Brainscape's Knowledge GenomeTM

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


See full index

Year 5 😊✌🏼 > Path - Immunology > Flashcards

Path - Immunology Flashcards

1
Q

HIV - how many affected, how many on ART, how many in the UK

A

37 mio worldwide, 21 mio on ART

101,200 affected in the UK
(70% of those on ART in the UK are undetectable)

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

What viral load in HIV is measured to be undetectable?

A

<20 copies / mm3(ml)

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

What type of virus is HIV and what does this mean?

A

it is an RNA retrovirus

it integrates itself into the hosts genome

lentivirus (from latin slow - long infection before symtoms of chronic infection seen)

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

Summarise the life cycle of HIV

A

1) virus binds to CD4 using gp120 (initial binding->conformational change). This causes releases of gp41 which causes fusion. (conformational change) receptors on CD4+ helper cells (also DCs and monocytes); also binds to CCR5 or CXCR4 chemokine co-receptors.

2) fuses with cell + uncoating

3) Reverse transcription from RNA -> DNA (via reverse transcriptase)

4) enters nucleus + integrates into genome via integrase

5) transcription -> nuclear export -> translation

6) assembly of viral products, Gag protein is infrastructural support for HIV.

7) budding, release and maturation of HIV

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

Immune response to HIV infection

A

innate:
- non specific activation of macrophages, NK cells and complement
- stimulation of dendritic cells via TLR
- release of cytokines and chemokines

adaptive:
- Neutralising antibodies: anti-gp41 IgM (first weeks) and anti-gp120 (later)
- non-neutralising antibodies: anti-p24 Gag IgG
- CD8+ cells kill infected CD4+ cells. They can also prevent HIV entry by producing chemokines (MIP-1a, MIP-1b, and RANTES which block co-receptors)

infected CD4+ cells are angergised.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Key immunological features of HIV-1 infection

A

CD4+ T-cell depletion
chronic immune activation
CD4 and cd8 T-cell exhaustion
disruption of lymph node architecture
loss of Ag specific humoral response

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

Why are quasi-species formed in HIV infection?

A

RT lacks proof reading mechanisms like DNA polymerases have and is therefore error prone

primary infection is usually with a single founder but quasi species develop rapidly

Issue - drug resistance mechanisms possible

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

What are the differences between HIV-1 and HIV-2?

A

HIV1&2 are endemic in West Africa, but HIV-2 is rarely found elsewhere -> HIV 1 is more common

higher viral loads seen in HIV-1-> easier transmission (MTCT is more likely in HIV-1, rare in HIV-2)

HIV-1 progresses to AIDS more rapidly and with higher incidence than HIV-2

HIV is the commonest cause of AIDS worldwide

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

3 Stages of HIV

A

1 - acute infection (70% people have flu like illness; during this time CD4+ T-cells drop and viral load is very high)

2 - asymptomatic (but progressive)

3 - AIDS

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

Untreated HIV - how long to progresss to AIDS?

A

typical progressors: 8-10 yrs

rapid progressors (10%) : 2-3 yrs

long term non-progressors (<5%) : show stable CD4 counts and no sx after 10 yrs

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

Important CD4 counts in HIV

A

400 - Kaposi’s sarcoma

300-350 - pulm TB

73 - MAC disease, PCP

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

MAC disease

A

seen in the context of low CD4 counts in HIV (<75)

mycobacterium avian complex

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

which tests are used to screen for and dx HIV?

A

screen: ELISA for HIV-Ab
confirm: HIV Ab via Western Blot

-> +ve test requires seroconversion therefore 45d post risk exposure (path guide says 10w)

HIV-1 RNA tests can be used when negative serology in the context of high clinical suspicion

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

In young children, what HIV test?

A

HIV-1 RNA +/- DNA

if less than 18m

serology not useful b/c passive transfer of Abs from mum

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

test to measure HIV viral load

A

PCR to detect viral RNA (very sensitive)

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

How is CD4+ T-cell count measured?

A

FACS flow cytometry

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

CD4+ count associated with AIDS

A

> 200 / mL of blood

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

resistance testing in HIV

A

phenotypic: viral replication measures in cell cultures under selective pressure of increasing concentration of antivirals - compared to wild type

genotypic: mutations determined by direct sequencing of the amplified HIV genome

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

HAART

A

highly active anti-retroviral therapy

2NRTIs + PI (or NNRTI)

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

Monitoring in HIV

A

usually every 6 months

viral load
CD4+ T-cell monitoring (not needed if CD4+ >350)
assess CVS, Osteoporosis risk + monitor LFTs, U&Es, renal, bone, lipid profile

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

Name drug classes for HIV

A

attachment inhibitors
fusion inhibitors

NRTI
NNRTI
NtRTI

Integrase inhibitors

protease inhibitors

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

Name a fusion inhibitor (ART)

A

enfuvirtide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Name an attachment inhibitor (ART)

A

maraviroc

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

Name NRTIs (ART)

A

zidovudine
abacavir
didanosine
emtricitabine
stavudine
lamavudine
zalcitabine
epzicom
combiner
trizivir

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

Name a NtRTI (ART)

A

tenofovir

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

what kind of drug is tenofovir?

A

NtRTI

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

Name NNRTIs (ART)

A

nevirapine
delavirdine
efavirenz

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

name integrase inhibitors

A

raltegravir
elvitegravir

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

name PIs (ART)

A

ritonavir
indinavir
nelfinavir
amprenavir
fosamprenavir
lopinavir
atazaanavir

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

name PIs (ART)

A

ritonavir
indinavir
nelfinavir
amprenavir
fosamprenavir
lopinavir
atazanavir
saquinavir

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Which live attenuated vaccines should PLWH get/not get?

A

MMR is safe

BCG and yellow fever vaccines should not be given

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Infectious causes of discharge in women

A

gonorrhoea
chlamydia
trichomonas
Mgen (mycoplasma genitalium)
candida
BV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

STI causes of ulceration

A

syphilis - painless ulcer in primary
HSV - painful lesions/blisters
LGV
Chancroid
Donovanosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Which organism causes gonorrhoea?

What type of organism is it?

A

Neisseria gonorrhoeae

obligate gram -ve diplococcus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Commonest STI in europe

A

gonorrhoea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Mx of gonorrhoea

A

1g Ceftriaxone IM single dose

injected with local anaesthetic for pain management

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What are the possible complications of gonorrhoea?

A

PID -> tubal infertility due to adhesions

ophthalmic neonatorum : neonatal conjunctivitis can develop if left unread when transfer to child from birth canal (can lead to keratitis, perforation and BLINDNESS)

disseminated gonococcal infection: sepsis with endocarditis, meningitis, osteomyelitis, or pneumonia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

who is at increased risk of disseminated gonococcal infection?

A

pts with complement deficiencies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What can gonorrhoea cause in men?

A

gonococcal urethritis
post-gonococcal urethritis (PGU)
epididymitis (unilateral)
rectal proctitis (mainly in MSM)
prostatitis (complicated infection)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

extra genital manifestations of gonorrhoea

A

Pharyngitis (sore throat, pharyngeal exudate, cervical lymphadenitis)

Proctitis
Purulent discharge, possible anorectal bleeding and pain
Rectal mucosa inflammation
Rectal abscess (less common)

Gonococcal conjunctivitis: may affect adults or neonates

DGI (arthritis, dermatitis, sepsis..)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

tests for gonorrhoea

A

microscopy (look for IC gram -ve diplococci)

culture in chocolate agar for sensitivity (gold standard)

NAAT - higher sensitivity than microscopy

specimens: (first catch) urine, urethra (95% sens), rectal (20% sens) endocervix, pharynx

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What types of chlamydia are there and what do they cause?

A

Chlamydia trachomatis (different serotypes)
- A-C cause eye infections (trachoma) which can cause blindness
- D-K cause GU infections (and can cause pneumonia in infants)
- L1-L3 cause LGV

Chlamydia pneumoniae
-> lungs

Chlamydia psittaci (pneumonia associated with birds)
-> lungs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

How commonly is chlamydia asymptomatic?

A

can be asymptomatic (in 50% men and 80% women)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

epidemiology of chlamydia (STI)

A

common in young adults

in the UK 10% of <25 are infected.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What type of pathogen is chlamydia trichomonas

A

obligate intracellular gram -ve

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Can chlamydia trichomonas be cultured on agar?

A

no

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What do chlamydia trichomonas serotypes A-C, D-K and L1-L3 cause?

A

A-C: eye infection, trachoma, blindnesss

D-K: genital infections, neonatal pneumonia, neonatal conjunctivitis

L1-L3: LGV (lympho-granuloma venereum)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Dx of chlamydia (STI)

A

NAAT from genital swabs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Mx of chlamydia (STI)

A

1st line:

Doxycycline 100mg BD for 7d

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Complications of STI chlamydia

A

PID -> tubal infertility, ectopic pregnancy, chronic pelvic pain

Epididymitis

Reiter’s syndrome

conjunctivitis, ophthalmic neonatorum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Obligate Intracellular bacteria examples

A

Chlamydia trachomatis
Rickettsia
Coxiella (Q fever)
Mycobacteria leprae

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Mx of LGV

A

Doxycycline 100 mg BD PO for 21d

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

presentation of LGV

A

Early (primary LGV): painless genital ulcer, cervicitis, proctitis, balanitis (3-12 d post infection)

Early Secondary LGV: painful inguinal buboes, fever, malaise, lymphadenopathy (unilateral in 2/3); rarely hepatitis, meningoencephalitis, pneumonitis (2w-6m post infection)

Late LGV: inguinal lymphadenopathy, genital elephantiasis, genital and perianal ulcers/abscesses, frozen pelvis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

epidemiology of LGV

A

L2 is the commonest strain involved

Globally: more common in tropical and subtropical regions, can be endemic in some developing countries

In high-income countries: increasing incidence among MSM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Dx of LGV

A

NAAT

genotypic identification of L1-L3 serotypes

Definitive diagnosis: genotyping (e.g., by PCR) of sample taken for NAAT to identify the C. trachomatis serotypes associated with LGV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

What is the horse groove sign and when is it seen?

A

If lymph nodes are enlarged above and below the inguinal ligament, the characteristic groove sign may be seen.

seen in LGV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What organism causes syphylis and what type of organism is it?

A

treponema pallidum

obligate gram -ve spirochete

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Syphylis disease course

A
  1. Infection and 10-90 (mean 21) days incubation
  2. Primary syphilis: paincless chancre, usually on genitals, resolves in 3-6 w
  3. Secondary syphilis: disseminated disease, maculopaular rash not sparing soles and palms; generalised non-tender lymphadenopathy, fever, fatigue, myalgia, headache, condylomata lata; begins 8-12 w following primary infection, lasts 2-6w.
  4. latent asymptomatic phase
  5. resolution or tertiary syphilis:
    - Gummatous: skin/bone/mucosa spirochetes scanty
    - CV: mimics any cardiac disease, especially causes aortic root dilatation/aortitis, +++ spirochetes and inflmaammation
    - Neurosyphilis: dementia, tabes dorsalis, Argyll Robertson pupil (can occur at any stage of syphilis infection) Spirochetes in CSF.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Mx of neurosyphilis

A

check this

1st line: Procaine penicillin 1.8 MU–2.4 MU
OD plus probenecid 500mg PO QDS for 14 days

Steroids should be given with all anti-treponemal antibiotics for neurosyphilis; 40–60 mg prednisol- one OD for three days starting 24h before the antibiotics.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Testing for syphylis

A

Antibody tests are the test of choice

  1. Non-treponemal (VDRL and RPR): look for non-specific antigens which are released by cells damaged by Tp. False +ves -> use treponemal tests to confirm
    useful in primary syphilis
    results given as a titre
    titre can be used to monitor responses
  2. treponemal tests
    detect abs against specific antigens from T. palladium (test examples: EIA, FTAA, TPHAA, TP-PA)
    more specific
    remain +ve despite effective treatment

Microscopy: treponemes seen in primary lesions by dark ground /darkfield microscopy and IF because they are small
can be detected with PCR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

microscopy in syphilis

A

in primary lesions, treponemes can be seen on dark ground microscopy

Darkfield microscopy, may be combined with immunofluorescence (light microscopy is unable to visualize treponemes because of their small size)

can confirm dx but -ve does not rule out

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

false +ve VRDL

A

False-Positive results on VDRL with

P-VDRL

Pregnancy
Viral infection (e.g., EBV, hepatitis)
Drugs (e.g., chlorpromazine, procainamide)
Rheumatic fever (rare)
Lupus, and Leprosy.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

TOC in syphylis

A

monitor RPR

there should be a 4x reduction to consider treatment successful

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

What reaction can be seen in syphilis mx?

A

Jarisch-Herxheimer reaction

flu like sx, sometimes exacerbation of syphilis sx

common, developed within h of abx, clears within 24h

can give NSAIDs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Congenital syphilis

A

may occur during pregnancy or birth
develops features over the first few years.

features:
hepatosplenomegaly, rash, fever, neurosyphilis, pneumonitis

is a cause of congenital osteomyelitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

What is chancroid?

A

STI caused by Haemophilus ducreyi.

Gram -ve coccobacillus (like Hib)
* Tropical ulcer disease mainly in Africa, rare in UK
* Multiple painful ulcers
* Diagnosis: culture (chocolate agar), PCR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

What is donovanosis? How do you treat it?

A

= Granuloma inguinale

STI

  • Klebsiella granulomatis. Gram negative bacillus
  • Africa, India, PNG, Australian aboriginal communities
  • Large, beefy red ulcers
  • Diagnosis: Giemsa stain of biopsy or tissue crush. Donovan bodies
  • Treated with azithromycin
68
Q

Can you get enteric pathogens causing STIs?

A

yes

Enteric pathogens (Oro-anal contact)
* Shigella, salmonella, Giardia (protozoan), Occasionally others (Strongyloides)

can also get campylobacter (notifiable)

69
Q

how does trichomoniasis present?

A

men: usually asymptomatic, can have urethritis sometimes

women: discharge, strawberry cervic

70
Q

Dx of trichomoniasis

A

wet prep microscopy -> flagellated organisms seen

PCR

71
Q

What pathogen causes trichominiasis

A

trichononas vaginalis

flagellated protozoan

72
Q

what to be careful about in trichomoniasis?

A

increased risk of HIV infection due to mucosal damage

73
Q

Mx of trichomoniasis

A

metronidazole
a. 400-500 mg BD for 5-7d
b. 2g once only dose

a. Can be given to pregnant women too, not b.

74
Q

strawberry cervix dx

A

trichomonas vaginalis

75
Q

What is BV?

A

abnormal vaginal flora
polymicrobial (e.g. Gardnerella vaginalis)
decrease in lactobacilli

sx: discharge and malodour

clue cells seen on microscopy
raised pH
whiff test +ve

76
Q

Mx of BV

A

lifestyle - use water for hygiene down below, no soaps

topical or PO metronidazole (400–500 mg twice daily for 5–7 days, alternatively 2 g for 1 dose)

77
Q

Candidiasis pathogen

A

usually candida albicans (yeast)

spores seen on microscopy

Not STI, can be seen in normal flora

78
Q

sx of candidiasis

A

women: vulvovaginitis
cottage cheese d/c
itching
redness
soreness

Men: balanitis

79
Q

What is vaginal candidiasis associated with?

A

Immunodeficiency (incl. pregnancy, DM)

hygiene practices (e.g. soaps)

80
Q

Mx of candidiasis

A

PO / topical antifungals

clotrimazole or fluconazole

81
Q

Who should not have candidiasis managed with a single dose of fluconazole?

A

pregnancy -> use vaginal pessaries/creams instead.

acute porphyria

82
Q

Who should not have candidiasis managed with a single dose of fluconazole?

A

pregnancy -> use vaginal pessaries/creams instead.

acute porphyria is a CI to fluconazole

83
Q

Molluscum contagiosum - STI presentation

A

genital lesions - spread via sexual contact (can also be spread by skin to skin contact e.g. in children and affects hands/faces)

widespread lesions in immunosuppressed/HIV

small smooth papules with central umbilication

84
Q

Which virus causes molluscum contagiosum?

A

molluscum contagiosum virus

pox virus, dsDNA

85
Q

Mx of genital molluscum contagiosum

A

usually no treatment needed - Spontaneous remission of the lesions usually happens within a few months

cryotherapy is first line if persistent/extensive

otherwise other approaches such as creams or curettage can be discussed.

86
Q

virus causing genital warts

A

HPV 6
HPV 11

dsDNA virus

included in Gardasil 9 (and 4 vax)

87
Q

Clinical presentation of genital warts

A

papular
planar
pedunculated
carpet
kerattinised
pigmented

88
Q

Mx of genital warts

A

Cryotherapy

Imiquod
Warticon (Podophyllotoxin) - contraindicated in pregnant women.

Do not use cream and cryotherapy at the same time, can cause skin damage.

89
Q

Viral causes of STIs

A

HIV
HAV (oro-anal sex)
HBV & HCV (mainly MSM)
HPV - warts
Molluscum contagiosum
Herpes

90
Q

What is the risk associated with complement deficiencies?

A

increased susceptibility to encapsulated bacterial infections

e.g. disseminated gonococcal infection, meningitis

91
Q

How do we manage complement deficiencies?

A

vaccination
prophylactic Abx
high levels of suspicion + early treatment
screen family members

92
Q

What tests are there to diagnose complement deficiencies?

A

CH50 (classical pathway) - looking at sheep erythrocyte lysis

AP50 (alternative pathway)

direct measurement of serum complement protein levels

FISH for serum complement (C3, C4)

93
Q

What part of the immune system is involved in MAC activation

A

complement

MAC is a protein complex that iss formed in response to Ab mediated complex activation

it is made up of 4 complement proteins (C5b, C6, C7, and C8)

94
Q

Complement pathways

A

classical (discovered first)

alternative (always active - discovered second)

MBL pathway

they all start differently but converge in a common pathway and end with a MAC (which is a complement protein complex that makes a hole in the bacterial wall, destroying it)

95
Q

What type of bacteria can the MAC damage?

A

gram -ve

makes holes in the bacterial wall

96
Q

What are the 3 main roles of the complement system?

A

inflammation
phagocytosis
generation of MAC

97
Q

What does C3 deficiency lead to?

A

severe clinical manifestations in severe susceptibility to bacterial infections (esp. encapsulated NHS)

there is also an increased risk of development of connective tissue diseases/worseining of AID like RA or SLE

98
Q

What can complement deficiencies cause?

A
  • underachieve immune response (e.g. C3 def)
  • overactive immune response (e.g. C1 inhibitor def)
99
Q

where are complement components produced?

A

liver

100
Q

Why should you not give NSAIDs in chicken pox?

A

increases the risk of necrotising fasciitis

101
Q

Why do you add an amino glycoside to the amoxicillin in mx of listeria meningitis.

A

synergistic effects

gentamicin would not have an effect on listeria by itself

amoxicillin damages the cell wall and then gentamicin can inhibit DNA synthesis

listeria is intrinsically resistant against ceftriaxone so it does not work for mx of listeria meningitis

102
Q

What is complement?

A

> 30 tightly regulated, linked proteins
produced mainly by the liver
present in circulation as inactive molecules

part of the innate immune system

activated by cleavage; then activate other proteins in a biological cascade -> rapid, highly amplified response.

103
Q

Which complement components are part of the common pathway forming the MAC?

A

C5-C9

104
Q

What does deficiency of terminal common pathway components of complement lead to?

A

inability to make MAC (membrane attack complex) -> inability to lyse encapsulated bacteria (NHS)

e.g. increased susceptibility to neisseria infections or disseminated gonococcal infections.

Risk of infection and subsequent potentially life-threatening sepsis increases with course of the disease.

105
Q

C5-C9 complement deficiency - are all component deficiencies equally severe?

A

no

e.g. component C9 deficiency does not cause symptoms.

C5,6,8 are most common.

106
Q

Alternative complement deficiency

A

rare!

def in Factor B/Factor D/ Factor P (properdin)

-> inability to mobilise complement rapidly in response to bacterial infections -> recurrent infections with encapsulated bacteria

-> Neisseria meningitis (Properdin)

Properdin normally stabilises C3 converts -> triggers MAC complex

107
Q

inheritance pattern of C5-C9 / terminal complement pathway deficiency

A

AR

108
Q

What are lectins?

A

Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules

109
Q

What are C1q, C1s and C1r?

A

components of C1

not cleavage products

110
Q

Is MBL deficiency clinically significant?

A

NO

it is associated with increased infection in patients with an additional cause of immune impairment (e.g. premature infants, chemotherapy, HIV, Ab deficiency)

5-30% people have a mutation in the MBL2 gene

111
Q

How to dx MBL deficiency

A
  • measure MBL proteins
  • genetic testing for MBL2 mutation (chromosome 10) - not everyone with mutation has deficiency though!

not clinically significant, presenting 5-30% pop -> common

112
Q

Components of the MBL complement pathway

A

MBL
C4
C2
ficolins
MASP (proteases)

113
Q

What complement components are involved in the classical pathway? Which one interacts with pathogen/Ab bound to pathogen surface?

A

C1 (C1q, C1r, C1s)
C2
C4

C1q interacts with pathogen/Ab bound to pathogen surface

114
Q

What complement components are involved in the alternative pathway?

A

Propedrin
Factor B
Factor D
C3

115
Q

What is more severe - C3 or C4 deficiency? why?

A

C3

because C3 is needed in higher amounts
all pathways converge in C3

C4-> decreased classical and leptin pathway activation

116
Q

C3 deficiency - how common and how does it manifest?

A

very rare

  • severe susceptibility to bacterial infections, especially encapsulated (NHS)
  • Pyogenic bacterial infection
  • C3 glomerulopathy

C3 is important in phagocytosis and for MAC formation

also increased risk of development / worsening of connective tissue/AID like SLE and RA (Due to deposition of immune complexes and insufficient clearance - complement is also involved in clearing Ag-Ab complexes C1-C4)

117
Q

Causes of secondary C3 deficiency

A
  • SLE (due to consumption)
  • nephritic factors: auto-Abs against parts of complement pathways
  • nephritic factors stabilise C3 convertase resulting in C3 activation and consumption
  • often associated with glomerulonephritis (classically membranoproliferative) and partial lipodystrophy
118
Q

What glomerulonephritis is associated with secondary C3 deficiency?

A

membranoproliferative

119
Q

How does classical complement deficiency present?

A
  • SLE ( C1q: 90% will develop SLE; almost all pts with C2 def have SLE)
  • Susceptibility to encapsulated bacterial infections (NHS)
  • severe skin disease
  • increased number of infections
  • deposition of immune complexes -> inflammation in skin, joints, kidneys (SLE)
  • increased load of self antigens (particularly nuclear components wich may promote autoimmunity and immune complexes)
120
Q

How common are classical complement deficiencies? commonest?

A

all are rare

C2 is the commonest one

121
Q

How common are classical complement deficiencies? commonest?

A

all are rare

C2 is the commonest one

122
Q

Which autoinflammatory condition is classical complement deficiency associated with and why?

A

SLE

b/c C1-C4 aware involved in removing Ab/Ag complexes

123
Q

Which autoinflammatory condition is classical complement deficiency associated with and why?

A

SLE

b/c C1-C4 aware involved in removing Ab/Ag complexes

124
Q

Do all complement deficiencies cause decreased immune responses?

A

no

some lead to an overactive immune system (e.g. C1 inhibitor deficiency)

125
Q

Deficiency of Complement regulatory proteins (3)

A

C1 inhibitor deficiency

Factor H, I, MCP (CD46) regulate C3 levels

CD55 and CD59

126
Q

C1 inhibitor deficiency - presentation and mx

A
  • Recurrent episodes of angioedema (skin, abdomen, larynx)
  • Bradykinin mediated angioedema
  • Low C4 normal C3 absent C1 inhibitor function
  • Emergency therapy with C1 inhibitor (NOT Adrenaline)
  • Maintenance therapy (C1 inhibitor concentrate, icatibant (bradykinin antagonist) kallikrein antagonist (ecallitanide and lanadelumab)
127
Q

Factor H, I, MCP (CD46) regulate C3 levels COMPLEMENT DEFICIENCY - signs, sx, ix

A
  • C3 glomerulopathy
  • Atypical Haemolytic uraemic syndrome
  • Low C3 normal C4 absent alternative pathway function (AP50)
128
Q

CD55 and CD59 deficiency - presentation

A
  • Adult presentation
  • Triad haemolysis, thrombosis and pancytopaenia

= PND (paroxysmal nocturnal haemoglobunuria)

129
Q

Ix for complement function

A
  • FBC
  • Serum immunoglobulin
  • Lymphocyte subsets
  • C3 and C4
  • Functional complement tests
  • CH50 classical pathway
  • AP50 alternative pathway
  • Complement genetic test
130
Q

What at CP50 and AP50?

A

tests for classical and alternative complement pathway respectively

131
Q

Ix in ?MBL deficiency

A

measure MBL proteins

can do genetic testing to MBL2 gene on chromosome 10

AP50 and CP50 look at different pathways!!

132
Q

Which T-cell markers indicate naive and memory T-cells?

A

CD45 RO - memOry
CD45 RA - nAive

133
Q

Do memory T-cells proliferate in the absence of infection?

A

Yes

They continue to proliferate at a lower rate

134
Q

How is a memory T-cell response different from the naive T-cell response?

A

Memory: rapid and robust response, easier to activate than naive

Cells have different cell surface markers -> influences migration and adhesion -> can enter non-lymphoid tissue (sites of microbe entry)

135
Q

What are HEVs?

A

high endothelial venules

venules of cuboidal endothelial cells that express markers to whih lymohocytes bind

they facilitate transmigration of lymphocytes from blood vessles to LNs and SLOs (secondary lymphoid organs)

136
Q

Where are central and effector memory cells found?

A

Central: LNs, tonsils, HEVs

Effector: Liver, lungs, gut

137
Q

What markers do central and effector memory cells have?

A

Central: CCR7+, CD62L high (allow entry/migrate via HEVs into peripheral LNs)

Effector: CCR7-ve, CD62 low (therefore not found in LNs)

138
Q

What do central and effector memory cells produce?

A

Central: IL-2 (to support other cells)

Effector: Perforin and IFN-gamma

139
Q

In what T-cell populations are more central and effector memory T-cells found?

A

Central: CD4+

Effector: CD8+

140
Q

Summarise B-cell immunity

A

Pool of memory B-cells (plasma cells)

Memory cells can differentiate into plasma cells
-> quicker response, more antibodies, higher affinity antibodies, more IgG, better antibodies.

141
Q

What is a cell surface marker associate with memory B-cells?

A

CD27

142
Q

Role of Th1 cells

A

cell mediated

help CD8+ and macrophages

produce: IL-2, IFN-gamma, TNF

143
Q

Role of Th2 cells

A

humoral response

helper T-cells

produce: IL-4, IL-5, IL-6

144
Q

Role of Th17 cells

A

help neutrophil recruitment

produce IL-17, IL-21, IL-22

145
Q

What do Th17 cells secrete?

A

IL-17
IL-21
IL-22

146
Q

What do Th1 cells secrete?

A

IL-2
IFN-gamma
TNF

147
Q

What do Th2 cells secrete?

A

IL-4
IL-5
IL-6

IL-13
IL-10

(humoral)

148
Q

How does the mantoux test work

A

incejt 0.1 ml of 5 tuberculin (purified protein derivative) units intradermally

examine arm after 48-72h

+ve result is induration >10mm (-> swelling, not erythema)

Looking at delayed immune reaction.
Shows previous exposure to TB or BCG vaccine.

149
Q

What do T-helper cells recognise?

A

peptides presented on MHC/HLA class 2 molecules (DP, DQ, DR)

150
Q

What is lactoferrin?

A

a protein binding protein produced by neutrophils and found in secretory fluids and mucosal barriers that inhibits microbial growth.

151
Q

What are the features of GvHD?

A

skin desquamation
Painful maculopapular rash (often neck, palms and soles)
rash
GI disturbance (N&V, abdo pain, diarrhoea, bloody stool)
liver failure (jaundice)
BM failure
culture -ve fever

152
Q

GvHD management and prophylaxis

A

mx: corticosteroids

prophylaxis: match as good as possible; methotrexate/cyclosporine; irradiate blood components for immunosuppressed patients.

153
Q

How do you prepare the recipient for a HSCT?

A

total body irradiation
cyclophosphamide
other drugs

154
Q

Indications for HSCT

A

life threatening primary immunodef (e.g. SCID, leukocyte adhesion defect)
haematological malignancy

155
Q

What is TRALI?

A

Transfusion related acute lung injury

  • due to the presence of leukocyte antibodies causing WBCs to aggregate in the pulmonary circulation as it passes through in the blood.
  • Sx: acute onset pulmonary oedema, dyspnoea, severe hypoxaemia and hypotension.
156
Q

complications of TRALI

A

severe TRALI can lead to ARDS

157
Q

Mx of TRALI

A

Mx: usually supportive with a good resolution within 2 days.

158
Q

What is needed for antibody class switching?

A

CD40 on the surface of B-lymphocytes needs to be activated

159
Q

What happens if CD40 is defective

A

only IgM antibodies can be produced

this is because CD40 on B-cell surfaces is needed in order to allow for class switching

PI: Hyper IgM syndrome is when T-cells lack CD40L (ligand) - NB X-linked recessive T-cell defect, not B-cell!

160
Q

How do corticosteroids act as immunosuppressant medication?

A

inhibiting phospholipase A2 and reduce the expression of pro-inflammatory cytokines

161
Q

Inheritance pattern of hyper IgM syndrome?

A

X linked recessive

162
Q

Blood findings in hyper IgM syndrome

A

high serum IgM
undetectable serum IgA, IgE and IgG (failure of class switch)
normal number of circulating B cells
Normal number of circulating T cells (do not express CD40 ligand)

163
Q

What cells are abnormal in hyper IgM syndrome?

A

T-cells

they lack CD40 ligand

164
Q

Lymph nodes in hyper IgM syndrome

A

lack germinal centre development within LNs and spleen

165
Q

When and how do patients present with hyper IgM syndrome?

A

boys present with failure to thrive in the first few years of life with:
- recurrent infections (bacterial)
- Pneumocystis jirovecii infection
- CMV hepatitis
- autoimmune disease
- malignancy

166
Q

What CD40 ligands can be missing in hyper IgM syndrome?

A

CD40L
CD154

Year 5 😊✌🏼 (53 decks)

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