4 immunodeficiencies Flashcards
What are immunodeficiency diseases?
A group of diseases where aspects of the immune system are lacking or hyperactive.
What are the two broad categories of immunodeficiency?
Primary: Genetic defect in the immune system.
Secondary: Immune system compromised by another condition/factor.
What causes primary immune deficiency?
Intrinsic defects in the immune system due to genetic mutations.
How are primary immune deficiencies inherited?
Can be dominant or recessive, autosomal or X-linked.
Are primary immune deficiencies common?
No, most are rare.
What are the major types of primary immune deficiencies?
Complement defects
Phagocytic cell defects
B cell defects (humoral immunity)
T cell defects (cell-mediated immunity)
Combined B and T cell defects
What causes secondary immune deficiency?
The immune system is initially intact but compromised by external factors.
Examples of causes of secondary immune deficiency?
Malnutrition
Splenectomy
Infections (e.g. HIV)
Medications (e.g. corticosteroids, chemotherapy)
Defects in physical barriers
How does secondary immune deficiency affect the immune system?
Impact depends on which part of the immune system is affected and how severely.
What are the two main types of immunity affected by immune deficiencies?
Specific (adaptive): T and B cells
Innate: Complement, phagocytes
What are the major functions of the immune system?
Defend against pathogens
Regulate inflammation
Tumour surveillance
Maintain self-tolerance
What happens when the immune system fails?
Infection: Failure to fight pathogens
Autoimmunity: Attack on self-antigens
Allergy: Response to harmless antigens
Malignancy: Failure of tumour surveillance
Autoinflammation: Dysregulated innate response
What are key signs of an immune system error?
Recurrent infections
Opportunistic infections
Increased malignancy risk
Autoimmune disorders
Autoinflammatory conditions
When should an immune deficiency be suspected?
Serious, persistent, unusual, or recurrent infections
Family history of immune deficiency
Failure to thrive
What is the function of neutrophils?
Engulf and destroy pathogens
Facilitate phagocytosis
What pathogens are common in neutrophil defects?
Bacteria: Staphylococcus, Pseudomonas
Fungi: Candida, Aspergillus
What is Chronic Granulomatous Disease (CGD)?
A defect in neutrophil oxidative burst, leading to recurrent infections.
How is CGD inherited?
X-linked (most common) or autosomal recessive.
What are symptoms of CGD?
Recurrent skin abscesses
Lymphadenitis
Pneumonia
Chronic inflammation
Causes of secondary neutrophil defects?
Post-infectious neutropenia
Nutritional deficiencies (e.g. folate, B12)
Medications
What is the role of antibodies?
Opsonization
Neutralisation
Complement activation
What infections are common in B cell defects?
Bacterial: Encapsulated bacteria (Streptococcus pneumoniae, H. influenzae)
Viral: Enteroviruses
Protozoal: Giardia
What is X-linked agammaglobulinaemia (XLA)?
A condition with very low or absent B cells and immunoglobulins.
Why do XLA symptoms start at 6-12 months?
Maternal antibodies provide initial protection.
Symptoms of XLA?
Recurrent respiratory infections
Sepsis, meningitis, osteomyelitis
Secondary causes of humoral immune deficiency?
Medications (e.g. rituximab, chemotherapy)
Protein loss (e.g. nephrotic syndrome)
What is the role of complement?
Opsonization
Immune complex clearance
Direct lysis of bacteria
What infections are common in complement deficiency?
C3 deficiency: Pneumococcal, H. influenzae infections
C5-C9 deficiency: Neisserial infections
What autoimmune disease is associated with complement deficiency?
Systemic Lupus Erythematosus (SLE).
What drug can cause secondary complement deficiency?
Eculizumab (C5 inhibitor).
Why do T cell defects also affect B cells?
Most B cell antibody production requires T cell help.
What infections are common in T cell deficiency?
Viral: CMV, RSV
Fungal: Pneumocystis jirovecii
Protozoal: Cryptosporidia, Toxoplasma
What is Severe Combined Immunodeficiency (SCID)?
A fatal disorder with combined T and B cell failure.
When should SCID be suspected?
Persistent lymphopenia (<2 × 10⁹/L), especially in infants <6 months.
Symptoms of SCID?
Failure to thrive
Chronic diarrhoea
Persistent viral infections
Treatment for SCID?
Haematopoietic stem cell transplantation (HSCT)
Gene therapy for some forms
Causes of secondary T cell deficiency?
HIV
Immunosuppressive drugs (e.g. calcineurin inhibitors, anti-TNF therapy)
What is used to treat antibody deficiencies?
Immunoglobulin replacement therapy.
What is the function of monoclonal antibodies (MoAbs)?
Depleting (e.g. anti-CD3)
Non-depleting (blocking function)
Is primary or secondary immune deficiency more common?
Secondary immune deficiency is more common.
Do primary immune deficiencies only affect infections?
No, they can also cause autoimmunity, allergy, and malignancy.
Which therapy expands immune deficiency risk?
Biological immunotherapies (e.g. CAR-T cells).
What therapy can be curative for some primary immunodeficiencies?
Haematopoietic stem cell transplantation (HSCT).
What increases the risk of inherited immune disorders?
Consanguinity (related parents).
What is the best approach to prevent infections in immunodeficient patients?
Prophylactic antibiotics, antifungals, and immunoglobulin therapy.
Which infection is common in complement deficiency?
Neisseria meningitidis.
What condition is linked to antibody loss in nephrotic syndrome?
Hypogammaglobulinaemia.
Why must SCID patients avoid live vaccines?
Risk of severe or fatal infection.
