IMMUNOLOGY Flashcards
What morphology will you see in hyperacute vs acute vs chornic transplant rejection?
hyperacute - gross motelling, fibronoid necrosis, thrombosis
acute - dense interstitial lymphocytic infiltrate
chronic - vascular thickening, interstitial fibrosis
what heart infection presents with pervascular infiltrate and abundant eosinophils
hypersensitivity myocarditis
(response often to new drug)
which ‘mab’ drugs inhibit PD-1 and PD-L1 action of tumour cells?
PD-1:
cemiplimab
nivolumab
pembrolizumab
PD-L1:
atezolizumab
durvalumab
avelumab
‘lumab’
‘zumab’
PD-1 on T cells
PD-L1 secreted by tumour cells to inhibit T cells.
blocking PD (programed death) restores immune attack system
Do ACEi increase or decrease bradykinin? What is the side effect?
yes - increases it (prevents its breakdown)
angioedema
vasodilation -> vascular permeability -> oedema
(angiontension converting enzyme breakds down & inactivates bradykinin)
If a live attenuated polio vaccine is given orally and an inactivated vaccine is given intramuscularly, which polio antibodies will show the greatest difference between the two patients?
duodenal luminal IgA
mucosal immunity
sabin (live) produces stronger musocal immunity response than killed (salk) vaccine.
what 2 things happen to mast cells / basophils to induce release of - histamine and tryptase
*IgE *receptor (on mast cells / basophils) binds Fc portion of circulating antibodies
receptors cross-link and cause agglutination
causes degranulatiON - release of preformed mediators (histamine, tryptase)
what is the reactant in delayed haemolytic transfusion reaction?
**minor blood group antigens **
i.e. RhD
from exposure from pregnancy, transfusions, IVDU
onset 24hrs - occurs 1-2 weeks
what valve deformity presents with ealry systolic sound with faint ejection murmur
bicuspid aortic valve
turner syndrome
(also assoc. with coarctition of aorta)
List the contents of the aortic arches 1-6
‘max stops common subway people’
artery and content
1
2
3
4
6
which Ig crosses placenta
IgG
What are the functions of IgG
neutralization
opsonization
complement activation
ADCC (NK cells)
macrophages do not have receptors for what Ig
IgM
anti-D IgM does not have same immunoprophylactic effect as anti-D IgG (i.e in Rh-)
in agammaglobulinaemia, germinal centres don’t form due to absense of
B cells
inhibiting PD-1 or PD-1L restores what T cells
increases immune mediated tumour destruction
(uninhbits T cells)
PD-1, PD-1L drugs = anticancer monoclonal AB
PD-1 on T cells
PD-1L on tumour cells
uses: Melanoma, NSCLC, RCC, Hodgkin lymphoma, MSI-H cancers
blocking PD-1/PD1-L interaction prevents immune suppression - more active to fight cancer
attenuated vaccine properties
non viable organism
still posses antigens
pathogens introduced to mucosal sites likely to stimulate production of ___
IgA immunoglobulins
mucosal defence
trafficking of IgA producing lymphocytes seed all mucosal sites -> immune response to mucosal expoure of antigen
7 stages of viral (HIV) replication
?
binding
fusion
reverse transcription
integration
replication
assembly
budding
Attachment
Penetration
Uncoating
Replication and Transcription
Translation
Assembly
Budding/Release
dehydrorhodamine test
nitroblue tetrazolium reduction test
used for
chronic granulomatous disease
no colour change
what enzyme deficiency results in chronic ganulomatous disease
NADPH oxidase
unabel to neutralise catalase+ bacteria
decreased **reactive oxygen species **(superoxide)
decresed respiratory bust
recurrent infections, granulomas
**normally: **
within neutrophils
uses O2 as subsrate for generation free radicals (superoxide anions)
used to create hydrogen peroxide & hypochlorous acid
respiratory burst –> bacterial death
common infecting pathogens of CGD
staphlococcus species
Burkholderia cepacia
Norcardia species
aspergillus species
recurrent pyogenic infections i.e. pneumonia
catalase (+) bacteria:
problematic because they can neutralize hydrogen peroxide, one of the reactive oxygen species that phagocytes typically use to kill pathogens.
Staphylococcus aureus
Serratia marcescens
Burkholderia cepacia
Nocardia species
Listeria monocytogenes
Klebsiella species
inheritence of CGD
X linked
what does this indicate
agammablobulinaemia
absense of Y spike
what does this indicate
multiple myeloma
increased Immunoglobulins
Waldenstrom macroglobulinaemia
Amyloidosis
blurring a and b regions
increased C-reactive protein or IgA
- respiratory infections
- RA
- cirrhosis
‘beta-gamma’ fusion
recurrent bacterial infections
low Immuoglobulins
hypogammablobulinaemia
primary - genetic - BTK gene (XL agammaglobulinaemia)
secondary
gene defect in agammablobulinaemia
BTK
Bruton tyrosine kinase
superoxide dismutase mutation seen in
ALS
familial amyotrophic lateral sclerosis
oxidative damage from lack of superoxide dismutase (preventing it)
acute arteritis
risk of aneurysms in coronary arteries
thrombocytosis
increased ESR
Kawasaki disease
multisystemic vasculitic disease
childhood vasculitides
CRASH & Burn
cause paediatric heart disease
sarcoidosis is a type ___ hypersensitivity reaction
HS IV
delayed
granulomas
fever
weakness
night sweats
axillary LN enlarged
acid-fast bacilli negative
sarcoidosis
**non-caseating **granulomas
type IV HS
bone marrow transplant
fever, diarrhoa
rash - maculopapular, blistering
increased liver enzymes
hepatitis
hyperbilirubinaemia
GVHD
donor cells attack host tissue
HLA-DRB1 should have high resolution typing and match 7/8 loci
serum sickness is type ___ hypersensitivity
HS III
acute monoarticular arthropathy
intra-articular inflammatory reaction
precipitation monosodium urate crystals
gout
m/c cause of gout
underexcretion of uric acid
also overproduction of uric acid
acute
atraumatic
single joint pain
erythema
swelling
first metatarsophalangeal joint
gout
knees or elbows
activating mutation in EGFR is associated with what lung neoplasm
adenocarcinoma
non-SCLC
EGFR uses what receptor
??
??
tyrosine kinase
phosphorylation
??
immune mediator released in response to vascularised injury
histamine
transient reflexive vasocontriction
vasodilation
increased permeability
innate immune response
localised inflammatory mediatores released
i.e. cat scratches your arm, red streaks
monoclonal antibodies use ___ to target cancer cells
antibody-dependant cellular cytotoxicity (ADCC)
NK cells
i.e. HER2
PAMPs are
give examples
pathogen associated molecualr patterns
will activate innate system
molecular structures found on pathogens
act as signal to immune system
germline encoded
examples of PAMPs
LPS (lipopolysaccharide) from Gram-negative bacteria
Peptidoglycan from bacterial cell walls
Flagellin from bacterial flagella
**Double-stranded RNA **from some viruses
CpG DNA sequences (common in bacteria)
Zymosan from fungi
nucleic acids (viruses)
what recognises PAMPs
*TLR: toll-like receptors
which are;
**PRR*
pattern recognition receptors
lead to activation NK-FB
Found on innate immune cells
variation for adaptive immunity occurs through
VDJ recombination
during lymphocyte development
immune privilage means
tissues that limit immune responses to foreign antigens
to limit damage of inflammatory sequale
allograft rejection less likely
i.e. eye, brain, placenta, testes
i.e. sympathetic opthalmia
HLA-A, HLA-B, HLA-C are loci of ___ and bind to ___
MHCI
CD8 & TCR
t cell receptor
HLA-DP, HLA-DQ, HLA-DR are loci of ___ and bind to ___
MHCII
CD4 & TCR
t cell receptor
defect in TAP is seen in
transporter associated with antigen processing
bare lymphocte syndrome
normal count T, B, NK
no activaiton
low / no MHCI
impaird CD8 response
immunodeficiency
susceptable to viral / cancer
peptides cannot be transported into the ER
= low or absent MHC class I expression
structure seen in
MHCI
1 short chain (b)
1 long chain (a)
1a, 2a, 3a / b2
structure seen in
MHCII
2 long chain (a, b)
1a, 2a / 1b, 2b
role of TAP protein
MHCI presentation
transport endogenous peptides from cytosol into ER
loaded onto MHCI
presented to CD8+ cells
name associations to HLA suptype:
B27
PAIR
psoriasis
ankylosing spondylitis
IBD
reactive arthritis
name associations to HLA suptype:
DQ2/DQ8
celiac disease
2 functions of IL-12
differentiation T cells to Th1 cells
acitvates NK cells
plus IFN-Y for Th1 differentiation
name associations to HLA suptype:
B57
abacavir sensitivity
name associations to HLA suptype:
DR3
DMT1
SLE
Graves
Hashimoto
Addison
addison + dmt1 = DR3/4
name associations to HLA suptype:
DR4
RA
DMT1
Addison
4 walls in a ‘rheum’
addison + dmt1 = DR3/4
what are the steps of NK cell activation
MILK
Macrophage release IL-12
IFN-a/b released from infected cells
Lack of MHCI on target triggers NK killing
Kill by granzymes/perforins & increase IFN-Y which activates macrophages
what inhibits Th1 activation
IL-4, IL-10
Th1 secretes
and function
IFN-Y
IL-2
activates macrophages & cytotoxic T cells
CD8+ T cells
what activates Th2
IL-2, IL-4
Th2 secretes
and function
IL-4, IL-5
IL-6, IL-10
IL-13
activate eosinophils (IL-4)
increase IgE (IL-5)
CD4+ T cells
E = 5th letter of alphabet
Th2 inhibited by
IFN-Y
what do Treg cells secrete
TGF-B
IL-10
IL-35
prevent autoimmunity
Treg cells express CD3, CD4, CD25, FOXP3
enteropathy (intestinal disease)
endocrinopathy
nail dystrophy
dermatitisautoimmune dermatologic conditions
diabetes in male infants
IPEX
(FOXP3) deficiency
XL
Treg cells express
CD3, CD4, CD25, FOXP3
IPEX
(FOXP3 deficiency)
Th17 induce
neutrophilic infiltration
what stimulates Th17
TBF-B
IL-1, IL-6
function of IL-4
induce class swithcing IgE, IgG
promote growth B cells
induce differentiation T cells to Th2
2 BEG 4 help
function of IL-5
class switching IgA
growth differentiation eosinophils
“ “ B cells
5 BAEs
FOXP3 promotes
IL-10
TGF-B
CTLA-4
IFN-Y vs TNF-a for granulomas
IFN-Y induce granuloma
TGF-b maintain granuloma (TB)
**IL-12 **also induce granuloma (TB)
IFN-Y acvtivates macrophages to induce granulomas
IL-1 has what effect on bones
osteoclast activating factor
function of IFN-Y
secreted by NK cells (stim by IL-12)
stimulate macrophages to kill pathogens
inhibit Th2 differntaiton
Induced IgG isotype switching
secreted by macrophages
IL-1
IL-6
IL-8
IL-12
TNF-a
What is a common marker for T cells (helper and cytotoxic)
CD3
CD8+ = CD3, TdT
CD4+ = CD3, CD4, TdT
reactive oxygen species (ROS) are neutralised by
NADPH
also produces glutathione
O2 –> (NADPH oxidase) –> superoxide
CGD if deficiency
where do patients with CGD aquire H2O2 from for respiratory burst?
from **catalase (-) **organisms
catalase (+) breakdown own H2O2 and that produced by phagocytes
catalase (+) can then evade killing (by H2O2 breakdown)
as phagocytes in CGD only produce very little/no H2O2
catalase (-) can donate H2O2 to phagocytes
CGD = more prone to catalse + organism infection
what is positive selection of T cells
occurs where
double positive (CD4+/CD8+) expressing TCR** bind self**-MHC
= survive
thymic cortex
‘bind self = survive’
what is negative selection of T cells
occurs where
T cell expressing TCR with high affinity for self
= apoptosis
thymic medulla
*or become T reg
bind self = apoptosis
cause of AIRE
T cell negative selection impaired
self-reactive T cells not eliminated
autoimmune responses
Autoimmune Polyendocrine Syndrome type 1 (APS-1)
chronic mucocutaneous candidiasis
hypoparathyroidism
adrenal insufficiency (addisons)
recurrent candida infectiosn
macrophage-lymphocyte interactino is enhanced by
IFN-Y secretin (Th1)
CD40 (T cell) - CD40L (macrophage)
macrophages activate lymphocytes by antigen presentation
Ig light chain
Ig heavy chain
found in what parts of AB
light chain = fab
heavy chain = fab + fc
FC compliment binding
RAG1 or 2 gene deficiency can cause a form of
SCID
severe combined immune deficiency
RAG genes cause recombintion of VJ (light) and VDJ (heavy) genes
what regions of AB determine:
ideotype (binding site)
isotype (IgM, IgD…)
ideotype = fab
isotype = fc
antibody specificy
antibody diversity
antigen independant or dependant
specificiy = dependant
diversity = independant
independant:
VDJ recombination
nucleotide addition during recombination (TdT)
random combination heavy chain + light chain
dependant:
somatic hypermutation (variable region)
isotype switching (constant region)
name 2 opsonins
IgG
C3b
what Igs fix compliment
IgM
IgG
what Ig mediates TIHS
IgE
cross links when exposed to antigen
MAC defends against
gram (-) bacteria
i.e. neisseria meningiditis
**CH50 **screens for ativation of classical compliment pathway
hot and cold autoimmune haemolytic anaemias
what Igs
IgG = warm
IgM = cold
G = good
M = miserable
what are inhibitors of compliement pathway
prevent complimetn activatino on self cells
(CD55) DAF
(CD59)
C1 esterase inhibitor
early or late compliment deficiency increases susceptability of SLE
C3b used in clearance of antigen-ab complexes
C1-4
pyogenic infections
respiratory tract infections
terminal compliemnt - mac deficiency - neisseria bacteremia
c1 esterase inhibitor deficiency causes
hereditary angioedema (HAE)
unregulated kallikrein -> increased bradykinin
onset childhood
recurrent, painless, non-pitting edema
GIt abdominal pain, vomiting
no urticaria
decreased C4
what drug is inhibited in C1-esterase inhibitor deficiency
ACE inhibitors
(they increase bradykinin)
increase risk angioedema
onset childhood
recurrent, painless, non-pitting edema
GIt abdominal pain, vomiting
no urticaria
decreased C4
hereditary angiooedema
C1 esterase inhibitor deficiency
uncontrolled activation C1
C1 cleaves C4 –> C4a + C4b
= C4 comsumption = low levels C4 seen
C1q normal in hereditary forms
PIGA gene in (PNH) prevent formation of
GPI
glycoslphosphadidylinositol anchors
Interferons interfere with ____
RNA and DNA viruses
IFN-a, IFN-b, IFN-y
infected cells secrete interferons which ____ protein synthesis and ____ MHC expression of neighbouring cells
downregulate
upregulate
cells infected by virus - secretes interferons (IFN)
priming local cells to downreg protein synthesis to resist viral rplication
upregulate MHC expression to facilitate recognition of infected cells
cell surface protein receptor for EBV
CD21
CD receptor for PAMPs on macrophages
CD14
MMR
rotavirus
influenza (intranasal)
BCG
yellow fever
varicella
polio
typhoid
adenovirus
type of vaccine
live attenuated
cellular + humoral responses
lifelong immunity
safe in HIV pts CD4+ >200
polio = sabin
in what infections are AB less effeive against re-infection
influenza
rhinovirus
change coat
Hepatitis A
typhoid (IM)
rabies
influenza (IM)
polio
vaccine type
killed vaccine
**A TRIP **could kill you
inactivated
humoral , booster needed
polio = salk
neisseria meningiditis
strep. pneumoniae
H. influenza
polysaccharide conjugate vaccine
PPSV23 - adult (t cell independant) IgM - polysaccharide (short lived, no memory)
PCV13, 15, 20 child (t cell dependant) IgG - conjugate (memory)
PPSV23 -
PCV13, 15, 20
** PPSV23: **adult (t cell independant) IgM - polysaccharide (short lived, no memory)
** PCV13, 15, 20: **child (t cell dependant) IgG - conjugate (memory) **
clostridium tetani
clostridium diptheriae
acellular pertussus (inactivated)
vaccine type
toxoid vaccine
(DTaP)
denatured bacterial toxin
needs booster
Tdap = booster for teens & adults (lower dose of diphtheria and pertussis antigens)
1-2 week onset
jaundice, nausea, abdo pain
liver pathology
fever, arthritis, itchy rash
decreased C3, C4
serum sickness
i.e. Hep B infection
_____ is a specific marker of mast cell activation
tryptase
histamine
heparin
eosinophilic chemotactic factors
also released T1HS
erythema, pruritus, and urticaria
well circumscribed pale papules
seen in what hypersensitivity
T1HS
wheals
flares
hypotension and hypovolemia also seen
vasodilation
recent vaccination (intradermal)
subacute
localised oedema
skin necrosis
neutrophil infiltration
complimetn deposition
Arthus reaction
(subacute immune complex mediated hs Rx)
HS III
pre-sensitised IgG circulating
oliguria
high serum creatinine
necrotising vasculitis URTI/LRTI
sinusitis, ulcertions, haemoptysis
RPGN - renal failure
diagnosis?
AB against what cell?
wegners
granulomatosis with polyangitis
C-ANCA
targets neutrophil proteinase 3
SCID is
impaired T and B cell development and function
cell mediated and humoral immunity affected
what infection affects mucosal surfaces in SCID
mucocutaneous candidiasis
atopic dermatitis (eczema) and allergic asthma are ____ type hypersensitivity
TIHS
list (5) causes of TIIHS
hypersensitivity
5G’s + haem
Good pasture
Graves
Myasthenia Gravis
Pemphigus VulGarus
Rheumatic Fever (Group A Strep)
also haemolytic causes:
- autoimmune haemolytic anaemia
(plus drug-induced form)
- immune thrombocytopenia
- transfusion reactions
- haemolytic disease of newborn
- hyperacute transplant rejection
list (7) causes of TIIIHS
2 + 5-‘itis’
SLE
polyareritis nodosa (PAN)
rheumatoid arthritis
reactive arthritis
post-strep glomerulonephritis
IgA vasculitis
hypersensitivity pneumonitis
serum sickness (foreign proteins)
arthus reaction (intradermal inj)
causes of Type IV HS
3 D’s and TB
Contact Dermatitis
GVHD
DRESS
TB
what do 1.5kb and 6kb bands symbolise in VDJ rearrangement
1.5-kb = single gene in region (rearrangement has occured)
6-kb = multiple genes within region (un-rearranged)
6-kb is larger
where does VDJ rearrangement occur for B and T cells
B cells = bone marrow
T cells = thymus
t cells circulare as completely rearranged or unrearranged
single gene - 1.5kb (rearranged ig)
multiple genes 6kb (unrearranged ig)
roseola infantum is most often caused by
HHV-6
*human herpes virus
other causes: HHV7, enteroviruses, andeoviruses
infant
high fevers
_followed_by a rash - blanching macular eruption on neck & trunk
spreads outward to face/extremities
can have seizures
treatment supportive
roseola infantum
m/c infants, can occur later childhood
m/c cause = HHV6 (herpes)
teenager/young adult
fever
lymphadenopathy (posterior Cx LN)
HSM
pharyngitis
respiratory secretions transmission
EBV
not typically develop mascular rash
rash can develop especially if treated with amoxicillin - occurs 2-3 days after Abx
= maculopapular
erythema infectiosum is caused by
parvo B19 virus
PARVOVIRUS
school aged child
pink patches bilateral cheeks
followed by lacy macular eruption trunk and extremities
erythema infectiosum
‘5th disease’
from parvo B19 virus
can pass respiratory droplets or vertical (mother to foetus)
infects RBC precursors and endothelial cells = RBC destruction
hydrops fetalis and death in fetus
pure RBC aplasia and rheumatoid arthritis-like in adults
what cells does parvo B19 virus infect
RBC precursors and endothelial cells
children
acute febrie illness
prodromal fever, cough, coryza
conjunctivities
maculopapular rash - starts on head/neck
spreads tro trunk (excludes palms/soles)
koplik spots
rubeola virus
‘measles’
paramyxovirusv(highly contageous)
complications: encephalitis, pneumonia
differentiate from rosela:
fever FIRST rosey cheeks second
rubeola:
fever + rash occur TOGETHER
recurrent sinus infections
flow cytometry normal T and B cells, incl memory cells
Ig staining B lymphocytes - maturation defect
deficiency of what Ig?
IgA
IgM and IgG may still be present or increased to compenate
most error prone step in viral replication
HIV reverse transcriptase
(reverse transcription)
NRTI, NNRI drugs block this phases
what does IL-1 promote in RA
one resorption
cartilage destruction
(osteoclast activating factor)
what levels are seen in RA
C3
segmented neutrophils
IL-1
TNF-a
decreased
increased
increased
increased
classic & alternative compliemnt ctivated
+ humoral response
compliment consumption
TNF-a stimulates macrophages and neutrophils - cytotoxic effects
IL1- bone resorption & cartilage destruction
calcinosis cutis - calcium salt nodules in skin
raynaud phenomenon
oesophageal dysmotility
sclerosis
telangiectasias
scleroderma
(CREST syndrome)
tightening skin/face
fibrosis of oesophageal sphincter - decreased tone
oesophageal dysmotility - infiltration msucular layer with fibrous tissue
myeloperoxidae deficiency is autosomal ___
recessive
myeloperoxidase deficiency results in an ability to produce
catalyses final step of respiratory burst
hydroxyl-halide radicals
(hypochlorite)
hydrogen peroxide & chloride
impaired but not absent bacterial killing
NADPH oxidase and superoxide dismutase are also bactericidal
MPO deficient patients typically present with
recurrent fungal infections
what diagnostic tests differentiate MPO deficiency from CGD?
findings
MPO deficiency:
dihydrorhodamine tes = abnormal
nitroblue tetrazolium = turns blue
CGD :
dihydro = abnormal
nitroblue = no colour change
what pattern will be seen on immunoflouresnce in dermatitis herpetiformis
granular pattern of IgA deposition
along BM at tips of dermal papillae
also seen in henoch-schoenin purpura, IgA nephropathy, alcoholic liver disease
histology: H&E staining
small collections neutrophils focally separate epidermis from dermis at dermal papillae (vesicle)
histology findings of dermatitis herpetiformis
histology: H&E staining
small collections neutrophils focally separate epidermis from dermis at dermal papillae (vesicle)
what mediator do inflammtory cells release that can injure normal tissue
reactive oxygen species
induced in immune response to infections
damage invading microbes & can damage host tissue
ROS used for creation of H2O2 and hypochlorus acid
large inflam response can damage surrounding tissue
may trigger apoptosis - further inflammation
M spike on electrophoresis is seen in
multiple myeloma
b lymphocyte neoplasia
M spike (IgG or IgA) –> increased Ig –> Ig are type of plasma cell –> erived fromB cell –> B lymphocyte neoplasia
**
waldenstrom macroglobulinaemia (b cell lymphooma) - IgM spike**
amyloidosis assoc. MM and WM
