This document discusses immunodeficiency disorders. It begins by defining immunity and the immune system. There are two types of immunodeficiency disorders: primary (congenital) and secondary (acquired). Primary disorders are inherited and cause susceptibility to infections from a young age. They are classified based on defects in humoral immunity, cell-mediated immunity, or both. Examples of specific primary disorders are provided for each category. Secondary immunodeficiency is caused by external factors like HIV/AIDS, which damages the immune system over time. The document outlines evaluation, characteristics, treatment and clinical manifestations of various primary and secondary immunodeficiencies.

1. IMMUNO DEFICIENCY
DISORDERS
Dr K V CHAKRADHAR
ASSISTANT PROFESSOR,
DEPARTMENT OF MICROBIOLOGY,
NRIIMS.

2. DEFINITIONS
• Immunity
• Immune system
• Components of Immune
systems

3. IMMUNODEFICIENCY DISORDERS
• Definition:
Immunodeficiency- an abnormality of the immune system that renders
a person susceptible to diseases normally prevented by a normal
functioning immune system.

4. CLASSIFICATION
• Immunodeficiency:
• Primary or Congenital:
•
•
•
•
Inherited (due to Mutation in genes controlling immune cells)
Susceptible to recurrent, severe infection; starting in children
Cannot recover without treatment
>125 immunodeficiency disorders
• Secondary or Acquired:
• As a consequence of other diseases or environmental factors
• E.g: Infection, Malignancy, Aging, Starvation, Medication & Drugs)
• Acquired Immuno Deficiency Syndrome – Human Immunodeficiency Virus.

5. PRIMARY OR CONGENITAL
IMMUNODEFICIENCY

6. • Four Categories Immune Mechanisms
• Humoral (Antibody or B-cell mediated)
• Specific type of mechanism
• Cell-mediated (T-cell mediated)
• Specific type of mechanism
• Complement system
• Non-specific type of mechanism
• Phagocytosis
• Non-specific type of mechanism

7. PHAGOCYTOSIS
CELL MEDIATED
IMMUNITY
HUMORAL IMMUNITY

8. DEFECTS IN HUMORAL MEDIATED
IMMUNITY
• Caused by the improper production of one or all of the
immunoglobins (antibodies)
• Results in an increased of infections from Staphylococcus,
Streptococcus, Haemophilus, and Pseudomonas.
• Humoral Immunodeficiencies include:
• Bruton’s X-Linked Agammaglobinulinemia
• Common Variable Immunodeficiency
• Selective Immunoglobin A Deficiency

9. DEFECTS IN CELL MEDIATED
IMMUNITY
• Caused by defects in T lymphocyte development (both CD4+ helper
cells and CD8+ cytotoxic killer cells)
• Symptoms are more severe than with humeral immunodeficiencies
• Children rarely survive beyond infancy or childhood
• Cell Mediated Immunodeficiency disorders include:
• DiGeorge Syndrome
• X-Linked Immunodeficiency with Hyper-IgM

10. COMBINED T-CELL AND B-CELL
IMMUNODEFICIENCIES
• Severe Combined Immunodeficiency (SCID)
• Ataxia Telangiecctasia
• Wiskott Aldrich syndrome

11. • Severe Combined Immunodeficiency (SCID)
• Caused by diverse genetic mutations resulting in the absence of
ALL immune function
• Infants with this disease lead a short life (~ 2 years) with chronic
opportunistic infections
• There is a milder form known as combined immunodeficiency
syndrome having a low, but not absent T-cell function.

12. • Ataxia Telangiectasia:
• Results from a mutation on chromosome 11
• Condition consists of worsening ataxia (lack of coordination) and
telangiectasia (dilated capillaries and arterioles) on the skin and
conjunctiva.
• Children have reduced levels of IgA, IgE, and IgG, and decreased
ratio of CD4+ helper T cells to CD8+ cells.
• Children are prone to recurrent upper and lower respiratory
infections and an increased risk of malignancy.
• Death from lymphoma is common

13. TELANGIECTASIS

14. • Wiskott-Aldrich Syndrome:
• Patient has decreased IgM and elevated levels of IgA and IgE.
• T-cell dysfunction is initially mild then progressively worsens
making child susceptible to Hodgkin’s disease and lymphoma
• They are also susceptible to infections (including septicemia and
meningitis) caused by encapsulated microorganisms
• Signs and symptoms:
• eczema
• chronic infections
• low platelet counts

15. DISORDERS OF COMPLEMENT SYSTEM
• Complement system is an important part of the non-specific immune
response.
• Complement promotes chemotaxis, opsonization, and phagocytosis
of invasive pathogens, bacteriolysis, and anaphylactic reactions.

16. • Primary complement disorders are caused by genetic problems
• Deficiency of C1 to C4 are not at increased risk for infection
because alternate pathways can be activated.
• These patients are more prone to autoimmune diseases such as
Lupus Erythematosus and increased susceptibility to pyogenic
infections
• Deficiency of late complement components (C5, C6, C7, C8)
results in systemic Neisseria infections such as meningococcal
sepsis, meningitis and disseminated gonococcal infections.

17. • Abnormalities of the control proteins of the alternative pathway
(factor H, factor I, properdin) may result in recurrent infections.
• Deficiency of complement inhibitors (C1 esterase inhibitor,
carboxypeptidase N) leads to Hereditary Angioneurotic Edema
• Secondary Disorders of Complement
• Occur in persons with normal complement systems who have
rapid activation or turnover of complement components
• Can also occur with conditions where there is a decreased
production complement components such as in liver cirrhosis or
malnutrition.

18. DISORDERS OF PHAGOCYTOSIS
• Phagocytic system:
• Composed primarily of:
• Neutrophils, Eosinophils and Monocytes.
• Phagocytic cells function to migrate to site of infection, adhere to the
tissue, engulf invading material, and then digest it.
• A defect in the phagocytic system results in a decreased number of
phagocytic cells.
• Persons are prone to bacterial infections, often by Candida and
filamentous fungi.

19. Disorder
Inheritance
Clinical Features
1) Chronic
granulomatous
disease
X-linked (66%);
autosomal
recessive (33%)
Infections with catalase producing bacteria
and fungi affecting skin, lungs, liver;
granuloma formation
2)Myeloperoxidase
deficiency
Autosomal
Recessive
Fungal infections (candidiasis) in deep tissues,
especially in presence of diabetes
3)Leukocyte
adhesion
deficiency
Auto-somal
recessive
Delayed separation of the umbilical cord; skin
infections; otitis media; pneumonia; gingivitis;
periodontitis
4)Abnormal
chemotaxis
-Hyper IgE
-chediak-Higashi
Variable
Recurrent skin infections with staphylococci.
enteric bacteria, Neuropathy, Occulocultaneous albinism in chediak higashi

20. GIANT GRANULES IN
NEUTROPHILS
CHEDIAK-HIGASHI
SYNDROME

21. CHRONIC GRANULOMATOUS
DISEASE
MECHANISM OF
RESPIRATORY BURST
-
Myeloperoxidase
MYELOPEROXIDASE
DEFICIENCY

22. EVALUATION OF IMMUNODEFICIENCY
Often present
Usually present
1. Recurrent respiratory
tract infections
2. Severe bacterial
infections
3. Recurrence of same
type of bacteria
4. Paucity of lymph nodes
and tonsils
1. Persistent sinusitis or
mastoiditis
2. Failure to thrive
3. Intermittent fever
4. Skin lesions
5. Diarrhea
6. Hearing loss due to chronic
middle ear infections
7. Chronic conjunctivitis
8. Bronchiectasis
9. Evidence of autoimmunity
10. Hematologic abnormality
Occasionally present
1.
2.
3.
4.
5.
6.
Lymphadenopathy
Hepatosplenomegaly
Severe viral illnesses
Chronic encephalitis
Deep infections
Delayed umbilical
detachment
7. Adverse reactions to
vaccines

23. CHARACTERISTIC FEATURES OF PRIMARY
IMMUNODEFICIENCY DISORDERS

24. Characteristic
T- cell defect
B- cell defect
Granulocyte defect
Complement defect
Age of onset of
infection
Early; 2-6 months
After 5-7 months
Early onset at birth
Any age
Specific pathogens
Mycobacteria,
Viruses, Fungus like
Candida and
parasites
Pyogenic bacteria
mainly Streptococci,
Staphylococci
Hemophilus
enteroviruses
Bacteria;
Staphylococcus
Pseudomonas
Klebsiella
Bacteria
Systemic effects
Failure to thrive,
Extensive
mucocutaneous
Candidiasis
Recurrent
sinopulmonary
infections
Malabsorption
Enteroviral
encephalitis
Skin abscesses,
impetigo, cellulitis
Recurrent
sinopulmonary
infections
Meningitis
Special features
GVHD, Post
vaccination
disseminated BCG or
Varicella
Hypocalcemic tetany
in infancy
Autoimmunity
Lymphoma
Thymoma
Post vaccination
paralytic polio
Prolonged
attachment of
umbilical cord
Poor wound healing
Autoimmune diseases

25. LABORATORY EVALUATION OF
IMMUNODEFICIENCY DISORDERS
• Routine investigations:
• Total and differential leucocyte counts
• Absolute lymphocyte count
• Normal result rules out T- cell defect
• Absolute neutrophil count
• Normal study rules out granulocyte defect
• Platelet count and morphology
• Normal result rules out WAS
• Howell- Jolly bodies
• ESR

26. Suspected B cell defect
Serum Electrophoresis
Hypogammaglobulinemia
Immunoglobulin pattern
B cell count
Low
XLA
Normal
Abnormal
Possible CVID
Normal
Consider complement or
phagocytic dysfunction

27. SECONDARY OR ACQUIRED
IMMUNODEFICIENCY

28. • Acquired immunodeficiency syndrome (AIDS) is a secondary
immunodeficiency
• AIDS is a disease caused by the retrovirus Human Immunodeficiency
Virus (HIV) which is a single stranded RNA virus
• It is characterized by profound immunosuppression that leads to
opportunistic infections, secondary neoplasms and neurologic
manifestations.

29. PATHOGENESIS OF
AIDS
AIDS

30. TRANSMISSION OF HIV INFECTION
• Sexual contact
• Most frequent mechanism
• 75-80% via unprotected sex
• The virus can pass from semen and vaginal secretions into the
bloodstream through mucous membranes and wounds in the skin.
• Blood-to-blood contact
• Needle stick injury
• Sharing of needles or
• Transfusion of blood and blood products.

31. • Perinatal transmission can occur in utero, during labor, or by breast
feeding
• Studies still show that HIV does not spread through casual contact or
by vectors such as mosquitoes

32. MAJOR ABNORMALITIES OF IMMUNE
FUNCTION IN AIDS
• Lymphopenia
• Predominantly due to selective loss of CD4+ helper inducer T cell
subset and reversal of CD4:CD8 ratio
• Decreased T cell function
• Preferential loss of memory T cells
• Susceptibility to opportunistic infections and neoplasms
• Decreased type IV hypersensitivity

33. • Polyclonal B cell activation
• Hypergammaglobulinemia and circulating immune complexes
• Altered monocyte and macrophage function
• Decreased chemotaxis
• Diminished antigen presenting to T cells.

34. Infected helper T-cell
The small blue globules are
HIV particles.

35. CLINICAL MANIFESTATIONS OF
AIDS
• An infection by microorganism that normally does not cause disease
but become pathogenic when the body’s immune system is impaired
and unable to fight off the infection are “opportunistic infections”
(OIs).
• OIs are the hallmark of immunodeficiency with HIV
• It is important to diagnose OIs as the acute infections are at times lifethreatening and effective prophylaxis and treatment renders better
survival.

36. AIDS DEFINING OPPORTUNISTIC INFECTIONS
AND NEOPLASMS
• Infections:
• Protozoal and helminthic infections
•
•
•
•
Cryptosporidiosis or Isosporidiosis
Pneumoncystitis jirovecii pneumonia or disseminated infection
Toxoplasmosis
Strongyloidiasis
• Fungal infections
•
•
•
•
Candiadisis (esophageal, tracheal or pulmonary)
Cryptococcosis
Coccidioidomycosis
Invasive Aspergillosis
• Bacterial infections
• Mycobacteriosis (M. tuberculosis or atypical mycobacteriosis)
• Nocardiosis (Pneumonia, Meningitis or disseminated)
• Salmonellosis

37. • Viral infections
• Cytomegalovirus (pulmonary, intestinal, retinitis or CNS infection)
• Herpes- simplex virus and varicella – Zoster virus (localized or disseminated)
• Progressive multifocal leucoencephalopathy
• Neoplasms
•
•
•
•
Kaposi’s sarcoma
B cell non Hodgkin lymphoma
Primary lymphoma of brain
Invasive cancer of the cervix.

38. • There is a correlation between CD4 count and HIV related infections.
> 500 cells/mm3 – Recurrent vaginal candidiasis
200-500 cells/mm3 – Pulmonary TB, Pneumococcal pneumonia,
Herpes zoster, Oropharyngeal candidiasis, Recurrent Salmonellosis
< 200 cells/mm3 – Pneumocystis jirovecii pneumonia, mucocutaneous
Herpes simplex, Cryptosporidiosis, Esophageal candidiasis, Miliary/
Extrapulmonary TB.
< 100 cells/mm3 – cerebral Toxoplasmosis, Cryptococcal meningitis
< 50 cells/mm3 – CMV retinitis & gastrointestinal disease and
disseminated Mycobacterium avium intercellulare

39. Laboratory parameters
during the course of the
illness

40. • Tests to detect the presence of infection
• Detection of viral antigens in the serum
• Detection of antibodies to viral antigens in the serum
• Detection of viral genomic material in the blood
• Tests to determine the extent of the disease
• Total CD4+ helper T-cell count
• Quantitative viral RNA copies in blood.
• Tests to detect the presence of various opportunistic infections.

41. TREATMENT

42. PRIMARY IMMUNODEFICIENCIES
• B cell deficiencies:
• IV Immunoglobulin 200-800mg/kg
• Culture and sensitivity of organisms causing infection
• Early drainage of abscess
• Early control of infection
• T cell deficiencies:
• Early treatment of infection
• Transplantation of foetal thymus or HLA matched bone marrow
• Topical and systemic antifungal therapy
• Stem cell transplantation is definitive therapy for SCID and most of
phagocytic disorders like LAD, CGD and Chediak- Higashi disease

43. • More recently Gene therapy has been attempted as an alternative to
the bone marrow transplant
• Transduction of the missing gene to hematopoietic stem cells
using viral vectors is being tested in ADA SCID and X-linked SCID
• In 1990, four-year-old Ashanthi DeSilva became the first patient to
undergo successful gene therapy. Researchers collected samples
of Ashanthi's blood, isolated some of her white blood cells, and
used a virus to insert a healthy adenosine deaminase (ADA) gene
into the defective cells.
• These cells were then injected back into her body, and began to
express a normal enzyme. This, augmented by weekly injections of
ADA, corrected her deficiency.

44. SECONDARY
IMMUNODEFICIENCIES
• Prompt and early instillation of anti retroviral therapy will help in control of the
disease
• Prophylaxis to prevent development of opportunistic infections.

45. Mobile: 99899 10303
Email ID: chaksdegr8@yahoo.co.in