Immunodeficiencies Flashcards
What are immunodeficiencies caused by?
Defects in one or more components of the immune system
What are the types of immunodeficiencies?
Primary (congenital)
Secondary
What do primary immunodeficiencies result from?
Genetic or developmental defects
When do primary immunodeficiencies originate and present?
There from birth but may not be clinically observed till later in life
What do secondary immunodeficiencies originate as a result of?
Malnutrition, cancer, drug treatment or infection
What’s the most common secondary immunodeficiency?
AIDS
What are clinical features of primary immunodeficiencies?
Recurrent infections
Severe infections by unusual pathogens in unusual sites
What are the causes of primary immunodeficiencies?
Defect in phagocytic or complement function
What do consequences of primary immunodeficiency depend on?
The number and type of immune system components involved
What do defects in earlier stem cells affect?
The entire immune system
What do defects in later stage haematopoietic cells show?
A more restricted pathology
What are examples of phagocytic disease?
Chronic granulomatous disease
Congenital agranulocytosis
Leukocyte-adhesion deficiency
What are examples of B cell and antibody diseases?
X-linked agammaglobulinaemia
Common variable hypogammaglobulinaemia
X-linked hyper-IgM syndrome
Selective immunoglobulin deficiency c
What is an example of a thymic epithelial cell mediated disease?
Digeorge syndrome
What are examples of combined B and T cell diseases?
Reticular dysgenesis
Severe combined immunodeficiency
Bare-lymphocyte syndrome
Wiskott-Aldrich syndrome
What is affected in primary component disorders?
Defects in lymphocyte development or activation
What causes X-linked agammaglobulinaemia?
Encodes brutons tyrosine kinase
Block in B cell development at pre-b stage
What are the clinical features of x-linked agammaglobulinaemia?
Absence of B cells and low/absent plasma cells
All IgGs absent/very low
T cells and T cell mediated response normal
How is x-linked agammaglobulinaemia treated?
IVIg at 2-3 week intervals
Or subcutaneous Ig weekly
Prompt antibiotic therapy
What is common variable immunodeficiency?
Selective IgA deficiencies
What are the symptoms of common variable immunodeficiency?
Mainly asymptomatic- some lead to respiratory, urogenital or GI infections
What are the lab findings with common variable immunodeficiency?
Low serum and secretory IgA
What are the causes of Severe combined immunodeficiency?
Defect in common cytokine receptor gamma chain
What is IL-7 needed for?
Survival of T cell precursors
What happens if you have defective IL-7?
Defective T cell development and concomitant lack in B cell help
What does a defect in RAG1/RAG2 lead to?
No T or B cells
What happens in adenosine Deaminase deficiency?
Accumulation of deoxyadenosine and deoxy-ATP which is toxic for rapidly dividing thymocytes
What are the lab signs of severe combined immunodeficiency?
Very low/absent T cell
Normal/absent B cell
Sometimes absent NK
Low Ig
What are the treatments for severe combined immunodeficiency?
No live vaccines IVIg replacement Infection prophylaxis Bone marrow/haematopoietic stem cell transplant Gene therapy
What are the survival rates for severe combined immunodeficiency?
High if early diagnosis and a good donor match with no infections pre-transplant
Low if late diagnosis and poor donor match with chronic infections
What is the treatment of di george syndrome?
Thymus transplantation
What does digeorge syndrome result in?
Failure of development of 3rd and 4th pharyngeal pouches
What are the symptoms of digeorge?
Dysmorphic face
Hypocalcaemia
Cardiac abnormalities
Variable immunodeficiency
What are the dysmorphic features of digeorge?
Cleft palate, low set ears, fish shaped mouth
What causes Wiskott-Aldrich syndrome?
Defect in WASP
What is WASP?
Protein involved in actin polymerisation
What does Wiskott-Aldrich syndrome cause?
Thrombocytopenia, eczema, infections
Progressive immunodeficiency
What are the two types of phagocyte defects?
Quantitative
Qualitative
What do quantitative phagocyte defects cause?
Low phagocyte numbers
What do qualitative phagocyte defects cause?
Altered function
What are some types of recruitment defects?
Transmigration defects
What are the types of innate immune system defects?
Phagocyte defects
Recruitment defects
Complement defects
What are some examples of innate immune system defects?
Chronic granulomatous disease
Chediak higashi syndrome
Leukocyte adhesion deficiency
What does chronic granulomatous disease cause?
Formation of granulomas
What causes chronic granulomatous disease?
Defective oxidative killing of phagocytosed microbes due to a mutation in phagocyte oxidase components
How do you diagnose chronic granulomatous disease?
Nitro blue tetrazolium reduction test
What causes Chediak higashi syndrome?
Defect in LYST gene
What are the lab signs of Chediak higashi syndrome?
Decreased number of neutrophils
What are the symptoms of Chediak higashi syndrome?
Repetitive severe infections
What are the mechanisms of leukocyte adhesion deficiency?
Defect in beta2-chain integrins
Defect in sialyl-Lewis X
Delayed umbilical cord separation -> diagnosis defect in beta2-chain integrins
How does leukocyte adhesion deficiency present?
Skin, GIT infections and perianal ulcers
What are the lab features of leukocyte adhesion deficiency?
Low neutrophil chemotaxis
Low integrin expression on phagocytes
What are the treatment aims of primary immunodeficiencies?
Minimise/control infection Prompt infection treatment Prevention of infection Nutrition Replace defective/absent component of the immune system
