Immunology Flashcards
(124 cards)
1
Q
Define the terms ‘allergen’ and ‘allergic disorder’
A
An allergen is a foreign protein that stimulates an IgE-mediated immune response
An allergic disorder is an immunological response that occurs after exposure to an allergen, with reproducibility
2
Q
Describe the pathogenesis of allergic disorder
A
- Allergens can cause epithelial stress -> cytokines released including TSLP, IL-25 +33
- Cytokines act primarily on Th2 cells (+Th9, ILC2) to cause more cytokine release (IL 4, 5, 13) which recruit eosinophils and basophils
- Also stimulate Tfh2 cells to produce IL-4 which recruits B cells to produce IgE and IgG4
*Key points: allergens cause epithelial cells to release TSLP, which stimulates Th2 cells to recruit eosinophils + basophils, and make B cells produce IgE
3
Q
Describe the role of mast cells in allergic disease
A
Allergens cause IgE crosslinking on mast cells -> release of histamine, leukotrienes and prostaglandins
- > vasodilation, permeability, smooth muscle contraction, etc
- > swelling, inflammation, airway obstruction, itching
4
Q
___ exposure is more likely to cause IgE formation and allergy compared to ___ exposure, because of ___ cells
A
Skin/respiratory exposure vs oral exposure because of Treg cells in the GI tract
5
Q
Describe the symptoms and signs of an IgE mediated immune response
A
Occurs minutes-hours after exposure, reproducible
- Lip + tongue swelling
- Difficulty breathing, stridor, wheeze
- Urticaria
- Nasal congestion + itching
- Watery red eyes
- D+V
- Hypotension
6
Q
How are IgE-mediated allergic disorders diagnosed? Describe the different tests, and positives + negatives
A
-Clinical evidence is essential for diagnosis. IgE adds to diagnosis but alone is not enough
-During an episode: serial mast cell tryptase (suspected anaphylaxis, unclear)
-Skin prick testing: prick skin to inject the allergen. Need a positive control (histamine) and negative control (diluent). Wait 15-20 minutes and measure the wheals (NO antihistamines in this time). 3+ mm over control is positive test for sensitivity. Rapid and easy, good NPV. Need experience, not great PPV, have to stop antihistamines.
-RAST: put patient IgE on solid polymer of allergen to cause binding. Add a fluorescent tagged IgE antibody that is specific to the patient IgE you are looking for (eg. anti-peanut protein IgE). If binds, this is positive for that IgE type. Used if widespread skin disease preventing SPT, can’t stop antihistamines. Expensive.
-Component resolved testing: IgE to single protein. Especially used in peanut allergy where there are 5 major allergens causing different symptoms
-Basophil activation test: looks at if basophils are activated in response to allergens. Activated cells express CD63, CD203 and CD300
GOLD STANDARD for food + drug: challenge test
-Exposed to slowly increasing quantities of allergen in a controlled medical environment w/ resusc ability. Double blind + placebo.
7
Q
Define anaphylaxis.
A
A life-threatening acute immunological response to allergen exposure. Affects airways and circulation.
Usually IgE mediated, also IgG or complement.
8
Q
Name some conditions that can mimic anaphylaxis
A
ACEi use can cause urticaria and angioedema
C1 inhibitor deficiency can cause throat swelling (hereditary angioedema)
Severe asthma, MI, PE, anxiety, phaeo, systemic mastocytosis
9
Q
Describe the management of anaphylaxis
A
- Elevate legs and give high flow O2
- IM adrenaline
- Inhaled bronchodilators
- IV fluids
- IV Hydrocortisone 200mg
- IV chlorphenamine 10mg
-Refer to allergy clinic for investigation, give written info, EpiPen x2, Medic Alert bracelet. Dietician if food allergy
10
Q
What is the difference between food allergy and food intolerance?
A
- Allergy: immunological mediated hypersensitivity to specific allergens in food
- Intolerance: non-immunological hypersensitivity
11
Q
What is oral allergy syndrome?
A
A type of allergic disorder caused by allergy to pollen causing cross-reactivity with fruits eg. apple. Only if raw.
Oral cavity symptoms: swelling, itching
12
Q
What are some skin barriers to pathogens?
A
Tightly packed cells, low pH, sebaceous glands with oils, lysozymes + ammonias
13
Q
Name some mucous membrane barriers to pathogens
A
Mucin, IgAs, lysozymes, lactoferrin, cilia, commensals
14
Q
ImportedName some components of the innate immune system
A
Neutrophils, eosinophils, basophils Monocytes/macrophages NK cells Dendritic cells Complement Cytokines
15
Q
Describe the function of polymorphs in the innate immune response
A
Migrate to sites of injury
Express pattern recognition receptors (PRRs)
Destroy pathogens by phagocytosis, oxidative and non-oxidative killing
16
Q
What is the difference between polymorphs and macrophages?
A
Polymorphs cannot present antigens to T cells
17
Q
Describe oxidative and non-oxidative killing
A
Oxidative: NADPH oxidase creates reactive oxygen species -> damage
Non-oxidative: release of enzymes
18
Q
What is opsonisation?
A
Opsonins (Igs) bind to bacteria and aid in phagocytosis
19
Q
Describe the function of NK cells
A
- Primarily regulated by Inhibition by normal T cells
- Cytotoxic when no inhibitory signals
20
Q
Describe the function of dendritic cells
A
Phagocytose pathogens
Migrate to lymph nodes to present antigens to lymphocytes
21
Q
What are the primary lymphoid organs? Secondary?
A
1˚: Bone marrow and thymus
2˚: spleen, lymph nodes
22
Q
What are some differences between the innate and adaptive immune responses?
A
Adaptive has much more pathogen recognition and is not genetically encoded, also has memory
23
Q
Describe the process of T cell maturation
A
T cells created in the bone marrow
Migrate to the thymus
Undergo affinity maturation (a process where they are checked for the correct response to antigens- self-reactive or non-reactive undergo apoptosis)
24
Q
What is the function of CD4+ cells? CD8+?
A
CD4+: detect foreign antigens presented on HLA class II (DR, DP, DQ). Immune regulatory function eg. activate B cells/CD8 CD8+: detect self antigens presented on HLA class I (A, B, C). Cytotoxic with FasL, perforin, secrete cytokines
25
Which cells express foxp3?
Treg cells
26
Describe the process of B cell maturation and differentiation
- Created in the bone marrow as pre B cells (IgM)
- Central tolerance check
- Can stay as IgM or
- Undergo reaction in germinal centre to differentiate into IgG, IgA, IgE (somatic hypermutation and isotype switching), with help of primed CD4+ Th cells and CD40L
27
Describe the structure of Igs
2 heavy chains, 2 light chains
Fc region: binds to receptor/produces effect
Fab region: variable, binds to antigen
28
What are the 3 pathways of complement activation?
Classical: C1, 2, 4. Activated by immune complexes
Alternative: C3 binds directly to pathogen cell wall components
Mannose binding pathway: MBL, C2, C4. Binds directly to cell surface.
--> common pathway: C3, C5-9 -> MAC
29
What type of virus is HIV? What is the key enzyme it has?
RNA retrovirus. Reverse transcriptase -> inserts into genome.
30
Describe the genetic makeup of HIV
9 genes encoding 15 proteins
- Envelope proteins: gp120 and gp41
- Gag proteins: p17, 24, 9, 7. 24- capsid
- Enzymes: RT, protease, IN
31
How is HIV transmitted? Which cells does HIV infect? Describe the process of HIV infection
Transmission through blood, sex (damaged mucosal surfaces), vertical.
CD4+ T cells, monocytes, dendritic cells
Uses CD4 and CCR5/CXCR4 to enter cells via gp120 binding.
32
Describe the immune response to HIV infection and how HIV persists
Innate: macrophage activation, CK release, NK cells
Adaptive:
-Antibodies to gp120, gp41, p24 gag IgG released -> HIV is still infective
-Both HIV infection and CD8+ cell response leads to decreased CD4 count
**Bc CD4 cells low/inactive -> poor CD8 response
-HIV replication is error prone -> lots of mutations -> evade immune defences
33
Describe the life cycle of HIV with relevant proteins/enzymes
1. Binding and entry via gp120 and gp41
2. RT converts RNA to DNA
3. Integration into host genome (integrase)
4. RNA transcription
5. Protein synthesis
6. Protein packaging and release (protease)
34
Describe the different targets of HIV drugs and name examples
1. Attachment inhibitors (Maraviroc)
2. RT inhibitors: nucleoside (Zidovudine), non-nucleoside (Efavirenz), nucleotide (Tenofovir)
3. Integrase inhibitors: raltegrivir
4. Protease inhibitors: ritonavir
35
What does a typical ART regime consist of?
2 NRTIs and PI/NNRTI
36
Describe the clinical course of HIV infection
- Primary infection with seroconversion. Asymptomatic/mild flu-like illness with generalised lymphadenopathy
- Asymptomatic phase, with slowly declining CD4 and stable viral load
- AIDS after 8-10 years: rapid decline in CD4 and CD8, increased viral load. Increased susceptibility to infections/disease (AIDS defining illnesses)
37
What are some reasons for long term slow progressors with HIV?
- Genetic factors eg. HLA subtypes, CCR5 mutations etc
- Less severe strains
- Strong immune response
38
Describe investigations for HIV
Screening: ELISA (HIV antibodies)
Confirm: Western blot (antibodies)
Viral load (PCR) and CD4 count (flow cytometry): baseline and monitoring
Resistance testing: phenotypic (basically sensitivity testing), genotypic (sequence for genes assoc w/ resistance). Used in determining treatment.
39
Who should be given HAART?
All patients should be offered!!!
| Old recommendations: when CD <200 or symptomatic
40
What are some benefits and limitations of HAART?
Benefits: suppresses viral load, improves CD4 count to improve host immunity, delays/prevents AIDS, prevents transmission
Limitations: does not cure infection, must be taken regularly without missing or risk of mutation, toxicity/SE, cost, high pill burden (adherence)
41
Which is the most common type of HIV in the world?
HIV-1. HIV-2 in parts of Africa
42
What is PEP? PrEP?
PEP: Truvada eg. Tenofivir/Emtricitabine + Raltegrivir
PrEP: Truvada
43
Name some examples of secondary immunodeficiency
HIV, leukemia, malnutrition, steroids, chemotherapy
44
What would make you consider the possibility of immunodeficiency?
- Recurrent minor infections or multiple major infection
- Unusual organism
- Unusual site
- Chronic infection
Primary: Family Hx, young age, poor growth
45
Name some primary immune deficiencies causing phagocyte deficiency and briefly describe the pathophysiology
- Kostmann syndrome: failure of maturation -> neutropenia
- Cyclic neutropenia: failure of maturation -> episodic neutropenia
- Reticular dysgenesis: severe SCID. Neutrophils + other cells do not develop. Fatal if no BMT.
- Leukocyte adhesion deficiency: neutrophils can't cross blood -> tissues. High levels in blood, no pus.
- Chronic granulomatous disease: neutrophils can't do oxidative killing -> build up -> granulomas. Also hepatosplenomegaly.
- Cytokine deficiency (IL-12, IFNg): deficiencies in the pathway that activates neutrophils/phagocytes when there is Mycobacterium infection.
46
How is chronic granulomatous disease diagnosed?
Nitro-blue tetrazolium test (NBT): tests for hydrogen peroxide -> blue. Negative in CGD
Dihydrorhodamine (DHR) flow cytometry: turns fluorescent. Negative in CGD
Both of these test for the presence of superoxide species formed by NADPH, which is deficient in CGD
47
What would you expect in a person with primary phagocyte deficiency? What investigations would you do?
```
Recurrent infections of skin/mouth esp bacterial, TB
Neutrophil count (FBC), CD18, NBT/DHR test, pus
```
48
Name some types of NK cell deficiency. How would NK deficiency present?
-Classical NK deficiency: no NK cells
-Functional NK deficiency: reduced action of NK cells
Increased viral infections (eg recurrent HSV, severe VZV)
49
What would you expect to see in someone with complement deficiency?
Increased susceptibility to bacterial infections, specifically encapsulated bacteria (N men, Haemophilus, Strep)
50
Why is complement deficiency associated with SLE?
Complement stimulates the clearing up of immune complexes/dead cells
If deficient -> build up of immune complexes
51
What are some complement deficiencies?
- Classical pathway: C1, 2, 4 deficiency. C2 is most common, almost all have SLE. Can also have 2˚ deficiency due to using up in SLE
- Mannose binding lectin: common to be heterozygotic, doesn't really cause issues unless another reason for immunocompromise eg. chemo.
- Alternative: rare
- Common pathway: C3 deficiency. Severe.
- MAC deficiency
52
How are complement deficiencies investigated?
```
Complement levels (quantitative)
Complement function (qualitative)- CH50 classical + common, AP50 alternative + common
SLE ABs eg. anti-dsDNA, ANA, anti-Sm
```
53
How does C1q deficiency present?
Severe SLE in childhood, normal C3 and C4 levels
54
How does MBL deficiency present?
Recurrent infections when new immunocompromise (eg chemo), but previously well
55
What is SCID? What are some types?
Severe combined immunodeficiency: a group of ~20 conditions all causing defects in B+T cell immune function (combined)
Reticular dysgenesis: most severe form. Lymphoid + myeloid affected
X-linked SCID: most common (45%). IL2 receptor mutation -> no cytokine response means no development of T cells and immature B cells.
ADA deficiency: poor development of all lymphocytes
56
How do you differentiate the types of SCID?
Reticular dysgenesis: low lymphocytes + polymorphs
X-linked: low T/NK cells, normal/high B cells, no Ig
ADA: low levels of T/B/NK cells
57
How does SCID present?
Illness from ~3 months old (before this, protected by maternal IgG)
- Infections
- Failure to thrive
- Persistent diarrhoea
- Skin disease
- Family Hx
58
Name some types of primary T cell deficiency and briefly describe
- DiGeorge syndrome (22q11 del): thymic aplasia -> low T cell count, normal B cells. Improvement with age
- Bare lymphocyte syndrome Type II: problems with MHC II expression -> CD4 deficiency -> no IgG/A
- IL12/IFNg deficiency: causes poor phagocyte + Th cell response.
- Wiskott-Aldrich syndrome (WAS): low Plts, high IgE (eczema), lymphopenia
59
What are some features of T cell deficiency?
Recurrent/severe viral infections eg. CMV
Fungal infections eg. PCP, crypto
Early malignancy
60
How would you investigate suspected T cell deficiency?
- FBC and differential
- Flow cytometry
- Ig levels
- HIV test!!!
61
Which test is a good marker of CD4 cell presence/function? Why?
IgG and IgA - the maturation/class switching of pre-B cells into IgG/A plasma cells is dependent on CD4 Th cells
62
T/F. The IgM response is T cell dependent
False. IgM does not require T cell support, but IgG/A/E does -> this is the germinal centre reaction/isotype switching
63
Name some primary B cell deficiencies and briefly describe
- Bruton's X linked hypogamma globulinaemia: tyrosine kinase mutation -> no maturation of pre-B cells into mature B cells -> no Ig
- Selective IgA deficiency
- Hyper IgM syndrome: no CD40L on T cells -> no isotype switching -> ONLY IgM, no IgG/A/E
- Common variable immune deficiency: unknown cause. Low Ig A and G, especially IgG.
64
How do B cell deficiencies present?
Typically ~3 months or later (due to loss of maternal Ig)
- Recurrent infections
- Especially URTIs in IgA deficiency
- Autoimmune disease and granulomas in CVID
- Boys more commonly affected in Bruton's and Hyper IgM
65
How would you investigate suspected B cell deficiency?
FBC and differential
Flow cytometry (lymphocyte subsets)
Ig levels and electrophoresis (gamma peak shows all Ig)
Functional testing eg. vaccination against tetanus/pneumovax -> check IgG levels after few weeks
66
What is the difference between auto-inflammatory and auto-immune disease?
Auto-inflammatory: activation of innate immune response -> local inflamamtion
Auto-immune: breakdown of immune tolerance to self (adaptive system) -> systemic/local inflammation
67
What is the basic pathophysiology of monogenic auto-inflammatory conditions? Give 1-2 examples
Mutations in the inflammasome complex (eg. pathways from pathogen -> local inflammation thru IL-1, TNF)
- Familial Mediterranean fever: MEFV mutation. Episodic neutrophil activation -> abdo pain, chest pain, rash, arthritis.
- TRAPS
68
What is the basic pathophysiology of monogenic auto-immune conditions? Give several examples
Mutations leading to breakdown in tolerance eg. Treg cell abnormality, apoptosis
- APCED: defect in AIRE protein responsible for T cell selection (central tolerance) -> too many self-reactive T cells
- IPEX: foxp3 mutation -> no Treg cells -> failure of peripheral tolerance
- ALPS: FAS pathway defect -> no apoptosis of lymphocytes (high lymphocytes, splenic enlargement)
69
Name some common polygenic auto-inflammatory disorders
- Crohn's
- UC
- Ankylosing spondylitis
70
Which HLA is associated with ankylosing spondylitis?
HLA-B27
71
T/F. HLA associations are more common in auto-inflammatory conditions, while auto-antibodies are more common in auto-immune conditions
False. Both are more common in auto-immune conditions
72
Name some common auto-immune conditions and classify them by Gel and Coombs method
Gel and Coombs method is the types of reaction (1-4)
Type II hypersensitivity reactions (AB mediated):
-Grave's disease
-Sjogren's syndrome
-Pemphigus
Type III hypersensitivity reactions (immune complex):
-SLE
Type IV hypersensitivity reactions (T cell mediated):
- Type 1 DM
- Rheumatoid arthritis
- MS
73
Which HLA is associated with Type 1 DM?
DR 3 + 4
74
What are the seronegative arthropathies? What does this term mean?
Psoriatic arthritis, reactive arthritis, ank spon
| They are associated with no RF/anti-CCP, but with HLA-B27
75
SLE is associated with which HLA?
DR3
76
Rhematoid arthritis is associated with which HLA?
DR4
77
What are the Grave's antibodies? What type of Ig are they?
| How about Hashimoto's?
IgG. anti-TSHR
| IgG. anti-TPO, anti-thyroglobulin. These are not specific though, and we often do not measure them as they are common.
78
Which antibodies are found in T1DM?
anti-islet cell, anti-GAD (glutamic acid dehydrogenase) and anti-IA2 (islet antigen), anti-insulin
79
Which antibodies are found in MG? What is the test used in diagnosis?
```
anti-nicotinic ACh R
Tensilon test (edrophonium- cholinesterase inhibitor)
```
80
Which antibodies are found in RA? Which is the most specific? Sensitive?
RF (IgM antibody) and anti-cyclic citrullinated peptide (CCP)
anti-CCP is the most specific (95%)
RF is the most sensitive (85%)
81
Which different immune mechanisms contribute to rheumatoid arthritis?
Type II: antibodies eg. RF, anti-CCP
Type III: immune complexes deposited in joints
Type IV: T cell mediated destruction
82
Which antibodies are found in SLE? Which is most sensitive and which is most specific? Which is used for monitoring disease activity?
anti-dsDNA (a type of ANA), anti-Sm, anti-Ro, anti-La
dsDNA is the most specific, also quite sensitive. Used for monitoring disease activity (along with complement)
anti-Ro and La not very specific, also found in others
83
Which antibodies are found in antiphospholipid syndrome?
Lupus anticoagulant
| Anti-cardiolipin
84
Which antibodies are found in the inflammatory myositis?
Dermatomyositis: Jo1 and Mi2
85
What are the types of ANCA? What are they antibodies towards?
cANCA: Ab to proteinase 3. Cytoplasmic staining
pANCA: Ab to myeloperoxidase. Perinuclear staining
86
What are the stages of immune response to transplanted organ?
1) Recognition
2) Activation of adaptive immune response
3) Effector phase (graft rejection)
87
Which are the most important antigens involved in transplant rejection?
ABO
| HLA molecules: most important are A, B, DR
88
What is HLA matching in transplantation? How is it done?
Compare the alleles at A, B and DR
Everyone has 2 alleles x 3 genes = 6 possible mismatches. Matching reduces graft rejection
PCR donor and recipient for HLA type -> maximise matching. Also check for preformed ABs + crossmatch
89
Describe the process of T cell mediated graft rejection
Recognition: T cell activation requires HLA molecule presenting an antigen, costimulatory signals and cytokine release
Activation: proliferation of T cells, cytokine rekease, B cell recruitment
Effector phase: lymphocytes migrate thru endothelium into the interstitium and release enzymes, destroy cells via FasL
90
What are the histological characteristics of T cell mediated graft rejection?
*Interstitial inflammation* and tubular epithelial inflamm
Lymphocytic infiltration
Inflammation of *arteries
91
Describe the process of antibody mediated graft rejection
Recognition: donor antigen detected + presented by APC
Activation: B cell proliferation (dependent on CD4 Th) after germinal centre reaction
Effector phase: antibodies produced that bind to endothelial surface HLA
92
What are the histological characteristics of antibody mediated graft rejection?
ABs on the endothelial surface (immunofluorescence), complement fixing
*Capillary* endothelial cell inflammation
93
What are some signs of graft rejection?
```
Rising Cr (kidney)
Abnormal LFTs (liver)
```
94
What are the different types of graft rejection? What is the mechanism in each?
Hyperacute (mins-hours): preformed ABs detect graft and activate complement (usually ABO)
Acute (<6 months): T cell or AB mediated. Usually direct recognition by donor APCs presenting antigen
Chronic (>6 months): T cell or AB mediated. Usually indirect by recipient APCs presenting antigen.
95
What is graft vs host disease? How does it present?
Where the donor lymphocytes found in the graft attack the host tissues.
Presents with rash, D+V, bloody stool, jaundice etc
96
Which drugs are used to prevent graft rejection?
Want to inhibit the immune response
- T cell: steroids, calcineurin inhibitors (Tacrolimus), cell cycle inhibitors (Mycofenilate mofetil), monoclonal ABs
- Antibody: rituximab, proteasome inhibitors, plasma exchange
97
Describe the immunosuppression regime in transplantation
1. Pre-transplant induction: OKT3/anti-CD25
2. Baseline immunosuppression: steroids, MMF, tacrolimus
3. Episodic treatment: steroids, OKT3, plasma exchange, IVIG
98
What are some complications of transplantation?
- Graft rejection
- GVHD
- Increased opportunistic infections eg. CMV
- Malignancy eg. Kaposi's, EBV related, skin cancer
- Atherosclerosis
99
What are some reasons for declining renal function in someone with a kidney transplant? What tests can be done?
-Graft rejection
-Drug toxicity
-Vascular disease
-Recurrence of disease (reason for transplantation)
BP, U+Es, Biopsy!
100
What is immunological memory? Which cells are involved?
The ability of the immune system to have an enhanced response to a subsequent infection
Includes both CD8 T cells and IgG B cells
101
Which antibodies are protective against influenza?
Antibodies to haemaglutinin (on the surface of influenza)
102
What is the effect of the BCG vaccine?
Does not prevent against primary infection
| Prevents against active infection (T cell response)
103
What are the different types of vaccines? Give examples of each
- Live attenuated: MMR, BCG, yellow fever, oral typhoid + polio (Sabin), chickenpox.
- Inactivated: influenza, polio (Salk), rabies, pertussis
- Component: Hep B, HPV, influenza
- Conjugate: tetanus, Hib, meningococcus, pneumococcus
- Toxoid: diphtheria, tetanus
- mRNA: Pfizer Covid vaccine
104
What are some advantages and disadvantages of live attenuated vaccines?
Advantages: longer lasting memory, protects against cross-reactive strains, activates innate + adaptive immune response
Disadvantages: should be used with caution in immunosuppression, harder to store, may revert
105
What are some advantages and disadvantages of inactivated vaccines?
Advantages: easy to store, cheaper, safe in immunosuppression, no reversion
Disadvantages: poorer + shorter immunity, need boosters
106
MMR is a type of __ vaccine
Live attenuated
107
Meningococcal is a type of __ vaccine
Conjugate
108
HBV is a type of __ vaccine
Component
109
What is a conjugate vaccine? Name some examples.
Protein + polysaccharide. The polysaccharide is from the capsule of the bacteria, but vaccination with only this causes B cell only response.
Protein stimulates a T cell response to boost the B cell response.
eg. Hib, meningococcus, pneumococcus (encapsulated bacteria)
110
What is the purpose of adjuvants in vaccines? Name some examples.
Adjuvants increase the immune response without altering the contents of the vaccine. Mimic PAMPs and bind to PRRs on innate immune cells
eg. aluminium, lipids CpG
111
What is passive immunisation?
Giving protection to pathogen without stimulating the recipient immune response
-eg. specific Ig for VZV, HBV, rabies
112
What is CAR-T cell therapy?
Remove T cells -> insert a vector containing a specifically engineered receptor to target tumour cell (eg CD19 for B cell malignancy) -> T cells express this receptor -> infuse -> T cells detect target cells and proliferate -> destroy malignant cells
113
What is the effect of steroids?
- Inhibit prostglandin formation: inhibit PLA2 (forms arachidonic acid)
- Inhibit phagocyte function: inhibit migration, phagocytosis
- Inhibit lymphocyte release + function: cause sequestration, block CK and AB release
114
Name some antiproliferative agents. How do they work?
Work by inhibiting DNA synthesis.
- Cyclophosphamide: alkylating agent -> damages DNA. B > T cell
- Azathioprine: antimetabolite. Prevents nucleotide synthesis. T > B cells
- Mycophenolate mofetil: blocks guanine synthesis. T > B cell
- Methotrexate: folate inhibitor
115
What are some uses and side effects of cyclophosphamide?
Uses: not widely used: malignancy, severe vasculitis
| Side effects: BM suppression, malignancy, sterility, haemorrhagic cystitis
116
What are some uses and side effects of azathioprine?
Uses: widely used in transplantation, auto-immune/inflammatory diseases eg IBD
Side effects: BM suppression, hepatotoxicity, neutropenia
**Severe response in people with TPMT polymorphism
117
What are some uses and side effects of mycophenolate mofetil?
Uses: widely used in transplantation. Also auto-immune/inflammatory disease
Side effects: BM suppression, PML (JC virus), HSV, malignancy
118
What is plasmapharesis? When is it used?
Remove patients blood, separate plasma from solid components -> reinfuse solid (eg cells)
Plasma is treated to remove Igs and reinfused/replaced with albumin solution (plasma exchange)
Used in severe antibody mediated disease eg anti-GBM
119
Name some cell signalling inhibitors
Calcineurin inhibitors eg. Tacrolimus, cyclosporin
| JAK inhibitor eg. Tofacitinib
120
How do calcineurin inhibitors work (broadly)? What are some side effects?
Inhibit production of IL-2 -> inhibits T cell proliferation
| SEs: nephrotoxicity, hypertension, neurotoxicity, DM
121
What is rituximab? What is it used for?
Anti-CD20 antibody. Destroys mature B cells (not plasma cells)
Uses: lymphoma, RA, SLE
122
Name some anti-TNFa antibodies. What are their uses? What are some side effects?
Infliximab, adalimumab
Uses: RA, ankspon, IBD
SEs: infection (TB, HBV), lupus-like conditions, demyelination
123
What is a monoclonal antibody used in the treatment of osteoporosis?
Denosumab
124
Which HLA is associated with coeliac?
DQ2
