Brainscape's Knowledge GenomeTM

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


See full index

Path - Immuno > primary immunodeficiencies 2 > Flashcards

primary immunodeficiencies 2 Flashcards

1
Q

Recurrent infections with high neutrophil count on FBC but no abscess formation is consistent with?

A

Leukocyte adhesion deficiency

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

Soluble components: Cytokines and chemokines are part of which immune system

A

adaptive

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

whichare the lymphoid organs? role?

A

bone marrow
- b cell maturation site

thymus
- t cell maturation site

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

what are the types of SCID? Aetiology?

A
  1. X-linked SCID:
    45% of all severe combined immunodeficiency.
    Mutation of common gamma chain (gc) on chromosome Xq13.1.
  2. ADA deficiency:
    16.5% of all severe combined immunodeficiency
    Adenosine Deaminase Deficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what are the types of SCID? Aetiology?

A
  1. X-linked SCID:
    45% of all severe combined immunodeficiency.
    Mutation of common gamma chain on chromosome Xq13.1.
  2. ADA deficiency:
    16.5% of all severe combined immunodeficiency
    Adenosine Deaminase Deficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what is the phenotype of ADA deficiency?

A

Very low or absent T cell numbers
Very low or absent B cell numbers
Very low or absent NK cell numbers

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

What protects the SCID neonate in the first 3 months of life?

A

Source of circulating maternal IgG in the neonate

after 3 months their igG production should increase but in scid it doesn’t

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

what is the clinical phenotype of severe combined immunodeficiency?

A

Unwell by 3 months of age
Infections of all types
Failure to thrive
Persistent diarrhoea

Unusual skin disease:
-Colonisation of infant’s empty bone marrow by maternal lymphocytes
-Graft versus host disease
Family history of early infant death

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

what is the state of t cells beefore and after thymus?

A

before - pre T cells

after - mature T cells

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

which receptors do T cells present?

A

CD3
+
CD4 OR CD8

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

which molecules do T cells bind to be activated?

A

CD8+ cytotoxic T cells recognise peptide presented by HLA class I molecules

CD4+ T cells recognise peptide presented by HLA class II molecules

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

what is the theory of Selection and Central Tolerance for T cells?

A

T cells with Low affinity for HLA are NOT selected in the thymus. prevent iniadequate reactivity

Those with High affiniity are NEGATIVELY selected - prevent autoreactvity

Only those with interrmediate affiinity get though - 10% of initial population

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

what iis thee theory of Selection and Central Tolerance for T cells?

A

T cells with Low and High affinity for HLA are NOT selected in the thymus.

only those with interrmediate affiinity get though - 10% of initial population

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

what is the role of CD8+ cytotoxic T cells ?

A

Kill cells directly
Perforin (pore forming) and granzymes
Expression of Fas ligand

Secrete cytokines eg IFNg TNFa

Particularly important in defence against viral infections and tumours

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

what is the role of CD4+ T helper cells ?

A

Immunoregulatory functions

via cell:cell interactions and expression of cytokines

Provide help for development of full B cell response
Provide help for development of some CD8+ T cell responses

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

what is the role of CD4+ T follicular helper cells ?

A

Immunoregulatory functions

via cell:cell interactions and expression of cytokines

Provide help for development of full B cell response
Provide help for development of some CD8+ T cell responses

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

which CD4 T Cell helps in neutrophil recruitment?

A

Th17

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

which CD4 T Cell helps in neutrophil recruitment?

A

Th17

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

what is the role of Th1?

A

helps in macrophage and CD8 T cell recruitment

secret IL2
TNFa
IFN-y

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

what is the role of Treg? what does it express?

A

regulates t cell responses

CD25
Foxp3 - a transcription factor

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

t helper cells express what?

A

CD4

Th2

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

List some examples of defects in T cell maturation?

A
  1. 22q11.2 deletion syndromeeg DiGeorge syndrome
  2. MHC Class II deficiency (absent) = cd4 not selected examples:Bare lymphocyte syndrome – type 2:
    • Regulatory factor X
    • Class II transactivator
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what is the aetiology of DiGeorge syndrome?

A

Deletion at 22q11.2
Usually sporadic not inherited

Developmental defect of pharyngeal pouch

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

what is the immune phenotyope of di george?

A

Normal numbers B cells
Reduced numbers T cells
Homeostatic proliferation of T cells
Immune function usually only mildly impaired and improves with age - due to the homeostatic proliferation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

the following features are pathognomic of what:

High forehead
Hypocalcaemia
Oesophageal atresia
Underdeveloped thymus
Complex congenital heart disease
A

DiGeorge syndrome

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

how does Bare lymphocyte syndrome – type 2 present?

A

Unwell by 3 months of age
Infections of all types
Failure to thrive
Family history of early infant death

ivx:
Profound deficiency of CD4+ cells as arent selected

Low IgG or IgA antibody due to lack of CD4+ T cell helper cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

list some Disorders of T cell effector function?

A

Cytokine production – IFN
Cytokine receptors – IL12 receptor
Cytotoxicity
T-B cell communication

28
Q

list some Disorders of T cell effector function?

A

Cytokine production – IFN
Cytokine receptors – IL12 receptor
Cytotoxicity
T-B cell communication

29
Q

how can we InvestigateT cell deficiencies?

A

Total white cell count and differential
Remember that lymphocyte counts are normally much higher in children than in adults

Lymphocyte subsets
Quantify CD8 T cells, CD4 T cells as well as B cells and NK cells

Immunoglobulins
If CD4 T cell deficient

Functional tests of T cell activation and proliferation
Useful if signalling or activation defects are suspected
HIV test

30
Q

what would ivx results show in DiGeorge?

A

Low CD4/8 t cells
Low igG

normal B cell and Igm

31
Q

what would ivx results show in DiGeorge?

A

Low CD4/8 t cells
Low igG

normal B cell and Igm

32
Q

what would ivx results show in SCID

A

everything low

B cell and igM may be normal occasionally

33
Q

what is the Management of Immunodeficiency involving T cells?

A

Aggressive prophylaxis/treatment of infection

Haematopoieitic stem cell transplantation
To replace abnormal populations in SCID
To replace abnormal cells - class II deficient APCs in BLS

Enzyme replacement therapy
PEG-ADA for ADA SCID

Gene therapy
Stem cells treated ex-vivo with viral vectors containing missing components. Transduced cells have survival advantage in vivo.

Thymic transplantation
To promote T cell differentiation in Di George syndrome

34
Q

what is the Management of Immunodeficiency involving T cells?

A

Aggressive prophylaxis/treatment of infection

Haematopoieitic stem cell transplantation
To replace abnormal populations in SCID
To replace abnormal cells - class II deficient APCs in BLS

Enzyme replacement therapy
PEG-ADA for ADA SCID

Gene therapy
Stem cells treated ex-vivo with viral vectors containing missing components. Transduced cells have survival advantage in vivo.

Thymic transplantation
To promote T cell differentiation in Di George syndrome

35
Q

what is the condition:

Severe recurrent infections from 3 months,CD4 and CD8 T cells absent, B cell present, Igs low. Normal facial features and cardiac echocardiogram

A

X-linked SCID

36
Q

what is the condition:

Young adult with chronic infection with Mycobacterium marinum

A

IFN gamma receptor deficiency

37
Q

what is the condition:

6 month baby with two recent serious bacterial infections. T cells present – but only CD8+ population. B cells present. IgM present but IgG low

A

Bare lymphocyte syndrome type II

38
Q

what is the B cell response when an antigen contacts the body ?

A

2 pathways:

  1. Early IgM response – T cell independent
    • IgM memory cell and Ab secreting plasma cell
  2. ii) Germinal centre reaction in lymph node –CD4+ T cell dependent;

A. Dendritic cells prime CD4+ T cells
B. CD4+ T cell help for B cell differentiation. Requires CD40L:CD40
C. B cell proliferation. Somatic hypermutation.Isotype switching to IgG, A , E

The somatic hypermutation leads to receptor editing which allows memory cells and plasma cells with higher affinity for antigens to be selected for.

39
Q

which chain on an anitbody determines the antibody class (eg IgM, IgE etc)?

A

Heavy chain

40
Q

which chain on an anitbody determines the antibody class (eg IgM, IgE etc)?

A

Heavy chain

41
Q

what is the structure of an IgM?

A

pentamer

42
Q

Effector function is determined by the ________ ?

A

constant region of the heavy chain (Fc)

43
Q

Effector function is determined by the ________ ?

A

constant region of the heavy chain (Fc)

44
Q

Antibody Interacts with other components* of immune response to remove pathogens. this is mediated by ____?

*Complement
Phagocytes
Natural killer cells

A

Fc mediated

45
Q

what is the aetiology and presentation of Bruton’s X linked agammaglobulinaemia?

A

Abnormal/ Muation in the B cell tyrosine kinase (BTK) gene on the X chromosome =

Pre B cells cannot develop to mature B cells

Absence of mature B cells - so cant make antibodies
No circulating Ig after ~ 3 months

46
Q

what is the presentation of Bruton’s X linked agammaglobulinaemia?

A

Boys present in first few years of life

Recurrent bacterial infections
Otitis media, sinusitis, pneumonia, osteomyelitis, septic arthritis, gastroenteritis

Viral, fungal, parasitic infections
Enterovirus, Pneumocystis,
Failure to thrive

47
Q

what is Hyper IgM syndrome? Aetiology?

A

B cell maturation defect due to Failure of T cell costimulation

X-linked recessive !!

Mutation in CD40 ligand (CD40L) gene - which is usually expressed by T cells not B

The Germinal centre reaction that allows for affinity maturation and isotype switching does NOT occur

only have IgM antibodies

48
Q

which of the following is correct:

A. Hyper IgM syndrome is caused by mutation in CD40 ligand gene, resulting in failure of activation of B cells (expressing CD40 ligand) by T cells (expressing CD40) (Failure of T cell costimulation).

B. Hyper IgM syndrome is caused by mutation in CD40 ligand gene, resulting in failure of activation of B cells (expressing CD40) by activated T cells (expressing CD40 ligand. Failure of T cell costimulation.

A

B

49
Q

what is isotype switching?

A

usually switching from IgM to A,E etc

50
Q

what results would be seen in ivx of Hyper IgM syndrome?

A

Normal number circulating B cells
Normal number of T cells but activated cells do not express CD40 ligand
No germinal centre development within lymph nodes and spleen

Failure of isotype switching
Elevated serum IgM
Undetectable IgA, IgE, IgG

51
Q

what is the clinical phenotype of hyper IgM syndrome?

A

Only difference from others is that:

There’s a subtle abnormality in T cell function predisposes to Pneumocystis jiroveci infection, autoimmune disease and malignancy

52
Q

what is the clinical phenotype of hyper IgM syndrome?

A

Only difference from others is that:

There’s a subtle abnormality in T cell function predisposes to Pneumocystis jiroveci infection, autoimmune disease and malignancy

53
Q

what results would be seen in Common variable immune deficiency CVID?

A

Marked reduction in IgG, with low IgA or IgM , low IgE

Poor/absent response to immunisation
Absence of other defined immunodeficiency

Recurrent bacterial infections

54
Q

what is the clinical phenotype of CVID?

A

Clinical features – ADULTS! and children

Recurrent bacterial infections
Pulmonary disease
Gastrointestinal disease
Malignancy - NHL

Autoimmune disease:
eg Autoimmune haemolytic anaemia or thrombocytopenia

55
Q

what is the aetiology and epidemiology of Selective IgA deficiency?

A

Prevalence = 1:600
2/3rd individuals asymptomatic
1/3rd have recurrent RESPIRATORY tract infections

Genetic component, but cause as yet unknown

56
Q

how can Investigation of B cell deficiencies be done?

A

Total white cell count and differential

Lymphocyte subsets - quantfy them

Serum immunoglobulins and protein electrophoresis

Functional tests of B cell function
- eg measure specific antibody responses to known pathogens

57
Q

Production of IgG is surrogate marker for _____?

why?

A

CD4 T cell helper function

because T helper cell costimulation via CD40 ligand iis required to activate B cell maturation which allows foramtion of plasma cells.

58
Q

on protein elctrophoresis, what would you see on Common variable immune deficiency CVID?

A

undetectable gamma/y band

because in this condition, there are no antibodies

59
Q

What is the management of Immunodeficiency involving B cells?

A

Aggressive prophylaxis / treatment of infection

Immunoglobulin replacement if required
Derived from pooled plasma from thousands of donors
Contains IgG antibodies to a wide variety of common organisms
Aim of maintaining trough IgG levels within the normal range
Treatment is life-long

Immunisation
For selective IgA deficiency

60
Q

What is the management of Immunodeficiency involving B cells?

eg for Bruton etc

A

Aggressive prophylaxis / treatment of infection

Immunoglobulin replacement if required
-Derived from pooled plasma from thousands of donors
Contains IgG antibodies to a wide variety of common organisms
Aim of maintaining trough IgG levels within the normal range
Treatment is life-long

Immunisation
For selective IgA deficiency

61
Q

Adult with bronchiectasis, recurrent sinusitis and development of atypical SLE

A

Common variable immunodeficiency

62
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 CD40ligand mutation

63
Q

1 year old boy. Recurrent bacterial infections. CD4 and CD8 T cells present. NO B cells, IgG, IgA, IgM absent

A

Bruton’s X linked hypogammaglobulinaemia

64
Q

Recurrent respiratory tract infections, absent IgA, normal IgM and IgG

A

IgA deficiency

65
Q

which antiibody is absent in Bruton’s X linked hypogammaglobulinaemia?

A

all antibodies because

gammaglobulins are antibodies - this word does NOT refer just to IgG

66
Q

At 3 months, a baby boy is discovered to have a BTK gene mutation. What should his vaccination schedule look like?

A

Cant get any live vaccines eg MMR

prophylaxis for infection

Path - Immuno (11 decks)

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