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TI2 > Intro to clinical immunology > Flashcards

Intro to clinical immunology Flashcards

1
Q

What is the difference between primary and secondary immunodeficiency?

A
  • Primary = defect in immune system

- Secondary = caused by non-immune

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2
Q

What are primary immunodeficiencies?

A
  • Usually genetic
  • infrequent but can be life-threatening
  • Can be in adaptive or innate immune system
  • Frequency - 50% Ab, 30% T-cell, 18% phagocytes, 2% complement
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3
Q

What are the major B lymphocyte disorders?

A
  • X-linked agammaglobulinaemia (Bruton’s)
  • Common variable immunodeficiency (CVID)
  • Selective IgA deficiency
  • IgG2 subclass deficiency
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4
Q

What is X-liked Agammaglobulinaemia?

A
  • First described immunodeficiency
  • Bruton’s disease
  • Defect in BTK gene on X chr
  • Encodes for Bruton’s tyrosine kinase
  • Causes a block in B-cell development (stops at pre B-cells) as needed for pre-B cell receptor signalling
  • causes recurrent severe bacterial infections
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5
Q

What would investigations for X-linked Agammaglobulinaemia show?

A
  • All Igs absent/ very low

- B cells absent/ low

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6
Q

How do we treat XLA?

A
  • IV Ig - 200-600mg/kg/month at 2-3 week intervals
  • Or subcutantaneous Ig weekly
  • Prompt antibiotic therapy (URI/LRI)
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7
Q

What is common variable immunodeficiency?

A
  • Commonest symptomatic Ab deficiency
  • Presents at any age, but peaks early childhood/ early adulthood
  • Recurrent bacterial infections (chest, sinus)
  • Autoimmune problems
  • Usually missed (exclusion diagnosis -> late diagnosis -> complications)
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8
Q

What would investigations for CVI show?

A
  • B cells normal or low - cant differentiate into plasma cells
  • One or more Igs low
  • T cells normal, CD4 T cells can be low
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9
Q

How do we treat CVI?

A
  • IV Ig

- Antibiotic prophylaxis

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10
Q

What other antibody deficiencies are there?

A

Selective IgA

  • 1:400-800
  • most cases asymptomatic, some have resp, urogenital or GI tract infections
  • Low serum and secretory IgA

Specific Ab deficiency with normal Igs

  • Hep B vaccination - 5% dont respond
  • Recurrent bacterial infections (URI/LRI)
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11
Q

What is severe combined immunodeficiency (SCID)?

A
  • Involves both B and T cells
  • 50-60% X-linked, rest AR
  • Well at birth, probs after 1st month
  • Diarrhoea, weight loss, persistent cadidiasis
  • Severe bacterial/ viral infections
  • Failure to clear vaccines
  • Usual infections - pneumocystis, CMV
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12
Q

What causes SCID?

A
  • RAG-1/ RAG-2 defect -> no T and B cells
  • Common cytokine receptor gamma-chain defect (signal transduction component of ILs); IL-7 needed for survival of T-cell precursors -> defective T cell development -> lack in B cell help (low Ab)
  • Adenosine deaminase deficiency (ADA) - causes accumulation of deoxyadenosine and deoxy-ATP - toxic for rapidly dividing thymocytes
  • Bare lymphocyte syndrome (MHCI or II)
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13
Q

What would investigations for SCID show?

A
  • Low total lymphocyte count
  • Very low/ absent T, normal/ absent B (if gamma-chain defect affecting IL-15, then absent NK)
  • Igs low
  • T cell function decline (proliferation and cytokines)
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14
Q

How do we treat SCID?

A
  • Isolation
  • Dont give live vaccines
  • Blood products from CMV negative donors
  • IV Ig
  • Treat infections
  • BM/HSC transplant
  • Gene therapy
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15
Q

What is the prognosis for SCID?

A
  • Dependent on promptness of diagnosis, donor match and infections pre-transplant
  • can be as high as 80%
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16
Q

What is DiGeorge syndrome?

A
  • 22q11 deletion - failure of development of 3rd and 4th pharyngeal pouches
  • Complex array of developmental defects
  • Dysmorphic face: cleft palate, low-set ears, fish shaped mouth
  • hypocalaemia, cardiac abnormalities
  • variable immunodeficiency (absent/ reduced thymus -> affects T cell development)
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17
Q

What is bare lymphocyte syndrome?

A
  • Mutations in TF that regualte expression of MHC class II gene
  • no MHC II, no CD4 T-cell development
  • Defect in CD4+ T cells, defective help for B cells, Ab production defects = combine T and B cell immunodeficiecny
18
Q

What is Wiskott-Aldrich syndrome?

A
  • X-linked
  • Defect in WASP (protein involved in actin polymerisation -> defect in signalling)
  • Thrombocytopaenia, eczema and infections
  • Progressive immunodeficiency
  • Progressive decrease in T cells and their proliferation
  • Ab production (decreased IgM and IgG, High IgE and IgA)
19
Q

What is ataxia-telangiectasia?

A
  • AR
  • Defect in cell cycle checkpoint gene - ATM senses DNA damage -> activates p53 -> apoptosis of cells
  • ATM stabilises dsDNA break complexes during VDJ recombination - defect = prob generating lymphocyte Ag receptors and development
20
Q

How does AT present?

A
  • Progressive cerebellar ataxia (poor coordination)
  • Telangiectasia - small dilated vessels (ear lobes and conjungtivae)
  • immunodefiency (B and T)
  • ## URI/LRI
21
Q

What is hyper-IgM syndrome?

A
  • Mutations in gene for CD40L, or loss of function mutations in CD40 or AID genes
  • Serum - increased IgM, very low IgG, no A or E
  • Normal numbers of B and T cells
  • Recurrent infections (low opsinisation)
22
Q

How does Hyper-IgM cause its problems?

A
  • Defect in T cell help to B cells/ macrophages
  • CD40L mutation - no binding to B cells, no B cell activation. Also no Macrophage binding or activation

Problem with AID -> problem with Ig class/ isotype switching and affinity maturation

23
Q

What phagocyte defects are there?

A
  • Quantitative (decreased number)

- Qualitative - Chronic granulomatous disease, Chediak-Higashi, Leukocyte adhesion defects (LADs)

24
Q

What is chronic granulomatous disease?

A
  • Defective oxidative killing of phagocytosed microbes
  • Mutation in NADPH oxidase
  • XLR
  • Susceptibility to infection with catalase +ve bacteria
25
Q

How do we diagnose CGD?

A
  • NBT test (nitroblue tetrazolium reduction) - stain

- Flow cytometry assay dihydrorhodamine

26
Q

What is Chediak-Hidashi syndrome?

A
  • rare genetic disease
  • Defect in LYST gene gives defective lysosome trafficking - failure of phagolysosome fusion
  • Repetitive severe infections
27
Q

How do we diagnose C-H syndrome?

A
  • decreased number of neutrophils

- Neutrophils have giant granules

28
Q

What is leukocyte adhesion deficiency (LAD)?

A
  • Defect in integrins
  • AR
  • Decreased chemotaxis of neutrophils to damaged area, and less integrins on phagocytes
  • Recurrent skin infections, intestinal and perianal ulcers
29
Q

What defects are there in TLR signalling?

A
  • Rare
  • Defect in TLR3 -> recurrent encephalitis (HSV)
  • Defect in MyD88 (signalling component downstream many TLRs) -> bacterial pneumonia
30
Q

What complement deficiencies are there?

A
  • Recurrent infections (neisseiria - MAC deficiency)
  • Severe/fatal pyogenic infections (C3 deficiency)
  • SLE-like syndrome (C1q, C2, C4 deficiency)
  • Hereditary angiogenic oedema - failure to inactivate complement (C1 inhibitor deficiency)
31
Q

What are the aims of PID treatment?

A
  • Minimise/ control infection
  • Replace defective/ absent component
  • Prompt treatment of infection
  • Prevent infection - isolation, prophylaxis, vaccination (NOT LIVE)
  • Nutrition
32
Q

What may cause SID?

A
  • Infections
  • Malignancy
  • Extremes of age
  • Nutrition
  • Chronic renal disease
  • Splenectomy
33
Q

What infections may cause SID?

A
  • Viral - HIV, CMV, EBV, measles, flu
  • Chronic bacterial - TB, leprosy
  • Chronic parasitic - malaria
  • Acute bacterial - septicaemia
34
Q

What malignancies may cause SID?

A
  • myeloma
  • lymphomas
  • leukaemias
35
Q

How can extremes of age cause SID?

A
  • Premature - infants less than 6 months use maternal IgG. Premature delivery interrupts placental transfer of IgG
  • Old age - decline in normal function
36
Q

What nutritional may cause SID?

A

Starvation, anorexia, iron deficiency protein-losing enteropathies

37
Q

How can chronic renal disease cause SID?

A

Uraemia
Dialysis
Nephrotic syndrome

38
Q

What other problems can cause SID?

A
  • Burns
  • Toxins - smoking, alcohol
  • Immunosuppressive drugs
  • Transplant
  • trauma and surgery
39
Q

Why do we do BMT?

A
  • Reconstitution of full haematopoeiti system by transfer of pluripotent stem cells
  • Used to replace defective, absent or malignant cells
40
Q

What are the different types of BMT?

A

By donor source

  • Allogenic - genetically matched
  • Autologous - pt is the source

By site of harvest

  • Puncture and aspiration of BM
  • Peripheral stem cells from blood
  • Umbilical
41
Q

What are some complications of BMT?

A
  • Infection (CMV, EBV, adenovirus)
  • Graft failure
  • Graft vs host disease
42
Q

What causes GvHD?

A
  • transplanted immunocompetent T cells of donor respond against recipient
  • Acute (rare now die to improved matching)
  • Chronic (main cause of death in BMT)
  • Graft vs tumour (leukaemia)

TI2 (20 decks)

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