Crash course: hypersensitivity, transplant, therapeutics, HIV Flashcards
(160 cards)
1
Q
What is Gel and Coomb’s Type 1 hypersensitivity reaction?
A
Anaphylactic
Immediate hypersensitivity
IgE mediated. Mast cells + Eosinophils. (Rarely self antigen)
2
Q
What is the pathophysiology of a T1 hypersensitivity reaction?
A
1st exposure: SENSITISATION
APCs take antigen to LN, presents to + primes Th2 cells
Cytokine release by Th2:
* IL-4: B cell class switching- produce specific IgE which primes mast cells via Fc region
* IL-5: promotes eosinophil development + proliferation
2nd exposure: ALLERGY
Allergens bind to IgE on mast cells → degranulation
Release histamine →
SM contraction + vasodilation
3
Q
What are the 2 types of IgE mediated allergic disease?
A
Anaphylaxis
Oral allergy syndrome
4
Q
What occurs in oral allergy syndrome?
A
Sx limited to mouth
- Inhale pollen, produce IgE
- Antibodies cross react with pollen proteins shared by fruits e.g. pear
Heat labile allergens- No Sx if cooked
5
Q
Give 1 example of mixed IgE + cell mediated allergic disease
A
Atopic dermatitis
6
Q
Give 1 example of non-IgE mediated allergic disease. What is the mechanism?
A
Coeliac
Local lymphocytic destruction, more chronic picture with damage occurring over time
7
Q
What is the management of anaphylaxis?
A
A-E
Call for help
Remove trigger, position supine, raise legs
IM adrenaline 1:1000, repeat if no response
IV crystalloid
Antihistamines only after airway, breathing + circulation corrected
NO steroids
8
Q
By what mechanism does adrenaline act on receptors in treatment of anaphylaxis?
A
Alpha1: causes peripheral vasoconstriction, reverses low BP + mucosal oedema
Beta1: increases HR + contractility + BP
Beta2: relaxation of bronchial SM + reduces release of inflammatory mediators from mast cells/ basophils
9
Q
What are the positives (3) and negatives (4) of skin prick testing?
A
+ve’s:
Rapid
Cheap
NPV 95%
-ve’s:
Need to stop antihistamine
Poor PPV
Affected by derm disease e.g. eczema
Risk of anaphylaxis
10
Q
When is IgE blood testing used for allergic disease? What is the disadvantage?
A
Test of choice if SPT/ IDT not possible
PREDICTION of allergy only (sensitisation- levels of IgE + affinity to allergen)
11
Q
What is the gold standard investigation for allergy? What does this involve? What are the disadvantages ?
A
Oral challenge
Give increasing doses of food suspected to be allergic to
High risk of anaphylaxis
Time consuming
12
Q
What is Gel and Coomb’s Type 2 hypersensitivity reaction?
A
Cytotoxic
Antibody reacts with CELLULAR antigen (intrinsic/ extrinsic)
13
Q
What is a pre-requisite for Type 2 hypersensitivity reactions?
A
Breaking of central tolerance
(Any cell that is capable of recognizing self proteins should be destroyed, sometimes this doesn’t happen → auto-reactive B cells)
14
Q
What are the intrinsic and extrinsic antigens targeted in type 2 hypersensitivity reactions?
A
Intrinsic (in cells/ on cell surface)
Extrinsic (if take meds, peptides end up on surface of host cells e.g. penicillin peptides→ auto-reactive cells attack the cells displaying the antigen)
15
Q
What occurs in Type II reactions?
A
B cells usually producing IgG to antigen within host trigger phagocytosis, complement cascade + MAC activation → cell lysis + cytolytic granules released
16
Q
Give 2 examples of Type 2 hypersensitivity reactions
A
Goodpasture disease
Pemphigus vulgaris
17
Q
What is the antigen targeted in Goodpastures disease? Give 2 symptoms
A
Basement membrane of collagen type IV
Glomerulonephritis
Pulmonary haemorrhage: haemoptysis
18
Q
What is the antigen targeted in Pemphigus vulgaris? Give 1 symptom
A
Epidermal cadherin
Skin blistering
19
Q
What is a variant of type 2 hypersensitivity reactions? What happens? Give 2 examples
A
Type 5 hypersensitivity reactions
Ab doesn’t cause destruction, but interferes with normal functions- blocks receptor or overstimulates
Graves disease
Myasthenia gravis
20
Q
What is the antigen targeted in Graves disease? What does this cause?
A
TSH receptor (overstimulation)
Hyperthyroidism
21
Q
What is the antigen targeted in Myasthenia gravis? What does this cause?
A
ACh receptor (blocks)
Muscle weakness (blocked action potentials)
22
Q
What is Gel and Coomb’s Type 3 hypersensitivity reaction?
A
Immune complex.
IgG antibody reacts with SOLUBLE antigen to form an immune complex.
23
Q
What is the pathophysiology of Type 3 hypersensitivity reactions?
A
Immune complexes form clumps → activation of complement
Complement acts as anaphylatoxins- causes oedema, inflammation, skin reactions
Recruitment of other immune cells. Phagocytes fail to phagocytose immune complexes, releasing enzymes in process
24
Q
What does the release of enzymes by phagocytes in type 3 hypersensitivity reactions lead to?
A
Inflammation + fibrinoid necrosis
(histological pattern seen on microscopy)
25
What is the antigen targeted in SLE? Give 3 broad symptoms
Nuclear antigens: dsDNA + Histone (drug induced)
Nephritis
Arthritis
Skin lesions
26
What is the antigen targeted in Polyarteritis nodosa? What is the consequence?
Hep B surface antigen
Systemic vasculitis
27
What is Gel and Coomb's Type 4 hypersensitivity reaction?
Delayed type.
T-cell mediated response: CD4 or CD8
28
What occurs in a CD4 mediated Type 4 hypersensitivity reaction?
1. DC takes antigen to LN, activates naive T cells
2. CD4 T cells recruit macrophages
3. Macrophages creates reactive oxygen species, release lysozymes + lots of inflammatory cytokines
4. Recruit many more immune cells
29
What occurs in a CD8 mediated Type 4 hypersensitivity reaction?
1. DC takes antigen to LN, activates naive T cells
2. CD8 T cells directly cause apoptosis via: perforin + granzyme
30
What 4 syndromes/ situations does a Type 4 hypersensitivity reaction occur?
Contact dermatitis
Tuberculin skin test
T1DM
Hashimoto's
31
What is the target and consequential symptoms in contact dermatitis ?
Poison ivy, metals e.g. nickel
Inflammation
Rash
Blister
+/- fever
32
What is the target and consequential symptoms in tuberculin skin test ?
Tuberculin
Induration, erythema at injection site
33
What is the target and consequential symptoms in T1DM?
Pancreatic islet cells
Insulin deficiency
34
What is the target and consequential symptoms in Hashimoto's?
Thyroglobulin on Thyroid epithelial cells
Hypothyroidism, goitre
35
What is the timeline of transplant rejection?
1. Antigens on graft are recognized as foreign proteins
2. Activation of antigen specific lymphocytes
3. Damage
36
Name 2 important determinants of transplant rejection
HLA/ MHC
ABO blood group
37
What is HLA encoded on? Which cells express HLA?
Chr6
HLA class I (A,B,C): all cells
HLA class II (DR, DQ, DP): only present on APCs as need to be able to present to T cells, but some other cells upregulate it in times of stress e.g. infection
38
Which HLA is most important to match? (from most important to least)
DR > B > A
39
What is the chance of HLA matching with a sibling?
HLA inherited via parents so:
25% chance of perfect match
50% chance of half match
25% chance of no match
40
What is the chance of a perfect HLA match with a stranger?
1 in 100,000
41
What is a perfect match in terms of HLA?
Perfect match = 0 mismatched
Completely unmatched = 6 mismatches
(2 alleles for each of HLA-A, HLA-B + HLA-DR)
42
What occurs in T cell mediated transplant rejection?
1. Recognition: Direct, Indirect or Semi-direct pathway
2. T cell activation
3. Organ damage: cytotoxic T cells + macrophages destroy foreign cells, graft begins to fail
43
What is the direct pathway of recognition in T cell mediated transplant rejection?
Some of donor APCs are present on organ/ in its vessels
Donor APCs present donor HLA to recipient T cells
44
What is the indirect pathway of recognition in T cell mediated transplant rejection? When does this occur?
Recipient APC presents peptides from donor to recipient T cells
Can occur when graft cells die + release proteins
45
What is the semi-direct pathway of recognition in T cell mediated transplant rejection? When does this occur?
Recipient APC presents donor HLA to recipient T cells
Occurs when cells swap HLA between themselves
46
What occurs in antibody mediated transplant rejection?
1. Recognition of something foreign body
2. B cell proliferation + maturation
3. Organ damage: graft specific Abs bind to graft ENDOTHELIUM
47
What antibodies are produced in antibody mediated rejection?
Anti-HLA Abs (not naturally occurring)
Pre-formed: Prior Transplantation, pregnancy, transfusion.
Post-formed: Arise after transplantation.
Other antibodies:
Anti-A or anti-B Abs (naturally occurring)
48
Describe the damage that occurs in antibody mediated rejection
Graft specific Abs bind to graft endothelium
Causes INTRAVASCULAR disease, leading to graft failure
49
How is transplant rejection screened and monitored?
Antibodies: before, during + after
T cells: organ function e.g. creatinine +/- biopsy
50
What investigation is used to confirm transplant rejection?
Biopsy
Antibody mediated: disease in vasculature
T cells: in zone
51
What is a defining histological feature of antibody mediated rejection?
Glomerulitis
Capillaries stuffed with inflammatory cells + swollen endothelial cells that are damaged
52
What footprint signature of antibody mediated rejection is sometimes identifiable with a stain?
Complement activation on endothelial cell surface with stain for C4d
53
Which is the main cell that is injured in the effector phase of antibody mediated rejection?
Endothelial cell
54
What induction agents are used prior to transplantation?
OKT3, ATG: Anti-CD3 monoclonal antibody (anti-thymocyte globulin)
Daclizumab: Anti-CD25 monoclonal antibody
Alemtuzumab: Anti-CD52 monoclonal antibody
55
What is used for baseline suppression in transplants to prevent rejection?
Calcineurin inhibitors: Cyclosporine, tacrolimus
+
Mycophenolate mofetil: MPA inhibitor
OR
Azathioprine: inhibits purine synth
+/- Steroids
56
What specific treatment can be used for T cell mediated transplant rejection?
Methylprednisolone
3 pulses 60mg/kg IV + oral taper
ATG/OKT3
57
What specific treatment can be used for B cell mediated transplant rejection?
Plasma exchange
IV Ig
Anti-B cell agents: Rituximab (anti-CD20), anti-CD5
58
What is autologous stem cell transplant?
Patients own SCs frozen
High dose- cytoreductive Tx for cancer
Thaw + reinfuse
59
Give 3 indications for autologous stem cell transplant
Multiple myeloma
Lymphoma (relapse)
Solid tumours
60
Give 4 advantages of autologous stem cell transplant
No GvHD risk
No immunosuppressant needed: thus lower infection risk
Readily available
More tolerable (elderly)
61
What are the disadvantages of autologous SCT?
Graft contaminated with malignant cells
No "graft vs leukaemia" effect
= Higher relapse rate
62
What is allogenic stem cell transplant?
HLA-matched donor Sis harvested
Patient BM destroyed
Introduce new Sis which colonise the marrow
63
What are the advantages of allogenic stem cell transplant?
Graft vs leukaemia effect
Graft free from malignant cells
= lower relapse/ recurrence
64
Give 3 disadvantages of allogenic stem cell transplant
GvHD risk
Opportunistic infections
Regimen toxicity: infection, 2nd malignancy
65
What is graft versus host disease?
Irreversible attack of donor lymphocytes on recipient HLA
Causes skin rashes, chronic diarrhoea, bone Sx
66
What is the course of GvHD?
Once started is IRREVERSIBLE
Can dampen down, but can't be cured)
67
What is graft vs leukaemia effect?
White cells in the graft can find + attack any left over malignant cells
68
A 35M requires a renal transplant following a diagnosis of renal malignancy. Rank the following potential donors from most to least preferable in terms of graft outcome.
Parent; unrelated cadaveric donor; twin; sibling; unrelated live donor
Twin
Sibling
Parent
Unrelated liver donor
Unrelated cadaveric donor
69
Which of the following investigations would provide a definitive diagnosis of humoral graft rejection following hepatic transplant?
ALT
Liver biopsy
Prothrombin time
CT Abdomen
Urine dipstick
Liver biopsy
70
Give 3 anti-immune states. What kind of drugs are needed?
Immunodeficiency
Malignancy
HIV/AIDS
Immune boosting therapies
71
What is vaccination reliant on? How does it work?
Rely on immune memory
Following resolution of infection/ exposure to antigen, body retains info of that antigen which allows body to respond in a better + faster way if exposed subsequently
Pre-formed pool of Ab's ready to go + residual pool of specific T + B cells
72
What are 3 requirements of a vaccine?
Generates immunological memory
No adverse reactions
Practical to administer
73
What can be used to boost vaccines? How is this achieved?
Adjuvants- Boost response without affecting specificity
Depot: More antigen over longer period
Stimulant: triggers immune system so it reacts more "assisted activation"
74
Give an example of a vaccine adjuvant
Aluminium salts
75
What is a live attenuated vaccine?
Live pathogen modified to limit pathogenesis
76
Give 3 advantages of live attenuated vaccines?
Lifelong immunity possible: no boosters
Protection against different strains likely
Activates all phases of immune system
77
Give 3 disadvantages of live attenuated vaccines?
Reversion to virulence– e.g. VAPP (Polio vaccine)
Risk for immunosuppressed / deficient
Storage issues (require refrigeration)
78
Which population CANNOT receive live vaccines?
Immunosuppressed e.g. HIV
Due to risk of reversion to virulence
79
Which vaccines are live attenuated?
MMR-VBOY
MMR
VZV
BCG
Oral- polio (Sabin), typhoid
Yellow fever
+ Influenza: Fluent tetra in 2-17y
80
What is an inactivated/ component vaccine?
Destroyed pathogen OR isolated antigenic proteins
81
Give 4 advantages of Inactivated/ component vaccines
No reversion
Safe in immunodeficiency
Easier storage
Low cost
82
Give 3 disadvantages of Inactivated/ component vaccines
Poor immunogenicity
Repeated boosters or modifications needed
Do not follow natural route of infection e.g., SC given for influenza
83
List 7 inactivated vaccines
Influenza (quadrivalent)
Polio (Salk)
Hep A
Rabies
Pertussis
Cholera
Bubonic plague
84
Name 3 component/ subunit vaccines
Hep B [HbS antigen]
HPV [Capsid]
Influenza recombinant: (quadrivalent) [haemagglutinin, neuraminidase]
85
Name 2 toxoid vaccines
Diphtheria
Tetanus
86
What are conjugate vaccines?
Polysaccharide + antigenic protein carrier to enhance response
87
Give 2 advantages of conjugate vaccines
Effective against encapsulated bacteria : NHS
Used for children + splenectomy patients
88
What are the disadvantages of conjugate vaccines?
Similar to inactivated/ component
89
Give 4 examples of conjugate vaccines
N meningitidis
H influenzae
Strep pneumonia (Prevenar)
Tetanus
90
What are DNA/ RNA vaccines?
Pathogen’s genetic material (DNA/RNA) delivered to host cells via viral vector/ lipid complex.
Host cells produce + express protein immune response
91
Give an advantage of DNA/ RNA vaccines
mRNA/lipid complex noninfectious + non integrating
92
Give 3 disadvantages of DNA/RNA vaccines
Relatively new technology: risk of DNA integrating into host
Possible AI responses e.g., SLE
Need target that invokes good immune response
93
Give an example of a DNA/RNA vaccine
mRNA: SARS-CoV-2
Adenoviral vector: AstraZeneca, Sputnik
94
List 4 ways in which the immune response can be boosted
Vaccination
Replacement of missing components
Cytokine
Checkpoint inhibition
95
Give 3 ways in which missing components can be replaced in immunodeficiency
HSCT
Antibodies: normal Ig or specific Ig
T cell transfer
96
What is normal immunoglobulin?
Collected from a number of donors, pooled: contains IgG to a wide range of organisms
Provides baseline broad protection
Doesn't protect against a specific type of infection
97
What are the indications for normal immunoglobulin replacement?
Primary antibody deficiencies: agammaglobulinaemia, Hyper IgM, CVID
Secondary antibody deficiencies: Haem cancer, BM transplant
98
What is specific immunoglobulin replacement?
Passive immunisation used as post-exposure prophylaxis
99
Give 3 conditions for which specific immunoglobulin replacement is indicated
Hepatitis B
Rabies
Varicella zoster
100
Give 4 types of T cell transfer
Virus specific T cells
Tumour infiltrating T cells (TIL–T cell therapy)
T cell receptor T cells (TCR-T cell therapy)
Chimeric antigen receptor T cells (CAR–T cell therapy)
101
What are indications for virus specific T-cell therapy?
EBV related B cell lymphoproliferative disease
Severe persistent viral infection in immunocompromised
102
What are indications for chimeric antigen receptor T-cell therapy?
Acute lymphoblastic leukaemia
Non-Hodgkin lymphoma
CAR-T cells less successful in solid tumours
103
How does CAR-T therapy work?
T-cells with chimeric receptors targeting CD19:
1. Patient’s own T cells removed
2. Genetically engineered to express receptor
3. Expanded in vitro
4. Reintroduced with enhanced capacity to recognise + kill target
104
What recombinant cytokine therapy can be used in renal cancer?
Interleukin 2 (IL-2): Stimulates T cell response in renal cell cancer
105
What can Interferon alpha cytokines be used for?
Antiviral effect: Hep B + C
Anti-cancer effect: Kaposi sarcoma, CML, melanoma
ABC: interferon *A*lpha for hep *B*, *C* + *CML*
106
What can Interferon gamma cytokines be used for?
To enhance macrophage function in Chronic granulomatous disease.
107
What can interferon beta cytokines be used for?
Relapsing-remitting MS
(dampens down immune system, halts further demyelination)
108
How does cancer affect the immune system? How can this be targeted?
Immunosuppressive signals upregulated by cancer
Removing immune checkpoints ("brakes") = boosted response
109
Name 2 examples of checkpoint inhibitors
CTLA-4 - Ipilimumab: Allows T cell activation
PD-1 - Nivolumab: Prevents T cell death (via PDL-PD1 receptor blockade)
110
Name 2 indications for checkpoint inhibition
Advanced melanoma
Metastatic renal cell cancer
111
List 3 pro-immune states. What intervention is needed?
Autoimmune
Autoinflammatory
Allergy
Immunosuppressant therapy
112
What is the immunosuppressant action of corticosteroids?
Within nucleus of cells at transcriptional level
Thus have widespread effects + can be given in different diseases
But NOT immediate effect- takes time to transcribe gene + see downstream effects
113
Give 3 key mechanisms of action of corticosteroids
Prostaglandins: inhibit phospholipase A2→ reduced prostaglandins→ less inflammation
Phagocytes: reduced trafficking→ neutrophil count RISES, **reduced phagocytosis**, reduced enzyme release
Lymphocytes: lymphopenia, cytokine gene expression blocked, **reduced Ab production**, pro-apoptotic
114
What may be seen on bloods after commencing corticosteroids?
Transient neutrophilia (can't escape blood vessels)
115
What do anti-proliferative agents do?
Inhibit DNA synthesis
Cells with rapid turnover e.g. immune cells= most affected
116
Give 3 examples of anti-proliferative agents
Mycophenolate mofetil
Azathioprine
Cyclophosphamide
117
Name 2 side effects of Mycophenolate mofetil
BM suppression:
Cells with rapid turnover (leucocytes + platelets) esp. sensitive.
Infection:
* Particular risk of herpes virus reactivation
* Progressive multifocal leukoencephalopathy (JC virus)
118
Name 2 cell signalling inhibitors
Calcineurin inhibitors: reduce IL-2 expression → reduce T cell proliferation + function
mTOR inhibitors: block T cell proliferation + function.
119
Give 2 examples of calcineurin inhibitors
Ciclosporin
Tacrolimus
120
Give 3 indications for calcineurin inhibitors
Transplantation
SLE
Psoriatic arthritis
121
Give 2 examples of mTOR inhibitors
Sirolimus
Rapamycin
122
Give 1 indication for mTOR inhibitors
Transplantation.
123
What are 5 agents directed at cell surface antigens?
Rabbit anti-thymocyte globulin
Basiliximab: anti-CD25
Abatacept: CTLA4-Ig
Rituximab: anti-CD20
Vedolizumab: anti-a4b7 integrin
124
What is the MOA of Basiliximab? Give 1 indication
binds CD25
Inhibits T cell proliferation
Indication: Rejection prophylaxis
125
What is the MOA of Abatacept? Give 1 indication
Fusion protein
Blocks T cell activation
Indication: Rheumatoid Arthritis
126
What is the MOA of Rituximab? Give 1 indication
Binds CD20
Triggers lysis of B cells- reduces amount of mature B cells circulating + reduces antibody production
Indication: Non-Hodgkin Lymphoma (+ other haem cancers)
127
What is the MOA of Vedolizumab? Give 1 indication
Targets Alpha 4 Beta 7 Integrin
Prevents leukocytes escaping from blood vessels (migration)- cant enter tissues, thus cant cause inflammation
Used in IBD
128
Which antibodies target TNF-alpha? Which conditions can these be used in?
Infliximab: RA, Ankylosing spondylitis, IBD, Psoriasis, Psoriatic arthritis
Adalimumab: Psoriatic arthritis, RA
129
Which antibody targets TNF-alpha AND beta? Which conditions can this be used in?
Etanercept
Ankylosing spondylitis
JIA
RA
Psoriatic arthritis
130
Which antibody targets p40 subunit of IL-12 and IL-23? Which conditions can this be used in?
Ustekinumab
Psoriasis
Psoriatic arthritis
Crohn’s
131
Which antibody targets IL-17A? Which conditions can this be used in?
Secukinumab
Psoriasis
Psoriatic arthritis
Ankylosing spondylitis
132
Which antibody targets Alpha-4 beta-1 integrin? Which condition can this be used in?
Natalizumab
MS
133
Which antibody targets RANK ligand? Which condition can this be used in?
Denosumab
Osteoporosis
134
Which antibody targets IL-6R? Which conditions can this be used in?
Toculizumab
RA
Castleman's disease
135
What is plasmapheresis and plasma exchange?
Aim: Removal of pathogenic Ab.
Patient’s blood passed through cell separator. Own cellular constituents reinfused.
Plasma treated to remove Ig + then reinfused (or replaced with albumin in ‘plasma exchange’).
136
Name 3 severe antibody mediated diseases in which plasmaphoresis/ plasma exchange can be used
Goodpasture's: anti-GBM
Myasthenia Gravis: anti-AChR
Humoral transplant rejection/ ABO incompatibility: anti HLA/AB
137
What is plasmapheresis/ plasma exchange limited by?
Rebound Ab production
Sometimes when return plasma, even though Ab's have been removed, body can recognize that + goes into overdrive + causes rebound antibody production
Give antiproliferative agent e.g. mycophenolate mofetil to prevent this happening
138
What are 3 generic complications of all immunosuppressive therapies?
INFECTION: more severe, atypical organisms, reactivation
MALIGNANCY: Lymphoma (EBV), Melanoma, Non melanoma skin ca.
AI disease due to system dysregulation
139
Give 6 complications of steroid use for immunosuppression
Metabolic: diabetes, dyslipidaemia, osteoporosis
Adrenal suppression: do NOT stop suddenly! (body can't produce steroids for self)
Peptic ulcers
Avascular necrosis
Cataracts, glaucoma
Pancreatitis
140
Give 5 complications of Cyclophosphamide, the anti-proliferative agent
Haemorrhagic cystitis
Bladder ca.
Non melanoma skin ca.
Infertility (M>F)
PJP pneumonia
141
Give 2 complications of Mycophenolate mofetil use as an immunosuppressant (anti-proliferative agent)
PML due to JC virus reactivation
Herpes reactivation
142
Give 2 complications of Mycophenolate mofetil use as an immunosuppressant (anti-proliferative agent)
PML due to JC virus reactivation
Herpes reactivation
143
Give 1 complication of Azathioprine use as an immunosuppressant (anti-proliferative agent)
BM suppression (risk in anyone)
Check for polymorphism of enzyme TPMT= can't metabolise drug properly so very HIGH risk of BM suppression
144
What is a complication of all antibodies targeted to cell surface antigens? Give 2 drug specific complications for Rituximab, Abatacept + Vedlizumab
All: infusion reactions
Rituximab: worsening CV disease, PML
Abatacept: TB, Hep B/C
Vedlizumab: hepatotoxic, PML
145
Give 4 complications of TNF alpha +/or beta antibodies
TB
Hep B/C
Lupus-like disease
Demyelination
146
Give 2 complications of Tocilizumab
Dyslipidaemia
Hepatotoxicity
147
Give 1 complication of Denosumab
Avascular necrosis of the jaw
148
Describe the natural history of HIV as defined by viral replication
Acute: Flu-like illness in 70%
Viral load peaks then dips after 3-6m to a set point whilst CD4 drops, then recovers slightly
Asymptomatic but progressive/ recurrent thrush, TB: Quiescent for 8-10y. Viral load pretty stable, starts to creep up + overtakes CD4 count
AIDS: increase in viral replication as immune system collapses (CD4 200-500). Severe, unusual infections + malignancy
149
Describe the risk of transmission through the natural history of HIV
Directly proportional to amount of virus in blood
Lots of transmission often in acute phase
Risk of transmission declines in asymptomatic, though more people in this category
Risk increases again but when pt is v sick
150
What are the caveats of using serology to detect HIV?
Looking for body's response
To detect Ab's must have been able to make them
If can't mount immune response (primary immunodeficiency) or too early (before 15-45d), test = -ve
Only +ve after seroconversion
151
In which population should serology not be used to detect HIV?
Neonates
because will have Ab transfer from mother, via placenta/ breast milk.
Even if baby not infected with HIV will see antibodies in their blood
Use RNA NAT tests for kids <18m
152
Which test is used first line to screen for HIV?
4th gen ELISA (Enzyme-linked immunosorbent assays): IgM + IgG, p24 antigen
HIV1/2 antibody differentiation immunoassay (or older Western blot)
If indeterminate: RNA
153
What confirmatory tests are used to diagnose HIV?
Nucleic acid testing for HIV RNA
154
What are the rapid 'point-of-care' tests for HIV?
3rd gen antibody only:
Detects IgM + IgG
No lab processing
155
What does HIV bind to? What can this be targeted by?
CD4 T cells via CD4 + CCR5
CCR5 inhibitors: Maraviroc
156
Describe the HIV life cycle
1. Binds to CD4 + then to chemokine co-receptor CCR5 or CXCR4
2. Fuses with host cell membrane
3. Reverse transcription: RNA→DNA
4. Integrates into host genome
5. Replication: HIV DNA transcribed to viral mRNA
6. Assembly: Viral RNA translated to viral proteins
7. Budding: Packaging + release of mature virus
157
Name 1 nucleoside/nucleotide reverse transcriptase inhibitor used in HIV treatment and pre exposure prophylaxis
Tenofovir
158
Give examples of infections seen at different cell counts in HIV
500: bacterial/ fungal skin infection, HSV, HZV
400: Kaposi sarcoma
300: TB
200: PCP
100: Toxoplasmosis, CMV, EBV brain lymphoma
75: Mycobacterium avium complex (MAC)
159
Which drugs can be used as part of antiretroviral therapy?
NRTI
NNRTI
Protease inhibitors
Integrase inhibitors
160
What therapy should all HIV patients be started on?
Triple therapy to reduce risk of resistance by targeting different areas: 2 NRTIs + 1 Protease inhibitor
