phagocytosis.
• Central necrosis and granulomatoid response
in lung, liver, bone , skin and lymph nodes.
• Presence of numerous pigmented
macrophages.

27. CGD patient with
skin infections
due to Serratia
marcescens

28. Chediak-Higashi Syndrome
• Rare autosomal disorder
• Abnormal large granules in leucocytes leading to:
– hypopigmentation/partial albinism
– severe immunodeficiency
– neurologic abnormalities
– mild bleeding tendencies
• Defective gene: CHS1

30. Leucocyte-Adhesion defect
• Autosomal recessive disorder
• Inability of phagocytic cells to adhere to
endothelial cells and migrate to infected sites
• Characteristics: delayed cord dehiscence and
scar formation, recurrent diarrhea and
respiratory symptoms, leucocytosis
• Defect in CD18 gene
• Treatment: Bone marrow transplantation

32. Other Primary ID’s
• Selective IgA deficiency
• Common variable Immunodeficiency
• X-linked lymphoproliferative disease
• Job’s syndrome

33. Complement deficiencies
• Involves 19 proteins:
11-classical, 3-alternate, 5-regulatory
• Alteration in the expression of these proteins
Autoimmune & Immunodeficiency diseases
Classical AI affecting vessels & glomeruli
Alternate Pyogenic infections
Regulatory Hereditary Angioneurotic edema

34. Diagnosis of Primary Immunodeficiencies
• Histopathology
• Immunohistochemistry
• Monoclonal Antibodies
• Cell separation by flow cytometry
• Insitu Hybridisation

35. Therapy
• Supportive therapy- antibiotics
• Replacement therapy-IV immunoglobulin
infusion, ADA-rich RBC infusions
• Definitive therapy- Fetal thymic grafts, bone
marrow transplantation
• Stem-cell therapy
• Gene therapy