Aani Immuno: Primary Immune Deficiencies Flashcards
What type of antibodies do immature B cells produce?
IgM only
How are IgG, IgA and IgE Abs produced?
Following CD4 cells + B cells class switch
What are the types of Primary Immune Deficiencies?
T cell
B cell
Phagocyte
Complement
What are the types of Deficiencies that affect T cells?
Bare Lymphocyte Syndrome
DiGeorge Syndrome
SCID (mixed B and T)
What are the types of Bare Lymphocyte Syndrome?
Type 1 and Type 2.
Type 1 = Low MHC Class 1
Type 2 = Low MHC Class 2
Which type of Bare Lymphocyte Syndrome is more common?
Type 2
Describe the cells of Type 2 Bare Lymphocyte Syndrome?
It would have NORMAL CD8 and B cells. But absent CD4 cells.
This means that the germinal centre reaction between B cells and CD4 cannot take place so IgM can be made by B cells but IgG/IgA and IgE cannot be made.
Which condition is associated with Bare Lymphocyte Syndrome?
Sclerosing Cholangitis
What is the chromosomal defect in DiGeorge Syndrome?
22q11.2 deletion
What happens in DiGeorge Syndrome (in terms of T cells)?
Impaired development of 3rd and 4th pharyngeal pouch, absent thymus so T cells cannot mature = low mature T cells.
What are the clinical features of DiGeorge Syndrome?
Low set ears
Cleft lip/palate
Infections
Low PTH (cos parathyroid gland defected, leads to low Calcium)
CHD (because aortic arch is alo made from 3/4 pharyngeal pouch)
Treatment of DiGeorge Syndrome?
Infection prophylaxis
Thymus transplant
Ig replacement
Treatment of Bare Lymph Syndrome type 2?
BMT
Infection prophylaxis
Ig replacement
What are the types of B Cell primary Immune Deficiencies?
Bruton's Agammaglobulinaemia Common Variable Immune Deficiency Selective IgA deficiency Hyper IgM Syndrome SCID (mixed B and T cell)
Which Igs are missing in Bruton’s?
ALL because no B Cells
Which Igs are missing in Common Variable Immune Deficiency?
IgA, IgG and IgE (basically the 3 ones that mature B cells are needed to make)
Which Igs are missing in Selective IgA deficiency?
IgA lol
What causes the Ig defect in Common Variable Immune Deficiency?
Failure of B cell differentiation
How to tell the diff between Common Variable Immune Deficiency and Brutons?
Common Variable will have IgM. Brutons wont have any Ig.
Which is the most common B Cell Immune Deficiency?
Selective IgA deficiency
Who Gets Bruton’s?
Boys - it’s X linked.
Presents between 3-6 months
What happens in Hyper IgM syndrome?
T cells and B cells cannot interact to class switch so IgA and IgG are not made. IgM are elevated
What is SCID?
Severe Combined Immune Deficiency. Impaired B and T cell development
Tx for SCID?
BMT
Mnemonic for remembering B Cell immune deficiencies?
Brutus - Brutons
Caesar - combined Variable
Soccrates - Selective IgA def
Hippocrates - HyperIgM
How to categorise the phagocyte deficiencies?
Low production
Low migration
Low killing
What are the Phagocyte Deficiences?
Kostmann
Cyclic Neutropenia
Leukocyte adhesion deficiency
Chronic Granulomatous Disease
What is Kostmann Syndrome?
Congenital neutropenia
What is Cyclic Neutropenia?
Low neutrophils every 3 weeks. Lasts 6 days
What is Leukocyte Adhesion Deficiency?
Low Leukocyte adhesion molecules due to B2 integrin mutation on subunit CD10
What is Chronic Granulomatous Disease?
NADPH Oxidase deficiency. Leading to poor oxidative killing of organisms. Patients susceptible to catalase positive organisms (PLACESS) Psuedo, Listeria, Aspergillus, Candida,E.Coli, Staph A
How do you investigate for Chronic Granulomatous Disease?
The colour change test and fizz test will be negative (NBT and DHR)
What is Reticular Dysgenesis?
A very severe form of SCID where you have absolute deficiency in Neutrophils, Lymphocytes, Platelets, Monocytes
Why can you get secondary complement deficiency from SLE?
SLE immune complexes are removed by classical pathway and so the complement gets used up and you get deficiency
What are the stages of the complement cascade?
- Classical pathway
- Lectin Pathway
- Alternative Pathway
They all activate C3, therefore C5
Which test do you do for Classical Pathway deficiency?
CH50 = will be abnormal
CH50 test is for C1,C2,C4,C3,C5-C9
What microorganisms are more likely to infect someone with a complement deficiency?
Encapsulated e.g. Niessera Meningitidis, Group B Strep
Which molecules involved in Classical pathway?
C1,C2,C4
Which molecules are involved in Alternative Pathway?
B,I,P
Which test do you do for Alternative pathway deficiency?
AP50 = will be abnormal
AP50 is for B,I,P,C5-C9
What can be wrong in the Lectin Pathway?
Mannose Binding Lectin deficiency
Which tests will be abnormal in a defect with the common/terminal complement pathway?
Both CH50 and AP50 because they both include tests for C5-C9
How can glomerulonephritis affect complement?
Nephritic factor causes constant activation of C3. so there is low C3
Meningococcal infections are quite common as a result of which deficiency of the component of the immune system?
Complement
Which infection is most common as a consequence of B cell deficiency?
Bacterial
Kostmanns syndrome is a congenital deficiency of which component of the immune system?
Neutrophil phagocytes
Which component of the innate immune system is usually one of the first to respond to infection through a cut?
Neutrophil phagocytes
Which complement factor is an important chemotaxic agent?
C3a
What is the functional complement test used to investigate the classical pathway?
CH50
Which Crucial enzyme is vital for the oxidative killing of intracellular micro-organisms?
NADPH oxidase
Leukocyte Adhesion Deficiency is characterised by a very high count in which molecule?
Neutrophils
A complete deficiency in this molecule is associated with recurrent respiratory and gastrointestinal infection?
IgA
