Immunodeficiency diseases

• Conditions where the defence

mechanisms of body are impaired ,
leading to repeated microbial infections
of varying severity & sometimes
enhanced susceptibility to malignancies .
 Classification
• Primary immunodeficiency
• Secondary immunodeficiency
 Primary immunodeficiency
• Resulting from a genetic or
developmental defect in the immune
system .
 Secondary immunodeficiency /
acquired immuno deficiency
• Loss of immune function & results from
exposure to various agents .
 Classification of primary
immunodeficiency
1. Antibody [ B cell ] immunodeficiencies.
2. Cellular [T cell] immunodeficiencies
3. Combined B cell (antibody )& T (cellular)
cell deficiencies
4. Phagocytic dysfunction diseases
5. Disorders of complement
 Antibody (B cell)
immunodeficiencies
1. X- linked agammaglobulinemia -*
2. Transient hypogamma globulinemia of infancy
3. Common variable immunodeficiency -*
4. Hyper IgM immunodeficiency ( T Cell defect )
5. IgA deficiency - *
6. IgM deficiency
7. IgG subclass deficiencies
8. Polysaccharide unresponsiveness
9. Transcobalamin deficiency
10.Netherton syndrome
 Cellular ( T cell )
immunodeficiencies
1. Digeorge syndrome -*
2. Chronic mucocutaneous candidiasis
3. Biotin dependent multiple cocarboxylase
deficiency
4. Natural killer cell deficiency
5. Idiopathic CD4 lypmhopenia
 Combined Bcell and T cell
deficiencies
1. Severe combined immunodeficiency [including X
linked SCID ,Nezelof syndrome ,etc] -*
2. Combined immunodeficiency with T cell
membrane
3. Wiskott –aldrich syndrome -*
4. Ataxia –telangiectasia -*
5. Nijmegen breakage syndrome
6. Graft versus host disease lymphocyte syndrome
7. Omenn syndrome
8. Reticular dysgenesis
9. X-linked lypmhoproliferative syndrome .
Phagocytic dysfuction diseases
1. Neutropenia syndromes
2. Chronic granulomatous disease
3. Leukocyte glucose -6- phosphate
dehydrogenase deficiency -*
4. Chediak - higashi syndrome - *
5. Myeloperoxidase deficiency
6. Specific granule deficiency
7. Glycogen storage disease type 1b
8. Hyper IgE / job’s syndrome -*
10. Leukocyte adhesion defect
11. Schwachman syndrome
12. Tuftsin deficiency
13. Periodontitis syndromes
Disorders of Complement :
1. Complement component deficiencies
2. Complement inhibitor deficiencies
 B cell immunodeficiencies
1 . X-linked Agammaglobulinemia [
Bruton’s agammaglobulinemia
• X- linked , gene governing the disorder
localised to the long arm of the X-
chromosome .
• Pre B cell no . Normal , maturation failure
• Boys
• Recurrent pyogenic infections
• I gG less than 200 mg/dl absence of IgM,
IgD ,IgA ,IgE.
 Dental perspective
• Recurrent periodontal disease &
abnormal degree of dental decay.
• Possible septicemia from odontogenic
infection .
 2. Common variable
immunodeficiency[CVID]
• Adult
• High incidence of infections ,autoimmune
disorders,malignant disease particularly
of lymphoid system.
• Recurrent pyogenic infections
• Male & female
• Total Ig level less than 300mg/dl with
IgG level below 250 mg/dl.
• Bcell numbers normal .
• Defect – Bcell inability to produce
immunoglobulins.
• Dental perspective –
possible septicemia from odontogenic
infection [sepsis from abscessed teeth]
 3. IgA deficiency
• Many are asymptomatic , prevalence 1:
800to1:400
• IgA level below 15 mg/dl ;other normal or
increased.
• CMI normal
• Allergies, recurrent sinopulmonary infection ,
GIT disease, autoimmune disease
• Defect – block in differentiation of B cell to
IgA antibody secreting plasma cells .
• Dental perspective – dental caries ,
periodontal disease ,candidiasis ,oral
ulcerations .
 T Cell immunodeficiencies
• DIGEORGE Syndrome – other names
• 22q 11.2 deletion syndrome
• DiGeorge anomaly
• Velo Cardio Facial Syndrome
• Shprintzen syndrome
• Conotruncal anomaly face syndrome
• Congenital thymi aplasia
• Strong syndrome
• Thymic hypoplasia
• Congenital malformation
• Defective development of thymus & para
thyroid glands .
• Defect - micro deletion of chromosome
at a location designated q 11.2 on the
long arm of one of the pair of
chromosomes 22.
• Dental perspective –
• Candidiasis , herpes infections , cleft
palate , hyper telorism , enamel
hypoplasia
 Effect
• CATCH 22
• Cardiac abnormality
• Abnormal facies
• Thymic aplasia
• Cleft palate
• Hypocalcemia
 Combined Bcell & Tcell
immunodeficiencies
1. Severe Combined Immunodeficiency [SCID]
• Lack of both T cell & Bcell functions.
• Onset of viral , bacterial ,fungal or
protozoal infections before 3 months of
age .
• Defect 1- x- linked & derived from
mutations in the common ϒ chain . It
arrest T cell development in the thymus .
• Defect 2 - genetic deficiency of purine
degradation enzymes.[Adenosine
deaminase].
• Patients get accumulation of adenosine ,
leads to inhibition of DNA synthesis &
destruction of cells .
 Effect
• Chronic pulmonary infections , diarrhea ,
candidiasis.
• Dental perspective –
• Oral candidiasis.
• Herpes infections.
• Recurrent oral ulcerations of the tongue &
buccal mucosa.
• Severe necrotizing gingival stomatitis .
 2.Wiskott Aldrich syndrome [WAS]

• X-linked disease
• Eczema ,thrombocytopenia, susceptibility
to bacterial infection .
• Decreased antibody responses to
polysaccharide antigens with decreased
IgM & elevated IgA & IgE levels.
• Decreased Tcell function – autoimmunity&
malignancy.
• Defect – mutations of gene encoding the
Wiskott – Aldrich syndrome protein [imp.
In organization of the cytoskeleton of
both lymphocytes & platelets ].
• Poor CMI & impaired antibody production .
• Dental perspective – gingival bleeding &
palatal petechiae .
 3.Ataxia -telangiectasia

• multisystem congenital disease

• Characterised by abnormal gait , vascular
malformations ,neurologic defects,
increased incidence of tumours ,
immunodeficiency.
• Defect - defective gene is on 11q22-23
• Dental perspective
oral telangiectasia
 Phagocytic Dysfunction Diseases

• Leukocyte Adhesion Deficiency [LAD]

• Defect in neutrophil adhesion
• Skin ulcers ,poor wound healing ,
recurrent bacterial infections .
• 3 genetic forms - LAD -1 ,2 & 3
• Defect- mutations in the gene encoding
the common β chain CD 18 .
• Dental perspective -
Early childhood periodontitis
delayed wound healing
Oral ulcerations
 Chediak - Higashi syndrome
• Impaired lysis of phagocytosed bacteria .
• Recurrent bacterial respiratory infections,
oculocutaneous albinism.
• Abnormal intracellular protein ,
lysosomes
cannot fuse with phagosomes , so
ingested bacteria cannot be lysed normally.
• Dental perspective –
• Early childhood peiodontitis
• Severe gingivitis & oral mucosal
ulceration
• Possible increased bleeding
Hyper IgE syndrome (job’s syndrome)

• Classical triad:
1. Recurrent staphylococcal skin abscesses.
2. Pneumonia with pneumatocele
formation.
3. Elevated levels of serum IgE

Defect – immunoregulatory Tcell

abnormality with excessive IL- 4 production
• Dental perspective –
• Prolonged oral infections
• Delayed resorption of primary teeth
• Candidiasis
• Broad nasal bridge .
Thank you