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Yr 3 - December lectures 2018 > Clinical immunology > Flashcards

Flashcards in Clinical immunology Deck (38)
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1

Why are antibodies important?

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

2

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

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

3

What is the aetiology of B cell defects?

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

4

What are examples of acquired forms of antibody deficiency ?

HIV
common variable antibody deficiency (cause mainly unknown)

5

What comes under secondary B cell depletion?

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

6

How are defects in B cell function diagnosed?

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

7

What is the treatment for B cell defects?

replacement treatment with IgG
antibiotics if there is established lung disease or GI symptoms

8

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?

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

9

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?

lymphocyte surface markers
serum immunoglobulins and electrophoresis

chemotherapy
antibiotics
treat underlying condition

10

With innate immunodeficiency what factors will have problems?

neutrophils / macrophages
complement
toll receptors, cytokines
NK cells
splenectomy

11

With adaptive defectives in immunodeficiency what factors will have problems?

antibody deficiency
T cell disorders

12

What arises with a C3 deficiency?

defective opsonin
pyogenic infections

13

What arises with a C1qrsC4C2 deficiency?

- defective clearance of apoptotic cells
- immunogenic
- SLE (ANA, DNA)
- immune complex disease

14

What arises with a C5-9 deficiency?

neiserria infections

15

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?

if this has happened before:
- 2 previous episodes and 1 episode of pneumonococcal septicaemia

16

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?

serum Igs
functional Abs
functional tests of complement
spleen

17

What can cause neutrophil defects?

drugs and leukaemia

18

How are neutrophil defects treated?

G-CSF
antifungals and abx

19

What happens in neutrophil defects?

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

20

What is absent in adhesion LFA-1 deficiency?

infection without pus

21

What are the features of chronic granulomatous disease?

defective neutrophil killing
- fungal and staphylococcal infections
- no respiratory burst
- X linked

22

Why are splenectomy's important to consider in patients?

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

How do you treat people with splenectomy?

immunize with menitorix and prevenar
prophylactic abx

24

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

downregulate expression of HLA class 1

25

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?

- IL-17, IL-22
- IL-6, IL-23
- IL-17 mucocutanoous candidiasis
- inflammatory bowel disease and some autoimmunity

26

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?

- IFN-gamma, GMCSF, TNF
- IL-12, IFN-gamma
- intracellular infections, particularly mycobacteria and TB
- autoimmunity, loss of self-tolerance

27

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?

- IL-4, IL-21
- ?
- no GC and high affinity antibody
- autoimmune diseases like SLE

28

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?

- tgf BETA, IL-10, CTLA4
- selected in thymus but also induced
- lethal multisystem autoimmunity driven predominantly by th1 but also th17 and th2

29

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?

- IL-4, IL-13, IL-5
- IL-33, IL-4
- in mice IL-4 deficiency associated with lethal schistosmiasis
- allergic asthma, allergic rhinitis

30

How does T cell immunodeficiency present in children?

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