Brainscape's Knowledge GenomeTM

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


See full index

Immunology > Respiratory immunology- primary immunodeficiencies > Flashcards

Respiratory immunology- primary immunodeficiencies Flashcards

1
Q

When might you suspect a patient of having an immune deficiency?

A 
With SPUR infections:
Serious infections
Persistent infections
Unusual infections
Recurrent infections
Other features:
Weight loss or failure to thrive
Severe skin rash (eczema)
Chronic diarrhoea
Mouth ulceration
Unusual autoimmune disease
Family history
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the difference between primary and secondary immune deficiencies?

A

Primary deficiencies are very rare : 1:10,000 live births

Secondary deficiencies are common, often subtle, and often involve more than one component of the immune system.

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

What types of phagocyte deficiency exist?

A

Defects of phagocyte production, mobilisation and recruitment
Defects in phagocyte adhesion
Failure of recognition of pathogens by phagocytes
Failure of oxidative killing mechanisms

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

a) Name or describe two conditions which are caused by a defect in phagocyte production and specify whether they are primary or secondary conditions.
b) Describe where the defect in production occurs

A

a) Reticular dysgenesis: primary disorder.
After stem cell transplantation: secondary disorder.
b) There is a failure of stem cells to differentiate along myeloid lineage.

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

Name two conditions caused by a failure of neutrophils to mature.

A

Kostmann syndrome: severe congenital neutropaenia.

Cyclic neutropaenia: episodic neutropaenia, occurs every 4-6 weeks.

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

How is Kostmann syndrome inherited?

A

It is a rate autosomal recessive disorder

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

What does Kostmann syndrome result in?

A

A decreased absolute neutrophil count

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

How does Kostmann syndrome present clinically?

A

Infections within 2 weeks after birth
Recurrent bacterial infections
Can be localised or systemic

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

Describe the management of Kostmann syndrome.

A

Definitive treatment: Stem cell transplant (because the defect is in the neutrophil precursor)
Granulocyte colony stimulating factor (a specific growth factor which assists maturation of neutrophils)
There is 70% mortality in the 1st year of life without definitive treatment.

Supportive treatment: Prophylactic antibiotics
Prophylactic anti-fungals.

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

What causes leukocyte adhesion deficiency?

A

A genetic defect in leukocyte integrins (CD18)

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

What does leukocyte adhesion deficiency result in?

A

A failure in neutrophil adhesion and migration

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

Describe the clinical picture of leukocyte adhesion deficiency

A

Leukocytosis

Localised bacterial infections that are difficult to detect

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

How do phagocytes recognise pathogens directly?

A

With pathogen recognition receptors:
Toll like receptors
Scavenger receptors
Lectin receptors

By recognising microbial-specific structures:
Bacterial sugars
Lipopolysaccharides

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

What do defects in direct pathogen recognition by phagocytes cause?

A

Some are associated with increased susceptibility to bacterial infection, however most do not cause significant disease.

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

Describe indirect recognition of pathogens by phagocytes.

A

By opsonins.
These act as binding enhancers for phagocytosis, and include complement C3b, IgG and CRP.
They bind to receptors on the phagocyte surface (after binding tot he pathogen) e.g. via FC receptors or complement receptor 1.

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

Describe the defects that can arise in indirect pathogen recognition by phagocytes and what they cause.

A

Defects in opsonin receptors:
Cause defective phagocytosis but does not cause significant disease.
Defects in complement/antibody production:
cause a functional defect in phagocytosis (but no defect in the phagocytes themselves).

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

What is the name for the condition caused by failure of oxidative killing mechanisms by phagocytes?

A

Chronic granulomatous disease

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

a) What causes the commonest form of chronic granulomatous disease?
b) What does it result in?

A

a) A deficiency of p47phox component of NADPH oxidase.
This is an x-linked condition.
b) There is an inability to generate oxygen free radicals and therefore impaired killing of intracellular micro-organisms, and an inability to clear organisms.
This causes excessive inflammation as there is a failure to degrade chemoattractants and antigens, and persistent accumulation of neutrophils, activated macrophages and lymphocytes. This leads to granuloma formation.

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

What are clinical features of chronic granulomatous disease?

A 
Recurrent deep bacterial infections
Recurrent fungal infections
Failure to thrive
Lymphadenopathy and hepatosplenomegaly
Granuloma formation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the investigation to test for chronic granulomatous disease?

A

Nitroblue tetrazoleum test (NBT)

The dye changes colour if H202 is produced.

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

What is the treatment for chronic granulomatous disease?

A 
Definitive:
Stem cell transplantation
Gene therapy
Supportive:
Prophylactic antibiotics
Prophylactic anti-fungals
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

a) What type of pathogens hide from the immune system within immune cells themselves?
b) Which immune cells in particular do these pathogens hide in?

A

a) Mycobacteria species

b) macrophages

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

Describe the immune response to an intracellular infection with mycobacteria (TB)

A

The mycobacteria infects the macrophages.
This activates the IL12- gIGN (interleukin-12 - gammer Interferon) network.
Infected macrophages are stimulated to produce IL-12.
IL-12 induces T cells to secrete gamma interferon (gIFN)
gIFN feeds back to macrophages and neutrophils.
This stimulates production of TNF, which activates NADPH, which stimulates the oxidative pathways.

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

Describe defects in the IL12- gIFN axis, and explain which infections affected people are susceptible to.

A

Single gene defects:
gIFN receptor deficiency
IL12 deficiency
IL12 receptor deficiency

These defects are associated with susceptibility to intracellular bacteria :
mycobacteria (TB and atypical)
salmonella.

25
Q

What is an important side effect of anti-TNF drugs used to treat inflammatory diseases?

A

Re-activation of latent TB.

26
Q

How is phagocyte recruitment investigated?

A

FBC and differential
Presence of pus
Expression of neutrophil adhesion molecules.

27
Q

How is the ability of phagocytes to recognise and catch pathogens investigated?

A

Chemotactic assays

Phagocytotic assays

28
Q

How is the ability of phagocytes to kill pathogens investigated?

A

NBT - test of oxidative killing.

29
Q

Describe the results of the following tests for a) Congenital neutropaenia (e.g. Kostmann syndrome) b) Leukocyte adhesion defect and c) Chronic granulomatous disease.

Tests:
Neutrophil count
Pus formation
Leukocyte adhesion markers
NBT
A

a) Neutrophil count: Absent
Pus formation: No
Leukocyte adhesion markers: normal
NBT: Usually absent (because no neutrophils)

b) Neutrophil count: normal/increased during infection
Pus formation: No.
Leukocyte adhesion markers: Absent
NBT: normal

c) Neutrophil count: normal
Pus formation: yes
Leukocyte adhesion markers: normal
NBT: abnormal.

30
Q

Describe the treatment for phagocyte deficiencies.

A

Aggressive management of infection:
Infection prophylaxis - Septrin, Itraconazole (anti-fungal)
Oral/IV antibiotics
Surgical draining of abscesses.

Definitive therapy:
Bone marrow transplantation
Specific treatment for CGD: Gamma interferon therapy, gene therapy.

31
Q

Describe the key features of the acquired immune system.

A

Response to an unlimited number of molecules.
Specificity: able to discriminate between very small differences in molecular structure
Memory: recall previous encounter with antigen and response more effectively than on the first occasion
Repertoire not generally encoded: cells must be “educated” within host.

32
Q

Describe the formation and maturation of T cells.

A

T cells arise from haematopoetic stem cells in the bone marrow.
Exported as immature cells (Pre T cells) to the thymus
Only 10% survive the selection process in the thymus
Mature T lymphocytes enter the circulation and reside in lymph nodes and secondary lymphoid follicles.

33
Q

What is reticular dysegenesis?

A 
A defect of haemopoetic stem cells.
It results in failure of production of:
Neutrophils
Lymphocytes
Macrophages/monocytes
Platelets
It is fatal unless corrected with a bone marrow transplant.
34
Q

Name a defect of lymphoid precursors, and describe its result.

A

Severe combined immunodeficiency

Results in a failure of production of lymphocytes

35
Q

Describe the clinical picture of severe combined immunodeficiency.

A 
Unwell by three months of ages
Failure to thrive
Persistent diarrhoea. 
Infections of all types: common infections which are more severe than usual, unusual and opportunistic infections, vaccine associated diseases.
Unusual skin disease
Family history of early infant death.
36
Q

Where do babies get their IgG from in the first 3 months of life?

A

They have maternal IgG, which they got across the placenta and in breast milk.

37
Q

What is transient hypogammaglobulinaemia of infancy?

A

When normal babies get infections at 3-4 months old because their immune systems are slow to mature, and to produce their own IgG.

38
Q

Name some possible pathways which can lead to SCID?

A

Deficiency of cytokine receptors
Deficiency of signalling molecules
Metabolic defects
Defective receptor re-arrangements

39
Q

a) What is the commonest form of SCID?

b) What causes it?

A

a) X-linked SCID

b) A mutation of a component of the IL2 receptor.

40
Q

What does X-linked SCID cause?

A

The mutation of the IL2 receptor component causes a failure to respond to cytokines, which results in failure of NK cells and T cell development, and production of immature B cells.

41
Q

Describe the clinical phenotype of an individual with X-linked SCID, in terms of their lymphocytes and lymphoid tissues.

A

Very low or absent T cells, because IL2 is so important for T cell development.
Normal or increased B cells
Poorly developed lymphoid tissue and thymus.

42
Q

Describe the treatment for SCID.

A 
Prophylactic treatment:
Prophylactic antibiotics and anti-fungals
No vaccines
Aggressive treatment of infections
Antibody replacement- IV Ig

Definitive treatment:
Stem cell transplant from HLA identical sibling possible
Stem cell transplant from other sibling or parent or matched unrelated donor.

Gene therapy- stem cells treated exvivo to express the missing component - these cells have a survival advantage in vivo.

43
Q

What is Di George’s syndrome and what causes it?

A

Failure of development of the thymus from the branchial arches, usually due to a deletion affecting chromosome 22q11.
Cumulative effect of deletion of several genes may be necessary for full phenotype.
Key gene responsible is probably TBX1- this is critical for embryonic development of the pharyngeal pouch.

44
Q

What is the result of Di George’s syndrome?

A

There is no suitable microenvironment for the maturation of T cells so there is T cell immunodeficiency.
This causes:
Congenital heart defects
Cleft palate
Hypocalcaemia secondary to hypoparathyroidism
Developmental delay
Psychiatric disorders- OCD, schizophrenia.
Patients are vulnerable to infection.

45
Q

What kind of infections are patients with Di George’s syndrome susceptible to and why?

A

Recurrent viral infections - because CD8 T cells are essential in killing of virally infected cells.
Recurrent bacterial infections- because T cells are essential for helping B cells make antibodies.
Frequent fungal infections- because T cells are essential for fungal defence.

46
Q

What lab investigations can help diagnose Di George’s syndrome?

A 
Absent or decreased number of T cells
Defective T cell activation response
Normal or increased B cells
Low IgG, IgA, IgE
poor antibody responses to specific antigens
Normal NK cell numbers
47
Q

Describe management of Di George’s syndrome

A

Correct metabolic and cardiac abnormalities
Prophylactic antibiotics
Early and aggressive treatment of infection
Some patients require Ig replacement
T cell function improves with age (possible due to extrathymic maturation of T cells)

48
Q

Name types of T cell effector function disorders.

A

Disorders of cytokine production
Disorders of cytotoxicity
Disorders in T-B cell communication

49
Q

a) Regarding the immune response to infection with mycobacteria (e.g. TB), where might there be disorders in T cell effector function?
b) What sorts of infections might this predispose to?

A

a) Deficiency in the IL12 receptor and gIFN.
b) TB
Atypical Mycobacteria
BCG infection after vaccination
Deep fungal infections e.g. aspergillus.

50
Q

List clinical features of T cell deficiencies.

A

Recurrent infections: Bacterial, viral, Fungal, intracellular
opportunistic infections
Malignancies at young age
Autoimmune disease

51
Q

What are the first and second line investigations of T cell deficiencies?

A

First line:
Total white cell count and differential (remember WBC much higher in children than adults)
Serum Ig and protein electrophoresis (surrogate marker of functional T cells)
Quantitation of lymphocyte subpopulations by flow cytometry.

Second line:
Functional tests of T cell activation and proliferation (may be useful if signalling or activation defects suspected)
Additional tests of lymphocyte lineage
HIV test essential.

52
Q

Describe how antibody deficiencies can present.

A 
As recurrent bacterial infections
Opportunistic infections
As antibody mediated autoimmune diseases:
Idiopathic thrombocytopaenia
Autoimmune haemolytic anaemia
53
Q

Name a condition which results in a failure to produce mature B cells, and list its consequences.

A

Bruton’s X-linked hypogammaglobulinaemia

There are no circulating B cells, no plasma cells, and no circulating antibody after the first 6 months of life.

54
Q

Name the antibody deficiency, in which 2/3 of patients are asymptomatic, and 1/3 has recurrent respiratory tract infections.
What is the cause of this?

A

Selective IgA deficiency

There is a genetic component, but the cause is currently unknown.

55
Q

Name the condition which is a heterogenous group of disorders, in which there are low IgG, IgE and IgA, recurrent bacterial infections and is associated with autoimmune disease, for which the cause and mechanism is unknown.

A

Common variable immune deficiency

56
Q

Describe the clinical features of Common variable immune deficiency

A

Recurrent bacterial infections, autoimmune disease and granulomatous disease.

57
Q

Name a condition (or two) for each effect:

a) Failure of lymphocyte precursors
b) Failure of B cell maturation
c) Failure of T cell costimulation
d) Failure of production of IgG antibodies
e) Failure of IgA production

A

a) Severe combined immune deficiency
b) X-linked agammaglobulinaemia
c) X-linked hyper IgM syndrome
d) Common variable immune deficiency
Selective antibody deficiency
e) Selective IgA deficiency

58
Q

What are the first and second line investigations of B cell deficiencies?

A

First line:
Total white cell count and differential
Serum Ig
Serum and urine protein electrophoresis

Second line:
Quantitation of B and T lymphocytes
Specific antibody responses to known pathogens:
Measure IgG antibodies against tetanus, Haemophilus influenzae and Strep. pnuemoniae.
If specific antibody levels are low, immunise with appropriate killed vaccine and measure antibody levels again 6-8 weeks later.
Failure to mount a response indicates a significant defect in antibody production.

59
Q

Describe the management of B cell deficiencies

A

Aggressive treatment of infection
Immunoglobulin replacement:
from a pooled plasma of thousands of donors
containts IgG antibodies to a wide variety of common organisms
Administered IV every 3-4 weeks
Treatment is life-longe

Stem cell transplantation in some situations

Immunology (3 decks)

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