CP5-3 immunodeficiency Flashcards
What are the 4 main physiological functions of the immune system?
Recognise pathogens
Cell-cell communication to initiate an immune response
Clear pathogens
Self-regulation to minimise host damage
What is immunodeficiency?
Clinical situations where the immune system is not effective enough to protect the body against infection
What are the two types of immunodeficiency?
Primary
Secondary
What is primary immunodeficiency?
An inherent defect within the immune system - usually of a genetic cause
What is secondary immunodeficiency?
Acquired immunodeficiency where external causes affect the immune system
What are common causes of secondary immunodeficiency?
CF
protein loss e.g. due to burns, protein losing enteropathy or malnutrition
malignancy (especially lymphoproliferative (cancers of B cells) and myeloma
drugs - steroids, DMARDS, rituximab, anti-consulvutants and myelosuppresives
Infection - HIV and TB
What is the function of pathogen recognition receptors (PRRs)?
For phagocytes to recognise conserved pathogen associate molecular patterns (PAMPs) which are unique to each pathogen.
What is an example of a PAMP?
Lipopolysaccharide
What is a PAMP?
Pathogen associated molecular pattern
What is an example of a PRR?
Toll like receptors
What are the main two cells that undergo phagocytosis?
Neutrophils
Macrophages
What PAMP is recognised by TLR4?
Lipopolysaccharide
What PAMP is recognised by TLR5?
Flagellin
What PAMP is recognised by TLR3?
Viral RNA
What can defects in TLR3 lead to?
Recurrent HSV encephalitis
What happens when a TLR recognised a PAMP?
A cascade of events involving various molecules (including MyD88 and IRAK4) intracellularly leads to production of inflammatory cytokines
What test can be done when testing for immunodeficiency?
Immunoglobulin tests
WCC
CRP
How does a patient with an IRAK4 deficiency present? (A patient with a MyD88 deficiency will present similarly)
Recurrent bacterial infection - especially streptococcus and staphylococcus leading to pneumonia, meningitis and arthritis
Poor inflammatory response e.g. no fever
Decrease of susceptibility to infection with age
How can you treat IRAK4 deficiency?
Prophylactic antibiotics
(+ IV immunoglobulin if severe)
What protein complex is found on the surface of phagolysosomes?
NADPH complex
What is one of the proteins found in the NADPH complex?
gp91phox
What chromosome is protein gp91phox coded for on?
X
What causes chronic granulomatous disease? How do patients with this present?
Mutation of gp91phox leading to granulomas formation.
Present with recurrent abscesses in liver, lung, bone, skin +/- gut caused by unusual organisms like klebsiella, serretia, aspergillus, fungi (and less strangely staphylococcus)
How is chronic granulomatous disease treated?
With a bone marrow/stem cell transplant and antibiotics
How do you test for chronic granulomatous disease?
Neutrophil function test which relies on reduction (gain of electrons) and is measure based on dihydrorhodamine reduction using flow cytometey or using nitro blue tetrazolium dye (if normal neutrophils turn purple)
If a patient has chronic granulomatous disease, what would the results of the nitro blue tetrazolium dye reduction test be?
Neutrophils will stay blue
Whic complement pathways is similar to the classical pathway?
MBL pathway
What are complement cells?
Non immunoglobulin proteins which are involved in bacteria cell lysis, control of inflammation and stimulating phagocytosis
How is complement function tested?
Haemolytic complement test
Testing whether complement lyses foreign cells if the foreign cells are covered in antibody
What are common complement deficiencies?
C2, C4 = SLE, inf3ctiom and myositis
C5-C9 (form of membrane attack complex) = repeated episodes of bacterial meningitis (particularly neisseria)
What are 4 common t helper cells involved in adaptive immunity?
T helper 1, 2, 9 and 17
What are 4 ways antibodies inactivate antigens?
Neutralise (block bing sites or coats bacteria)
Agglutination of microbes
Precipitation of dissolve antigens
Activation of complement system
(First three increase phagocytosis and last leads to cell lysis)
What will blood show in patients with X linked agammaglobulinaemia?
Normal T cells
No B cells
No immunoglobulins (IgG, IgA, IgM)
Why are there no B cells in patients with X linked agammaglobulinaemia?
Defect in bruton’s tryrosine kinase
What is the role of bruton’s tryrosine kinase?
B cell signalling, maturation in bone marrow
What are common B cell defects?
X-linked Agammaglobulinaemia
CVID
IgA deficiency
X linked hyper IgM syndrome
Transient hypogammaglibulinaemia of infancy
What are consequences of B cell defects?
Loss of antibody secretion
Recurrent bacterial infection with pyogenic organisms
How do you treat B cell defects?
Antibiotics
IgG for life
What increases risk of IgA deficiency?
Having an autoimmune disease like coeliac
What can long term treatment with rituximab lead to?
Secondary antibody deficiency
What are clinical signs of SCID (severe combine immunodeficiency)?
Normal levels of IgG
No IgA
Reduced IgM
Absent/reduced T and NK cells
B cells are present
What type of deficiency causes SCID?
T cell deficiency
Why do T cell defects tend to be more severe than B cell defects?
As B cells need T cell help so with T cell defects, even if B cells are normal, B cells won’t function properly
What are symptoms of T cell defects?
Recurrent infections with opportunistic infections including by bacteria, viruses, fungi (e.g. candida) and protozoa (pneumocystis)
What are 2 examples of disease with T cell defects?
SCID
DOCK8 deficiency
How is SCID treated?
IV antibiotics/antivirals/antifungals
Asepsis
Only cure = haemopoietic stem cell transplant
What causes SCID?
Defects/absence of T cells - So absence of TCR and common gamma chain
MHCII deficiency = loss of communication
Metabolic causes like adenosine deaminase deficiency
By what inheritance pattern are T cell defects usually inherited?
Autosomal recessive of X-linked
