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YR5 Immunology > Crash course: hypersensitivity, transplant, therapeutics, HIV > Flashcards

Crash course: hypersensitivity, transplant, therapeutics, HIV Flashcards

1
Q

What is Gel and Coomb’s Type 1 hypersensitivity reaction?

A

Anaphylactic
Immediate hypersensitivity
IgE mediated. Mast cells + Eosinophils. (Rarely self antigen)

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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

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3
Q

What are the 2 types of IgE mediated allergic disease?

A

Anaphylaxis

Oral allergy syndrome

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4
Q

What occurs in oral allergy syndrome?

A

Sx limited to mouth

  1. Inhale pollen, produce IgE
  2. Antibodies cross react with pollen proteins shared by fruits e.g. pear

Heat labile allergens- No Sx if cooked

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5
Q

Give 1 example of mixed IgE + cell mediated allergic disease

A

Atopic dermatitis

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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

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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

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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

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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

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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)

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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

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12
Q

What is Gel and Coomb’s Type 2 hypersensitivity reaction?

A

Cytotoxic
Antibody reacts with CELLULAR antigen (intrinsic/ extrinsic)

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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)

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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)

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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

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16
Q

Give 2 examples of Type 2 hypersensitivity reactions

A

Goodpasture disease

Pemphigus vulgaris

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17
Q

What is the antigen targeted in Goodpastures disease? Give 2 symptoms

A

Basement membrane of collagen type IV

Glomerulonephritis
Pulmonary haemorrhage: haemoptysis

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18
Q

What is the antigen targeted in Pemphigus vulgaris? Give 1 symptom

A

Epidermal cadherin

Skin blistering

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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

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20
Q

What is the antigen targeted in Graves disease? What does this cause?

A

TSH receptor (overstimulation)

Hyperthyroidism

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21
Q

What is the antigen targeted in Myasthenia gravis? What does this cause?

A

ACh receptor (blocks)

Muscle weakness (blocked action potentials)

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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.

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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

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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)

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25
Q

What is the antigen targeted in SLE? Give 3 broad symptoms

A

Nuclear antigens: dsDNA + Histone (drug induced)

Nephritis
Arthritis
Skin lesions

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26
Q

What is the antigen targeted in Polyarteritis nodosa? What is the consequence?

A

Hep B surface antigen

Systemic vasculitis

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27
Q

What is Gel and Coomb’s Type 4 hypersensitivity reaction?

A

Delayed type.
T-cell mediated response: CD4 or CD8

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28
Q

What occurs in a CD4 mediated Type 4 hypersensitivity reaction?

A
  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
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29
Q

What occurs in a CD8 mediated Type 4 hypersensitivity reaction?

A
  1. DC takes antigen to LN, activates naive T cells
  2. CD8 T cells directly cause apoptosis via: perforin + granzyme
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30
Q

What 4 syndromes/ situations does a Type 4 hypersensitivity reaction occur?

A

Contact dermatitis
Tuberculin skin test
T1DM
Hashimoto’s

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31
Q

What is the target and consequential symptoms in contact dermatitis ?

A

Poison ivy, metals e.g. nickel

Inflammation
Rash
Blister
+/- fever

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32
Q

What is the target and consequential symptoms in tuberculin skin test ?

A

Tuberculin

Induration, erythema at injection site

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33
Q

What is the target and consequential symptoms in T1DM?

A

Pancreatic islet cells

Insulin deficiency

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34
Q

What is the target and consequential symptoms in Hashimoto’s?

A

Thyroglobulin on Thyroid epithelial cells

Hypothyroidism, goitre

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35
Q

What is the timeline of transplant rejection?

A
  1. Antigens on graft are recognized as foreign proteins
  2. Activation of antigen specific lymphocytes
  3. Damage
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36
Q

Name 2 important determinants of transplant rejection

A

HLA/ MHC
ABO blood group

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37
Q

What is HLA encoded on? Which cells express HLA?

A

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

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38
Q

Which HLA is most important to match? (from most important to least)

A

DR > B > A

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39
Q

What is the chance of HLA matching with a sibling?

A

HLA inherited via parents so:

25% chance of perfect match
50% chance of half match
25% chance of no match

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40
Q

What is the chance of a perfect HLA match with a stranger?

A

1 in 100,000

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41
Q

What is a perfect match in terms of HLA?

A

Perfect match = 0 mismatched
Completely unmatched = 6 mismatches

(2 alleles for each of HLA-A, HLA-B + HLA-DR)

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42
Q

What occurs in T cell mediated transplant rejection?

A
  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
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43
Q

What is the direct pathway of recognition in T cell mediated transplant rejection?

A

Some of donor APCs are present on organ/ in its vessels

Donor APCs present donor HLA to recipient T cells

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44
Q

What is the indirect pathway of recognition in T cell mediated transplant rejection? When does this occur?

A

Recipient APC presents peptides from donor to recipient T cells

Can occur when graft cells die + release proteins

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45
Q

What is the semi-direct pathway of recognition in T cell mediated transplant rejection? When does this occur?

A

Recipient APC presents donor HLA to recipient T cells

Occurs when cells swap HLA between themselves

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46
Q

What occurs in antibody mediated transplant rejection?

A
  1. Recognition of something foreign body
  2. B cell proliferation + maturation
  3. Organ damage: graft specific Abs bind to graft ENDOTHELIUM
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47
Q

What antibodies are produced in antibody mediated rejection?

A

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)

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48
Q

Describe the damage that occurs in antibody mediated rejection

A

Graft specific Abs bind to graft endothelium
Causes INTRAVASCULAR disease, leading to graft failure

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49
Q

How is transplant rejection screened and monitored?

A

Antibodies: before, during + after

T cells: organ function e.g. creatinine +/- biopsy

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50
Q

What investigation is used to confirm transplant rejection?

A

Biopsy
Antibody mediated: disease in vasculature
T cells: in zone

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51
Q

What is a defining histological feature of antibody mediated rejection?

A

Glomerulitis

Capillaries stuffed with inflammatory cells + swollen endothelial cells that are damaged

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52
Q

What footprint signature of antibody mediated rejection is sometimes identifiable with a stain?

A

Complement activation on endothelial cell surface with stain for C4d

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53
Q

Which is the main cell that is injured in the effector phase of antibody mediated rejection?

A

Endothelial cell

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54
Q

What induction agents are used prior to transplantation?

A

OKT3, ATG: Anti-CD3 monoclonal antibody (anti-thymocyte globulin)

Daclizumab: Anti-CD25 monoclonal antibody

Alemtuzumab: Anti-CD52 monoclonal antibody

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55
Q

What is used for baseline suppression in transplants to prevent rejection?

A

Calcineurin inhibitors: Cyclosporine, tacrolimus
+
Mycophenolate mofetil: MPA inhibitor
OR
Azathioprine: inhibits purine synth

+/- Steroids

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56
Q

What specific treatment can be used for T cell mediated transplant rejection?

A

Methylprednisolone
3 pulses 60mg/kg IV + oral taper

ATG/OKT3

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57
Q

What specific treatment can be used for B cell mediated transplant rejection?

A

Plasma exchange
IV Ig
Anti-B cell agents: Rituximab (anti-CD20), anti-CD5

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58
Q

What is autologous stem cell transplant?

A

Patients own SCs frozen
High dose- cytoreductive Tx for cancer
Thaw + reinfuse

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59
Q

Give 3 indications for autologous stem cell transplant

A

Multiple myeloma
Lymphoma (relapse)
Solid tumours

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60
Q

Give 4 advantages of autologous stem cell transplant

A

No GvHD risk

No immunosuppressant needed: thus lower infection risk

Readily available

More tolerable (elderly)

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61
Q

What are the disadvantages of autologous SCT?

A

Graft contaminated with malignant cells

No “graft vs leukaemia” effect

= Higher relapse rate

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62
Q

What is allogenic stem cell transplant?

A

HLA-matched donor Sis harvested
Patient BM destroyed
Introduce new Sis which colonise the marrow

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63
Q

What are the advantages of allogenic stem cell transplant?

A

Graft vs leukaemia effect

Graft free from malignant cells

= lower relapse/ recurrence

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64
Q

Give 3 disadvantages of allogenic stem cell transplant

A

GvHD risk
Opportunistic infections
Regimen toxicity: infection, 2nd malignancy

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65
Q

What is graft versus host disease?

A

Irreversible attack of donor lymphocytes on recipient HLA
Causes skin rashes, chronic diarrhoea, bone Sx

66
Q

What is the course of GvHD?

A

Once started is IRREVERSIBLE
Can dampen down, but can’t be cured)

67
Q

What is graft vs leukaemia effect?

A

White cells in the graft can find + attack any left over malignant cells

68
Q

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

A

Twin
Sibling
Parent
Unrelated liver donor
Unrelated cadaveric donor

69
Q

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

A

Liver biopsy

70
Q

Give 3 anti-immune states. What kind of drugs are needed?

A

Immunodeficiency
Malignancy
HIV/AIDS
Immune boosting therapies

71
Q

What is vaccination reliant on? How does it work?

A

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
Q

What are 3 requirements of a vaccine?

A

Generates immunological memory

No adverse reactions

Practical to administer

73
Q

What can be used to boost vaccines? How is this achieved?

A

Adjuvants- Boost response without affecting specificity

Depot: More antigen over longer period
Stimulant: triggers immune system so it reacts more “assisted activation”

74
Q

Give an example of a vaccine adjuvant

A

Aluminium salts

75
Q

What is a live attenuated vaccine?

A

Live pathogen modified to limit pathogenesis

76
Q

Give 3 advantages of live attenuated vaccines?

A

Lifelong immunity possible: no boosters

Protection against different strains likely

Activates all phases of immune system

77
Q

Give 3 disadvantages of live attenuated vaccines?

A

Reversion to virulence– e.g. VAPP (Polio vaccine)

Risk for immunosuppressed / deficient

Storage issues (require refrigeration)

78
Q

Which population CANNOT receive live vaccines?

A

Immunosuppressed e.g. HIV
Due to risk of reversion to virulence

79
Q

Which vaccines are live attenuated?

A

MMR-VBOY
MMR
VZV
BCG
Oral- polio (Sabin), typhoid
Yellow fever

+ Influenza: Fluent tetra in 2-17y

80
Q

What is an inactivated/ component vaccine?

A

Destroyed pathogen OR isolated antigenic proteins

81
Q

Give 4 advantages of Inactivated/ component vaccines

A

No reversion
Safe in immunodeficiency
Easier storage
Low cost

82
Q

Give 3 disadvantages of Inactivated/ component vaccines

A

Poor immunogenicity
Repeated boosters or modifications needed
Do not follow natural route of infection e.g., SC given for influenza

83
Q

List 7 inactivated vaccines

A

Influenza (quadrivalent)
Polio (Salk)
Hep A
Rabies
Pertussis
Cholera
Bubonic plague

84
Q

Name 3 component/ subunit vaccines

A

Hep B [HbS antigen]

HPV [Capsid]

Influenza recombinant: (quadrivalent) [haemagglutinin, neuraminidase]

85
Q

Name 2 toxoid vaccines

A

Diphtheria
Tetanus

86
Q

What are conjugate vaccines?

A

Polysaccharide + antigenic protein carrier to enhance response

87
Q

Give 2 advantages of conjugate vaccines

A

Effective against encapsulated bacteria : NHS

Used for children + splenectomy patients

88
Q

What are the disadvantages of conjugate vaccines?

A

Similar to inactivated/ component

89
Q

Give 4 examples of conjugate vaccines

A

N meningitidis
H influenzae
Strep pneumonia (Prevenar)
Tetanus

90
Q

What are DNA/ RNA vaccines?

A

Pathogen’s genetic material (DNA/RNA) delivered to host cells via viral vector/ lipid complex.

Host cells produce + express protein immune response

91
Q

Give an advantage of DNA/ RNA vaccines

A

mRNA/lipid complex noninfectious + non integrating

92
Q

Give 3 disadvantages of DNA/RNA vaccines

A

Relatively new technology: risk of DNA integrating into host

Possible AI responses e.g., SLE

Need target that invokes good immune response

93
Q

Give an example of a DNA/RNA vaccine

A

mRNA: SARS-CoV-2

Adenoviral vector: AstraZeneca, Sputnik

94
Q

List 4 ways in which the immune response can be boosted

A

Vaccination

Replacement of missing components

Cytokine

Checkpoint inhibition

95
Q

Give 3 ways in which missing components can be replaced in immunodeficiency

A

HSCT

Antibodies: normal Ig or specific Ig

T cell transfer

96
Q

What is normal immunoglobulin?

A

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
Q

What are the indications for normal immunoglobulin replacement?

A

Primary antibody deficiencies: agammaglobulinaemia, Hyper IgM, CVID

Secondary antibody deficiencies: Haem cancer, BM transplant

98
Q

What is specific immunoglobulin replacement?

A

Passive immunisation used as post-exposure prophylaxis

99
Q

Give 3 conditions for which specific immunoglobulin replacement is indicated

A

Hepatitis B
Rabies
Varicella zoster

100
Q

Give 4 types of T cell transfer

A

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
Q

What are indications for virus specific T-cell therapy?

A

EBV related B cell lymphoproliferative disease

Severe persistent viral infection in immunocompromised

102
Q

What are indications for chimeric antigen receptor T-cell therapy?

A

Acute lymphoblastic leukaemia

Non-Hodgkin lymphoma

CAR-T cells less successful in solid tumours

103
Q

How does CAR-T therapy work?

A

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
Q

What recombinant cytokine therapy can be used in renal cancer?

A

Interleukin 2 (IL-2): Stimulates T cell response in renal cell cancer

105
Q

What can Interferon alpha cytokines be used for?

A

Antiviral effect: Hep B + C
Anti-cancer effect: Kaposi sarcoma, CML, melanoma

ABC: interferon Alpha for hep B, C + CML

106
Q

What can Interferon gamma cytokines be used for?

A

To enhance macrophage function in Chronic granulomatous disease.

107
Q

What can interferon beta cytokines be used for?

A

Relapsing-remitting MS
(dampens down immune system, halts further demyelination)

108
Q

How does cancer affect the immune system? How can this be targeted?

A

Immunosuppressive signals upregulated by cancer

Removing immune checkpoints (“brakes”) = boosted response

109
Q

Name 2 examples of checkpoint inhibitors

A

CTLA-4 - Ipilimumab: Allows T cell activation

PD-1 - Nivolumab: Prevents T cell death (via PDL-PD1 receptor blockade)

110
Q

Name 2 indications for checkpoint inhibition

A

Advanced melanoma
Metastatic renal cell cancer

111
Q

List 3 pro-immune states. What intervention is needed?

A

Autoimmune
Autoinflammatory
Allergy

Immunosuppressant therapy

112
Q

What is the immunosuppressant action of corticosteroids?

A

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
Q

Give 3 key mechanisms of action of corticosteroids

A

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
Q

What may be seen on bloods after commencing corticosteroids?

A

Transient neutrophilia (can’t escape blood vessels)

115
Q

What do anti-proliferative agents do?

A

Inhibit DNA synthesis

Cells with rapid turnover e.g. immune cells= most affected

116
Q

Give 3 examples of anti-proliferative agents

A

Mycophenolate mofetil
Azathioprine
Cyclophosphamide

117
Q

Name 2 side effects of Mycophenolate mofetil

A

BM suppression:
Cells with rapid turnover (leucocytes + platelets) esp. sensitive.

Infection:
* Particular risk of herpes virus reactivation
* Progressive multifocal leukoencephalopathy (JC virus)

118
Q

Name 2 cell signalling inhibitors

A

Calcineurin inhibitors: reduce IL-2 expression → reduce T cell proliferation + function

mTOR inhibitors: block T cell proliferation + function.

119
Q

Give 2 examples of calcineurin inhibitors

A

Ciclosporin
Tacrolimus

120
Q

Give 3 indications for calcineurin inhibitors

A

Transplantation
SLE
Psoriatic arthritis

121
Q

Give 2 examples of mTOR inhibitors

A

Sirolimus
Rapamycin

122
Q

Give 1 indication for mTOR inhibitors

A

Transplantation.

123
Q

What are 5 agents directed at cell surface antigens?

A

Rabbit anti-thymocyte globulin

Basiliximab: anti-CD25

Abatacept: CTLA4-Ig

Rituximab: anti-CD20

Vedolizumab: anti-a4b7 integrin

124
Q

What is the MOA of Basiliximab? Give 1 indication

A

binds CD25
Inhibits T cell proliferation

Indication: Rejection prophylaxis

125
Q

What is the MOA of Abatacept? Give 1 indication

A

Fusion protein
Blocks T cell activation

Indication: Rheumatoid Arthritis

126
Q

What is the MOA of Rituximab? Give 1 indication

A

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
Q

What is the MOA of Vedolizumab? Give 1 indication

A

Targets Alpha 4 Beta 7 Integrin
Prevents leukocytes escaping from blood vessels (migration)- cant enter tissues, thus cant cause inflammation

Used in IBD

128
Q

Which antibodies target TNF-alpha? Which conditions can these be used in?

A

Infliximab: RA, Ankylosing spondylitis, IBD, Psoriasis, Psoriatic arthritis

Adalimumab: Psoriatic arthritis, RA

129
Q

Which antibody targets TNF-alpha AND beta? Which conditions can this be used in?

A

Etanercept

Ankylosing spondylitis
JIA
RA
Psoriatic arthritis

130
Q

Which antibody targets p40 subunit of IL-12 and IL-23? Which conditions can this be used in?

A

Ustekinumab

Psoriasis
Psoriatic arthritis
Crohn’s

131
Q

Which antibody targets IL-17A? Which conditions can this be used in?

A

Secukinumab

Psoriasis
Psoriatic arthritis
Ankylosing spondylitis

132
Q

Which antibody targets Alpha-4 beta-1 integrin? Which condition can this be used in?

A

Natalizumab

MS

133
Q

Which antibody targets RANK ligand? Which condition can this be used in?

A

Denosumab

Osteoporosis

134
Q

Which antibody targets IL-6R? Which conditions can this be used in?

A

Toculizumab

RA
Castleman’s disease

135
Q

What is plasmapheresis and plasma exchange?

A

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
Q

Name 3 severe antibody mediated diseases in which plasmaphoresis/ plasma exchange can be used

A

Goodpasture’s: anti-GBM

Myasthenia Gravis: anti-AChR

Humoral transplant rejection/ ABO incompatibility: anti HLA/AB

137
Q

What is plasmapheresis/ plasma exchange limited by?

A

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
Q

What are 3 generic complications of all immunosuppressive therapies?

A

INFECTION: more severe, atypical organisms, reactivation

MALIGNANCY: Lymphoma (EBV), Melanoma, Non melanoma skin ca.

AI disease due to system dysregulation

139
Q

Give 6 complications of steroid use for immunosuppression

A

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
Q

Give 5 complications of Cyclophosphamide, the anti-proliferative agent

A

Haemorrhagic cystitis
Bladder ca.
Non melanoma skin ca.
Infertility (M>F)
PJP pneumonia

141
Q

Give 2 complications of Mycophenolate mofetil use as an immunosuppressant (anti-proliferative agent)

A

PML due to JC virus reactivation

Herpes reactivation

142
Q

Give 2 complications of Mycophenolate mofetil use as an immunosuppressant (anti-proliferative agent)

A

PML due to JC virus reactivation

Herpes reactivation

143
Q

Give 1 complication of Azathioprine use as an immunosuppressant (anti-proliferative agent)

A

BM suppression (risk in anyone)

Check for polymorphism of enzyme TPMT= can’t metabolise drug properly so very HIGH risk of BM suppression

144
Q

What is a complication of all antibodies targeted to cell surface antigens? Give 2 drug specific complications for Rituximab, Abatacept + Vedlizumab

A

All: infusion reactions

Rituximab: worsening CV disease, PML

Abatacept: TB, Hep B/C

Vedlizumab: hepatotoxic, PML

145
Q

Give 4 complications of TNF alpha +/or beta antibodies

A

TB
Hep B/C
Lupus-like disease
Demyelination

146
Q

Give 2 complications of Tocilizumab

A

Dyslipidaemia
Hepatotoxicity

147
Q

Give 1 complication of Denosumab

A

Avascular necrosis of the jaw

148
Q

Describe the natural history of HIV as defined by viral replication

A

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
Q

Describe the risk of transmission through the natural history of HIV

A

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
Q

What are the caveats of using serology to detect HIV?

A

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
Q

In which population should serology not be used to detect HIV?

A

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
Q

Which test is used first line to screen for HIV?

A

4th gen ELISA (Enzyme-linked immunosorbent assays): IgM + IgG, p24 antigen

HIV1/2 antibody differentiation immunoassay (or older Western blot)

If indeterminate: RNA

153
Q

What confirmatory tests are used to diagnose HIV?

A

Nucleic acid testing for HIV RNA

154
Q

What are the rapid ‘point-of-care’ tests for HIV?

A

3rd gen antibody only:
Detects IgM + IgG
No lab processing

155
Q

What does HIV bind to? What can this be targeted by?

A

CD4 T cells via CD4 + CCR5
CCR5 inhibitors: Maraviroc

156
Q

Describe the HIV life cycle

A
  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
Q

Name 1 nucleoside/nucleotide reverse transcriptase inhibitor used in HIV treatment and pre exposure prophylaxis

A

Tenofovir

158
Q

Give examples of infections seen at different cell counts in HIV

A

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
Q

Which drugs can be used as part of antiretroviral therapy?

A

NRTI

NNRTI

Protease inhibitors

Integrase inhibitors

160
Q

What therapy should all HIV patients be started on?

A

Triple therapy to reduce risk of resistance by targeting different areas: 2 NRTIs + 1 Protease inhibitor

YR5 Immunology (14 decks)

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