Primary Immune Deficiency Flashcards
Dendritic cells
- Cebtral role in generating immune responses
- Act as sentinels
- Interface between innate and adaptive immunity
- Functions include:
- Recognition of microbial patterns (PRRs/TLRs)
- Co-stimulation for T-Lymphocytes
- Response determined by environment (eg cytokines)
Regulatory T-cells
Control inflammation, allergy and autoimmunity- dampen down the immune response
PID
- Approx 150 different conditions
- Inherited (present at birth)
- Defect in one or more components of the immune system (innate and adaptive)
- Symptoms may not appear until adulthood
Classifications of PID
- Combined B and T lymphocye imunodeficiencies
- MHC class I/II deficiency
- Hyper IgM syndrome 9CD40-CD40L deficiency
- Agammaglobulinaemias (Ab deficiency)
- Common Variable Immunodeficiency (CVID)
- Selective IgG, IgM orIgA(and subclass) deficiencies
- Wiskott-Aldrich disease
- DiGeorge Syndrome
- Chronic granulomatous deficiency (phagocytes)
- NK deficiencies, complement deficiencies
Clinical signs of PID
- > 10 episodes acute otitis media per year (ear infection) in infants and hildren
- > 2 episodes consolidated pneumonia per year
- > 2 life threatening infections/lifetime
- Two or more serious sinus infections within 1 year
- Abnormal response to microbes
Diagnosis of PID
Diagnosis is a combination of clinical history and laboratory evaluation of immune system.
Pathologicalfeatures of PID
- Recurrent deep skin ir irgan absceses
- Two or more deep-seated infections such as meningitis, osteomyeltitis, cellulitis or sepsis
- Persistent oral thrush or candida infection elsewhere on the skin (>1 year age)
- Recurrent autoimmune phenomena
- Dysmorphic features associated with recurrent infections
- Infections that worsen chronic disorders (eg asthma)
- Infections with pathogen despite vaccine (eg pneumococcal)
Common variable Immunodeficiency (CVID)
-One of the most common PIDs
-Characterised by low levels of serum Igs, hypogammaglobulineamia
-Increased susceptibility to infections
Genetic causes unknown, but related to TACI
-Nature and type of deficiency varies with patient
-Affect on multiple organs
-Normal numbers of B cells, but do not differentiate into plasma cells, deficiency in memory B cells an poor response to vaccines
-Recurrent and severe lung infections
-Enlarged lymph nodes and spleen
Specific Antibody Deficiency (SAD)
- Patients have normla Ig levels and normla Ig subclasses (IgG2)
- Responds to protein antigens/vaccines normal
- Fail to produce protective antibody levels in response to polysaccharide antigens
- pneumococcus
Pneumococcal disease
- Affects young children, older adults and immunocompromised
- Can be commensal
- Encapsulated (polysaccharide- no T-cell help)
- Significant pathogen, causes various infections
SAD Diagnosis
- Evaluate response to pneumococcal polysaccharide vaccine (which contains 23 serotypes), if they don’t produced the appropriate memory B cells, indicative of SAD
- Treat with IV Ig and/or antibiotics
Severe Combined Immunodeficiency (SCID)
- Rare, potentially fatal
- Lack of T and B cell function (also NK)
- Several genetic defects identified, often an X linked one
- Extreme susceptibility to infections
IPEX syndrome
- Immunodysregulation polyendocrinopathy enteropathy x linked syndrome
- Very rare condition caused by mutation in FoxP3
- Lack of functional Treg cells
- Multiple autoimmune disorders- diabetes, thyroiditits, haemolytic anaemia
- Allergic phenotypes also occur
- Absence of small bowel mucosa
- Inflammatory infiltrate in many organs
- Liver: fatty change, kidney:nephritis, skin:eczematous
Chronic granulomatous disease
- X-linked disorder
- Defect in intracellular bacterial killing by neutrophils and monocytes due to mutations in NADPH oxidase (which usually works in phagolysosome)
- Increased susceptibility to infections by catalase organisms which already have an advantage
IRAK-4 Deficiency
- Interleukin-1 receptor-associated kinase-4
- Extremely rare conditions
- Essential role in TLR and IL-1 receptor signalling
- Innate immune receptors for pathogen binding
- Affects NFkB signalling
- Inability to activate T cells
- Susceptibility to pyogenic bacteria, not viruses, fungi
- Vaccinations can be beneficial
