Clinical immunology Flashcards

1
Q

Why are antibodies important?

A

Bacteria = opsonisation of non-encapsulated and encapsulated bacteria
Viruses = neutralisation (intracellular killing of non-enveloped viruses) and NK ADCC killing of enveloped viruses
underpin vaccination strategies
bacterial exotoxins - high affinity germinal centre dependent

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2
Q

What issues arise when there are defects in B cell function?

A

Recurrent pyogenic infections
Upper and Lower RTI (pneumonia, sinusitis)
Diarrhoea - campylobacter jejuni, giariasis
Organisms - encapsulated and non-encapsulated bacteria
Viruses - rare except for enteroviruses, avoid live polio in past
fungal infections uncommon
infections with intracellular organisms are not usually a problem although there is some evidence

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3
Q

What is the aetiology of B cell defects?

A

Genetics: X linked so males affected and females carriers, presents when maternal antibodies wane
In pts >50 B cell malignancy

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4
Q

What are examples of acquired forms of antibody deficiency ?

A

HIV

common variable antibody deficiency (cause mainly unknown)

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5
Q

What comes under secondary B cell depletion?

A

secondary to immunosuppresion- B cell depletion in autoimmune disease - RA, vasculitis, SLE

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6
Q

How are defects in B cell function diagnosed?

A

serum Igs and electrophoresis - total Ig levels, paraprotein (multiple myeloma)
functional antibodies - tetanus and diptheria toxins, pneumococcal and H influenzae polysaccharides
Test immunization - prevenar 13, menitorix

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7
Q

What is the treatment for B cell defects?

A

replacement treatment with IgG

antibiotics if there is established lung disease or GI symptoms

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8
Q

Case 1:
2 year old - septic arthritis in R knee, Haemophilus influenzae b isolated, had recurrent chest infections and otitis media

normal Hb, normal total lymphocyte, normal neutrophils
CRP >40

What investigations do you arrange and how do you treat?

A

serological = immunoglobin GAM, electrophoresis
Functional serological tests = functional ab, test immunisation, menitorix and prevenar 13 (conjugate vaccinations)
cell tests = surface markers for B and T cells

treatment: IV or SC immunoglobulin replacement

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9
Q

Case 2:
54 year old man, 2 day hx cough with purulent sputum and fever with chills
R sided pleuritic pain

WBC = 50x10^9/L

Physical exam:

  • consolidation, abnormal breath sounds (?pneumonia)
  • lymphadenopathy, splenomegaly, anaemia, bruising
  • Hb 10, Neutrophil 15x10^9, lymphocyte 35x10^9, normal platelets

blood and sputum culture - s. pneumoniae

What tests would you perform and what treatments?

A

lymphocyte surface markers
serum immunoglobulins and electrophoresis

chemotherapy
antibiotics
treat underlying condition

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10
Q

With innate immunodeficiency what factors will have problems?

A
neutrophils / macrophages
complement 
toll receptors, cytokines 
NK cells 
splenectomy
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11
Q

With adaptive defectives in immunodeficiency what factors will have problems?

A

antibody deficiency

T cell disorders

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12
Q

What arises with a C3 deficiency?

A

defective opsonin

pyogenic infections

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13
Q

What arises with a C1qrsC4C2 deficiency?

A
  • defective clearance of apoptotic cells
  • immunogenic
  • SLE (ANA, DNA)
  • immune complex disease
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14
Q

What arises with a C5-9 deficiency?

A

neiserria infections

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15
Q
Case 3:
3 year old, photophobia, fever, drowsiness of 6h, fine day before 
? bacterial meningitis
Clinical signs:
- neck stiffness
- Rash 
What do you need to ask in PMH?
A

if this has happened before:

- 2 previous episodes and 1 episode of pneumonococcal septicaemia

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16
Q

Case 3:
3 year old, photophobia, fever, drowsiness of 6h, fine day before
? bacterial meningitis
Clinical signs:
- neck stiffness
- Rash
What specific immunological tests would you order?

A

serum Igs
functional Abs
functional tests of complement
spleen

17
Q

What can cause neutrophil defects?

A

drugs and leukaemia

18
Q

How are neutrophil defects treated?

A

G-CSF

antifungals and abx

19
Q

What happens in neutrophil defects?

A

neutrophil migration and adhesion

neutrophil killing- respiratory burst = acidification inside the phagosome, allows the activation of neutrophil enzymes

20
Q

What is absent in adhesion LFA-1 deficiency?

A

infection without pus

21
Q

What are the features of chronic granulomatous disease?

A

defective neutrophil killing

  • fungal and staphylococcal infections
  • no respiratory burst
  • X linked
22
Q

Why are splenectomy’s important to consider in patients?

A

2nd major phagocytic organ that filters blood
increased risk of septicaemia - pneumoococci, meningocooci, malaria
critical contribution of IgM in early infection - IgM opsonizes encapsulated bacteria that are phagocytosed in kuppfer macrophages in the liver
splenic vein joins mesenteric veins to form portal vein

23
Q

How do you treat people with splenectomy?

A

immunize with menitorix and prevenar

prophylactic abx

24
Q

What can viruses do? e.g. herpes virus zoster, CMV

A

downregulate expression of HLA class 1

25
Q

TH17 cells

  • What cytokines do they release?
  • What cytokines induce them?
  • What disease is associated with its deficiency?
  • What human diseases are associated with an exaggerated response?
A
  • IL-17, IL-22
  • IL-6, IL-23
  • IL-17 mucocutanoous candidiasis
  • inflammatory bowel disease and some autoimmunity
26
Q

TH1 cells

  • What cytokines do they release?
  • What cytokines induce them?
  • What disease is associated with its deficiency?
  • What human diseases are associated with an exaggerated response?
A
  • IFN-gamma, GMCSF, TNF
  • IL-12, IFN-gamma
  • intracellular infections, particularly mycobacteria and TB
  • autoimmunity, loss of self-tolerance
27
Q

TFHcells

  • What cytokines do they release?
  • What cytokines induce them?
  • What disease is associated with its deficiency?
  • What human diseases are associated with an exaggerated response?
A
  • IL-4, IL-21
  • ?
  • no GC and high affinity antibody
  • autoimmune diseases like SLE
28
Q

Tregs cells

  • What cytokines do they release?
  • What cytokines induce them?
  • What disease is associated with its deficiency?
  • What human diseases are associated with an exaggerated response?
A
  • tgf BETA, IL-10, CTLA4
  • selected in thymus but also induced
  • lethal multisystem autoimmunity driven predominantly by th1 but also th17 and th2
29
Q

TH2 cells

  • What cytokines do they release?
  • What cytokines induce them?
  • What disease is associated with its deficiency?
  • What human diseases are associated with an exaggerated response?
A
  • IL-4, IL-13, IL-5
  • IL-33, IL-4
  • in mice IL-4 deficiency associated with lethal schistosmiasis
  • allergic asthma, allergic rhinitis
30
Q

How does T cell immunodeficiency present in children?

A

diarrhoea and failure to thrive from birth
opportunistic infections e.g. candida albicans, p. carinii, varicella, adenovirus, respiratory syncytial virus, CMV
GvH- bloods need to be irradiated
lymphopenia
lymphocytes fail to proliferate when stimulated

31
Q

What is the commonest cause of T cell immunodeficiency in adults?

A

HIV is the commonest cause of CD4 deficiency

32
Q

What infections arise from T cell immunodeficiency in adults?

A
  • intracellular infections (bacterial protozoal)e.g. mycobacteria, TB, salmonella - pneumocystitis, toxoplasmosis
  • viral infections - kaposi’s sarcoma is caused by herpes virus, CMV
  • encapsulated bacteria
  • cutaneous fungal and yeast infections
33
Q

What are cutaneous manifestations of HIV?

A

kaposi’s
sarcoma
candidiasis

34
Q

How is HIV monitored?

A

viral load

absolute CD4 count

35
Q

CASE 4
40 year old M, severe SOB, thin, cyanosed with a temp 39, multiple 1-2 cm lymph nodes in cervical, axillary and inguinal region, raised red nodules on R forearm
CXR - diffuse interstitial changes
initial investigations= lymphopenia

What infection can present with all these features and how would you test for it ?

A

HIV
test for surface markers for CD4 count
- best prognostic indicators = CD4 count and viral load

36
Q

CASE 5:
7 year old asian child, recurrent salmonella infections, atypical mycobacterium avium infection (refractory in tx)
multiple draining cold abscesses from M avium infected cervical lymph nodes and is febrile
normal B and T cells, HIV negative, normal ab levels after immunisation
What genetic hx is relevant?

A

consanguinity
distinguishing feature of these infections= intracellular bacterial infections, immunity depends on CD4 T cells
interferon gamma is the CD4 cytokine crucial for immunity to mycobactria

37
Q

When should you suspect immunodeficiency?

A

anatomy = recurrent infections in one location
persistent infections - unexplained chronic chest infections
are the infections unusual

38
Q

What does pneumocystitis jirovecii indicate?

A

severe T cell defect