16- Paediatric immunology Flashcards
innate immune system
- Non-specific
- Rapid
- Key protection
o Macrophages
o Neutrophils
o Complement
Adaptive
- Specific
- Slower onset
- Pathogen specific
- Key protection
o T cells
o B cells/ plasma cells
types of antibodies
IgG, IgA, IgM, IgE, IgD
IgG
– main one in the blood, multiple subtypes, memory response
IgA
in the mucosa, most abundant overall
IgM
early response, binds complement, limited memory response
IgE
mast cell activation, allergy and parasitic response
types of primary immunodeficiency disorders
- Antibody (B cell)
- Combined (+T cells)
- Complement
- Phagocyte (chronic granulomatous disease
types of immunodeficiency related to Antibodies
o X linked agammaglobulinaemia (XLA)
o Specific Antibody deficiency
o Transient hypogammaglobulinaemia of Infancy
o IgG subclass deficiency/IgA deficiency
history taking for immunodeficiency
Infection history
o Site
o Frequency
o Need for admission/ IV antibiotics
Immunisation status
Family history
o Infections
o Autoimmunity
o Consanguinity
o Neonatal deaths
presentation of primary immunodeficiency disorders
- Serious e.g. recurrent deep abscess
- Persistent e.g. long course of antibiotics, thrush
- Unusual
- Recurrent e.g. >4 ear infection, >2 sinusitis, >2 pneumonia
investigations for PID (primary immunodeficiency)
- FBC
- Lymphocyte subsets
- Total antibodies
- Specific antibodies
o Vaccination history - Neutrophil oxidative burst
- Complement (CH50/AP50)
- HIV
antibody deficiency syndrome types
o X linked agammaglobulinaemia (XLA)
o Specific Antibody deficiency
o Transient hypogammaglobulinaemia of Infancy
o IgG subclass deficiency/IgA deficiency
cause of antibody deficiency syndrome
mutation in genes which code for correct production of antibodies
presentation of antibody deficiency syndrome
- Starts at 6-12 months after maternal antibodies have waned
- Bacterial infection
- Sino-pulmonary infection
o Tricky as these are common
o Hospital admission, CXR changes
o Recurrent otitis media with discharge - Giardia
management of antibody deficiency syndrome
- Immunoglobulin replacement – IgG subcut (or IV)
- Prompt, prolonged courses of antibiotics
- Antibiotic prophylaxis
complement disorders background
Functions of complement
- Opsonisation flags cells for phagocytosis
- Chemo-attraction to recruit more phagocytes
- Membrane attack complex creates holes in certain types of bacteria (encapsulated)
complement disorders background
Functions of complement
- Opsonisation flags cells for phagocytosis
- Chemo-attraction to recruit more phagocytes
- Membrane attack complex creates holes in certain types of bacteria (encapsulated)
presentation of complement disorders
- Recurrent invasive bacterial disease
o Meningitis, pneumonia - Meningococcal, Pneumococcal, Hib
- Usual, but frequent, sinopulmonary infection organisms in early pathway defects
managment of complement disorders
- Penicillin prophylaxis
- Additional immunisations
o Men ACWY, Men B, Pneumovax - Check ‘green book’
- Immunisation against Infectious Disease
phagocyte disorders background
Role of phagocytes
- Neutrophils
- Phagocytosis
- This is primarily bacteria, but remember fungi as well
- Act as Antigen Presenting Cells, so a loss of neutrophil function is a problem
- Most of these have normal neutrophil numbers and there are few functional tests
types of phagocyte disorders
- Chronic Granulomatous Disease
o X linked
o Or Autosomal recessive - Severe Congenital neutropenia
- Leucocyte Adhesion Defects
presentation of phagocyte disorders
- Recurrent abscesses – Staph aureus
- Fungal chest infections
- Liver abscess
- Osteomyelitis
- BCG -it is
- Early onset Inflammatory Bowel Disease
management of phagocyte disorders
- Anti fungal and antibiotic prophylaxis
- Avoid fungal spores eg compost, leaf mulch.
- Avoid BCG.
- Consider Bone Marrow Transplant, esp with early diagnosis
Combined immune deficiencies background
- T cell defects +/- others
- Due to complex T cell interaction with B cells, impacts antibody response also.
types of combined immune deficiencies
- Severe combined immunodeficiency (SCID)
o Many categories e.g. all are T- but can also be B+ or B- - Hyper IgM syndrome
- Complete Di George (missing thymus)
role of T cells
- CD4 T cells – helper cells, activate macrophages and B cells
- CD8 T cells – anti-viral, induce apoptosis, anti tumour
- Tregs – immunoregulatory, loss leads to autoimmunity
investigation for combined deficiency
- Lymphocytes <2.8x10^9 <1 year
presentation for combined deficiency
- EVERY infection
- Recurrent bacterial infections
- Viral- systemic, persistent
- Mycobacteria
- Candida
- Aspergillus
- Cryptosporidium
- PJP
- Chronic diarrhoea and faltering growth
management of SCID
- Bone marrow transplant is aim, before significant morbidity- curative
- Prophylactic antibiotics and antifungals
- Immunoglobulin replacement
- Infection prevention measures
- CMV neg, irradiated blood products
- Avoid live vaccines
syndromes related to immune deficiencies
- Di George (no thymus)
- Ataxia telangiectasia
- CHHARGE syndrome
Many syndromes may have other features that predispose to frequent infections
e.g.
- Poor tone leading to weak cough
- Indwelling devices
- Reflux
