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Pathology and final year > Immunology > Flashcards

Immunology Flashcards

1
Q

what are the constitutive/ physical barriers to infection?

A

SKIN
tightly packed keritanised skin cells
low pH of skin

MUCOSA
secretory igA
lyzozyme
lactoferin- starves invading bacteria of iron
cilia

COMMENSAL BACTERIA
skin microflora
gut microflora

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2
Q

what are the specific names for macrophages in each of these organs:

liver
kidney
spleen
bone
lung
neural tissue
connective tissue
skin

A

liver- kupfer cells
kidney- mesangial cell
spleen- sinusoidal lining cells
bone- osteoclast
lung- alveolar macrophage
neural tissue- microglia
connective tissue- histocyte
skin- langerhans cells

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3
Q

briefly describe oxidative killing of microbia

A

NADPH oxidase complex converts oxygen to ROS (eg. superoxide, hydrogen peroxide)

myeloperoxidase catalyses production of hydroclorus acid which is antimicrobial

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4
Q

describe non oxidative killing of microbia

A

granular release of lyzozyme and lactoferrin into the phagolysosome

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5
Q

What happens during phagocytosis

A

phagocyte engulfs microbia via endocytosis. This process depleats phagocytes glycogen reserves leading to cell death

build up of dead neutrophils at site of infection –> abscess

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6
Q

what is migration of dendritic cells to lymph nodes mediated by?

A

CCR7 on DC recognise the chemokines CCL19 and CCL21

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7
Q

cell markers on T cells

A

all express CD3 (TCR)
CD8+ cells are cytotoxic T cells
CD4+ cells are T helper cells

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8
Q

Which HLA subtypes are there in class II and which cells express?

A

HLA-DR, HLA-DQ, HLA-DP
class II expressed by APCs
recognised by CD4+ cells

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9
Q

What are the different effector subtypes of CD4+ cells and what are their actions

A

Th1 cell-
polarised by IL12, IFNg
helps CD8+ and macrophages.
secretes IL2, IFNg, TNFa, IL10

Th2
polarised by IL4 and IL6
secretes IL4, IL5, IL13, IL10
helps humoral response

Th17
polarised by IL6, TGFb
helps neutrophil recruitment and generation of autoantibodies
secretes IL17, I21, IL22

Tfh
polarised by IL6, IL1b, TNFa
follicular helper T cells in B cell maturation
secretes IL2, IL10, IL21

Treg
polarised by TGFb
regulates T cell response expressing foxp3

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10
Q

Which HLA subtypes are there in class I and which cells express?

A

HLA A, B, C
expressed by ALL cells
recognised by CD8+ cells

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11
Q

How do CD8+ cells directly kill

A

secretes perforin and granzymes into cell –> apoptosis

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12
Q

which portion of Abs recognise antigens and which portion interacts with other components of the immune system?

A

Fab –> pathogen/antigen
Fc –> immune cells

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13
Q

briefly describe the different pathways of complement

A

classical:
Ab-Ag complex causes a conformational change of Ab, exposing binding site for C1 which activates cascade

mannose:
activated by direct binding of mannose binding lectin to mannose on bacteria cell surface carbohydrates . Directly stimulates activation of C4 and C2 (but not C1)

Alternate:
triggered by binding of C3 to bacterial cell wall eg. LPS or teichoic acid

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14
Q

Primary immune deficiencies:

feature of IgA deficiency

A

recurrent resp and GI infections

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15
Q

Primary immune deficiencies:

Kostmann syndrome

A

autosomal recessive severe congenital neutropenia
(eg <500/ul)

no pus formation

due to mutation oin HCLS1-associated protein X-1 (HAX1)

positive NBT test

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16
Q

Primary immune deficiencies:

Cyclic neutropenia

A

autosomal dominant
episodic neutropenia every 4-6 weeks and lasts ~6days

mutation in neutrophil elastase (ELA-2)

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17
Q

Primary immune deficiencies:

Reticular dysgenesis

A

failure of stem cells to differentiate along the myeloid or lympoid lineage
(failure of production of granulocytes, lymphocytes, monocytes and platelets)

fatal in very early life

autosomal recessive
mutation in mitochondrial energy metabolism enzyme AK2

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18
Q

Primary immune deficiencies:

Leukocyte adhesion deficiency

A

neutrophils lack CD18 (b2 integrin subunit) so cant adhere to endothelial cells and transmigrate

feature:
- very high neutrophil count in blood
- absence of pus formation
- delayed umbilical chord separation

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19
Q

Primary immune deficiencies:

chronic granulomatous disease

A

X-linked
deficient in NADPH so fails to make ROS
impaired killing on pathogens
–> excessive inflammation and neutrophil/macrophage accumulation

non caseating granuloma formation, hepatosplenomegaly, lyphadenopathy

susceptable to PLACESS microbes (pseudomonas, listeria, aspergillus, candida, E.coli, staph aureus, serratia)

Ix:
negative Nitro-blue tetrazolium test (pos: yellow-> blue when incontact with hydrogen peroxide)

normal neutrophil count

Mx:
IFNg

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20
Q

Primary immune deficiencies:

deficiency of IL-12 and IFNg

A

susceptibility to mycobacteria, BCG and salmonella

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21
Q

Primary immune deficiencies:

complement deficiencies

A

deficiency in C1, C2 or C4 (C2 most common)

almost all with C2 deficiency have SLE

increased susceptibility to encapsulated bacteria:
-Haemophilus influenzae type B (Hib)
-Streptococcus pneumoniae (pneumococcus)
-Neisseria meningitides (meningococcus)
-Group B streptococcus (GBS)
-Salmonella typhi.

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22
Q

Primary immune deficiencies:

severe combined immunodeficiency (SCID)

A

unwell by 3 months of age
before protected by maternal IgG

  • infections of all types
  • failure to thrive
  • persistent diarrhoea

FHx of early infant death

diminished T cells and non-functional B cells

hypoplasia and atrophy of the thymus

mucosal associated lymphoid tissue (MALT)

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23
Q

X-linked SCID

A

45% of SCID
- X-linked recessive
mutation of gamma chain of IL2 receptor on chromosome Xq13.1

inability to respond to cytokines causes arrest of T cell and NK cell development and production of immature B cells

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24
Q

Di George syndrome

A

22q11.2 deletion
developmental defect of pharyngeal pouch (embryological abnormality in 3rd and 4th brachial arches)

CATCH-22
Cardiac abnormalities
Atresia (oesphageal)
[Abnormal face (high forehead, low set ears)]
Thymic aplasia
Clef palate
Hypocalcaemia/hypoparathyroidism
22- chromosome

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25
Q

Investigtions for phagocytic immune deficiencies

A

Nitro blue tetrazolium test:
yellow - blue in the presence of hydrogen peroxide ROS

DRH flow cytometry reaction
DRH- rhodamine in the presence of hydrogen peroxide which is very fluorescent

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26
Q

investigations for complement deficiencies

A

CH50 and AP50 tests

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27
Q

investigations for lymphocyte deficiencies

A

WCC, lymphocyte subsets, serum Ig, protein electrophoresis

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28
Q

autoimmune polyendocrine syndrome type 1(APS1)

A

monogenetic autoimmune disease

autosomal recessive
abnormality in tolerance

defect in AIRE so failure of central tolerance –> autoreactive T and B cells

Features:
multiple autoimmune diseases
hypothyroidism, addisons, hypopaarathyroidism, T1DM, vitiligo, enteropathy

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29
Q

Immune dysregulation, polyendocrinopathy, enteropathy (IPEX)

A

X linked
abnormality of Tregs
mutation in FOXP3

features:
T1DM, hypothyroidism, enteropathy

diabetes, diarrhoea and dermatitis

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30
Q

autoimmune lymphoproliferative syndrome (ALPS)

A

abnormality of lymphocyte apoptosis
autosomal dominant
mutation in Fas pathyway

features:
autoimmune cytopenias
lymphoma

‘APOPtosis to the ALPS would be FASt’

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31
Q

HLA associations with Ankylosing spondylitis

A

HLA B27

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32
Q

HLA associations with goodpastures syndrome

A

HLA DR15/DR2

‘Dr Too Good’

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33
Q

HLA associations with Graves disease

A

HLA DR3

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34
Q

HLA associations with SLE

A

HLA DR3

‘SLE and DR3’

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35
Q

HLA associations with T1DM

A

HLA DR3/DR4

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36
Q

HLA associations with RA

A

HLA DR4

‘RA-dR4’

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37
Q

autoantibodies and associated condition:

anti-Smooth muscle

A

autoimmune hepatitis or primary sclerosing cholangitis

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38
Q

autoantibodies and associated condition

p-ANCA

A

eosinophilic granulomatosis with polyangiitis
(aka: Churg strauss syndrome)

blood vessels of lungs, GIT and peripheral nerves most commonly affected

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39
Q

autoantibodies and associated condition

anti-Jo1

A

dermomyositis with interstitial pulmonary involvement
–> autoimmune inflammation of muscle fibre in skin

and polymyositis

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40
Q

autoantibodies and associated condition

anti-cyclic citrullinated protein

A

RA

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41
Q

autoantibodies and associated condition

anti-centromere

A

CREST syndrome
(limited cutaneous form of systemic sclerosis)

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42
Q

autoantibodies and associated condition

anti-double stranded DNA

A

SLE

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43
Q

autoantibodies and associated condition

anti-parietal cell

A

pernicious anaemia

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44
Q

autoantibodies and associated condition

anti-TSH

A

graves

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45
Q

autoantibodies and associated condition

anti-topoisomerase

A

diffuse systemic scleroderma

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46
Q

autoantibodies and associated condition

anti-mitochondrial

A

Primary billiary cirrhosis

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47
Q

autoantibodies and associated condition

c-ANCA

A

Granulomatosis with polyangiitis
(aka wengers granulomatosis)

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48
Q

autoantibodies and associated condition

anti-cardiolipin

A

antiphospholipid syndrome
SLE
syphilis?

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49
Q

autoantibodies and associated condition

anti-ribonucleoprotein and anti-U1RNP ab

A

mixed connective tissue disease

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50
Q

autoantibodies and associated condition

anti-glutamic acid decarboxylase

A

T1DM

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51
Q

autoantibodies and associated condition

anti-Ro and anti-La

A

Sjogrens and SLE

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52
Q

autoantibodies and associated condition

anti-intrinsic factor

A

pernicious anaemia

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53
Q

autoantibodies and associated condition

anti-endomysial

A

Coeliac and dermatitis herpatiformia

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54
Q

Primary immune deficiencies:

Bruton’s agammaglobulinaemia

A

X linked disease
mutation of BTK gene which expresses tyrosine kinase
‘BruTonsX(K)’

mutation inhibits B cell maturation and therefore low Ig levels

bloods:
notmal T cell
low B cell, absent plasma cells
low IgA, IgM and IgG

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55
Q

immune deficiencies:

hyper IgM syndrome

A

mutation in CD40 ligand on T cells required in the germinal centre development of B cells
- unable to class switch and thereofre leads to high IgM
- deficient IgA, IgG and IgE

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56
Q

Wiskott Aldrich syndrome

A

X-linked
mutation in WASp gene
WAS protein expressed in developing haematopoetic stem cells

mutation is linked to development of lymphomas, thrombocytopenias and eczema

Sx: easy bruising, nose bleeds, GI bleeds, petechiea,

recurrent bacterial infections caused by haemophilus influenzae and strep pneumoniea

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57
Q

what are you at risk of of with hyposplenism

A

risk of infections by encapsulated bacteria, for example strep pneumoniea
(spleen has lots of lymoid tissue)

  • vaccinations and prophylactic Abx
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58
Q

clinical features of dermatomyositis

A

heliotrope rash around eyes
gottrons papules on dorsum of finger
proximal limb weakness

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59
Q

features of CREST syndrome

A

Calcinosis
Raynauds
Esphageal dysmotilisty
Sclerodactyly
Telangectasia

hypergammaglobulinaemia
anaemia
raised ESR

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60
Q

Features of Sjogrens syndrome

A

Dry eyes (confirmed by schirmers test)
dty mouth
parotid swelling
fatigue
arthralgia
myalgia

autoimmune destruction of exocrine glands

salivary gland biopsy reveals infiltrate of T and B

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61
Q

features of granulomatosis with polyangiitis

A

saddle nose deformity (due to perforated septum)

pulmonary haemorrhage (haemoptysis)
glomerulonephritis (haematuria)

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62
Q

examples of type I hypersensitivity reaction

A

Anaphylaxis
food allergy
oral allergy syndrome
allergic rhinitis
atopic dermatitis
acute urticaria

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63
Q

examples of type II hypersensitivity reaction

A

ANY DISEASE WITH AUTOANTIBODIES TO ANTIGEN ATTACHED TO TISUE
autoimmune haemolytic anaemia
AITP
Goodpastures syndrome
Graves
myesthenia gravis
pernicious anaemia

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64
Q

examples of type III hypersensitivity reaction

A

SLE
Mixed essential cryoglobulinaemia
serum sickness
polyarteritis nodosa

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65
Q

examples of type IV hypersensitivity reaction

A

T1DM
multiple sclerosis
RA
contact dermatitis
Mantoux test
Chrons disease

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66
Q

what is a type I hypersensitivity reaction?

A

immediate IgE mediated reaction provoked by are-exposure to an allergen

mast cell release of histamines

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67
Q

what is a type II hypersensitivity reaction?

A

IgG or IgM autoantibody reacting to self tissue or matrix

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68
Q

what is a type III hypersensitivity reaction?

A

IgG or IgM immune complexes reacting to a soluble antigen causing tissue damage

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69
Q

what is a type IV hypersensitivity reaction?

A

delayed type hypersensitivity which is T cell mediated

70
Q

autoantibodies in hashimotos thyroiditis

A

anti-TPO and anti-thyroglobulin

71
Q

autoantibodies in hashimotos thyroiditis

A

anti-TPO and anti-thyroglobulin

72
Q

autoantibodies in T1DM

A

anti-glutamate decarboxylase and anti- pancreatic B cells

73
Q

autoantibodies in ITP/AITP

A

anti-glycoprotein IIb-IIa or Ib-IX Ab

74
Q

autoantibodies in goodpastures syndrome and features

A

anti-glomerular basement membrane Abs

glomerulonephritis and pulmonary haemorrhage

75
Q

What antibody tests are there for coeliac?

A

anti-endomysial Ab (95% specific, 85% sensitive)

anti-transglutaminase Ab (95% sensitive, 95% specific)

anti-gliadin antibody (30-50% specific, 60% sensitive)

76
Q

Associations with coeliac

A

Trisomy 21
Dermatitis herpatiformis
DQ2 or DQ8 (2 8 or not to eat)

77
Q

What primary immune deficiency is associated with delayed umbilical chord detachment

A

leukocyte adhesion deficiency type 1

78
Q

Conditions that may lead to impaired primary barrier function

A

Coeliac –> impaired mucociliary clearance

Keratoconjunctivitiis sicca–> dry eyes (lysozyme in tears)

79
Q

What measures total complement activity?

A

CH50 (measures all components of classical and final pathways (C1-9)

AH50 measures components of alternative pathway

80
Q

what is reduced C3 and C4 associated with?

A

SLE

81
Q

What is reduced C3 but normal C4 associated with?

A

membranoproliferative glomerulonephritis

82
Q

What is the role of IgD?

A

found on cell surface of immature B cells and plays a role in lymphocyte activation

83
Q

HLA associations with coeliac

A

HLA DQ2

‘DQ2 i need a poo’

84
Q

Features of APECED

A

mild immune deficiency
dysfunctional parathyroid
dysfunctional adrenal
hypothyroidism
gonadal failure
alopecia
vitiligo

Mutation of AIRE gene

85
Q

what are some mechanisms of autoimmunity?

A

molecular mimicry and cross reactivity

defect in central tolerance (AIRE gene mutation)

defect in peripheral tolerance immune regulation (FOXP3 defect)

IL2 therapy associated with autoimmune thyroid disease

Release of ‘hidden’ atigens after damage eg. Dresslers syndrome where MI causes release of proteins and generation of auto-Abs –> pericarditis

86
Q

What is Von Gierke’s disease

A

Glycogen storage disease casued by a deficiency in G6PD

present with severe hypoglycaemia and neutropenia

87
Q

What is a positive Nikolsky’s sign indicative of?

A

Pemphigus vulgaris

88
Q

how long after transplantation would an acute cellular reaction occur?

A

~1 week

89
Q

MOA of cyclosporine

A

inhibits protein phosphate calcineurin which reduces IL2 secretion from T cells and T cell proliferation

90
Q

MOA of azathioprine

A

metabolised to 6-mercaptopurine which acts as a purine analogue and prevents DNA synthesis mostly affecting lymphocytes

91
Q

MOA of methotrexate

A

anti-metabolite and anti-folate drug
inhibits dihydrofolate reductase used in the synthesis of nucleoside thymidine, essential for DNA synthesis

92
Q

MOA of corticosteroids

A

inhibits phospholipid A2 preventing prostaglandin production and other inflammatory

–> Blocks arachidonic acid and prostaglandin formation and so reduces inflammation

Also decreases traffic of phagocytes to site of infection by interfering with adhesion molecules
–> high neutrophils

sequestration of lymphocytes to tissue
–> low lymphocyte count

blocks cytokine gene expression

decreased Ab production

93
Q

function of IL2R mAb and example

A

eg. daclizumab

targets CD25 of IL2 receptors expressed on activated T cells

esp used in kidney transplant

94
Q

MOA of rituximab

A

targets CD20 on B cells
used in lymphomas

95
Q

development of lymphomas, thrombocytopenia and eczema

A

Wiscott-Aldrich syndrome

96
Q

mutation in MHC III

A

common variable immunodeficiency

97
Q

mechanism of action of mycophenolate mofetil

and indicaiton

A

anti-metabolite which prevents guanine synthesis

blovks de novo nucleotide synthesis preventing DNA replication

targets T cells more then B cells

used in transplantation, autoimmune diseases and vasculitis

98
Q

what is progressive multifocal leukoencephalopathy a complication of

A

from the JC virus in immunosupressed pts ge. after mycophenolate mofetil therapy

99
Q

mechanism of action of tacrolimus

A

inhibirts calcineurin preventing T cell proliferation/ function via reduced IL2 expression

100
Q

side effects of cyclosporin

A

gingival (gum) hypertrophy
nephrotoxicity
HPTN
neurotoxic

101
Q

mechanism of action of infliximab

A

anti-TNFa

102
Q

what is the receptor binding and membrane binding glycoprotein on influenza

A

haemagglutanin

103
Q

what does influenza bind to on human cells?

A

sailic acid on RBCs

104
Q

examples of toxoid vaccines

A

diphtheria
tetanus

105
Q

what are adjuvents, examples and how do they work

A

ALUM- most common. antigens absorbed into alum so are released at a slower steady rate in the body which improves B cell priming

stimulatory ajuvants mimic the action of PAMPs on TLRs to boost immune response eg:
CpG- activates TLRs on APCs
Freunds ajuvent- water in oil emulsion containing mycobacterial cell wall components. not clinically used

106
Q

what are mRNA vaccines complexed with in vaccine

A

lipids

107
Q

how do adenovirus vector vaccines work?

A

DNA of virus (eg. Sars-CoV-2) into viral vector (adenovirus)

Infect cells in vivo

Transcription/translation to produce protein

Stimulates immune
response including T cells and B cells with production of antibodies

108
Q

How do dendritic cell vaccines work

A

take out DCs and pump them with tumour specific antigens
- incubate with recombinant protein
- conjugated with GMCSF
-APC back into patient which can stimulate immune response against tumour

109
Q

Examples of cytokine therapy and what is it used for

A

IL-2 therapy for renal cell cancer

IFNgamma used in chronic granulomatous disease to boost oxidative phosphorylation

110
Q

Examples of therapies that replace missing parts of immune response

A

Haematopoetic SCT
Ab replacement (IVIg)

111
Q

Indications for Ab replacement

A

Brutons
X linked hyper IgM
common variable immuno def
Haem malignancy
post exposure prophylaxis

112
Q

Examples of ID with post exposure prophylaxis Abs given

A

VZV in non immune preganat women
Hep B
Rabies
Tetanus

113
Q

example of virus specific T cell therapy

A

EBV related B lymphoproliferative disease

114
Q

Cancers where tumour infiltrating lymphocyte T cell therapy is uesd

A

head and neck
melanoma
lung
gynae

115
Q

Uses for CAR-T cell therapy

A

ALL
Non-Hodgkins lymphome

116
Q

examples of immune checkpoint blcockade

A

anti-PD1- Abs- prevents PD1 from binding to PD!L and therefore prevent programmed cell death of T cells

anti-CTLA4- CD80/86 on APC bind to CT4A4 which blocks nagative regulation of T cells

117
Q

exaples of PD1 checkpoint blockade and what is it used for

A

Pembrolizumab and Nivolumab

used in melanoma

118
Q

example of CTLA4 checkpoint blockade and what is it used for

A

Ipilimumab

melanoma

119
Q

function of CTLA4

A

inhibitory checkpoint on t cells. completes with CD28 to bind to CD80/86 on APCs

120
Q

which vaccine should NOT be given to an immunosuppresed person

(inc pts with RA, IBD on immunosupressive drugs)

A

BCG
Yellow fever

121
Q

side effects of steroids

A

diabetes, central obesitiy, chushingoid, adrenal supression

cataracts, glaucoma, peptic ulcer, pancreatitis, avascular necrosis

psychosis

infection

122
Q

examples of drugs that inhibit DNA synthesis (anti proliferative agents) affecting lymphocytes prodominently

A

cyclophosphamide (most toxic)
mycophenolate mofetil
azathioprine

123
Q

side effects of anti proliferative agents

A

Bone marrow suppression
Infection
- Malignancy
- Teratogenic

124
Q

complications of cyclophosphamide

A

Toxic to proliferating cells:
Bone marrow depression
Hair loss
Sterility (male»female)

Haemorrhagic cystitis
–>Toxic metabolite acrolein excreted via urine

Malignancy:
Bladder cancer
Haematological malignancies
Non-melanoma skin cancer

Infection
–>Pneumocystis jiroveci

125
Q

side effects of azathioprine

A

Bone marrow suppression
Some people have a thiopurine methyltransferase polymorphism which means they can’t metabolise azathioprineso are very susceptible

Hepatotoxicity

126
Q

risks of mycophenolate therapy

A

infection:
- herpes virus reactivation
- Progressive multifocal leukoencephalopathy (JC virus)

127
Q

mechanism of plasmaphoresis and diseases its used in

A

remove pathogenic Ab and replaced with albumin.

type 2 hypersensitivity reactions (eg. MG, goodpastures)

128
Q

role of calcineurin

A

involved in expression of IL2

stimulates NFATc which upregulates IL2 expression

129
Q

examples of drugs that inhibit calcineurin

A

Tacrolimus
cyclosporin

130
Q

examples of mTOR inhibitors and how do they work

A

sirolimus
rapamycin

mTOR involved in IL2 pathway

131
Q

mechanism of tofacitinib (jakinibs)

A

inhibits JAK-STAT pathway so blocks cytokine production

132
Q

mechanism of anti-thymocyte globulin

A

lymphocyte depletion
modulation of T cell activation and migration

133
Q

Drugs that target CD25 and whats the pathway that is affected

A

Basiliximab and daclizumab

blocks IL2 induced T cell proliferation

134
Q

how does anti-CTLA4-Ig fusion protein work

A

eg. abatacept

blocks the interaction between CD28 and CD80/86 so prevents

????

135
Q

mechanism of rituximab

A

anti-CD20 expressed on mature B cells
- depletes B cells but not plasma cells

136
Q

mechanism of TNFa blockers and indications for use

A

TNFa pivitol in inflammation affecting many cell types

inhibition leads to a broad effect on immune response

used in: RA, IBD, psoriasis, ank spond, familial Mediterranean fever

137
Q

side effects og TNFa blcockers

A

TNFa is important in protection against TB

other infections HBV/HCV

lupus like conditions

demyelination

138
Q

function of IL1

A

secretion dirven by procaspase within the inflammasome

used in familial mediterranean fever, gout, adult onset stills disease

139
Q

function of IL6 and indication for blockade

A

affects T and B cells
affects synoviocytes
affects osteoclast activation

IL6 receptor blocker used in RA

140
Q

IL pathwyas key in eosinophilic pathway and eczema, asthma

A

IL4/5/13

141
Q

mechanism of blockade used in osteoporosis

A

anti-RANK-ligand which blocks osteoclast stimulation and reduces bone resorption

142
Q

risks of immunosupressive therapy

A

INFECTION:
TB risk - epdemiology, IGRA/manteaux test
–> prophylactic TB treatment

HBV/HCV

JCV activation

HIV

MALIGNANCY:
lymphoma (EBV associated)
non melanoma skin cancer

dysregulation of immune response leading to autoimmune conditions
- lupus like disease, antiphospholipid, vasculitis, demyelination

143
Q

describe john cunningham virus disease

A

Common polyomavirus that can reactivate
- Infects and destroys oligodendrocytes
-Progressive multifocal leukoencephalopathy
-Associated with use of multiple immunosuppressive agents
- AIDS defining disease

144
Q

what do mast cells release when activated by allergen in allergy

A

histamine
tryptase
proteoglycans
cytokines

145
Q

mechanism of symptoms of allergic reactions

A

skin: urticaria, angiooedema
degranulation causes vasodilation to skin or mucosa- more blood flow = red and leakage

Itching due to nerve stimulation

respiratory: bronchoconstriction, nasal discharge, sneezing

GI:
oedema of intestine= gut discomfort

CVS: vasodilation

146
Q

management of anaphylaxis

A
  1. remove trigger
  2. lie pt flat and lift legs (fluid bolus)
  3. IM adrenaline
  4. A-E
  5. IV fluids
  6. repeat adrenaline if no change after 5 mins
147
Q

mechanism of adrenaline in anaphylaxis

A

vasoconstriction (a1)
bronchodilation (b2)
acts on B2 receptor on immune cells preventing degranulation

148
Q

why not to give anti-histamines in anaphylaxis?

A

doesnt do anything to vasculature or bronch but does improve urticaria so may be decieving that the pt is improving when they are still in anaphylaxis

149
Q

what are released from mast cells minutes to hours after (late phase reaction)

A

leukotriene
prostaglandins
prostacyclins
thromboxane A2

150
Q

what inherited immunodeficiency is particularly associated with recurrent meningococcal disease

A

complement deficincies (encapsualted bacteria)

151
Q

important condition to screen for in SLE pts. and how is it done

A

anti-phosopholipid syndrome

anti-cardiolipin Ab
anti-b2glycoprotein 1 ab
lupus anticoagulant test

152
Q

tests for complement

A

C3, C4 levels
CH50
AP50

153
Q

features of antiphospholipisd syndorme

A

thrombocytopenia
livedo reticularis (mottled rash)
libmann sacks endocarditis

154
Q

pathophysiology of SLE

A

abnormality in clearance of apoptotic cells

abnormalities in cellular

155
Q

drugs used in SLE

A

prednisolone
anifrolumab
azathioprine
hydroxychloroquine
Rituximab
Belimumab
Mycophenolate Mofetil (more than aza and cyclo as steroid sparing)
Cyclophosphamide

156
Q

what is Rheumatoid factor

A

antibody against Fc portion of IgG

moderate sensitivity and specificity to RA
Sjorgrens may have positive RF

157
Q

what increases your risk of RA and why

A

smoking
PADI polymorphism
gingivitis
–> leads to increased citrullination of proteins which can form Abs to

158
Q

first line tx of RA

A

DMARDS
- methotrexate
- sulhasalazine
- hydroxychloroquine
-IL6 receptor blockers
- TNFa blockers
- anti CD20
- CTLA4 fusion protein

159
Q

what to screen for when starting on immunosupressants

A

TB, HBV, HCV exposure
prior Hx of septic arthritis that may not have fully cleared
inc risk of melanoma so skin protection

160
Q

what is ESR and why is it raised in myeloma

A

measures rate of fall of erythrocytes in plasma in a centrifuge

clumping of RBC in myeloma causes them to fall more rapidly

161
Q

what inherited immunodeficiencies leads to increased risk of viral infections eg. recurrent otitis media and URTI

A

immunoglobulin deficiencies
eg. Brutons X linked agammaglobulinaemia

162
Q

Pathogenic antibody in bullous pemphigoid

A

anti-hemidesmosome (adhesion molecules of BM)

163
Q

pathogenic antibody in pemphigus vulgaris

A

anti-desmoglein 1&3

164
Q

What viral enzyme is predominantly responsible for the high mutation rate of HIV and other RNA viruses?

A

reverse transcriptase

165
Q

what is the defective protein in XSCID

A

common gamma chain

166
Q

mechanism of the CH50 test

A

looks at complement activity

tests the ability for the patient serum to lyse sheep RBCs coated in rabbit anti sheep antibodies

167
Q

what mAb is used in osteoporosis and what is the target?

A

denosumab
targets RANKL

168
Q

what is measured in anyphylaxis to monitor response to treatment

A

mast cell tryptase

169
Q

what is the specific target of p-ANCA Abs

A

myeloperoxidase

170
Q

what is the specific target of c-ANCA Abs

A

proteinase 3

171
Q

gold standard test for diagnosing food allergy

A

double blind oral food challenge

172
Q

most common inherited primary immunodeficiency

A

selective IgA deficiency

Pathology and final year (21 decks)

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