1
Q
What deficiency is found in Hereditary Angioneurotic Oedema (HAO)?
A
C1 esterase inhibitor deficiency
2
Q
What is the effect of C1 esterase deficiency?Which complement is found to be low?
A
Persistent activation of the classical complement pathway and low C4 levels due to consumption.
3
Q
If Hereditary Angioneurotic Oedema (HAO) is refractory to treatment and the C4 levels stay low, what complication may develop?
A
SLE
4
Q
For the following drug prefixes that occur just before mab (monoclonal antibody) comment on the type of monoclonal Ab:
- o
- xi
- zu
- u
A
- o = mouse
- xi = chimeric
- zu = humanized
- u = fully human
5
Q
What are the 4 types of hypersensitivity reactions and give the mechanism and an example of each.
Clue: ACID
A
ACID:
Type 1 - Allergic
Mechanism: IgE-mediated (quick)
Example: Penicillin drug allergy, Bee stings
Type 2 - Cytotoxic
Mechanism: Cytotoxic/IgG-mediated
Examples: Goodpasture’s syndrome, AIHA
Type 3 - Immune complex mediated
Immune complex deposition and IgG/IgM mediated
Examples: SLE, polyarteritis nodosa, serum sickness
Type 4 - Delayed or cell-mediated
Mechanism: cell-mediated (T-helper cells activate macrophages and cytotoxic T-cells)
Example: contact dermatitis (latex)
NB: grossly simplified!
6
Q
That is Job’s syndrome?
A
AKA: AD-HIES - autosomal dominant hyperimmunoglobulin IgE syndrome associated with high IgE level.
Characterised by the triad (SEE):
Skin and pulmonary infections
Eczema
Eosinophilia
Mnemonic: SEE if I can GEt him a JOB?
–> SEE-IGE-JOB
7
Q
In a patient with severe allergic rhinitis and severe asthma, which of the following is TRUE (may be more than one answer):
A. Desensitisation will improve allergic rhinitis but not asthma
B. Desensitisation carries higher risk of morbidity in this patient.
C. Inhaled nasal corticosteroids are indicated
D. Omalizumab may be of benefit for both allergic conditions
E. Serum tests for specific IgE will show results similar to skin testing.
A
A. Desensitisation will improve allergic rhinitis but not asthma - FALSE (both would benefit)
B. Desensitisation carries higher risk of morbidity in this patient - TRUE
C. Inhaled nasal corticosteroids are indicated - TRUE
D. Omalizumab may be of benefit for both allergic conditions - TRUE
E. Serum tests for specific IgE will show results similar to skin testing - TRUE
8
Q
What is the MOA Omalizumab?
What is the indications?
A
MOA:
- Recombinant humanised antibody of IgG1 subclass targeted at IgE.
- Binds free IgE in serum
- Decreases expression of high-affinity receptors upon mast cells/basophils/eosinophils
- Decreased inflammatory mediator release
Indications:
- mod-severe asthma
- Refractory idiopathic chronic urtcaria
9
Q
How do Quantiferon Gold assays work?
A
- They are Interferon-gamma release assays (IGRA)
- Mycobacterium TB peptides stimulate the release of IFN-gamma via Th1 cells (T helper cells)
10
Q
Which of the following T helper cells are implicated in the Quantiferon Gold assay (Th1, Th2 or Th17)?
A
Th1
11
Q
Which cell type is the major antigen-presenting cell (APC) responsible for initiating immune response?
A
Dendritic cells
12
Q
Dendritic cells (DC) present processed antigen to T-cells (TC) via the MHC complex to T-cell receptors.
Name 2 co-stimulatory pathways that ACTIVATE the T-cell.
A
- [DC] CD80/CD86 : CD28 [TC]
2. [DC] CD40 : CD40L [TC]
13
Q
Dendritic cells (DC) present processed antigen to T-cells (TC) via the MHC complex to T-cell receptors.
Name 3 co-stimulatory pathways that INHIBIT the T-cell.
A
- [DC] CD80/CD86 : CTLA4 [TC]
- [DC] PD-L1/PD2-L2 : PD1 [TC]
- [DC] OX40L : OX40 [TC]
14
Q
Dendritic cells present processed antigen to T-cells via the MHC complex to T-cell receptors (TCR).
Name a co-stimulatory pathways that either activates or inhibits depending upon CD28-signalling of the T-cell
A
[DC] ICOSL : ICOS [TC]
Activates with CD28 signalling.
15
Q
With the activation of the co-stimulatory pathway of ICOSL (dendritic cells) and ICOS (T-cells), which 2 interleukins are released?
A
IL-3 and IL-10
16
Q
Which 2 places do plasma dendritic cells migrate to to maximise interaction with circulating B-cells and T-cells?
A
LNs and spleen.
17
Q
What is Sifalimumab?
Which condition may it be beneficial in?
A
Anti-IFN-alpha mAb that may be used in the treatment of adult SLE
18
Q
What type of pathogens cause interferons release?
A
Viruses.
19
Q
Describe type I and type II interferons in terms of:
- Receptor type
- Categories of interferons
- Prototypic cell(s) of origin
A
Type I interferons (type I receptors):
IFN-alpha - leukocyte (most cells)
IFN-beta - fibroblast (most cells)
IFN-omega - leukocyte
Type II interferons (type II receptors):
IFN-gamma - T-cells and NK-cells (lymphocytes)
20
Q
What triggers the release of the following IFNs:
- IFN-alpha and IFN-beta
- IFN-gamma
A
- IFN-alpha and IFN-beta: viral dsRNA
2. IFN-gamma: mitogens
21
Q
What are effects of type I interferons?
A
Interferes with viral replication:
- Induces resistance to viral replication in all cells
- Increases MHC-I expression and Ag-presentation on all cells.
- Activates dendritic cells (DC) and macrophages (Mp)
- Activates NK-cells
22
Q
Which 3 cells lines are activated by interferons?
A
- Dendritic cells
- Macrophages
- NK-cells
23
Q
How are plasmacytoid dentritic cells (pDC) distinct from conventional dendritic cells (cDC)?
A
- pDC respond to viral infections by secreting a lot of type I IFNs (i.e. IFN-alpha and IFN-beta)
- pDC (unlike cDC) are LESS involved in Ag-processing, , co-stimulatory molecules and MHC-II expression
24
Q
What is the function of follicular helper T-cells (Tfh)?
Which co-stimulatory signals do they use?
A
Tfh migrate to lymphoid follicles and help B-cells class-switch and affinity maturation.
They use the following 2 co-stimulatory signals:
- [Tfh] ICOS : ICOSL [B-cell]
- [Tfh] CD40L : CD40 [B-cell]
25
Which 3 cytokines are secreted by follicular helper T-cells?
IL-21
| IL-4 or IFN-gamma
26
What are the 2 typical manifestations of CVID (Common Variable Immunodeficiency)?
Recurrent:
1. Sinopulmonary infections +/- bronchiectasis
2. Gut infections
27
Which immunoglobulin are usually deficient in CVID (Common Variable Immunodeficiency)?
IgG and IgA or IgM.
28
In CVID (Common Variable Immunodeficiency), B-cells are typically:
```
A. Increased
B. Normal
C. Decreased
D. Normal or decreased
E. Normal or increased
```
D. Normal or decreased
29
Patients with CVID (Common Variable Immunodeficiency) are at increased risk of which 4 types of conditions?
Complications of CVID:
1. Lymphoproliferation
2. Neoplasm (stomach and lymphoma)
3. Autoimmunity (immune cytopenias)
4. Granulomatous disease
30
What is the treatment of CVID (Common Variable Immunodeficiency)?
- IV or SC immunoglobulins (IVIg / SCIg)
| - Prophylactic antibiotics
31
T/F: there is a clear genetic cause in MOST cases of of CVID.
False - genetic explanation is found in less than 30% of cases.
32
Granulomatosis with polyangiitis (GPA) classically presents with:
1. What clinical features?
2. What ANCA findings?
3. What immunohistopathology?
1. Goodpasture's syndrome = haemoptysis and haematuria
2. c-ANCA+ with PR3
3. Pauci-immune vasculitis of small/medium vessels with necrotising granulomatous inflammation
REMEMBER:
- CPR (c-ANCA and PR3 positive)
- GPA may also rarely by pANCA + with MPO
33
Patient with Granulomatosis with polyangiitis (GPA) presents with severe end-organ involvement (i.e. haemoptysis and haematuria). What aggressive treatment should be instigated?
1. Pulsed steroids
| 2. Second agent: Cyclophophamide or Rituximab
34
Cyclophosphamide has side effects that affect multiple organs, describe the complications in the following:
1. Bone marrow
2. Bladder
3. Endocrine
4. GIT
5. Immune system
6. Lungs
1. Bone marrow: marrow suppression, neutropenia
2. Bladder: haemorrhagic cystitis, cancer, fibrosis
3. Endocrine: infertility, osteoporosis
4. GIT: nausea, vomiting, abdominal discomfort
5. Immune system: hypogammaglobulinaemia, lymphoma/leukaemia
6. Lungs: interstitial pulmonary fibrosis
35
Which cells release 'soluble' CTLA4 molecules?
Regulatory T-cells (Treg)
36
In a local immune response, what is function of soluble CTLA4 molecules?
Bind to B7 (aka CD80/CD86) on APC and INHIBIT T-cell activation
37
What are the 3 main cytokines produced by the B-cell?
- IFN-gamma
- IL-6
- IL-10
38
What are the 2 main co-stimulatory molecules found on B-cells?
1. CD40
| 2. B7 (aka CD80/CD86)
39
What are the 4 main functions of B-cells?
1. Ingestion of complement-coated antigens
2. Antigen presentation to T-cells (ingests via smIg)
3. Differentiate to form antibody-forming cells
4. Release cytokines (IFN-gamma / IL-6 / IL-10)
40
Which 3 monokines induce the 'liver' to produce acute phase reactants during an acute phase response?
IL-1
IL-6
TNF
41
Give 3 functions of acute phase reactants produced by the liver in response to monokines during an acute phase response. Give an example of each.
1. Fight infection - CRP, MBL
2. Prevent tissue destruction - alpha-1-anti-trypsin
3. Promote tissue healing - fibrinogen
42
Describe the story of the B-cell with respect to the following chapters:
1. Bone marrow
2. Lymph node
1. Bone marrow (site of maturation): stem cell to Pro-B to Pre-B (MHC+) to Immature-B (IgM) to Mature-B (IgM +/- IgD)
Mature B-cell migrates via blood to lymph node
2. Lymph node (site of interaction):
- Within primary follicle of LN: B-cell interacts follicular dendritic cells (APC) and T-cells
- Form Plasmablasts (short-lived)
- Form Plasma Cells (long-lived)
43
What is primary vs. secondary lymphoid tissue?
Primary lymphoid tissue = red bone marrow and thymus
Secondary lymphoid tissue = lymph nodes, tonsils, spleen, Peyer's patches (ileum) and MALT (mucosa-associated lymphoid tissue)
44
Where is MALT (mucosa-associated lymphoid tissue) found in the body?
Many places: GIT, thyroid, breast, lung, salivary glands, eye, and skin.
45
What is CD40L also known as?
CD154
46
Which co-stimulatory pathways between Memory T-cells (mTC) and APC do the following biologics disrupt?
Give MOA for each.
1. Abatacept
2. Belatacept
3. CD28 domain Ab
4. Anti-ICOS mAb
5. Oxelumab
6. Alefacept
7. Efalizumab
[APC] CD80/CD86 : CD28 [mTC] - activates mTC
1. Abatacept (CTLA4/IgG1 fusion molecule) binds CD80/CD86 on APC and inactivates mTC
2. Belatacept: same MOA as Abatacept
3. CD28 domain Ab binds CD28 on mTC and inactivates mTC
[APC] ICOS-L : ICOS [mTC] - activates mTC if CD28:CD80/CD86 costimulation is also present
4. Anti-ICOS mAb binds ICOS on mTC and inactivates mTC.
[APC] OX40L : OX40 [mTC] inactivates mTC
5. Oxelumab binds to OX40L on APC
[APC] LFA3 : CD2 [mTC]
6. Alefacept binds to CD2 on mTC and attracts macrophages and NK-cells leading to mTC death and hence mTC inactivation.
[APC] ICAM : LFA1 [mTC]
7. Efalizumab binds to LFA1 on mTC leading to mTC inactivation.
47
T/F: pregnancy and post-natal foetal life are predominantly Th2 immune phenomena.
True - Th2 response reduces the risk of miscarriage.
48
T/F: anti-IL4R Ab (Dupilumab) is useful in atopic eczema.
True - IL4 mediates the atopy in Th2 response, therefore inhibition of the IL4R (IL4 receptor on B-cells and marophages) leads to clinical improvement.
49
In which of the following conditions is house dust-mite 'desensitisation' are useful (route of administration options include; sublingual and subcutaneous):
1. Allergic rhinitis
2. Asthma
3. Atopic dermatitis
4. Anaphylaxis
1. Allergic rhinitis: effective, sublingual or subcutaneous desensitisation have equal efficacy
2. Asthma: risk of asthma attack , not worth risk
3. Atopic dermatitis: not effective
4. Anaphylaxis: risk of anaphylaxis, not worth risk
50
VDJ rearrangement of both alpha and beta chain T-cell receptor genes yields a wide range of receptor possibilities.
Where does positive and negative selection of T-cells occur?
Selection occurs in the 'thymus' before selected cells are released into the periphery.
51
What is the trigger for clonal expansion of T-cells?
Exposure to degraded Ag presented on MHC by DCs.
52
What are the principles of treating a patient with SLE in terms of:
1. What should all patients receive?
2. What should only patients with severe manifestations (i.e. renal, cerebral and other end-organ complications) receive?
3. What should patients mild manifestations to skin and joints receive?
1: All:
- Hydroxychloroquine (i.e. Plaquenil) reduces flares and CVS morbidity.
- Effective with skin/joint SLE
2. Severe manifestations (renal/cerebral/other):
- High-dose steroids (initially pulse)
- MMF / cyclophophamide / cyclosporin
3. Mild manifestations (skin/joints):
- Joint pain: NSAIDs, COX2-inhibitors, low-dose steroids
- Skin: topical steroidss
53
Regarding hypersensivity pneumonitis:
1. What type of hypersensivity reaction is it?
2. What is the pathophysiology?
3. Is lung fibrosis possible?
1. Type III hypersensitivity - immune-complex mediated.
2. IgG Ab to the inhaled Ag (e.g. fungal precipitins in Aspergillus)
3. Yes, chronic exposure may lead to lung fibrosis.
54
What are the Th 1 response cytokines?
```
IL 1
IL 6
IL 8
IL 12
TNF-alpha
IFN-gamma
```
55
What are the Th 2 response cytokine?
IL 4
IL 5
IL 9
IL 13
56
What are the Th 17 response cytokines?
IL 12
IL 17
IL 23
57
Reduced function in which of the following branches of the immune system mediated the reactivation of VZV in shingles:
```
A. Complement
B. Neutrophils
C. Specific Ab
D. NK-cells
E. Specific cell-mediated immunity
```
E. Specific cell-mediated immunity
58
Which test following an episode of presumed anaphylaxis is most useful to confirm this diagnosis?
Tryptase.
- Mast cells release tryptase and histamine.
- Tryptase is secreted by both mast cells and basophils, however mast cells secrete 500x more tryptase.
59
What is allergen immunotherapy used for?
What does it involve?
How long does the treatment take?
- Allergen immunotherapy is recommended for life-threatening allergic reactions:
1. Stinging insects (i.e. anaphylaxis to wasp/bee sting).
2. Refractory allergic rhinitis to pollen / dust mites
- Involves gradually increasing doses of allergen extract resulting in eventual tolerance of antigen.
- Duration of treatment 3-5 years.
60
What is the histopathology of direct immunofluorescence of perilesional skin lesion in a patient with bullous pemphigoid?
Linear deposition of IgG and C3 at the dermal-epidermal junction (found in >90% of cases)
61
What is the treatment of bullous pemphioid?
Topical (high-potency) +/- systemic corticosteroids
62
What is Mixed Cryoglobulin Syndrome?
A. Clinically
B. Pathophysiology
C. What type of vasculitis does it cause?
D. Which 3 chronic viral infections is it associated with?
A. Clinically (PLAN + low C4 + cryoglobulins):
- Palpable purpura
- Lumps: LNs / hepatosplenomagely
- Arthralgia
- Neuropathy (peripheral)
- low complement + presence of cryoglobulins.
B. Deposition of Ag-Ab complexes in capillaries and arterioles.
C. Small vessel leukocytoclastic vasculitis
D. HCV / HBV / HIV
63
T/F: Mixed Cryoglobulin Syndrome may be associated with renal impairment in 50% of case and is associated with higher mortality.
True.
64
What is the treatment of HCV-associated mixed cryoglobulinaemia?
Pegylated IFN-alpha + Ribavirin or Rituximab
65
Regarding Sjogren's Syndrome (SS):
A. What autoantibodies are positive?
B. Which if SSA (Ro) and SSB (La) is more specific to SS?
C. T/F: patient with NEGATIVE SSA / SSB can not have SS.
A. ANA / RF / SSA (Ro) / SSB (La)
B. SSB (La) is more specific, SSA (Ro) is non-specific.
C. False: SSA/SSB often absent
66
What are the "NARLy" complications of Sjogren Syndrome?
NARLy:
Nephrocalcinosis
Arthritis
Raynaud's phenomena
Lymphoma (last to develop)
67
Activation of which complement cascade is suggested in the following 2 scenarios:
A. Low C3 / Low C4
B. Low C3 / Normal C4
A. Low C3 / Low C4 - Classic pathway activation
B. Low C3 / Normal C4 - Alternate pathway activation
68
T/F: ANA is usually positive is diseases of complement deficiency.
False - ANA is generally negative in diseases of complement deficiency.
69
What are the 2 possible causes of low C4?
1. Activation of the 'Classical' complement cascade
| 2. Complement deficiency e.g. C1 INH
70
Patient has an infection. What do you anticipate the level of C4 to be?
High C4 - acute phase reactant
71
What does the CH100 test detect?
CH100 screening test detects INHERITED complement deficiency.
72
Patient has INHERITED complement deficiency. What do you anticipate the CH100, C3 and C4 to be?
- Low CH100
| - Low C3 / Low C4 (suggesting classical pathway activation)
73
Patient is noted to have normal C3 and low C4.
A. What pathway is activated?
B. What other test should be ordered to elucidate cause?
C. Which 2 conditions are suggested if the test in part B is positive?
A. What pathway is activated?
Alternate pathway activation
```
B. What other test should be ordered to elucidate cause?
C3 NEF (C3 nephritic factor)
```
C. Which 2 conditions are suggested if the test in part B is positive?
- MPGN (type II)
- Lipodystrophy (partial)
74
Describe the different mechanisms of the 3 complement pathways:
1. Classical pathway
2. Lectin pathway
3. Alternate pathway
1. Classical pathway - Ag-Ab complexes
2. Lectin pathway - MBL (mannose-binding lectin) pathogen surfaces
3. Alternate pathway - Pathogen surfaces
75
What complements are implicated in the 3 complement pathways:
1. Classical pathway
2. Lectin pathway
3. Alternate pathway
1. Classical pathway: C1q, Clr-Cls, C4, C2
2. Lectin pathway: MASP-1, MASP-2, C4, C2
3. Alternate pathway: C3b, Factor-B, Factor-D, P (no C4)
76
All 3 complement pathways converge on which enzyme in the complement cascade?
C3 convertase
77
Patient has low C4 and C1 INH.
A C1 inhibitor deficiency is suspected.
What is the difference between hereditary and acquired C1 inhibitor deficiencies?
HEREDITARY C1 inhibitor deficiencies:
- heterozygous deficiencies, as homozygous deficiencies are fatal.
- Type 1 (1 allele) expressed vs. Type 2 (2 alleles expressed)
- C1 INH are 5-30% of normal
ACQUIRED C1 inhibitor deficiencies:
- associated with malignancy and SLE
- secretes an antibody that binds and inactivated C1 inhibitor.
- C1 INH may be normal if C4 normal
78
What are the 2 potential mechanisms for angioedema?
1. Histamine-related angioedema
| 2. Bradykinin-related angioedema e.g. hereditary (HAO) or acquired (ACEi-related)
79
T/F: all forms of bradykinin-related angioedema respond to Icatibant (bradykinin inhibitor).
False.
hereditary (HAO) - responds to Icatibant
acquired (ACEi-related) - does NOT respond to Icatibant.
80
What is HAO (hereditary angioedema)?
What are the 3 treatments?
Mutation of C1 inhibitor gene leading to low C1 inhibitor levels that allows overactivation of kallikrein that converts kininogen to bradykinin.
Therefore the 3 treatments:
1. C1 inhibitor concentrate
2. Kallikrein inhibition = Ecallantide
3. Bradykinin inhibition = Icatibant
81
Which clinical symptom distinguishes histamine-related angioedema from bradykinin-related angioedema?
Urticaria is peculiar to histamine-related angioedema.
82
Patient is known to have an immediate hypersensitive reaction to radiocontrast media.
A. Which 2 pretreatment drugs are recommended?
B. Change to which type of contrast media is recommended?
C. T/F: desensitisation to radiocontrast media is indicated.
A. Which 2 pretreatment drugs are recommended?
- Corticosteroids PO/IV
- Diphenhydramine (H1 antihistamine) PO/IM/IV
B. Change to which type of contrast media is recommended?
- Low or iso-osmolar (non-ionic) radiocontrast media
C. False - desensitisation is NOT useful
83
Which of the following is NOT an appropriate use of adrenalin in anaphylaxis:
A. Adrenalin 1mg STAT IM bolus
B. Adrenalin infusion (0.1 mcg/kg/min) IV
C. Adrenalin 5mL (5x 1:1000 ampoules) nebulised
D. Adrenalin 1mg STAT IV bolus
D. Adrenalin 1mg STAT IV bolus - increased risk of cardiac arrhythmia.
84
Which of the following 2 drugs is used as first-line treatment in haemodynamically unstable anaphylaxis:
1. Antihistamines
2. Corticosteroids
Neither.
1. ABC
2. Adrenalin (IM or IV infusion)
3. IVF
4. Antihistamine / Corticosteroids
85
What are 5 common indications for Skin Prick testing for specific IgE?
ARAFL - skin prick tests are a bit of raffle!
1. Asthma
2. Rhinitis / Rhinoconjunctivitis / Rhinosinusitis / Allergic Conjunctivitis
3. Atopic dermatitis
4. Food allergies that cause anaphylaxis e.g. peanuts
5. Latex allergy
86
What are 3 absolute CI and 3 relative CI for Skin Prick testing for specific IgE?
Absolute CI:
1. Diffuse skin disorder (need normal skin for test)
2. Severe dermatographism
3. Unable to cease drugs/antihistamines/cooperate
Relative CI:
1. Severe astham
2. Pregnancy / babies / infants
3. Beta-blockade
87
Patient on beta blocker for HF presents with anphylaxis and persistent hypotension despite repeated adrenalin / IVF / antihistamine.
What treatment should be added?
How is this though to work?
Glucagon activates adenyl cyclase and exerts an inotropic and chronotropic effect by a pathway that bypasses the beta receptors.
88
Patient develops a diffuse severe blistering rash with haemodynamic instability. You suspect Toxic Epidermal Necrolysis.
Which test is used to confirm this?
None required - clinical diagnosis, do NOT test (e.g. skin test, PO challenge, RAST etc. all contraindicated), second exposure may be worse.
89
How is SJS (Stevens-Johnson Syndrome) and TEN (Toxic Epidermal Necrolysis) differentiated?
- Both implicate the mucous membranes (>90%)
- SJS < 10% of BSA
- TEN > 30% of BSA
90
A patient started on a new drug develops a fever > 38 degrees, mucositis, skin tenderness and blistering rash.
What is your concern?
SJS/TEN
91
T/F: Peri-pregnancy consumption of peanuts or tree nuts leads to increased risk of peanut or tree nut allergies in the offspring.
False - the converse is true, the infant becomes sensitised.
92
What is the treatment of mod-severe chronic rhinosinusitis with nasal polyps?
1. Saline nasal irrigation and intranasal corticosteroid
2. Intranasal/PO antihistamine
3. +/- montelukast
4. Refer to surgery for nasal polypectomy
93
What is the treatment of mild chronic rhinosinusitis without nasal polyps
Intranasal/PO antihistamine
94
Patient has chronic rhinosinusitis with nasal polyps.
What other conditions should be considered if:
1. Patient is a child
2. Patient is an adult
1. Patient is a child
- Consider cystic fibrosis
2. Patient is an adult
- Consider aspirin sensitivity and coexisting asthma
95
Which 4 prophylactic drugs can prevent an episode of hereditary angioedema?
1. Anabolic steroids (Danazol) - increases endogenous production of complement
2. Transexamic acid
3. C1 inhibitor concentrate (if >8x attacks per month)
4. FFP
96
T-lymphocytes that encounter it's specific antigen in the presence of a co-stimulatory signal (CD28) will proliferate.
What happens if there is an ABSENCE of co-stimulatory signal during the encounter with it's specific antigen?
- Anergy (unresponsive to appropriate stimulation)
- Produces low levels of Th1 and Th2 cytokine
- +/- Apoptosis
97
Which of the the following 'best' describes SCID (Severe Combined Immune Deficiency).
A. T-cell deficiency / B-cell deficiency / NK-cell deficiency
B. T-cell deficiency / B-cell normal / NK-cell deficiency
C. T-cell deficiency / B-cell normal / NK-cell normal
D. T-cell normal / B-cell normal / NK-cell deficiency
E. T-cell deficiency / B-cell deficiency / NK-cell normal
E. T-cell deficiency / B-cell deficiency / NK-cell normal
- SCID is always associated T-cell deficiency
- B-cells may be normal in SCID but as humoral immunity depends on T-cell signalling, the result is a 'functional' B-cell deficiency.
- NK-cell may be preserved in 50% of SCID and provide the only protection against bacterial and viral infections.
98
What is the only cure for SCID (Severe Combined Immune Deficiency)?
Haemopoietic Cell Transplant (HCT)
99
T/F: NK-cells are large granular lymphocytes that require detection of MHC complex and Abs on the surface of virus infected cells to cause cytokine release that results in cell lysis and apoptosis.
False - they do not require these, can act fast and are part of the early cellular response to virus infected cells.
100
Which of the following drugs has the LEAST effect on cytokine regulation (esp. IL-2):
```
A. Glucocorticoids
B. Mycophenolate
C. Cyclosporin
D. Tacrolimus
E. Rapamycin
```
B. Mycophenolate
101
For Th1 cells, describe the following:
1. Name cytokine that promote T0 --> Th1 differentiation
2. Cytokine secreted by Th1
3. Diseases Th1 response is implicated in
1. Name cytokine that promote T0 --> Th1 differentiation
IFN-gamma / IL-12
2. Cytokines secreted by Th1
IL-1, 2, 6 / TNF-alpha / IFN-gamma
3. Diseases Th1 response is implicated in
- Cell-mediated immunity
- Intracellular pathogens (viruses/bacteria)
- Autoimmunity and Inflammation
102
For Th2 cells, describe the following:
1. Name cytokine that promote T0 --> Th2 differentiation
2. Cytokine secreted by Th2
3. Diseases Th2 response is implicated in
1. Name cytokine that promote T0 --> Th2 differentiation
IL-2, 4
2. Cytokines secreted by Th2
IL-4, 5, 6, 10, 13
3. Diseases Th2 response is implicated in
- Ab-mediated immunity
- Extracellular pathogens (parasites)
- Asthma / allergies
103
For Treg cells, describe the following:
1. Name cytokine that promote T0 --> Treg differentiation
2. Cytokine secreted by Treg
3. Diseases Treg response is implicated in
1. Name cytokine that promote T0 --> Treg differentiation
TGF-beta / IL-12
2. Cytokines secreted by Treg
TGF-beta / IL-10, 35
3. Diseases Treg response is implicated in
- Immune tolerance
- Lymphocyte homeostasis
- Regulates immune response
104
For Th17 cells, describe the following:
1. Name cytokine that promote T0 --> Th17 differentiation
2. Cytokine secreted by Th17
3. Diseases Th17 response is implicated in
For Th17 cells, describe the following:
1. Name cytokine that promote T0 --> Th17 differentiation
TGF-beta / IL-6
2. Cytokines secreted by Th17
IL 17, 21, 22
3. Diseases Th17 response is implicated in
- Extracellular bacteria (skin, intestines)
- Fungi
- Autoimmunity
105
What does the MAC (membrane attack complex) consist of?
What effect does it have on bacterial pathogens?
MAC = C5b-C6-C7-C8-C9 - results from activation of any of the 3 complement pathways (classic, alternate, lectin)
Inserts into the surface of bacteria leading to lysis.
106
CRP is an acute phase reactant that rises the most rapidly in infection or inflammation.
A. Where is CRP synthesised in the body?
B. Which interleukin and from which types of cells trigger provides the trigger for CRP synthesis?
C. What is it's physiological purpose?
A. Where is CRP synthesised in the body?
- Hepatic origin
B. Which interleukin and from which types of cells trigger provides the trigger for CRP synthesis?
- Macrophages and T-cells secrete IL-6 to promote hepatic synthesis of CRP
C. What is it's physiological purpose?
- bind to LPC (lysophosphotidylcholine) on the surface of dying/dead cells and some bateria and activates the complement system via C1Q
107
T/F: Fibrinogen is synthesised in the liver.
True
108
What are the 4 types of hypersensitivities?
What are the mechanisms of each?
Give examples of each.
ACID:
Allergy (I) - IgE mediated and immediate e.g drug anaphylaxis/allergy)
Cytotoxic (II) - cytoxic or Ab-mediated (IgG or IgM) e.g. ABO incompatibility, goodpastures, hyperacute graft rejection
Immune complex (III) - IgG and gM e.g. SLE, PAN, serum sickness, hypersensitivity pneumonitis
Delayed (IV) - cell-mediated e.g. contact dermatitis, chronic graft rejection, latex, TB, T1DM
109
What cell type is most responsible for driving the pathogenesis of sarcoidosis?
Th1 mediated response.
110
In simple terms, compare Th1 and Th2 response.
Th1 response:
- Cell-mediated immunity
- Intracellular pathogens (viruses/bacteria)
- Autoimmunity and Inflammation
Th2 response:
- Ab-mediated immunity
- Extracellular pathogens (parasites)
- Asthma / allergies
111
In simple terms, give the mechanism that the following cell types use to eradicate pathogens:
1. Neutrophils
2. Eosinophils
3. Macrophages
4. CD8 T-cells
5. NK-cells
1. Neutrophils - phagocytosis
2. Eosinophils - release toxic granules into ECF aroung pathogen
3. Macrophages - phagocytosis
4. CD8 T-cells - perforin-mediated cytolysis
5. NK-cells - phagocytosis
112
What target is C3 nephritic factor (C3NF) an autoantibody to?
When is testing indicated?
Which 2 conditions is this autoantibody found in?
C3NF is an autoantibody that is found in MPGN and lipodystrophy. C3NF stabilises C3 convertase (C3bBb) allowing protracted C3 activation and consumption leading to marked reduction in levels.
Therefore C3NF is indicated when C3 levels are very LOW.
113
What are the functions of following complements that occur after C3 convertase in the complement cascade:
A. C3a / C5a
B. C3b
C. C5b / C6 / C7 / C8 / C9
A. C3a / C5a - mediates inflammation and phagocyte recruitment
B. C3b - binds to complement receptors on phagocytes, opsonises pathogens and removes immune complexes
C. C5b / C6 / C7 / C8 / C9 - forms MAC leading to cell/pathogen lysis
114
What is Efalizumab?
What is it's MOA?
What was it used for?
Why was it withdrawn from the US and European market in 2009?
- Efalizumab is humanised mAb against adhesion molecule CD11a that interferes with extravasation of circulating T-cells into skin.
- Previously used in moderate to severe psoriasis.
- Caused severe progressive multifocal leukoencephalopathy (PML) due to reactivation of JC virus.
115
Compare the the initial complements implicated in the 3 pathways of the complement cascade (i.e. prior to converging at C3 convertase).
1. Classical pathway
2. MB-lectin pathway
3. Alternate pathway
1. Classical pathway:
- C1q, C1r, C1s
- C4, C2
2. MB-lectin pathway
- MBL, MASP-1, MASP-2
- C4, C2
3. Alternate pathway
- Factor B, Factor D
- C3b
116
Which of the following is actually C3 convertase?
1. C3bBb
2. C4b2a
Both.
1. C3bBb - from alternative pathway
2. C4b2a - from classic and MB-lectin pathways
117
T/F: Desensitisation is most effective in IgE-mediated immediate type I hypersensitivity e.g. drug causing anaphylaxis.
True.
118
How does drug desensitisation work?
- Gradual and regular administration of allergen via PO or SC route over 3 years
- APC promotes T-reg cell proliferation that release IgG4 that neutralises the IgE, that would have otherwise activated mast cells.
119
A naive T-cell is given the following cocktails of polarising factors, which effector T-cell subset occurs with each:
```
A. IL-12 / IFN-gamma
B. IL-6 / IL-4
C. IL-6 / TGF-beta
D. IL-6 / IL-1-beta / TNF-alpha
E. TGF-beta / IL-2
```
A. IL-12 / IFN-gamma = Th1
B. IL-6 / IL-4 = Th2
C. IL-6 / TGF-beta = Th17
D. IL-6 / IL-1-beta / TNF-alpha = TFh
E. TGF-beta = Treg
120
What are the effector cytokines for the following T-cell subsets:
```
A. Th1
B. Th2
C. Th17
D. TFh
E. Treg
```
A. Th1: IL-1 / IL-10 / TNF-alpha / IFN-gamma
B. Th2: IL-4 / IL-5 / IL-10 / IL-13
C. Th17: IL-17 / IL-21 / IL-22
D. TFh - IL-2 / IL-10 / IL-22
E. Treg: IL-10 / Foxp3 / CD25
121
What is the putative function of Treg cells?
Which 2 conditions may theoretically benefit from enhanced Treg function?
- Maintain peripheral immune tolerance by suppressing CD4+ T-cells that mediate autoimmune responses.
- Multiple sclerosis and Myasthenia Gravis may benefit from enhanced Treg function.
122
What are the cell markers of Treg cells?
CD4+
CD25+
FoxP3+
123
Amyloidosis is the extracellular deposition of insoluble proteins.
What type of amyloid deposits occur in the following types of amyloidosis:
1. AL (Primary) Amyloidosis from monoclonal gammopathies
2. AA (Secondary) Amyloidosis from chronic infection/infammation
3. TTR (Familial) Amyloidosis
4. SSA (Senile systemic) Amyloidosis in the elderly (>70yrs)
5. AB2M Amyloidosis in dialysis patients
1. AL (Primary) Amyloidosis = immunoglobulin light chains produced in BM by plasma cells
2. AA (Secondary/Reactive) Amyloidosis = SSA (Serum Amyloid A) (SAA)
3. TTR (Familial) Amyloidosis = unstable mutant transthyretin produced in liver
4. SSA (Senile systemic) Amyloidosis = wild-type (normal) tranthyretin
5. AB2M Amyloidosis = beta-2 microglobulin
124
You suspect amyloidosis in a patient.
What would expect from histology of a biopsy site to confirm the diagnosis?
Apple-green birefringence of amyloid deposits when stained with congo red dye viewed under polarised light.
125
Which is the only biologic that may be used in SLE?
Belimumab = anti-BAFF
- inhibits B-cell activating factor (BAFF) - aka B-lymphocyte stimulator (BLyS)
- B cells have over-aggressive immune response in SLE.
126
T/F: Glucocorticoids cause eosinophil apoptosis.
True
127
What are the functions of Th1 pathway?
- INTRACELLULAR organisms (bactrerial/viral)
- Autoimmunity
- Inflammation
128
What are the functions of Th2 pathway?
- Parasitic infections
| - Allergies
129
What are the functions of Th17 pathway?
- EXTRACELLULAR organisms (bacteria and fungi)
| - Autoimmunity
130
What are the functions of Treg pathway?
- Self-tolerance
| - Minimises Th1/Th17 (inflammation/autoimmunity) and Th2 (allergy)
131
Correlate the following protein with the type of T-cell they are found on:
```
STAT 1
STAT 3
STAT 4
STAT 5
Foxp3
```
```
Th1 = STAT 1 + STAT 4
Th2 = STAT 6
Th17 = STAT 3
Treg = STAT 5 + Foxp3
```
MCQ knowledge
flashcards
Decks in class (22)
# Cards
-
Psychiatry8
-
Infectious Diseases91
-
Immunology131
-
Haematology62
-
Gastroenterology105
-
Respiratory33
-
Renal72
-
Dermatology5
-
Rheumatology22
-
Neurology84
-
EBM and Statistics16
-
Pharmacology12
-
Pregnancy and Reproduction22
-
Weird and wonderful7
-
Oncology35
-
Genetics50
-
Endocrine163
-
Toxicology1
-
Cardiology117
-
Geriatrics49
-
Drugs27
-
Multisystem Diseases3
