MLS 704: ADVANCED CLINICAL IMMUNOLOGY

IMMUNODEFICIENCY
STATES

By
Njeodo Njongang Vigny
Ph.D. student, Chemical Pathology
(HS20P207)
18 June 2021
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 OUTLINE

1. Types of immunodeficiency
2. Major patterns of microorganisms causing
immunodeficiency
3. Characteristic features of immunodeficiency
4. Indicators of immunodeficiency
5. Types of primary immunodeficiency disorders
6. Laboratory investigation of immunodeficiency
disorders
7. Laboratory management of immunodeficiency
disorders

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 What is Immunodeficiency?

• Entire absence or compromise of the immune

system’s ability to fight infectious disease.

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1. CLASSIFICATION OF
IMMUNODEFICIENCY

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 Classification of Immunodeficiency

 Primary (Hereditary or Inherited)

1. Recurrent infections – most common feature.
Other non-immune related infections e.g., CF,
ciliary dyskinesia, and TE fistula.
2. Complicated by malignancy and autoimmunity

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 Classification of Immunodeficiency

 Primary (Hereditary or Inherited)

1. Predominant antibody (B cell) defect
2. T cell defect
3. Combined T cell and B cell defect
4. Immunodeficiency syndromes

5. Phagocytic defect
6. Complement defect
7. Others
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Classification of Immunodeficiency

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 Classification of Immunodeficiency

 Secondary (Acquired)
1. Immunosuppressive treatments: cytotoxic
chemotherapy, radiation therapy, and
corticosteroids
2. Systemic disorders: Diabetes, HIV,
Undernutrition
3. Prolonged serious illness (hospitalized or
critically ill patient)

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 Classification of Immunodeficiency
B cell deficiency T cell deficiency Phagocytic defects Complement
deficiencies
Onset 7-9 months Onset before 5 Neutrophil number Early classical
months (severe congenital pathway (C1, 2, 3
neutropenia) and 4): vasculitis,
pyogenic infections
Recurrent Recurrent viral, Adhesion (leukocyte
infections with fungal or adhesion defect)
encapsulated mycobacterial
microorganisms pathogens
Little growth failure Severe failure Chemotaxis (Chediak-
Higashi syndrome)
Patients usually Often associated Intracellular killing
develop recurrent with B cell defect (Chronic granulomatous
sinusitis, disease)
pneumonia.
May Also recurrent
sepsis, meningitis

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 2. MAJOR PATTERNS OF
MICROORGANISMS CAUSING
IMMUNODEFICIENCY

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Major patterns of organisms causing
Immunodeficiency
Immunodeficiency Bacterial Viral Fungal Protozoa
infection infection infection Infection
T cell defect or +++ +++ +++ +++
combined T and B
cell defects
B cell defects +++ + - +++

Phagocyte defect +++ +++

Compliment defect +++ - - -

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3. CHARACTERISTIC
FEATURES OF
IMMUNODEFICIENCY

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 Characteristic features of
Immunodeficiency
IMMUNODEFICIENCY MICRO-ORGANISMS INFECTIONS
IDENTIFIED
Predominant T cell defect
Early onset (2-6 months) Gram + and – organisms, fungi – Lungs and GIT
candida, mycobacterium, CMV, infections
EBV

Predominant B cell defect

Onset after 5-7 months Pneumococci, staph, strep, GI and sinopulmonary
gardia infections
Phagocyte defect
Early onset Staph, pseudomonas, candida Skin abscess, oral
cavity infections
Compliment defect
Early onset at any age Pneumocococci and neisseria Meningitis, sepsis,
arthritis

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 4. INDICATORS OF
IMMUNODEFICIENCY
DISORDERS

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 Indicators of Immunodeficiency

General:
• Recurrent infections
• Severe infections
• Complicated infections (Malignancy and
autoimmune diseases)
• In multiple locations
• Caused by unusual organisms
• Resistant to infections
• No secondary cause
• Family members affected
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 Indicators of Immunodeficiency

Primary related:
• Most prominent signs: dermatological conditions
such as eczema, cutaneous infections.
• Recurrent respiratory infections
• Persistent bacterial infections: sinusitis, otitis,
bronchitis.
• Increased susceptibility to opportunistic
infections
• Skin and mucous membrane infections

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5. CLASSIFICATION OF
PRIMARY
IMMUNODEFICIENCY
DISEASES

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 Classification of Primary
Immunodeficiency diseases
1. B cell related: • Leukocyte adhesion
• Bruton’s disease deficiency
• Selective IgA deficiency • Chediak-Higashi
• Common variable syndrome
Immunodeficiency • Chemotaxis deficiency
diasease • Wiskott –Aldrich
2. T cell related: syndrome
• Di George syndrome • Ataxia Telangiectasia
• Acquired immunodeficiency 3. Complement
• Chronic granulomatous deficiency
disease 4. Phagocytes

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 Classification of Primary
Immunodeficiency diseases
1. CVID:
• B cell fails to mature into
plasma cells
• Onset at 4-5 months of
infants
• Recurrent infection with
viruses, protozoans,
bacteria
• Poor prognosis, early
infant death
• Opportunistic infections
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 Classification of Primary
Immunodeficiency diseases
2. Bruton’s disease (XLA):
• Failure of pre-B cell transforming to a immature B
cell
• Caused by tyrosine kinase deficiency
• < 1% B cells in peripheral blood
• Profound hypogammaglobulinaemia involving all
immunoglobulin classes
• Signs are skin infections (strep and staph Group
A), persistent viral or parasitic infections, increased
susceptibility to bacteria infection.
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 Classification of Primary
Immunodeficiency diseases
3. Selective IgA deficiency:
• Caused by intrinsic B cell defect
• IgA < 5 mg/dL with normal levels of other Igs
• Half of the patients present with chronic otitis,
sinusitis or pneumonia
• Susceptible to sinopulmonary infections,
asthma, autoimmune diseases, neurological
disorders etc

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 Classification of Primary
Immunodeficiency diseases
4. Severe combined immunodeficiency disease
(SCID):
• Both T and B cells are deficient with markedly
low levels of IgG, IgA, IgE
• Persistent and recurrent diarrhea, otitis, and
respiratory infections
T cell immunodeficiency diseases:
• Patients are susceptible to repeated candida
infections as well as viral and protozoan
infections
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 Classification of Primary
Immunodeficiency diseases
5. Di George syndrome (Thymic aplasia)
• Underdevelopment of the 3rd and 4th pharyngeal
pouches
• Absence of thymus
• Profound lymphopenia – CD3 T cells (< 1200
μL)

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 Classification of Primary
Immunodeficiency diseases

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 Classification of Primary
Immunodeficiency diseases
6. Ataxia Telangiectasia:
• Lack of coordination (early age) and dilation of
facial blood vessels (after 2 years)
• Defective mechanisms of DNA repairs
• Extremely sensitive to radiation exposure and
susceptible to chronic respiratory infections

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 Classification of Primary
Immunodeficiency diseases
7. Wiskott-Aldrich syndrome
• Caused by gene defect of WAS protein
• High IgA and IgE and Low IgM
• Signs: ears, lungs and sinuses are affected;
recurrent pyogenic bacterial infections, increased
lymphomas and autoimmune diseases.
• Triad of thrombocytopenia, eczema, and
recurrent pyogenic infections
• T and B cell dysfunction

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6. Laboratory investigation
of Immunedeficiency
disorders

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 Laboratory investigation of
Immunodeficiency disorders

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 Laboratory investigation of
Immunodeficiency disorders
 Screening test for B cell defect
1. IgA
2. IgM, IgG (if IgA is abnormal)

 Screening test for T cell defect

1. Absolute lymphocyte count (normal result rules
out T cell defect)
2. Flow cytometry (To check for naïve T cells –
CD3+, CD45RA)

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 Laboratory investigation of
Immunodeficiency disorders
 Screening test for Phagocyte disorder
1. Absolute neutrophil count
2. Respiratory burst assay

 Screening test for complement deficiency

1. CH50 (measures intactness of entire
complement pathway, low value implies
complement deficiency)

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 Laboratory investigation of
Immunodeficiency disorders

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7. Laboratory management
of Immunodeficiency
disorders

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 Management of Primary
Immunodeficiency Diseases
• General treatment: diet, avoid pathogens,
antibiotics, avoid whole blood transfusion, avoid
live virus vaccine
• Replacement therapy
• Immune reconstitution: treatment of severe
antibody disorders (frozen plasma, Intravenous
immunoglobulin)
• Gene therapy

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 Phagocytic disorders treatment

• Interferon gamma
• Granulocyte transfusion

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 Treatment for cellular deficiency

• Bone marrow transplantation

• Replacement therapy
– Enzyme, gene, cytokines, thymic hormones, Fetal
thymus transplantation

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 References

• Fawzia AA. Approach to the patient with suspected immune deficiency.

Accessed May 20, 2021. Available at https//: www.slideshare.net
• Fawzia AA. Immunoglobulin deficiency – Common variable Immune
deficiency. Accessed May 20, 2021. Available at https//:
www.slideshare.net
• Fawzia AA. Approach to the patient with suspected immune deficiency.
Accessed May 20, 2021. Available at https//: www.slideshare.net
• Fawzia AA. Immunodeficiency. Accessed May 20, 2021. Available at
https//: www.slideshare.net

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