Immunodiefiency Flashcards
What is an IRAK4 defiency /
an inherited disorder of the immune system (primary immunodeficiency).
IRAK4 gene mutation
IRAK4 gene responsible for response to infection - involved in early recognition of pathogens and imitation of inflammation to fight infection.
*may not develop fever in response to infection as body does not know it is under attack.
0 leads to recurrent infections - most commonly caused by bacteria:
- Streptococcus pneumoniae,
- Staphylococcus aureus
- Pseudomonas aeruginosa
- most people have their infection within 2 years - can be life threatening in infancy.
infection become less frequent with age.
Example case of IRAK4 deficiency.
0 Blood count
Normal WBC
immunoglobin -normal
lymphocyte - T , B , NK cells normal
CRP does not rise despite serious infection.
** CRP - c reactive protein - Produced by the liver in response to inflammation.
Has a periumbilical lesion - not inflamed , very clean wound, not hot , no pus etc
* indicates IRAK4 deficiency - lack of transcription of inflammatory cytokines —- > no signalling to other immune cells e.g. macrophages to come to site of the infection.
Treatment of IRAK4 deficiency ?
0 IVIG - intravenous immunoglobulin therapy (replacement immunoglobin )
0 Immunisation
0 Prompt treatment of infection
What is Chronic Granulomatous Disease ?
Autosomal ressessive (affects both sexes) and X - linked (Women carriers and men are affected )
-primary immune deficiency - effects certain WGC - Phagocytes e.g Neutophil , macrophages, monocytes , eosophills.
Neutrophils do not function properly - mutation in the gene which encodes for NADPH oxidase (make toxic substance to kill bacteria/pathogen once it has been engulf by WBC )
Leads to :
*reduced levels of NADPH oxidase ——- > Reduce levels for reactive oxygen species (reduced / no oxidative burst ——–> pathogen not killed.
Typical presentation of Chronic Granulomatous Disease ?
0 Frequent bacterial and fungal infections
0 Granulomas (areas of inflamed tissue), most commonly in the gastrointestinal tract and/or the genitourinary system
0 * Abscesses that involve the lungs, liver, spleen, bones, or skin
0 Swollen lymph nodes
0 Persistent diarrhoea
0 Chronic runny nose.
Reatment of CGD ?
- Antibiotics -
treat infection - Ciproflaxin
prophylaxis (to prevent infection) - Co - trimoxazole
Antifungals -
Prophylazis - Itraconzaole
- immunisation
including Flu vaccination- risk of secondary bacteria complications if catch the flu.
Bone marrow transplant- used in severe cases - used treat or cure.
(better do before deep seated infections)
How do you diagnose CGD ?
Nitroblue tetrazolium test (NBT): - measure of oxidative burst capacity. -
- cells treated with yellow Nitroblue tetrazolium
- Normal cells turn it into formazan ( Blue black compound) - as oxygen reactive species present
No colour change - no oxidative burst
0 dihydro-rodhamine assay (DHR) - similar principle to NBT but uses different dye
* performed on flow - cytometer
What is antibody deficiency ?
Lack of antibodies -Primary immunodeficiency disease -PIDD
- Low levels of IgG , IgA , IgM (profoundly low)
- T and B lymphocytes normal - just no antibodies.
characterised by - recurrent bacterial infections.
Diagnosis - 2 ways - both needed to confirm
Measurement of serum protective immunoglobulin concentrations, IgA, IgG and IgM
Measure - measure response to vaccination e.g. tetanus vaccine etc.
* sometimes a person with have antibody deficiency - but IgG , A ,M will be normal, however they cannot produce antibodies in response to pathogen.
- increased chance of autoimmune disease.
Treatment of Antibody deficiency ?
Replacement therapy - IgG replacement - plasma donor ( cannot be made synthetically - risk associated)
- prompt treatment of infection - antibiotics
Antibiotic prophylaxis
What is CD40 deficiency ?
CD40 ligand not present
Primary immunodeficiency disease - defect in class switching and somatic hypermutation
- part of hyper immunoglobulin M syndromes
lack of class switching so :
elevated levels of serum IgM
Deficiency in IgA, IgG, IgE
hypogammaglobulinemia
characterised - by recurrent bacterial infections.
