What is the importance of immuno-defiency?
- Immunodeficiency is associated with an increase in the frequency and severity of infections
- Immunodeficiency is associated with autoimmune diseases and malignancy
- Failure to recognize and diagnose leads to increased morbidity and mortality
Why is immunodeficiency considered to be subversive?
• Long gap between symptom onset and immunodeficiency
Define “immunocompromised”
• State in which the immune system is unable to respond appropriately and effectively ot infectious microorganisms
What are two types of defects involved in immunocompromised hosts?
Qualitative or quantitative defect of one or more components of the immune system
Give three components of innate immunity which could potentially go wrong?
- Innate barriers
- Phagocytes
- Complement
Give three components of adaptive immunity which could potentially go wrong
- B cell
- Antibodies
- T cells
Give four features of infections which come about as a result of immunocompromise?
• SPUR ○ S - Severe ○ P - Persistent ○ U - Unusual ○ R - Reccurent
What are two types of immunodeficiency?
- Primary
* Secondary
What is a primary immunodeficiency?
• Intrinsic defect
○ Single-gene disorder
○ Polygenic
○ Polymorphisms
What is a secondary immunodeficiency?
• Underlying disease or condition affecting immune components
○ Decreased production
Loss or catabolism
How is a primary immunodeficiency classified?
• By the part of the immune system which is damaged
What types of patients are primary immunodeficiency? (age and gender)
- 80% patients <20 yrs
* 70% males (x-linked)
What factors can be affected in a primary immunodeficiency?
B cell (50%)
• T cell (30%)
• Phagocytes (18%)
• Complement (2%)
Name three important B cell deficiencies (primary immunodefiency)
- Common variable immunodeficiency
- IgA deficiency
- Bruton’s disease
What is the most common type of primary immunodeficiency?
- Common variable immunodeficiency
* Inability of B cells to mature into plasma cells
What does the immunoglobulin/cell levels of someone with B cell CVID look like?
- IgG <5g/l
* IgA and IgM variable
What is the clinically defining feature of IgA deficiency
- IgA <0.05g/l
* B cell unable to switch to IgA
what is the clinically defining feature of Bruton’s disease (3)
- Impaired B cell development
- IgG <2g/l
- IgA undetectable
- Low B cells
How do patients with primary immunodeficiency present?(5)
- Recurrent upper and lower respiratory bacterial infection (bronchiectasis)
- GI complications including infections
- Arthropathies
- Increased incidence of autoimmune disease
- Increased incidence of lymphoma and gastric carcinoma
How are primary immuno-deficient patients treated? (4)
- Prophylactic antibiotics
- Immunoglobulin replacement therapy
- Management of respiratory function
Avoid unnecessary exposure to radiation
What is immunoglobulin replacement therapy and what is its goal?
- IgG >8g/l
* Replacement of immunoglobulin
What is immunoglobulin replacement therapy used to treat?
• CIVD
Bruton’s disease
Given two phagocyte deficiencys
- Leukocyte Adhesion Deficiency (LAD)
- Chronic granulomatous disease (CGD)
Cyclic neutropenia
What occurs in Leukocyte Adhesion Deficiency?
• Phagocytes cannot adhere to endothelium
What occurs in Chronic granulamatous disease?
- Phagocytes can produce respiratory burs
* Granulomas form
What is the presentation of someone with a phagocyte deficiency?
- Prolonged and recurrent infection
- Ulcers
- Abscesses (granuloma)
- Invasive aspergillosis
What is the management of someone with phagocyte deficiency?
- Prophylactic antibiotic
- Interferon-g
Steroids
How do you recognise someone with phagocyte deficiency?
ABSCESS
Name three main T cell deficiencies
- Di George deficiency
* Severe combined Immunodeficiency (SCID)
What is DiGeorge syndrome?
- Defect in thymus embryogenesis and incomplete development
* Characterised by lack of thymus
Why is DiGeorge syndrome called CATCH-22 Syndrome
CATCH 22 • Cardiac abnormalities • Abnormal faces • Thymic hypoplasia • Cleft palate • Hypocalcaemia • MORE SUSCEPTIBLE TO VIRAL AND FUNGAL INFECTIONS
What is the genetic cause of Catch 22 syndrome/DiGeorge?
• chromosomal abnormalities
What is the management of Di George syndrome?
• Neonatal cardiac surgery
supplement to correct hypocalcaemia
What non-related medical treatment is prohibited in Di George syndrome
• Live vaccines
What causes SCID?
• Stem cell defect in g chain used by many T cell receptors
Death of developing thymocytes
What does SCID look like?
- Failure to thrive
- Protracted diarrhoea
- Hepato-splenomegaly
Low lymphocyte count
What is a short term management for SCID?
- aggressive treatment of infections
* Prevention of new infections
Give a long term treatment for SCID?
• Bone marrow transplant
Gene therapy
Name one complement component deficiency
- C1 inhibitor deficiency
* Hereditary angiooedema
What are secondary immune deficiencies caused by?
- Malnutritition
- Infection
- Liver diseases
- Lymphoproliferative diseases
- Drug induced neutropenia
Splenectomy
Give three causes of asplenia
- Infarction (SICKLE CELL DISEASE)
- Trauma
- Autoimmune
Give three causes of neutropenia
• Bone marrow infiltration with malignancy
Chemotherapy - Cytotoxics and immunosupressants
What is the management of neutropenia?
• Treat suspected neutropenic spesis as an acute medical emergency and offer empiric antibiotic therapy immediately
Asses patient’s risk of septic complications
What is the standard presentation of an asplenic patient?
• Susceptibility to encapsulated bacteria
○ Haemophilus influenzae
○ Streptococcus pneumoniae
Neisseria meningitidis
Why are asplenic patients susceptible to encapsulated bacteria?
- Contains B cells which do not need T cell activation
- Encapsulated bacteria difficult to break down and present
- Spleen required to clear them
What is OPSI?
- Overwhelming post-splenectomy infection
* Causes sepsis and meningitis
What is the mangement of an asplenic patient?
- Penicillin prophylaxis
- Immunisation against encapsulated bacteria
- Patient information; Medic alter bracelet
What are the three main immune functions of the spleen?
• Removal of blood borne pathogens ○ Encapsulated bacteria • Antibody production ○ Acute response IgM production ○ Long term protection IgG production • Splenic macrophages ○ Removal of opsonized microbes ○ Removal of immune complexes
Taking a history from a patien
Age - at presentation
– Sex
– Site(s) and frequency of infection(s)
– Type of organism(s)
• Viruses and bacteria -> T cell deficiency
• Bacteria and fungi -> B cell/granulocytes deficiency
– Sensitivity and type of treatment (surgery)
– Family history
Give two general investigations of ID
- FBC and differential
* Exclusion of secondary immunodeficiency
Give four specific investigations for ID
- Test of humoral antibodies
- Tests for cell mediated immunity
- Tests for phagocytic cells
Test for complement
What do you test for in cell mediated immunity?
• IgG, IgA, IgM (+/- IgE)
• IgG1-4
subclasses
• IgG levels to specific previous vaccines
tetanus toxoid / HiB / pneumococcus
measles , mumps, rubella
• Measure antibody in response to “test” immunization
Where is CRP produced?
Liver
What is the role of CRP in the innate immune response?
CRP acts as an opsonin.
An opsonin binds to the microbial surface leading to enhanced attachment of phagocytes and clearance of microbes.
i. What triggers the production of CRP?
Microbial toxins – e.g. endotoxin – triggers the production of cytokines by monocytes and macrophages. These in turn circulate in the blood to the liver where they stimulate the production of the acute phase proteins.