Path - Immunology Flashcards
HIV - how many affected, how many on ART, how many in the UK
37 mio worldwide, 21 mio on ART
101,200 affected in the UK
(70% of those on ART in the UK are undetectable)
What viral load in HIV is measured to be undetectable?
<20 copies / mm3(ml)
What type of virus is HIV and what does this mean?
it is an RNA retrovirus
it integrates itself into the hosts genome
lentivirus (from latin slow - long infection before symtoms of chronic infection seen)
Summarise the life cycle of HIV
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
Immune response to HIV infection
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.
Key immunological features of HIV-1 infection
CD4+ T-cell depletion
chronic immune activation
CD4 and cd8 T-cell exhaustion
disruption of lymph node architecture
loss of Ag specific humoral response
Why are quasi-species formed in HIV infection?
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
What are the differences between HIV-1 and HIV-2?
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
3 Stages of HIV
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
Untreated HIV - how long to progresss to AIDS?
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
Important CD4 counts in HIV
400 - Kaposi’s sarcoma
300-350 - pulm TB
73 - MAC disease, PCP
MAC disease
seen in the context of low CD4 counts in HIV (<75)
mycobacterium avian complex
which tests are used to screen for and dx HIV?
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
In young children, what HIV test?
HIV-1 RNA +/- DNA
if less than 18m
serology not useful b/c passive transfer of Abs from mum
test to measure HIV viral load
PCR to detect viral RNA (very sensitive)
How is CD4+ T-cell count measured?
FACS flow cytometry
CD4+ count associated with AIDS
> 200 / mL of blood
resistance testing in HIV
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
HAART
highly active anti-retroviral therapy
2NRTIs + PI (or NNRTI)
Monitoring in HIV
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
Name drug classes for HIV
attachment inhibitors
fusion inhibitors
NRTI
NNRTI
NtRTI
Integrase inhibitors
protease inhibitors
Name a fusion inhibitor (ART)
enfuvirtide
Name an attachment inhibitor (ART)
maraviroc
Name NRTIs (ART)
zidovudine
abacavir
didanosine
emtricitabine
stavudine
lamavudine
zalcitabine
epzicom
combiner
trizivir
Name a NtRTI (ART)
tenofovir
what kind of drug is tenofovir?
NtRTI
Name NNRTIs (ART)
nevirapine
delavirdine
efavirenz
name integrase inhibitors
raltegravir
elvitegravir
name PIs (ART)
ritonavir
indinavir
nelfinavir
amprenavir
fosamprenavir
lopinavir
atazaanavir
name PIs (ART)
ritonavir
indinavir
nelfinavir
amprenavir
fosamprenavir
lopinavir
atazanavir
saquinavir
Which live attenuated vaccines should PLWH get/not get?
MMR is safe
BCG and yellow fever vaccines should not be given
Infectious causes of discharge in women
gonorrhoea
chlamydia
trichomonas
Mgen (mycoplasma genitalium)
candida
BV
STI causes of ulceration
syphilis - painless ulcer in primary
HSV - painful lesions/blisters
LGV
Chancroid
Donovanosis
Which organism causes gonorrhoea?
What type of organism is it?
Neisseria gonorrhoeae
obligate gram -ve diplococcus
Commonest STI in europe
gonorrhoea
Mx of gonorrhoea
1g Ceftriaxone IM single dose
injected with local anaesthetic for pain management
What are the possible complications of gonorrhoea?
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
who is at increased risk of disseminated gonococcal infection?
pts with complement deficiencies
What can gonorrhoea cause in men?
gonococcal urethritis
post-gonococcal urethritis (PGU)
epididymitis (unilateral)
rectal proctitis (mainly in MSM)
prostatitis (complicated infection)
extra genital manifestations of gonorrhoea
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..)
tests for gonorrhoea
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
What types of chlamydia are there and what do they cause?
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 commonly is chlamydia asymptomatic?
can be asymptomatic (in 50% men and 80% women)
epidemiology of chlamydia (STI)
common in young adults
in the UK 10% of <25 are infected.
What type of pathogen is chlamydia trichomonas
obligate intracellular gram -ve
Can chlamydia trichomonas be cultured on agar?
no
What do chlamydia trichomonas serotypes A-C, D-K and L1-L3 cause?
A-C: eye infection, trachoma, blindnesss
D-K: genital infections, neonatal pneumonia, neonatal conjunctivitis
L1-L3: LGV (lympho-granuloma venereum)
Dx of chlamydia (STI)
NAAT from genital swabs
Mx of chlamydia (STI)
1st line:
Doxycycline 100mg BD for 7d
Complications of STI chlamydia
PID -> tubal infertility, ectopic pregnancy, chronic pelvic pain
Epididymitis
Reiter’s syndrome
conjunctivitis, ophthalmic neonatorum
Obligate Intracellular bacteria examples
Chlamydia trachomatis
Rickettsia
Coxiella (Q fever)
Mycobacteria leprae
Mx of LGV
Doxycycline 100 mg BD PO for 21d
presentation of LGV
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
epidemiology of LGV
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
Dx of LGV
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
What is the horse groove sign and when is it seen?
If lymph nodes are enlarged above and below the inguinal ligament, the characteristic groove sign may be seen.
seen in LGV
What organism causes syphylis and what type of organism is it?
treponema pallidum
obligate gram -ve spirochete
Syphylis disease course
- Infection and 10-90 (mean 21) days incubation
- Primary syphilis: paincless chancre, usually on genitals, resolves in 3-6 w
- 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.
- latent asymptomatic phase
- 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.
Mx of neurosyphilis
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.
Testing for syphylis
Antibody tests are the test of choice
- 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 - 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
microscopy in syphilis
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
false +ve VRDL
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.
TOC in syphylis
monitor RPR
there should be a 4x reduction to consider treatment successful
What reaction can be seen in syphilis mx?
Jarisch-Herxheimer reaction
flu like sx, sometimes exacerbation of syphilis sx
common, developed within h of abx, clears within 24h
can give NSAIDs
Congenital syphilis
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
What is chancroid?
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
What is donovanosis? How do you treat it?
= 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
Can you get enteric pathogens causing STIs?
yes
Enteric pathogens (Oro-anal contact)
* Shigella, salmonella, Giardia (protozoan), Occasionally others (Strongyloides)
can also get campylobacter (notifiable)
how does trichomoniasis present?
men: usually asymptomatic, can have urethritis sometimes
women: discharge, strawberry cervic
Dx of trichomoniasis
wet prep microscopy -> flagellated organisms seen
PCR
What pathogen causes trichominiasis
trichononas vaginalis
flagellated protozoan
what to be careful about in trichomoniasis?
increased risk of HIV infection due to mucosal damage
Mx of trichomoniasis
metronidazole
a. 400-500 mg BD for 5-7d
b. 2g once only dose
a. Can be given to pregnant women too, not b.
strawberry cervix dx
trichomonas vaginalis
What is BV?
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
Mx of BV
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)
Candidiasis pathogen
usually candida albicans (yeast)
spores seen on microscopy
Not STI, can be seen in normal flora
sx of candidiasis
women: vulvovaginitis
cottage cheese d/c
itching
redness
soreness
Men: balanitis
What is vaginal candidiasis associated with?
Immunodeficiency (incl. pregnancy, DM)
hygiene practices (e.g. soaps)
Mx of candidiasis
PO / topical antifungals
clotrimazole or fluconazole
Who should not have candidiasis managed with a single dose of fluconazole?
pregnancy -> use vaginal pessaries/creams instead.
acute porphyria
Who should not have candidiasis managed with a single dose of fluconazole?
pregnancy -> use vaginal pessaries/creams instead.
acute porphyria is a CI to fluconazole
Molluscum contagiosum - STI presentation
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
Which virus causes molluscum contagiosum?
molluscum contagiosum virus
pox virus, dsDNA
Mx of genital molluscum contagiosum
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.
virus causing genital warts
HPV 6
HPV 11
dsDNA virus
included in Gardasil 9 (and 4 vax)
Clinical presentation of genital warts
papular
planar
pedunculated
carpet
kerattinised
pigmented
Mx of genital warts
Cryotherapy
Imiquod
Warticon (Podophyllotoxin) - contraindicated in pregnant women.
Do not use cream and cryotherapy at the same time, can cause skin damage.
Viral causes of STIs
HIV
HAV (oro-anal sex)
HBV & HCV (mainly MSM)
HPV - warts
Molluscum contagiosum
Herpes
What is the risk associated with complement deficiencies?
increased susceptibility to encapsulated bacterial infections
e.g. disseminated gonococcal infection, meningitis
How do we manage complement deficiencies?
vaccination
prophylactic Abx
high levels of suspicion + early treatment
screen family members
What tests are there to diagnose complement deficiencies?
CH50 (classical pathway) - looking at sheep erythrocyte lysis
AP50 (alternative pathway)
direct measurement of serum complement protein levels
FISH for serum complement (C3, C4)
What part of the immune system is involved in MAC activation
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)
Complement pathways
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)
What type of bacteria can the MAC damage?
gram -ve
makes holes in the bacterial wall
What are the 3 main roles of the complement system?
inflammation
phagocytosis
generation of MAC
What does C3 deficiency lead to?
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
What can complement deficiencies cause?
- underachieve immune response (e.g. C3 def)
- overactive immune response (e.g. C1 inhibitor def)
where are complement components produced?
liver
Why should you not give NSAIDs in chicken pox?
increases the risk of necrotising fasciitis
Why do you add an amino glycoside to the amoxicillin in mx of listeria meningitis.
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
What is complement?
> 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.
Which complement components are part of the common pathway forming the MAC?
C5-C9
What does deficiency of terminal common pathway components of complement lead to?
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.
C5-C9 complement deficiency - are all component deficiencies equally severe?
no
e.g. component C9 deficiency does not cause symptoms.
C5,6,8 are most common.
Alternative complement deficiency
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
inheritance pattern of C5-C9 / terminal complement pathway deficiency
AR
What are lectins?
Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules
What are C1q, C1s and C1r?
components of C1
not cleavage products
Is MBL deficiency clinically significant?
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
How to dx MBL deficiency
- 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
Components of the MBL complement pathway
MBL
C4
C2
ficolins
MASP (proteases)
What complement components are involved in the classical pathway? Which one interacts with pathogen/Ab bound to pathogen surface?
C1 (C1q, C1r, C1s)
C2
C4
C1q interacts with pathogen/Ab bound to pathogen surface
What complement components are involved in the alternative pathway?
Propedrin
Factor B
Factor D
C3
What is more severe - C3 or C4 deficiency? why?
C3
because C3 is needed in higher amounts
all pathways converge in C3
C4-> decreased classical and leptin pathway activation
C3 deficiency - how common and how does it manifest?
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)
Causes of secondary C3 deficiency
- 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
What glomerulonephritis is associated with secondary C3 deficiency?
membranoproliferative
How does classical complement deficiency present?
- 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)
How common are classical complement deficiencies? commonest?
all are rare
C2 is the commonest one
How common are classical complement deficiencies? commonest?
all are rare
C2 is the commonest one
Which autoinflammatory condition is classical complement deficiency associated with and why?
SLE
b/c C1-C4 aware involved in removing Ab/Ag complexes
Which autoinflammatory condition is classical complement deficiency associated with and why?
SLE
b/c C1-C4 aware involved in removing Ab/Ag complexes
Do all complement deficiencies cause decreased immune responses?
no
some lead to an overactive immune system (e.g. C1 inhibitor deficiency)
Deficiency of Complement regulatory proteins (3)
C1 inhibitor deficiency
Factor H, I, MCP (CD46) regulate C3 levels
CD55 and CD59
C1 inhibitor deficiency - presentation and mx
- 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)
Factor H, I, MCP (CD46) regulate C3 levels COMPLEMENT DEFICIENCY - signs, sx, ix
- C3 glomerulopathy
- Atypical Haemolytic uraemic syndrome
- Low C3 normal C4 absent alternative pathway function (AP50)
CD55 and CD59 deficiency - presentation
- Adult presentation
- Triad haemolysis, thrombosis and pancytopaenia
= PND (paroxysmal nocturnal haemoglobunuria)
Ix for complement function
- FBC
- Serum immunoglobulin
- Lymphocyte subsets
- C3 and C4
- Functional complement tests
- CH50 classical pathway
- AP50 alternative pathway
- Complement genetic test
What at CP50 and AP50?
tests for classical and alternative complement pathway respectively
Ix in ?MBL deficiency
measure MBL proteins
can do genetic testing to MBL2 gene on chromosome 10
AP50 and CP50 look at different pathways!!
Which T-cell markers indicate naive and memory T-cells?
CD45 RO - memOry
CD45 RA - nAive
Do memory T-cells proliferate in the absence of infection?
Yes
They continue to proliferate at a lower rate
How is a memory T-cell response different from the naive T-cell response?
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)
What are HEVs?
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)
Where are central and effector memory cells found?
Central: LNs, tonsils, HEVs
Effector: Liver, lungs, gut
What markers do central and effector memory cells have?
Central: CCR7+, CD62L high (allow entry/migrate via HEVs into peripheral LNs)
Effector: CCR7-ve, CD62 low (therefore not found in LNs)
What do central and effector memory cells produce?
Central: IL-2 (to support other cells)
Effector: Perforin and IFN-gamma
In what T-cell populations are more central and effector memory T-cells found?
Central: CD4+
Effector: CD8+
Summarise B-cell immunity
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.
What is a cell surface marker associate with memory B-cells?
CD27
Role of Th1 cells
cell mediated
help CD8+ and macrophages
produce: IL-2, IFN-gamma, TNF
Role of Th2 cells
humoral response
helper T-cells
produce: IL-4, IL-5, IL-6
Role of Th17 cells
help neutrophil recruitment
produce IL-17, IL-21, IL-22
What do Th17 cells secrete?
IL-17
IL-21
IL-22
What do Th1 cells secrete?
IL-2
IFN-gamma
TNF
What do Th2 cells secrete?
IL-4
IL-5
IL-6
IL-13
IL-10
(humoral)
How does the mantoux test work
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.
What do T-helper cells recognise?
peptides presented on MHC/HLA class 2 molecules (DP, DQ, DR)
What is lactoferrin?
a protein binding protein produced by neutrophils and found in secretory fluids and mucosal barriers that inhibits microbial growth.
What are the features of GvHD?
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
GvHD management and prophylaxis
mx: corticosteroids
prophylaxis: match as good as possible; methotrexate/cyclosporine; irradiate blood components for immunosuppressed patients.
How do you prepare the recipient for a HSCT?
total body irradiation
cyclophosphamide
other drugs
Indications for HSCT
life threatening primary immunodef (e.g. SCID, leukocyte adhesion defect)
haematological malignancy
What is TRALI?
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.
complications of TRALI
severe TRALI can lead to ARDS
Mx of TRALI
Mx: usually supportive with a good resolution within 2 days.
What is needed for antibody class switching?
CD40 on the surface of B-lymphocytes needs to be activated
What happens if CD40 is defective
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!
How do corticosteroids act as immunosuppressant medication?
inhibiting phospholipase A2 and reduce the expression of pro-inflammatory cytokines
Inheritance pattern of hyper IgM syndrome?
X linked recessive
Blood findings in hyper IgM syndrome
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)
What cells are abnormal in hyper IgM syndrome?
T-cells
they lack CD40 ligand
Lymph nodes in hyper IgM syndrome
lack germinal centre development within LNs and spleen
When and how do patients present with hyper IgM syndrome?
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
What CD40 ligands can be missing in hyper IgM syndrome?
CD40L
CD154
