Immune Disorders Flashcards
(29 cards)
Define an immunocompromised host. Why may someone be immunocompromised?
State in which the immune system is unable to respond appropriately and effectively to infectious microorganisms
QUALITATIVE DEFECT = non-functional component(s)
(tends to be due to a PRIMARY immunodeficiency)
QUANTITATIVE DEFECT = loss of component(s)
(tends to be due to a SECONDARY immunodeficiency)
What are some features which are associated with immunodeficiency?
Increase in frequency and severity of infections
Non-infectious complications e.g. autoimmune diseases, malignancy
What are some features of infection which suggest an underlying immunodeficiency?
SEVERE
PERSISTENT
UNUSUAL (either opportunistic infections or site of infection e.g. osteomyelitis, cellulitis, deep organ abscesses)
RECURRENT
What is a primary immunodeficiency?
Intrinsic defect
e.g. single gene mutation (unknown whether polygenic mutations are a factor)
HLA polymorphisms
e.g. resistant to malaria (Africa), elite HIV controllers
Classified according to the defective immune component
note: Type 1 diabetes mellitus (childhood) & cystic fibrosis are counted as primary immunodeficiency syndromes
What is a secondary immunodeficiency?
Underlying disease affecting immune components
Either reduced production or increased loss/catabolism of immune components
Outline the aetiology of primary immunodeficiency disorders.
Occur in the first months of life (80% of patients < 20yrs)
70% of patients male (X-linked genes affected)
Most antibody deficiencies present young e.g. XLA, Hyper-IgM, SCID but some can present at any age e.g. CVID, IgG subclass deficiency, specific antibody deficiency
Give some examples of primary B-cell deficiencies.
Common variable immunodeficiency (CVID) = defect in ability of B cells to mature to plasma cells —> low IgG+ (panhypogammaglobulinaemia)
- most common immunodeficiency requiring treatment
- increased risk of cancer & autoimmune diseases
IgA deficiency = B cell unable to switch to IgA —-> low IgA
- most prevalent primary immunodeficiency
- usually asymptomatic
- increased risk of cancer & autoimmune diseases
IgG subclass deficiency = total Ig normal but low IgG2 subclass
- unknown defect cause
- IgG2 required for immune response to encapsulated bacteria
Bruton’s disease = X-linked agammaglobulinaemia (XLA) which impairs B cell development —> low IgG & IgA & low B cells
Hyper-IgM syndrome = X-linked; IgM cannot switch to IgG —> low IgG & high IgM
What the signs and symptoms of primary B-cell deficiencies?
- recurrent upper and lower resp. infections
- multiple resp. infections causes bronchiectasis
- GI complications e.g. Giardia infection
- arthropathies e.g. arthritis caused by Mycoplasma or Ureaplasma
- increased incidence of autoimmune disease
- increased incidence of lymphoma & gastric cancer
note: pyogenic bacteria e.g. Pneumococcus, H. influenzae, enterovirus, Mycoplasma
How are primary B-cell deficiencies managed?
ANTIBIOTICS ASAP (prophylactic + treatment)
- management of respiratory function due to frequent resp. infections
- avoid unnecessary radiation exposure (reduce cancer risk)
- lifelong Ig replacement therapy (IV or subcutaneous)
note: Ig replacement indicated for CVID, XLA, hyper-IgM syndrome & SEVERE IgA deficiency (IgA NOT GIVEN - causes transfusion reaction)
Give some examples of primary phagocyte deficiencies.
note: phagocyte deficiency usually due to secondary immunodeficiency
Cyclic neutropenia = unknown defect causing low neutrophils approx. every 3-4 weeks
Leukocyte adhesion deficiency (LAD) = lack of CD18 protein on phagocytes which is required for adhesion to endothelium (in order to reach site of infection)
Chronic granulomatous disease = lack of neutrophil oxidative burst
Chediak-Higashi syndrome = failure of phagolysosome to form
What are some signs and symptoms of primary phagocyte deficiencies?
- skin & mucous membrane infections (causing ulcers)
- osteomyelitis
- deep abscesses (Staphylococci)
- invasive aspergillosis (most common cause of death)
- granulomas
note: catalase +ve Staph., E.coli, B. cepacia, Klebsiella, Candida, Aspergillus
What is the management for primary phagocyte deficiencies?
- prophylactic antibiotics/anti-fungals
- immunisation (esp. against pneumococcal bacteria - encapsulated)
- surgical
- interferon-gamma (boosts phagocytic activity)
- steroids (reduces granuloma formation)
- stem cell transplantation
Give an example of a primary T-cell deficiency.
Di George syndrome = defect in thymus embryogenesis leading to incomplete development/lack of thymus
note: T-cells drive antibody production from B-cells (so T-cell deficiency often leads to functional B-cell deficiency)
What are the signs and symptoms of primary T-cell deficiencies?
CATCH-22 SYNDROME
Cardiac abnormalities Abnormal facies Thymic hypoplasia Cleft Palate Hypocalcaemia 22 - defect on chromosome 22
What is the management for primary T-cell deficiencies?
- neonatal cardiac surgery
- calcium supplements
- antibiotic prophylaxis for pneumocystis pneumonia (if T cells < 0.4 x 10^9/l)
- bone marrow transplant
- blood transfusions with no lymphocyte activity (prevent graft v.s. host) and no CMV activity
- no live vaccines
What is severe combined immunodeficiency?
- defect in gamma-chain causing stem cell defect
- enzyme defect causing death of developing thymocytes
- defect in genes required for T-cell receptor rearrangement & maturation causing defective T-cell development
- low lymphocyte count
What are the signs and symptoms of SCID?
- FAILURE TO THRIVE = failure of infant to grow satisfactorily compared with the average for that community (use centile charts)
- long term antibiotics
- deep skin & organ abscesses
- protracted diarrhoea
- high susceptibility to fungal & viral infections e.g. pneumocystis pneumonia, varicella-zoster virus, CMV, Epstein-Barr virus, Mycobacteria, Candida, Aspergillus, Cryptosporidium
What is the management of SCID?
FATAL IF NOT TREATED
Short term:
- no live vaccines
- only CMV free, irradiated blood products
- aggressive treatment of infections
- IV Ig
- reverse barrier nursing + laminar air flow
- prophylactic antibiotics & anti-fungals
Long term:
- bone marrow/stem cell transplantation (CHECK FOR MICROBES)
- gene therapy
Give an example of a primary complement component deficiency.
Hereditary angioedema (various kinds) = C1-inhibitor deficiency
note: pyogenic bacteria e.g. pneumococcus, H. influenzae, CMV, HSV, Neisseria meningitidis
What are some causes of secondary immunodeficiency due to reduced production of immune components?
- malnutrition (most common global cause)
- infection e.g. HIV
- liver disease
- lymphoproliferative diseases e.g. cancer (+ chemotherapy)
- drug induced neutropenia
- splenectomy (infarction, trauma, autoimmune haemolytic disease, infiltration, coeliac disease, congenital)
- age (physiological)
Give some examples of factors causing neutropenia.
- aplastic anaemia
- vitamin B12/folate/iron deficiency
- drugs e.g.phenytoin, chloramphenicol, alcohol abuse
- autoimmune neutropenia
- chemicals e.g. benzene, organophosphate
- infection e.g. HIV, infectious mononucleosis, hep. B or C, CMV, typhoid
- bone marrow infiltration/malignancy + chemotherapy (cytotoxic & immunosupression)/radiotherapy
What is the management for neutropenia?
ACUTE MEDICAL EMERGENCY (when neutrophils < 1.0 x 10^9/l)
- NEUTROPENIC SEPSIS/FEBRILE NEUTROPENIA
Empiric antibiotic therapy ASAP + treat septic symptoms
Common cause of death in patients receiving cytotoxic/myelosuppressive chemotherapy
What are some important management considerations in the asplenic patient?
- increased susceptibility to encapsulated bacteria (due to impaired opsonisation, which is required for phagocytes) e.g. H. influenzae, S. pneumoniae, N. meningitidis (pneumonia causative organisms)
- ——> life-long penicillin prophylaxis & immunisation before splenectomy (if possible)
- medic alert bracelet
- overwhelming post-splenectomy infection (OPSI) = sepsis & meningitis
What are the immune functions of the spleen?
Splenic macrophages -> removal of opsonised microbes & immune complexes
Opsonisation of encapsulated bacteria
Lymphocyte production —> antibody production —> IgM & IgG
Acute (IgM): agglutination of antigens & activation of complement system
Chronic (IgG): phagocytosis via osponisation & activation of complement system
