Immunodeficiency Flashcards
Primary immunodeficiency
Inherent defect within the immune system, usually genetic and rare
Secondary immmunodeficiency
Immune system is affected due to external causes
Secondary causes of immmunodeficiency
- Breakdown of physical barriers - cystic fibrosis
- Protein loss
- Malignancy
- Drugs
- Infection
Pathogen recognition receptors
Recognise conserved pathogen associated patterns (PAMPS)
- Phagocytes used receptors to detect pathogens
Examples of pathogen recognition receptors
TLR4 - lipopolysaccharide
TlR5 - Flagellin
IRAK4 deficiency features
- Cant recruit more immune cells very well
- Can recognise bug but can’t produce response
- Recurrent bacterial infection - pneumonia
IRAK4 treatment
- Prophylactic antibiotics
- IV immunoglobin if severe
What occurs in the phagolysosome to kill the pathogen
- Oxygen is reduced to superoxide which forms hypochlorous acid
- Acid kills pathogen
Chronic Granulomatous disease features
- Macrophages cannot destroy pathogen as acid is not produced
- Stops NADPH complex
- Women typically carriers, men affected - X linked
- Chronic abscesses
What is granuloma
A collection of macrophages
Treatment of Chronic Granulomatous disease
Hemopoietic stem cell transplant
Test for Chronic Granulomatous disease
- Neutrophil function test
- Nitro blue tetrazolium dye - electron released by NADPH is not reducing oxygen so it ca be detected.
- Healthy neutrophils turn clear to purple - unhealthy remain clear
What is Complement
- Non immunoglobin proteins that contribute to:
- Cell lysis
- Control of inflammation
- Stimulate phagocytosis
Complement function
Complement should lyse foreign cells
- patients serum should lyse sheep erythrocytes
Complement deficiency
- C2,C4 deficiency = SLE, infections, myositis
- C5-C9 deficiency = form membrane attack complex
- Recurrent bacterial meningitis
Treatment of Complement deficiency
Prophylactic penicillin B + vaccinated against meningitis
X-Linked agammaglobulinaemia
- Defect in Burtons Tyrosine Kinase
- BTK needed for B cell signalling and maturation
- B cell maturation not completed in bone marrow
- normal T cells, No B cells
IgA deficiency
- IgA not produced- more prone to autoimmune disease
-
X linked hyper IgM syndrome
patients cannot switch from IgM to IgG during immune response so get left with high levels of IgM
Defects in B cells
- Loss of antibody secretion
- Leads to recurrent bacterial infection with pus-forming organisms
Secondary antibody deficiency due to drugs
- Rituximab kills B cells
- Methotrexate hits fast growing cells - can attack neutrophils
- Azathioprine works on B/T cells
- Prednisolone works on whole organism
How does HIV create immunodeficiency
HIV kills CD4 cells
Chicken pox clinical features
Mild disease forms typical vesicles
- Severe = fulminant disease
- Haemorrhagic lesions + can get into lungs
Severe combined Immunodeficiency (SCID)
- No T cells
- B cells don’t function without T cells
SCID treatment
- Treated with antibiotics, antifungals, antivirals
- Only cure is a stem cell transplant
SCID causes
- Defect/absence of critical T receptors - TCR common gamma chain
- Loss of communication - MHCII deficiency in B cells means cannot get T cell help
- Adenosine deaminase deficiency - no enzyme so metabolite accumulate and it toxic to lymphocytes
