Lecture 7 - Immunodeficiencies Flashcards

1
Q

what are the 4 mechanisms of immune effector strategies?

A

complement, neutrophils, B cells and T cells

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2
Q

what does the early stage of an immune response involve?

A

cytokines, interferons and IgM

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3
Q

what are the secondary immune response molecules?

A

dendritic cells, Nk cells

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4
Q

what are the final immune response molecules?

A

immune response of T cells and B cells

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5
Q

what are the features of primary immunodeficiency?

A

usually genetic, X-linked of autosomal, rare, biochemical abnormality

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6
Q

what are the features of secondary immunodeficiency?

A

external influences on cells, due to viral infections, chronic infections, malignancy, radiation, toxins

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7
Q

what are the warning signs of immunodeficiency?

A

eight or more new infections in 12 months or 2 new sinus infections in 12 months, two+ months on antibiotics with little effect, complication with a live vaccination, family history

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8
Q

what are the secondary indications of ID?

A

bone marrow transplant, biological therapy, chemotherapy causing immunosuppression

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9
Q

what are the useful first line investigations?

A

FBC, immunoglobulin levels in the blood, complement levels, response to a vaccination, lymphocyte population analysis

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10
Q

how are immunoglobulins measured?

A

nephelometry

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11
Q

how does nephelometry work?

A

input of purified and clear anti-Ig (antiserum) to the patients serum and measure the turbidity to determine binding

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12
Q

how is complement activity measured?

A

gel contains sheep blood cells with rabbit antibody, lysis via complement causes clear zone in the gel so can measure complement activity

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13
Q

what complement deficiencies cause bacterial infections?

A

C3 and factor B

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14
Q

what complement deficiencies cause severe systemic lupus?

A

C1, C4, C2

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15
Q

what is the protein vaccine used for immunisation response?

A

tetanus toxoid

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16
Q

what is the polysaccharide vaccines?

A

pneumovax and haemophilia influenzas type B capsular polysaccharide

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17
Q

what type of vaccines do children not respond too? what is used instead?

A

polysaccharide vaccines and so Prevnar used

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18
Q

how is immunisation response measured?

A

take some serum after vaccine to carry out an ELISA to test for antibody presence

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19
Q

how are lymphocyte populations identified?

A

using CD markers and monoclonal antibodies

20
Q

what CD markers does T lymphocytes have?

A

CD3 and CD4/8

21
Q

what CD markers does T lymphocytes lack?

A

CD19 and CD56

22
Q

what is the first step in evaluating a sample?

A

a full blood count

23
Q

how do you confirm a FBC result?

A

T, B, NK tests

24
Q

what is the percentage T sum?

A

the difference between CD3 and CD4+CD8

25
Q

what should the percentage T sum be?

A

less than 5%

26
Q

what should the CD4/8 ratio be?

A

around 2

27
Q

what CD marker is used for T cells?

A

CD3

28
Q

what CD marker is used for B cells?

A

CD19

29
Q

what CD marker is used for NK cells?

A

CD56

30
Q

what are the advantages of immunophenotyping?

A

rapid, small sample, whole blood analysis, lots of info on small sample

31
Q

what are the limitations of immunophenotyping?

A

needs to be fresh, rarely sufficient for diagnosis

32
Q

why might problems arise with immunophenotyping?

A

different antibody specificities, mutations may be in part of molecule undetected by antibody

33
Q

when are lymphocyte extended panels used?

A

under 5 years old

34
Q

when are B cell panels used?

A

adults where globulin levels are low

35
Q

what is a monocyte extended panel?

A

whole blood incubated with antibody panel for 20 mins with coloured antibodies, red cells lyse, samples washed and resuspended then analysed on flow cytometer

36
Q

what CD are monocytes?

A

CD14

37
Q

what is expressed on monocytes and B cells?

A

HLA-DR

38
Q

what HLA is expressed on T cells?

A

HLA-DA

39
Q

what are naive T cells positive for?

A

CD3, CD4, CD45, CD27

40
Q

what are the signals required for T cell activation?

A

T cell recognising antigen on MHC, CD28 on TC binds to CD80 on APC and cytokines provide a third signal for full activation

41
Q

what is used in order to carry out a proliferation assay?

A

peripheral blood and mononuclear cells which will contain B and T lymphocytes

42
Q

how are the mononuclear cells obtained from blood sample?

A

diluted and centrifuged, mononuclear cells form at interphase so pipetted off to be counted

43
Q

how is DNA levels measured in proliferation assay?

A

3H-thymine added and incorporated and beta counter assess the level of isotope

44
Q

what are the issues with proliferation assays?

A

use of isotope, exposure to radiation, disposal of radioactive waste, does not indicate which cells are proliferation

45
Q

how does a flow based proliferation assay work?

A

CFSE diffuses into cells and becomes fluorescent when acetate groups removed by esterase’s, this fluorescence decreases with each cell division, to then be plotted on a graph of cells vs fluorescence

46
Q

what is intracellular protein staining?

A

activate T cells and prevent protein export, cytokines build up inside and antibodies diffuse inside, binding to the cytokines

47
Q

what is chronic granulomatous disease?

A

defect in phagocytic NADPH oxidase function which reduces activity of the enzyme, therefore unable to create oxygen intermediates to kill bacteria