Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Immunology > Primary immune deficiencies > Flashcards

Primary immune deficiencies Flashcards

1
Q

AR mutation in mitochondrial enzyme AK2

Failure to produce myeloid or lymphoid cells

A

Reticular dysgenesis (type of SCID)

Reticular dysgenesis is caused by a mutation in AK2 that is a mitochondrial energy enzyme. It is the most severe form of SCID, preventing HSCs in the BM from maturing to either lymphocytes or myeloid cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

AR mutation in HAX1

Failure of neutrophils to mature

A

Kostmann’s

Kostmann’s is a mutation in HAX1 (Hax of neutrophils) which prevents neutrophil maturation only.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q 
AD mutation in ELA2
Cyclical neutropenia (every 3w for 6d)
A

Cyclical neutropenia

Cyclical neutropenia is a mutation in ELA2 which results in a dip in neutrophil maturation every few weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Deficiency of CD18 adhesion molecule (binds ICAM-1 on epithelial cells)
Neutrophilia, no pus formation

A

Leukocyte adhesion deficiency

In Leukocyte adhesion deficiency, there is a mutation in the CD18 adhesion molecule (think ‘eighteen (hating) to join’). This prevents it from binding to ICAM-1 on epithelial cells and migrating into tissues.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Failure of oxidative killing (NADPH oxidase deficiency)
Chronic inflammation forms lots of granulomas
Catalase +ve organisms (PLACESS)
NBT + DHR tests negative

A

Chronic granulomatous disease
(‘Can’t get ‘em destroyed)

(NBT + DHR tests indicate whether oxidative killing has occurred - NBT should change from yellow to blue, NHR oxidised to fluorescent rhodamine - negative in CGD as lack of oxidative killing)

PLACESS organisms - catalase positive - Pseudomonas, Listeria, Aspergillus, Candida, E coli, SA, Serratia (they are really hard to kill and need oxidative killing to get them)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Chronic Mycobacteria / Salmonella infection

Lack of granuloma formation

A

IL12-IFN-gamma network deficiency

(Normally intracellular organisms like mycobacteria / salmonella infect macrophages + stimulate IL12 production - this then induces IFN-gamma production by T cells to form granulomas)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are PLACESS organisms and in what immunodeficiency do they predominate?

A

Catalase positive organisms - Pseudomonas, Listeria, Aspergillus, Candida, E coli, S aureus, Serratia
More likely in CGD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the innate primary immunodeficiencies?

A 
Reticular dysgenesis
Kostmann's syndrome
Cyclic neutropenia
Leukocyte adhesion deficiency
CGD
IFN-gamma deficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Mutation in reticular dysgenesis

A

AR in AK2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Mutation in Kostmann’s

A

HAX1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Mutation in cyclical neutropenia

A

ELA2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the definitive treatment for phagocyte deficiencies?

A

Stem cell transplant

IFN-gamma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the two types of NK cell deficiency?

A
  • Classical (absence)

- Functional (abnormal function)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Absent NK cells in blood
GATA2 and MCM4 mutations
Severe chicken pox + CMV infections

A

Classic NK cell deficiency (absence)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

NK cells in blood that do not function

FCHR3A mutation

A

Functional NK cell deficiency (abnormal function)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe the complement pathway

A
  • Classical (C1, C2, C4) - antigen-antibody complex triggered
  • MBL (C2, C4) - mannose-binding lectin carbohydrate (MBL) on microbe triggers
  • Alternate (B, D, H, properidin) - bacterial cell wall triggers

Result in formation of C3, C5-C9 then join to form MAC complex. MAC complex is pro-inflammatory - pt. for lysis of encapsulated bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Classical complement pathway

A

Antigen-antibody complex trigger

C1, C2, C4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

MBL pathway

A

MBL - microbe carbohydrate trigger

C2, C4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Alternate pathway

A

Bacterial cell wall trigger

Factors B, D, H, Properidin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Encapsulated bacteria

A

Some Killers Have Pretty Nice Capsules

S pneumoniae, Klebsiella, H influenzae, Pseudomonas, Neisseria, Cryptococcus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Recurrent childhood pyogenic infections

A

MBL / alternative pathway deficiency

22
Q

Failure to clear complexes
Lack of C1, C2, C4
Severe childhood onset SLE
CH50 reduced

A

Primary classical pathway deficiency

(Classical pathway involves the formation of antigen-antibody complexes that need to be cleared, therefore a deficiency will cause accumulation. CH50 is a measure of classical pathway function. Classical pathway involves C1, C2 and C4 and therefore deficiency in any of these will result in classical pathway deficiency. SLE occurs because there is accumulation of the complexes that deposit in organs / vessels)

23
Q

Recurrent meningitis infections

A

Primary common pathway deficiency (C5-C9)

(This is not really specific for the common pathway (can happen with any complement deficiency but the common pathway is integral to all pathways hence important)

24
Q

Glomerulonephritis with presence of nephritic factor

Loss of adipose tissue

A

Common pathway deficiency (C3)

(In glomerulonephritis, nephritic factor is produced which attack C3 by stabilising C3 convertase enzyme - basically just think of nephritic factor being produced which destroys C3. This also causes partial lipodystrophy, in which there is a failure to maintain adipose tissue

25
Q

Reduced C3 and C4

A

SLE (secondary complement deficiency)

In SLE there is formation of lots of antigen-antibody complexes which need to be cleared, Just remember that this particularly uses up C3 and C4

26
Q

What are the two main causes of secondary complement deficiency?

A
  • Active SLE: Persistent immune complex formation uses up classical / common (pt. C2) to clear complexes
  • Membranoproliferative GN: nephritic factors pt. attack C3
27
Q

What is true about SLE in complement deficiency?

A

SLE can both cause complement deficiency (secondary) AND result from complement deficiency (primary classical) - failure to clear complexes

28
Q

Mutation of common gamma chain of IL2 receptor

A

X-linked SCID

29
Q

When do adaptive immune deficiencies tend to appear?

A

3m - before this age maternal IgG crosses placenta / enters breast milk and protects

30
Q

X-linked WASp gene
Lymphoma, thrombocytopenia, eczema
Easy bruising, nose bleeds, GI bleeds
Low IgM, raised IgA and IgE (not sure why)

A

Wiskott-Aldrich syndrome

31
Q

Most severe form of SCID
AK2 mutation (mitochondrial metabolism)
Unable to differentiate from BMSCs

A

Reticular dysgenesis

32
Q

Low T cells, lots of non-functioning B cells
Failure to thrive, unwell by 3 months
IL-2R gamma chain mutation

A

X-linked SCID

(In X-linked SCID (the most COMMON type of SCID) there is a mutation in the gamma chain of IL2 receptor (think X has two lines). Just remember that there are low T cells as they stop being produced with the absent receptor) + the B cells accumulate because they can’t be activated by the T cells. Babies become unwell by 3 months because they lose mothers IgG)

33
Q

What are the 3 main types of T cell immunodeficiency?

A

DiGeorge Syndrome
Bare Lymphocyte syndrome 1
Bare Lymphocyte syndrome 2

34
Q

Describe the process of T lymphocyte production

Describe the 3 step process of B cell activation by T lymphocytes

A

HSCs in BM exported as pre-T cells to thymus - selection by central tolerance (does it bind HLA?) - differentiation to CD4 (binds best to MHC II) or CD8 (binds best to MHC I)

B cells are activated by CD4 (Th2) T cells
1. CD40-CD40L
2. Th2 TCR - MHC II
3. IL4 release
Once activated B cells will undergo class switching- before class switching they just produce IgM but after class switching they can produce IgAGE and more IgM

35
Q

Absent / hypoplastic thymus
Low T cells, Normal B cells, normal IgM, decreased IgG/IgA
CATCH-22

A

Di George syndrome

(T cells leave the BM and go to the thymus for maturation. When there is an absent thymus they cannot mature fully so there are low T cells and they cannot activate B cells to class switch and produce IgAGE)

36
Q

CATCH-22

A 
Cardiac abnormalities
Atresia of oesophagus
Thymic aplasia
Cleft palate
Hypocalcaemia
22q11
37
Q

Absence of HLA II / I expression in thymus
Low CD4 / CD8 production
Chronic mild diarrhoea, sclerosing cholangitis, hepatomegaly, jaundice

A

BLS 1 / 2

(In BLS HLA is not expressed in the thymus for T cell maturation so they do not express MHC (type depends on HLA absence). There are lots of GI complications - think ‘bare bum’ as they are constantly on the toilet with diarrhoea)

38
Q

What are the 4 main types of B lymphocyte deficiency?

A

Bruton’s X-linked hypogammaglobulinaemia
Hyper IgM
Common variable (CVID)
Selective IgA

39
Q

What is class switching?

A 
B cells initially only produce IgM
Once class switching has occurred they produce more IgG, IgA, IgE and more IgM
40
Q

Recurrent GI and respiratory tract infections

Anaphylaxis in blood transfusion

A

Selective IgA deficiency
(IgA = mucosal immunity; anaphylaxis can occur in blood transfusions because IgA is seen as a foreign substance and there is a sudden increase in donor IgA - the body is not used to it and anaphylaxis will occur)

41
Q

Why can anaphylaxis occur when blood transfusion is given in IgA deficiency?

A

Sudden increase in donor IgA - body is not used to presence of IgA

42
Q

Mutation of MHC III
Bronchiectasis, recurrent sinusitis + atypical SLE
Predisposition to NHL
Poor immunisation response

A

CVID (Common variable immune deficiency)

(There is a mutation in MHC III - the mechanism is not understood, but seems to prevent B cell maturation + class switching. Look for respiratory tract signs)

43
Q

What are the two main categories of B cell deficiency?

A 
Affect BM - all B cells and Ig low = SCID, Bruton's
Affect class switching - B cells and IgM usually high, other Igs (AGE) low = Hyper IgM, selective IgA, CVID
44
Q

BLS1 vs. BLS2

A 
BLS1 = Reduced MHC class I expression = Reduced CD8+
BLS2 = Reduced MHC class II expression = Reduced CD4+ (CD4+ activate B cells so also reduced IgAGE)
45
Q

BTK gene mutation
Recurrent bacterial infections + FTT
Low B cells and Ig
Boys (X-linked)

A

Bruton’s
(Bruton’s is selective lack of B cell maturation in the BM. B cells are important for bacterial infection fighting. Think of B cells as starts with B)

46
Q

CD40-L mutation = B cells without CD40L
Normal T and B cells
Lots of IgM, no IgAGE
P jiroveci infection

A 
Hyper IgM
(One of the 3 steps of B cell activation requires CD40-CD40L interaction. Therefore there is no class switching so only IgM is produced (think of as M has 4 lines))
47
Q

Low Ig

Renal symptoms, swelling

A

Nephrotic syndrome

48
Q

3w Hx of diarrhoea
Recurrent chest infections since first episode
Tired + feverish

A

Protein losing enteropathy

49
Q

Encapsulated bacteria infection

Dactylitis

A

Sickle cell anaemia

Hyposplenism

50
Q

T cell vs. B cell deficiencies

A

T cell: Viral infections (e.g. CMV), Intracellular bacteria infections, Fungal infections
B cell: Bacterial infections (e.g. Staph, Strep), Toxins (Tetanus, Diphtheria)

51
Q

What are AP50 and CH50 measures of?

A

AP50 is a measure of alternate pathway function
CH50 is a measure of classical pathway function
If both AP50 and CH50 are reduced

52
Q

SERPING1 gene mutation

Hereditary angioedema

A

Hereditary condition due to mutation in SERPING1 gene

Leads to hereditary angioedema

Immunology (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions