Immunology Flashcards
Signal One:
T cells are generated in the Thymus and are programmed to be specific for one particular antigen. Once they leave the thymus, they circulate throughout the body until they recognise their antigen on the surface of antigen presenting cells (APCs). The T cell receptor (TCR) on both CD4+ helper T cells and CD8+ cytotoxic T cells binds to the antigen as it is held in a structure called the MHC complex, on the surface of the APC. This triggers initial activation of the T cells. The CD4 and CD8 molecules then bind to the MHC molecule, stabilising the whole structure. This initial binding between a T cell specific for one antigen and the antigen-MHC it matches sets the whole response in motion. This normally takes place in the secondary lymphoid organs.
Signal Two:
In addition to TCR binding to antigen-loaded MHC, both helper T cells and cytotoxic T cells require a number of secondary signals to become activated and respond to the threat. In the case of helper T cells, the first of these is provided by CD28. This molecule on the T cell binds to one of two molecules on the APC - B7.1 (CD80) or B7.2 (CD86) - and initiates T-cell proliferation. This process leads to the production of many millions of T cells that recognise the antigen. In order to control the response, stimulation of CD28 by B7 induces the production of CTLA-4 (CD152). This molecule competes with CD28 for B7 and so reduces activation signals to the T cell and winds down the immune response. Cytotoxic T cells are less reliant on CD28 for activation but do require signals from other co-stimulatory molecules such as CD70 and 4-1BB (CD137).
Signal Three:
Once the T cell has received a specific antigen signal and a general signal two, it receives more instructions in the form of cytokines. These determine which type of responder the cell will become - in the case of helper T cells, it will push them into Th1 type (cells exposed to the cytokine IL-12), Th2 (IL-4), or IL-17 (IL-6, IL-23). Each one of these cells performs a specific task in the tissue and in developing further immune responses.
The correct answer is: Interaction between CD28 on T cells and CD80/86 on antigen presenting cells
What is CVID?
defect in B-cell differentiation into plasma cells and impaired secretion of Ig
Erythema nodosum
- form of panniculitis with features of a delayed-type hypersensitivity reaction
- erythematous, tender nodules on the shins
- septal panniculitis without vasculitis
- resolves spontaneously within a few weeks
- Leg elevation, rest, and compression aid in reducing symptoms.
lceration should be absent
Erythema nodosum
- form of panniculitis with features of a delayed-type hypersensitivity reaction
- erythematous, tender nodules on the shins
- septal panniculitis without vasculitis
- resolves spontaneously within a few weeks
- Leg elevation, rest, and compression aid in reducing symptoms.
lceration should be absent
What is the strogest predictive marker of disease progression in all stages of HIV?
CD38 expression on CD8
Chronic granulomatous diseae
Defect in PHOX enzymes
which has 4 subunits
>400 known defects
Inability to produce superoxide radical to kill engulfed bacteria
Lipid and protease inhibitors
lipdystrophy
Which CD molecules do memory T cells express?
CD45Ro
Roles of
IL2, IL3, IL4, IL5, IL6, IL8, IL11:
IL2: T-cell proliferation
IL3: hematopoietic lymphoid growth and proliferation
IL4: acts on B cells to promote IgE class switch
IL5: regulates esinophil growth and activation
IL6: differentiation of activated B –> plasma cells
IL8: Neutrophil chemotaxis
IL11: stimulate megakaryocytopoiesis –> produce platelets
PAMPs
Gram +ve bacteria: Peptidoglycan bacterial DNA lipoteichoic acids
Gram -ve: LPS
RNA virus: dsRNA
Yeast: Mannans
Which TLR bind to LPS?
TLR-4
Responsible for toxic shock syndrome in G-ve bacterial sepsis
ILC cells
part of the innate immunity
mirror Th1, Th2, Th17 and CD8 T-cell actions
Rapid produceer sof effector cytokines
Fucntion in fetal development (LTI) - involved in the development of secondary lymphoid organs
**PLZF **is important in developedment of ILC
ILC 1
NK and non-NK cells
Produe IFNg, TNF
intracellular pathogens
May drive IBD and RA
ILC 1
NK and non-NK cells
Express TF-Tbet
Produe IFNg, TNF
intracellular pathogens
May drive IBD and RA
Toxo, lupus, MS, alzheimers
- ILC precursor influenced by IL15,IL7 produce ILC1
- IL12, 15, 18 activates ILC to produce IFN-g and TNF
- *defence against viruses
*NK cells are activated by IL15
ILC 2
express GATA3
Produce IL4,5,9, 13
heminths/protozoa
Drive allery and atopy
Asthma, Schistosoma
ILC precursor –> IL7 –> ILC2
L25, 33,TSLP activates ILC2 –> IL5, IL13
ILC3
Express RORgt
Produce IL17, IL22
**extracellular organism
**
implicated in IBD and MS
Associated with obesity
ILC3 is activated by IL-1beta, IL23 to produce IL17, IL22
iNK T cells
Rapid responders
Distince T-cell population express invariant** alpha, beta TCR,** as well as surface proteins common for NK cells (CD16, 56, granzyme production)
REcognise glycolipid antigen on CD1d, and express R for IL12, IL18 (which are innate cytokines)
positively selected from DP thymocytes by mild affinity binding to self antigen when presented on CD1d R and co stimulated by SLAM
MAIT cells
Innate-like T cells
Semi invariant alpha/beta TCR
lack diversity
**Recognise riboflavin synthesis derivatives **via MR1
- common in gut bacteria and fungus
they do have a memory phenotype
abundant in** liver** and lungs
Gamma delta T-cells
TYpe 1: in thymus and peripheral tissue: recognise stress-related antigents
Type 2: peripheral blood, mainly recognise phosphoantigens
Roles:
- Cytokines: produce IFN-g in the presence of IL2, IL15
> IL17+ gamma delta TC differentiation in the presence of IL7
- Cytotoxicity: induce cell death by apoptosis or antibody dependent cellular toxicity
- Antigen presentation: to CD4/CD8 cells, and induce **DC maturation via TNF alpha **
Other roles in infection:
- neutrophil mobilisation and clearance
- Antimicrobial peptides, maintain barrier, kill infected cells
- neutrophil recruitmetn and granuloma formation
Associated with IBD, inflammatory arthropathy etc
Neutrophils
NETOSIS:
- sheets of DNA and histones with granules contents (lysozyme, elastase, defensins)
- TRAP bacteria and fungi –> death of organism
Implicated:
- sepsis
- thrombosis
- gout
- SLE, RA
- Athrosclerosis
IF type 1
IFNa(13-14 subtypes) with INF-beta
- dependent on phosphyralation of IRF3 and NFkB
antiviral response
Associated with SLE, other autoimmune disease
inadequate/defect: severe or prolonged viral infections:
- TLR3 defect –> HSV encephalitis
- worse covid infection(Esp in men)
IF type 3
similar in structure to IL-10
STAT1-STAT2 dimerisation
NFkB
widerange of role
Classical - canonical:
- response to various immune receptors (PAMPs,DAMPs, TLR ligands, IL1R, TCR, TNFR1)
- rapid and transient
- activation of p50, RELA and cREL
important for inflammation, cell proliferation, differentiation and survival
Alternative:
- induced by ligands of TNF-receptor superfamily, and can also be induced by viruses and some bacteria –> negative regulator and dampner of virus induced Type1 IF response
- Activation of p100
- required for lymphoid development, B-cell maturation, regulation of innate and adaptive immune response
Defect is associated with primary immunodeficiency (i.e. CVID)
Relopathies
Overactivation NFkB which regulates B-cell survival, and generate inflammation
Hyper IgE syndrome
is a T-cell deficiency - Th17 deficiency
due to STAT3 mutation
Recurrent staph and candida infection
Which cells produce IL-1?
Monocytes, Macrophages, DC
critical for inflammatory response against infection
Resets the hypothalamus thermoregulatory center
Which cytokine is associated with hyperalgesia?
IL 1beta
IL-7 R signalling defect
SCID
B cell markers
CD 19: Pan B cell marker
CD 20: mature B cell
CD 21: C3d receptor/EBV entry
CD 40: B and T cell interaction
what is the outcome of low MBL?
Increased risk of bacterial, fungal, viral and protozoal infections
Which organisms are protected against MAC dependent lysis?
Gram +ve bacteria
Hereditary angioedema
Type 1: marked reduction in C1INH level
Type 2: dysfunctional protein (C1-INH level is normal)
Type 3: Estrogen related (only in women)
Acquired angioedema
Type 1: consumption of C1-INH
Type2: Autoantibody against C1INH (level is normal)
Differentiated from hereditary by c1q level, which is low in acquired
How some viruses evade MHC presentation?
HSV: TAP inhibitor protein –> prevent transport of peptides onto MHC
Adenovirus: produces protein that anchors MHC in the ER –> prevent surface expression
CMV accelerates transport of peptide out of the ER –> reduces the chance of binding to MHC
Which test is specific for diagnosis of NSAIDs hypersensitivity?
Basophil activation test
how long does the desensitised state lasts?
4 half lifes
how long does the desensitised state lasts?
4 half lifes
Which complement product is linked to antibody mediated reaction (in renal transplant)?
Also describe the findings in ABMR?
- C4b along the PTCs
- Histological features: capillary endothelial swelling, arteriolar fibrinoid necrosis, fibrin thormbi in glomerular capillaries
- Severe vasculitis, gloerulitis with nt in glomerular capillary and PTC, fibrin thrombi, fibrinoid necrosis and interstitial haemorrhage are commonly seen in ABMR
what is the temp threshold for cryoglobulin precipitation
<37
food dependent, exercise induced anaphylaxis
Exercsie is required to be the proximate trigger , sx resolves with rest
Initial allergen is in food: Wheat compound, shelffish
Allergen needs to be ingested within 4 hours of exercise
Usually had co-stimulatory factors such as NSAIDs, alcohol (both increase antigen permeability and reduce mast cell activation threshold) - other factors: temp, infection, lack of sleep
Measure serum tryptase to rule out systemic mast cell disorder
Potential preventative tx:
Cromolyn sodium, misoprostol, omalizumab
Polysaccharide vaccines:
inactivated subunit vaccine composed of long chains of sugar molecules that make up the surface capsule of certain bacteria
i.e. pneumococcal and salmonella typhi vaccines
First recombinant antigen vaccine
HepB
Live attenuated vaccines:
BCG
measles, mumps, chickenpox, yellow fever, rabies
Amphiphysin ab
paraneoplastic stiff-man syndrome and breast cancer
Paraneoplastic ab/sx associated with SCLC
LEMS: P/Q VGCC
Retinopathy
Neuromuscular excitability syndrome presenting with myotonia: VGKC
Encephalomyelitis: Anti Hu
Opsoclonus-myoclonus-ataxia sx
breast ca, paraneoplastic syndrome and ab
stiff man sx: amphiphysin ab
cerebellar degen: Anti-yo
retinopathy, opsoclonus-myoclonus-ataxia sx
Thymoma: paraneoplastic
MG - AchR ab
hyperexcitability sx: VGKC
AI encephalitis with leucine-rich glioma inactivated protein 1 ab
paraneoplastic AI encephalitis with NMDA-R ab
teratoma, younger pts
vaccines needed post splenectomy
13vPCV
ACWY congugate vaccine
MenB recombinant vaccine
Hib congugate vaccines
Annual influenza vaccines
Conjugate vax
antigen or toxoid of microbe is linked to polysaccharides from outer surface
lasts longer than polysaccharide vaccine - longer memory cells allowing rapid boosting immunity with booster doses up to many years later.
Where as polysaccharide vaccines don’t generate long term memory cell, so you don’t get the boosting effect. in fact, repeated doses results in fewer ab than previous dose
RF for developing angioedema related to ACEi
thought to be related to bradykinin, substance P
can occur anytime during therapy
RF:
>65, asthma, COPD, allergy, RA
>CCB or NSAIDs
RF for developing angioedema related to ACEi
thought to be related to bradykinin, substance P
can occur anytime during therapy
RF:
>65, asthma, COPD, allergy, RA
>CCB or NSAIDs
Mechanism of ecallantide
inhibits bradykinin
Icatibant
inhibits bradykinin binding to it’s receptor
CVID
M=F
1,25,000 to 50,000
B-cells fail to differentiate - low IG levels esp IgG and IgA +/- IgM
Diagnostic criteria:
>4years old
1. clinical: recurrent infection, granulomatous dx, autoimmunity, lymphadenopathy
2. reduced IgG, IgA and or IgM
3. Poor response to vaccines and or absent isohaemoglutinins
4. secondary causes excluded
Tx:
IVIG, or SCIg
IgG4 disease
Chronic relapsing-remitting inflammatory disease
Major presentations:
- Type 1 AI pancreatitis
- Salivary gland disease
- orbital disease
- retroperitoneal fibrosis
May have elevated IgG or IgG4
Gold standard is biopsy:
- lymphoplasmacytic infiltrates rich in IgG4 positive plasma cells, storiform fibrosis, obliterative phlebitis
Tx:
- usually responsive to steroids
- Rituximab: induction and relapse tx
- ## IgG4-RD tends to affect males more often than females.
IgG4 RD
- 4 main types
1: Pancreato-biliary
OLD WHITE MAN
IgG4 ^^, IgE ^
Treatment responsive
Complications: - DM, malabsorption
- biliary stenosis, infectious cholangitis, hepatic failure
2: Retroperitoneal/Aortitis:
OLD WHITE MAN
IgG4 ^ or =
ESR/CRP ^
Fibrotic disease, thus can be treatment refractory. Needs higher cumulative GC
Complications:
- Pericardium: constrictive pericarditis
- CAD
- Inflammatory thoracic or abdominal aortic aneurysms
- Retroperitoneum: renal atrophy or injury due to hydronephrosis, chronic abdominal pain sx
- Mediastinal disease can cause compression
-
Head and neck limited
YOUNG ASIAN FEMALE
history of atopy
IgG4^^
Fibrotic disease, thus can be treatment refractory. Needs higher cumulative GC
Complications:
- orbit: proptosis, vision loss, diplopia
- meninges: cranial nerve palsy
- Ear: hearing loss, bone destruction
- Chronic sinusitis, midline destructive lesions, anosmia
- hypothyroidism and hypopituitarism
-
Systemic disease
MALE, OLD
IgG4^^^, IgE^
Higher responder index, RESPONSIVE to tx
Complications:
Lacrimal and salivary glands: sicca
Pancrease: DM and malabsorption
Lung: fibrosis, ILD
Pleural effusion and thickening
Kidneys: interstitial/GN –> failure
Treatment:
Induction: PO Predisone for 3 weeks, then taper over 3-6 months
Rituximab: 1g 15 days apart
Maintenance:
1. low dose GC
2. DMARDs
3. Rituximab every 6 months
Regular peanut consumption from introduction of solids reduces peanut allergy in those at high risk for to at least 60 months of age
true
NPV of skin prick test for penicillin and cephalosporin
Penicillin >95%
not high for ceph
TB reactivation
High RF:
- AIDS
- HIV
- Transplantation
- Silicosis
- CKD on RRT
- Carcinoma of head/neck
- Recent TB <2yrs
- abnormal CXR with apical fibronodular changes
- TNF alpha inhibitors
Moderate RF:
- Treatment with GC
- DM
- Young age when infected <4y
