Brainscape's Knowledge GenomeTM

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


See full index

Year 5 Pathology > Primary immunodeficiencies > Flashcards

Primary immunodeficiencies Flashcards

1
Q

primary vs secondary immunodeficiencies

A

Primary immunodeficiencies

  • rare (1 in 10,000)
  • occurs when mutated gene -> altered protein involved in immune response

Secondary immunodeficiencies

  • common
  • subtle clinically
  • often involve more than 1 component of immune system
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

4 examples of secondary immunodeficiences

A

1) Infection (HIV, measles, mycobacteria)
2) Biochemical (Zn/Fe deficiency, renal impairment, malnutrition)
3) Drugs (corticosteroids, anti-proliferative immunosuppressants and cytotoxic drugs used in Ca therapy)
4) Malignancy (myeloma, leukaemia, lymphoma)

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

Physiological immunodeficiency

A

1) neonates (rely on maternal IgG in first few months of life)
2) pregnancy
3) elderly (immune senescence)

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

Criteria for immune deficiency

A
  • 2 major infections or
  • 1 major and recurrent minor infections
  • in 1 year
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

other features of immune deficiency

A

unusual sites/organisms
chronic infections
unresponsive to Tx
early tissue damage

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

Clinical features of primary immune deficiencies

A

FHx (as primary is INHERITED)
young age at presentation
failure to thrive

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

Split primary immune deficiencies into…

A

1) cells of innate system (phagocyte and NK cell deficiencies)
2) complement
3) cells of adaptive immune system

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

Autosomal recessive severe SCID
mutation in mitochondrial energy metabolism enzyme AK2
failure myeloid and lymphoid stem cells to differentiate
No neutrophil/lymphocyte/monocyte/macrophage/platelet production

A

Reticular dysgenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

recurrent infections in child with no neutrophils on FBC

A

Kostmann syndrome

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

congenital neutropenia
autosomal recessive
specific failure of neutrophil maturation
mutation in HCLS1- associated HAX-1 in classical form

A

Kostmann syndrome

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

Recurrent episodic infections with episodic neutropenia on FBC

A

Cyclic neutropenia

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

failure of neutrophil maturation
autosomal dominant
episodic neutropenia every 4-6wks
mutation in neutrophil elastase (ELA-2)

A

Cyclic neutropenia

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

Recurrent infections in child with high neutrophil count on FBC but no abscess formation

A

Leukocyte adhesion deficiency

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

Failure of neutrophils or leukocytes to migrate to site of infection
production still normal
deficiency of CD18 (b2 integrin subunit) adhesion molecule on neutrophil
Neutrophils cannot migrate from blood -> tissue

A

Leukocyte adhesion deficiency

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

High neutrophil count in FBC
Absence of pus formation/abscess
delayed umbilical cord separation in neonate

A

Leukocyte adhesion deficiency

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

Recurrent infections with hepatosplenomegaly and abnormal dihydrorhodamine test (does not fluoresce)

A

Chronic granulomatous disease

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

deficiency in component of NADPH oxidase
cannot generate O2 free radicals (hydrogen peroxide)
DHR and NBT test negative

A

Chronic granulomatous disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q 
excessive inflammation 
granulomas 
lymphadenopathy
hepatosplenomegaly
susceptibility to catalase +ve bacteria (Pseudomonas, Listeria, Aspergillus, Candida, E.coli, S. Aureus, Serratia)
A

Chronic granulomatous disease

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

Infection with atypical mycobacterium. Normal FBC

A

IFN gamma receptor deficiency

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

deficiency of IFN-g and IL-12 and their receptors
susceptibility to mycobacterium infection (MTB or atypical), BCG, salmonella
Inability to form granulomas

A

deficiency of IFN-g and IL-12 and their receptors

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

severe chicken pox, disseminated CMV infection

A

Classical natural killer cell deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Absence NK cells in peripheral blood

GATA2 and MCM4 subtype 1 and 2 abnormality

A

Classical natural killer cell deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

NK cells present in blood but function abnormal

FCGR3A subtype 1 gene abnormality

A

Functional NK cell deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Recurrent S. Aureus or enteric or Candida or Aspergillus infections of skin or mouth
or mycobacterium infection
in a young person

A

phagocyte deficiency

  • reticular dysgenesis
  • Kostmann syndrome
  • cyclic neutropenia
  • leukocyte adhesion deficiency
  • IL-12/IFN-g and receptor deficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Diagnosis of phagocyte deficiencies

A 
NBT test (stays yellow)
DHR test (no fluorescence)

…. as no hydrogen peroxide produced as no oxidative killing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Treatment phagocyte deficiencies

A 
Prophylactic antimicrobials (Septrin)
Prophylactic antifungals (Itraconazole)
Bone marrow transplant is definitive treatment
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Treatment for Chronic Granulomatous disease

A

IFN gamma (cytokine therapy)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Neutrophil - low
Leukocyte Adhesion Markers - normal
NBT - usually low
Pus - no

A

Kostmann syndrome (congenital neutropenia)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Neutrophil - high
Leukocyte Adhesion Markers - low
NBT - normal
Pus - no

A

Leukocyte adhesion deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Neutrophil - normal
Leukocyte Adhesion Markers - normal
NBT - low
Pus - yes

A

Chronic granulomatous disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Neutrophil - normal
Leukocyte Adhesion Markers - normal
NBT - normal
Pus - yes

A

IL-12/IFN-g or receptor deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

> 20 proteins produced by liver
present in blood, inactive
when activated, engage in rapid biological cascade

A

Complement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

3 pathways in complement activation

A

Classical (C1,C2,C4)
MBL
Alternative pathway

…. all converge to activate C3, then final common pathway (C5-9), then activate membrane attack complex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q 
Which Complement pathway is:
 Activated by Ab-Ag immune complexes
 C1 binds to complex
 Activated late as dependent on antibodies
dependant on acquired immune response
A

Classical pathway (C1/2/4)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Which Complement pathway is:
Activated by direct binding MBL to microbial cell surface carbohydrates
Stimulates C4 and C2

A

Mannose binding lectin pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Which Complement pathway is:
Constantly at low level of activation that is negatively regulated
Bacterial cell walls increase activation of pathway
involves factors B, D and Properidin
Controlled by Factor H protein

A

Alternate pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Convergence of 3 complement pathways

A

… onto C3 (major amplification step)

triggers formation of membrane attack complex via C5-9)

MAC forms holes in bacterial cell membrane -> cell death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Roles of complement fragments released during complement cascade

A
  • increase vascular permeability and cells to site of inflammation
  • promote clearance of immune complexes
  • opsonisation to promote phagocytosis
  • activates phagocytes
  • promotes mast cell/basophil degranulation
  • punches holes in bacterial membranes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Alternate pathway deficiency
(rare)
prone to recurrent encapsulate bacterial infections

A

Factor B/ I / P deficiency

40
Q

prone to infections and SLE (skin and joint disease)

A

classical pathway complement deficiency
C2 deficiency commonest in SLE
Also C1q, C1r, C1s, C4 in SLE

41
Q

How does deficiency in complements of classical pathway lead to SLE?

A

1) less promotion of phagocyte-mediated clearance of apoptotic cells/immune complexes
2) increased load of self-antigens and antibodies to seld-antigens

42
Q

Active lupus causes depletion of complement (usually C4, also C3)

A

acquired SLE

leads to persistent production immune complexes and -> depletion of complement

43
Q

recurrent infections when neutropenic after receiving chemotherapy but previously well

A

MBL deficiency

44
Q

not usually associated with immunodeficiency

increased infection rates in chemotherapy patients, HIV, antibody deficiency, premature infants

A

MBL deficiency

45
Q

Severe childhood onset SLE with normal levels of C3 and C4

A

C1q deficiency (inherited)

46
Q

Encapsulated bacteria (NHS)

A

Neisseria meningitidis (meningococcus)
Haemophilus Influenzae
Streptococcus Pneumonia

47
Q

High risk infection from encapsulated bacteria (NHS)

high risk of connective tissue disease

A

C3 deficiency (primary_)

48
Q

Membranoproliferative nephritis and bacterial infections

A

C3 deficiency with presence of a nephritic factor

49
Q

Glomerulonephritis and partial lipodystrophy

and bacterial infections

A

C3 deficiency (secondary/acquired)

50
Q

Meningococcus meningitis with FH of sibling dying of same condition aged 6

A

C7 or C9 deficiency

51
Q

high risk of severe encapsulated bacterial infections

FH of death due to severe infection

A

terminal common pathway deficiency

-> inability to make membrane attack complex -> cannot use complement to lyse encapsulated bacteria (NHS)

52
Q

test for classical pathway complement

A

CH50

tests C1,2,4, C3, C5-9

53
Q

test for alternate pathway complement

A

AP50

tests for factors B,D, properidin, C3, C5-9

54
Q

C3 +
C4 +
CH50 low
AP50 +

A 
C1q deficiency 
(deficiency in classical pathway, associated with SLE)
55
Q

C3 +
C4 +
CH50 +
AP50 low

A

Factor B deficiency

alternate pathway deficiency

56
Q

C3 +
C4 +
CH50 low
AP50 low

A

C7 or C9 deficiency

AP50 and CH50 both low, hence deficiency in terminal common pathway C5-9

57
Q

C3 + or low
C4 low
CH50 + or low
AP50 +

A

SLE

C3/CH50 may be low as SLE depletes complement levels

58
Q

Treatment of complement deficiencies

A

1) Vaccinations (HIB, Pneumovax, Meningovax)
2) Prophylactic Antibiotics
3) High level suspicion and early Tx
4) Screen family members (and Tx with 1 and 2)

59
Q

Cell components of adaptive immune system

A 
T cells (CD4 and CD8 Tc)
B cells (Bc, plasma cells, antibodies)
Soluble components (cytokines and chemokines)
60
Q

T cell Immunodeficiencies

1) Disorder of Bone marrow
2) Disorder of thymus (x2)
3) Disorder in periphery

A

1) SCID (X-linked)
2) Di George syndrome (22q11 deletion syndrome), and Bare lymphocyte syndrome Type 1+2
3) IL-12/IFN-g and their receptors deficiency

61
Q

Clinical features of SCID

A

Unwell by 3m (maternal IgG lost at this point)
Infections of all types
Failure to thrive
FH of early infant death
Persistent diarrhoea
- unusual skin disease
- colonisation of infant’s empty bone marrow with maternal lymphocytes
- graft vs host disease (often eczematous presentation)

62
Q

No pathways for SCID to develop

Causes of SCID

A 
>20 possible pathways
Causes:
 - deficiency of cytokine receptors
 - deficiency of signalling molecules
 - metabolic defects 
can affect Bc, Tc or NK cells dependent on exact mutation
63
Q

3 Types of SCID

A 
X-linked SCID (45% of all SCID)
ADA deficiency (16.5%)
Reticular dysgenesis (severe form, stem cells cannot differentiate)
64
Q

mutation of common gamma chain of IL-2 receptor on chromosome Xq13.1 (shared by receptor for IL-2,4,7,9,15,21)

Inability to respond to cytokines -> early arrest of Tc and NK cell development, and immature Bc

Low NK cells, low Tc
normal/high Bc
low Igs

A

X-linked SCID

NB immunoglobulins low as B cells are immature

65
Q

low Tc
low Bc
low NK cells

Adenosine deaminase deficiency (enzyme required by lymphocytes for cell metabolism)

inability to respond to cytokines and causes early arrest Tc and NK cells, and production of immature Bc

A

ADA deficiency SCID

66
Q

Developmental defect of PHARYNGEAL POUCH

Normal Bc, low Tc
Low immune function in early years (why?)

Deletion of 22q11.2
TBX1 may be responsible for some features
Usually sporadic

A

DiGeorge Syndrome

homeostatic proliferation increases with age -> immune function improves with age

67
Q

CATCH-22O

A

(clinical features of DiGeorge)
Cardiac abnormalities (tetralogy of Fallot)
Abnormal face (high forehead, small jaw/mouth, low set ears)
Thymus aplasia (-> low Tc)
Cleft palate
Hypocalcaemia/hypoparathyroidism

22q11.2 delection syndrome
Oesophageal atresia

68
Q

Defect in regulatory protein involved in Class I or II gene expression
(what are proteins called?)

A

proteins involved = regulatory factor X and Class II transactivator

Bare lymphocyte Syndrome

  • Type 1 = low HLA class I -> low CD8 Tc
  • Type II = low HLA class II -> low CD4 Tc
69
Q

very low CD4 Tc
normal CD8 Tc
normal Bc
low IgF or IgA

A

Bare lymphocyte syndrome type II

70
Q

normal CD4 Tc
low CD8 Tc
normal Bc

A

Bare lymphocyte Syndrome Type I

71
Q

Clinical features of Bare lymphocyte syndrome

A

Unwell by 3m
Infections of all types
may be associated with SCLEROSING CHOLANGITIS
FH of early infant death

72
Q

abnormality in cytokine release by Tc

risk of mycobacterium infections, BCG and salmonella

A

Deficiency of IL-12, IFN-g and their receptors

73
Q

Failure to express CD40L on activated Tc

leads to abnormal T-Bc communication

A

Hyper IgM syndrome

74
Q 
Severe recurrent infections from 3m
CD4  and CD8 Tc absent
Bc present
Igs low
Normal facial features and cardiac ech
A

X-linked SCID

75
Q

Young adult with Mycobacterium marinum infection

A

IFN gamma receptor deficiency

76
Q 
Recurrent infections in childhood 
abnromal facial features
congenital heart disease
normal Bc
low Tc
low IgA and G
A

DiGeorge Syndrome

77
Q

6m old baby with 2 recent bacterial infections
Only CD8 Tc present
Bc present
IgM present, IgG low

A

Bare lymphocyte syndrome Type 2

78
Q

Adult with bronchiectasis, recurrent sinusitis and development of atypical SLE

A

Common variable immunodeficiency

79
Q

Recurrent bacterial infections in a child, episode of pneumocystis pneumonia, high IgM, absent IgA and IgG

A

X-linked hyper IgM syndrome due to CD40 ligand mutation

80
Q

1 year old boy recurrent bacterial infections. CD4 and CD8 Tc present Bcells absent, IgG/A/M absent

A

Brutons X linked hypogammaglobulinaemia

81
Q

Recurrent respiratory tract infections, absent IgA , normal IgM/G

A

IgA deficiency

82
Q

Increased risk mycobacterium infections, BCG, Salmonella
Cannot form granulomas
T cells cannot interact with macrophages

A

IL-12, IFN-g and receptors deficiency

83
Q

Failure to express CD40L on activated T cells
Hence no T-B cell interaction
IgM B cells cannot undergo germinal centre reaction

A

Hyper IgM Syndrome

84
Q

Normal Bc
Normal Tc
High IgM
low IgA, IgG, IgE

A

Hyper IgM Syndrome

85
Q

Boys present with failure to thrive in first few years of life with
Recurrent bacterial infections

Higher risk Pneumocystis jiroveci infections, autoimmune disease and malignancy

A

Hyper IgM Syndrome

86
Q

Defective B cells tyrosine kinase gene
Pre B cells cannot develop into mature B cells
No mature B cells
No circulating Ig after 3m

A

Bruton’s X-linked hypogammaglobulinaemia

87
Q

Defective B cell tyrosine kinase gene
Boys present in 1st few years of life, failure to thrive, recurrent bacterial infections:
Otitis media, sinusitis, pneumnia, osteomyelitis, septic arthritis, gastroenteritis

Viral, fungal, parasitic infections (enterovirus, pneumocystis)

A

Bruton’s X-linked hypogammaglobulinaemia

88
Q

2/3 asymptomatic
1/3 recurrent respiratory tract infections and GI infections

Incidence 1 in 600

Genetic component but cause unknown

A

Selective IgA deficiency

89
Q

failure in differentiation/function of B cells
Heterogeneous group of disorders, cause unknown

Low IgG, A, E
Poor response to immunisation

A

Common variable immune deficiency

90
Q

recurrent bacterial infections with severe end-organ damage (bronchiectasis, persistent sinusitis, recurrent GIT infections)
Higher risk AI disease (AIHA, thrombocytopenia, RA< pernicious anaemia, thyroiditis, vitiligo)
Higher risk granulomatous disease, malignancy (Non-Hodgkin’s Lymphoma), pulmonary disease (interstitial lung disease)

A

Common variable immune deficiency

91
Q 
Defined by:
 - markedly low IgG, low IgA or IgM
 - poor/absent response to immunisation 
 - absence of other defined 
   immunodeficiency
A

Common variable immune deficiency

92
Q

Clinical phenotype of Antibody deficiency (or CD4 T cell deficiency)

A

Bacterial infections (Staph, Strep)
Toxins (Diptheria, Tetanus)
Some viral infections (Enterovirus)

93
Q

Diagnosis of B cell immunodeficiency

A
  • White cell count
  • lymphocyte subsets (quantify B cells,
    CD4/8 T cells, NK cells)
  • serum Ig and protein electrophoresis
  • functional test of B cell function (measure IgG antibodies against tetanus, HIB etc to see if specific levels low, then immunise against those
94
Q

Result of protein electrophoresis where no Antibodies being produced

A

no peak in gamma wave

95
Q

Mx of B cell deficiencies

A
  • Aggressive treatment of infection
  • Lifelong Ig replacement (every 3 weeks) of pooled plasma containing diverse IgG against lots of different organisms
  • bone marrow transplant
  • immunisation in IgA deficiency (not effective if no IgG)

Year 5 Pathology (13 decks)

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