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BPT Sadness πŸ˜” > Immunology > Flashcards

Immunology Flashcards

1
Q

What is the mechanism behind frequent infections in DiGeorge syndrome/22q11.2 deletion?

A

Absence of the thymus gland; thus T cell deficiency

CATCH22

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2
Q

Which cell in the body is non-nucleated, thus does not express MHC class I?

A

RBC

(Platelets are also non-nucleated, however they actually do express MHC class I)

MHC 1 = almost every1
MHC 2 = expressed by APC only

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3
Q

What condition is characterised by NK cell hyporesponsiveness?

A

Chediak-Higashi syndrome
- Autosomal recessive
- Fusion of cytoplasmic granules and defective degranulation of neutrophil lysosomes

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4
Q

What does dupilumab target, and what conditions does it treat?

A

IL4 and IL13
- Asthma
- COPD with high eosinophil counts
- Atopic dermatitis

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5
Q

What does infliximab target, and what conditions does it treat?

A

TNF
- IBD
- Ankylosing spondylitis
- RA
- Psoriasis

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6
Q

What does ocrelizumab target, and which conditions is it used to treat?

A

CD20
- MS

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7
Q

What condition is omalizumab/Xolair used for, and what does it target?

A

IgE
- Moderate to severe asthma
- OmaLEEEEEzumab

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8
Q

WTF is CTLA-4 (cytotoxic T-lymphocyte-associated protein 4)?

A

AKA CD152
- Expressed by activated T cells and transmits inhibitor signals to T cells
- Mediates immunosuppression by indirectly downregulating signalling via CD28

When CTLA-4 is bound to B7, it prevents T cells from killing cancer cells; i.e. a β€œbrake” on T cells
- Thus CTL4 inhibitors are used

E.g. ipilimumab for melanoma

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9
Q

What does natalizumab/Tysabri target, and what condition does it treat?

A

Alpha-4 integrin
- MS

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10
Q

What does tocilizumab target, and what conditions does it treat?

A

IL6R
- RA
- Juvenile idiopathic arthritis

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11
Q

What are the 3 antigen presenting cells?

A

DC, macrophage, B cell

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12
Q

Cells which display MHC class 2 present to which type of T cell?

A

Helper T cell/CD4

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13
Q

Cells which display MHC class I presents to which T cell?

A

CD8, cytotoxic T lymphocyte (CTL)
- MHC class 1 > e1ght letters in cytotox1c
- Kill v1ral cells

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14
Q

What are 3 key complement control proteins?

A

DAF
CR1
MCP

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15
Q

Which complement deficiency is the most common?

A

C2

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16
Q

Early complement (C1, C2, C4) deficiency leads to
A) immune complex
B) recurrent bacterial infection?

A

A = immune complex

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17
Q

Terminal complement deficiencies lead to?

A

Neisseria infection

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18
Q

Causes of raised complement vs. decreased?

A
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19
Q

What are the types of hypersensitivity?

A
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20
Q

Where are NLRP3 (NOD-, lRR and pyrin domain-containing protein 3) expressed?

A

On macrophages
- PRR that recognises PAMPs and DAMPs

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21
Q

What is DC SIGN and which condition is it associated with?

A

DC SIGN is a lectin/glue/PRR on dendritic cells
- Associated with HIV1

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22
Q

Dectin 1 and dectin 2 are major receptors for which type of pathogen?

A

Fungi

Lack of dectin 1
* Impairs Th17 differentiation in response to fungi
* Increases fungal susceptibility e.g. mucosal Candida

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23
Q

Acute rheumatic fever is which type of hypersensitivity reaction?

A

Type II, cytotoxic reaction

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24
Q

Nonsense mutation in RAG1/RAG2 linked to which condition?

A

SCID

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25
Q

Latex-fruit syndrome

A

Banana, pineapple, avocado, chestnut, kiwi fruit, mango, passionfruit, strawberry

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26
Q

Diagnosis of dermatitis herpetiformis?

A

Skin biopsy: direct immunofluorescence shows deposition of IgA in a granular pattern in the upper dermis

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27
Q

What is the most useful screening tool for hereditary angioedema?

A

C4; always low, including in between attacks (C2 also low)
- C1-INH low during attacks; thus variable

ALSO NOT RELATED TO ANAPHYLAXIS
- HISTAMINE IS COMPLETELY DIFFERENT

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28
Q

Characteristics CVID?

A

Hypogammaglobulinaemia (low IgG, IgM, IgA), recurrent chest infections
- Associated with autoimmune disorders and lymphoma
- Still have lymphocytes

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29
Q

SCID characteristics? Bubble boy disease

A
  • Recurrent infections (viral, bacterial, fungal)
  • Autosomal recessive
  • Neonatal screening: T cell receptor excision circle (TREC test)

Lymphopaenia, low or no T cells
- Flow cytometry

RAG1, RAG2, IL-2RG

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30
Q

What role does B-cell activating factor (BAFF) play in immunology?

A

A cytokine which is a potent B cell activator
- High BAFF > high Ab production > SLE, RA, autoimmune diseases

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31
Q

PAN associated with which infection in 20%?

A

Hep B

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32
Q

List of anti-CD20 mABs?

A
  • Rituximab
  • Ocrelizumab
  • Obinutuzumab
  • Ubilituzimab
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33
Q

Biggest S/E of plaquenil?

A

Retinal toxicity

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34
Q

Structure of immunoglobulins
- What is role of variable end vs. constant region?

A

Variable - binds to target
Constant - enacts function

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35
Q

Which complements are strong anaphlatoxins?

A

C3a, C5a
(C4a is weak)

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36
Q

Role of C3b?

A

Opsonisation
- Cobra venoum mimics C3b

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37
Q

Cytotoxic T cells kill which type of cells?

A

Viral cells

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38
Q

COVID is sensed by which type of TLR?

A

TLR2

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39
Q

Gram negative bacteria release LPS into circulation, recognised by which TLR?

A

TLR4, which leads to cytokine release

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40
Q

Which autosomal recessive mutation occurs in FMF?

A

Gain of function in pyrin gene
- IL1
- Tx: colchicine

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41
Q

Different types of anti-TNF?

A

AEI
- Adalimumab
- Eternacept
- Infliximab

Crohn, PA, RA, ank spond, Still’s disease

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42
Q

Examples of anti-IL1?

A

ARC
- Anakinra
- Canakinumab
- Rilonacept

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43
Q

Which is the most critical cytokine?

A

IL6
- Stimulates haemoatopoesis
- Activates osteoclasts
- Activates lymphocytes > B cell activation

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44
Q

Which TLR is associated with HSV1?

A

TLR3

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45
Q

Which is the most variable region on immunoglobulins?

A

CDR3
- Complementarity-determining region 3

46
Q

Why might you need additional tests with tissue transglutaminase?

A

IgA deficiency
- Because it is an IgA-dependent test
- Thus also test gliadin

47
Q

Infections in T cell deficiency?

A
  • Mycobacterium avium complex
  • HSV, VZV, CMV
  • Listeria
  • Fungal incl. candida
  • Cryptococcus
  • PJP
48
Q

Interleukins and pathogen associations

A

Helminths - IL4, IL5, IL13
Bacteria, viruses - IFN, TNF
IL10, TGFB - regulation
fungal infection - IL17, generalised inflammation
B cell help with ICOS - IL21

49
Q

What are the acute phase cytokines?

A

IL1, IL6

50
Q

What do Th17 cells secrete?

A

IL17
- General inflammation
- Anti-fungal e.g. chronic mucocutaneous candidiasis
- Psoriasis

51
Q

IL17 blocker?

A

Ustekinumab
- Psoriasis
- Chron’s

52
Q

Causes of elevated IgE

A
  • Atopic dermatitis
  • ABPA
  • Parasitic infections
  • Lymphoma esp. Hodgkins
  • Wiskott-Aldrich (ezcema, thrombocytopaenia, immunodeficiency syndrome)
  • Hyper IgE syndrome
53
Q

Most common dust mites?

A
  • D. pteronyssinus, D. farinae
54
Q

When does tryptase peak?

A

60-90 minutes

55
Q

What to think of in recurrent anaphylaxis?

A

Systemic mastocytosis
- Tryptase always elevated
- D816V

56
Q

HLA associated with SJS?

A

HLA B5801 - allopurinol
HLA 1502 - carbemazepine, lamotrigine
HLA B5701 - abacavir

57
Q

Does SPT help with SJS diagnosis?

A

No, because it is mediated by T cells

58
Q

PNH associations?

A

PIGA
- CD55, CD59

59
Q

What are the functions of interleukin-4?

A

Promotion of B-cell growth and induction of class switching to immunoglobulin E and immunoglobulin G

60
Q

Which cytokine stimulates bone marrow?

A

IL3
- Secreted by activated T cells

61
Q

Which cells secrete IL1?

A

Macrophages

62
Q

Which cytokine is a major chemotactic factor for neutrophils?

A

IL8
- Secreted by macrophages

63
Q

What are the effects of IL2?

A

Interleukin-2 stimulates growth of helper and cytotoxic T cells

64
Q

Which cell surface proteins are found on helper T cells?

A

CD4, TCR, CD3, CD23, CD40L

65
Q

Which cell surface proteins are found on cytotoxic T cells?

A

CD8, TCR, CD3
- CD8 - 3ighT

66
Q

Which cell surface proteins are found on B cells?

A

IgM, CD19, CD20, CD21, CD40, MHCII, B7

67
Q

Which cell surface proteins are found on macrophages?

A

MHCII, B7, CD40, CD14, receptors for Fc and C3b

68
Q

Triad of the following makes you think of…?
1. Recurrent boils (staph/skin infections)
2. Eosinophillic dermatitis
3. Sinopulmonary infections

A

Job’s syndrome/hyper-IgE syndrome
- STAT-3 gain-of-function mutation (AD) or TYK2/DOCK8 mutation (AR); i.e. genetics depends on mutation

69
Q

What is avacopan?

A

C5a inhibitor

70
Q

Inhibitory cytokines?

A

IL-10
IL-35
TGF Ξ²

71
Q

Functions of T helper cells?

A
72
Q

Which expresses B2 microglobulin - MHC1 or MHC2?

A

MHC1

73
Q

What order of pneumococcal vaccination is given in setting of splenectomy?

A

Conjugate vaccine (PCV) > polysaccharide (PPSV) > polysaccharide (PPSV)
- 8 weeks apart

74
Q

Autoimmune hypoparathyroidism, autoimmune Addison’s and chronic mucocutaneous candidiasis makes you think?

A

Autoimmune polyendocrine syndrome type A/autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED)
- Defective AIRE gene

75
Q

Recurrent Neisseria infections makes you think?

A

Terminal complement deficiency

76
Q

What does baricitinib inhibit?

A

JAK 1 and JAK 2
- JAK inhibitor = ATP mimic; thus blocks cytokone signal transduction

77
Q

STAT4 is associated with which conditions?

A

RA, SLE

78
Q

The mechanism of beta cell destruction in type 1 diabetes is?

A

T cell

79
Q

Defects in NFKB 1 or 2 arises in which immunodeficiency?

A

CVID

80
Q

Which TLR recognises LPS

A

TLR4

81
Q

TLR3 deficiency makes you more prone to which infection?

A

HSV encephalitis

82
Q

DC-SIGN and Dectin 1/2 are types of what?

A

C type lectins
- Glue to stick to pathogens
- DC-SIGN > HIV
- Dectin 1/2 > fungal

83
Q

Inflammasome e.g. NOD1 recognises what microbe?

A

NOD1 recognises Gram negative bacterial protein
NOD2 recognises MDP (muramyl dipeptide) from Gram positive bacteria

84
Q

IL1

A
  • β€œEndogenous pyrogen”
  • Stimulates IL6, TNF
  • Released in autoinflammatory diseases incl. FMF
85
Q

Key pro-inflammatory mediators in innate system

A

Monokines TNF, IL1, IL6 > stimulate acute phase reactants CRP, Pct, MBL

86
Q

Plasmacytoid dendritic cells recognise which microbe?

A

Recognises viruses > makes type 1 interferons > makes you feel like shit during viral infections

87
Q

2 signal hypothesis T cell activation

A
88
Q

Initiation of complement cascade

A

MBL, ficolins > lectin
Pathogen > alternate; C3 > C3b
C1q (recognises Ab molecules; CRP) > classical

89
Q

What is opsonisation?

A

Coating of the target pathogen with complement to make it easier to recognise > engulf and breakdown
- IgG is an example of opsonin

90
Q

Examples of anaphlatoxins

A

C3a, C5a (and C4a)

91
Q

Hereditary angioedema is due to?

A

C1 inhibitor deficiency
- Uncontrolled activation of C1 > activation and consumption of C4 and C2, not C3
- Autosomal dominant

Types
- Type 1 (most common): reduced levels of C1-INH
- Type 2: dysfunctional
- Acquired: B cell lymphoproliferative (lymphoma, MGUS), autoimmune (e.g. SLE)

Treatment:
- Acute: icatibant (bradykinin 2 receptor antagonist); if severe/life-threatening - then purified C1-INH protein
- Preventative: anabolic steroid (danazol), TXA, C1-INH infusion, lanadelumab (anti-kallikrein mAb)

92
Q

Chronic granulomatous disease

A

Deficiency of NADPH oxidase - which is required for oxidative burst to kill intracellular organisms
- Coagulase positive bacteria and fungi; Staph and Aspergillus

Skin, lungs, gut (Crohn’s), LNs
Dx - NBT test

Severe recurrent bacterial and fungal infections and dysregulated inflammatory responses resulting in granuloma formation
- Macrophage

GP91 on X chromosome

Can be X-linked or AR

93
Q

Most common immunoglobulin in the body?

A

IgA

94
Q

IgM

A

Low affinity (weaker bonding) but HIGH avidity (10 sites of binding)
- Big mama
- Complement activation

95
Q

BAFF (B cell activating factor) inhibitor used in SLE?

A

Belimumab

96
Q

IgG big response to repeat infection is called?

A

Somatic hypermutation > affinity maturation > differentiated B cells (memory B cell [causes IgG surge] or plasma cell [effector cell])

97
Q

In isotype switching, which part of immunoglobulin is changed?

A

Constant region (not VDJ)
- Preserve pre-set variable region

98
Q

CVID features

A

Occurs at any age
- Low IgG and IgM; usu. associated with IgA deficiency; relatives with IgA deficiency
- Low/lack of switch memory B cells
- Only 10% is familial
- Recurrent sinopulmonary infection +/- gut +/- skin infection/boils
- CVID enteropathy; malabsorption, diarrhoea, LOW
- Associated with lymphoma

99
Q

Bruton’s agammalobulinaemia AKA X-linked agammaglobulinaemia features

A

Onset 6 months age (when maternal IgG declines)
FHx in 50%
B cell maturation arrest > never make B cells
Chronic echovirus meningoencephalitis

BTK

100
Q

Autoimmune regulator (AIRE) gene mutation leads to what?

A

Autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED)
- Autoimmune hypoparathyroidism
- Addison’s disease
- Chronic mucocutaneous candidiasis (IL17, IL22)

101
Q

Hyper IgM syndrome is deficiency in what?

A

CD40 ligand deficiency
- Deficiency of B cell activation (non-switched memory B cells) and T cell APC-T cell interaction

102
Q

Central tolerance in T cells occur where?

A

Thymus

103
Q

Th 17 deficiency leads to what?

A

Chronic mucocutaneous candidiasis

104
Q

T cell immunodeficiency leads to

A

Viral infections (CMZ, VZV, HSV), protozoa e.g. PJP, fungi, mycobacterial infection (TB, MAC)

105
Q

When does LOCID - late onset combined immunodeficiency look like

A

Mild form of SCID
- I.e. CVID with T cell
- Both B cells and T cells are cooked

106
Q

How to diagnose idiopathic CD4 T cell lymphopaenia

A

Exclude other causes
Measure CD4 count <300 twice, 6 weeks apart

107
Q

Which IL helps development of T cell and NK cell?

A

IL7 AKA interleukin 7
- Drive differentiation into T cells and NK cell

108
Q

Genetic disorders involving defective VDJ rearrangement leads to what?

A

Absent B and T cells
- Need VDJ for T and B cell development
- Associated with severe combined immunodeficiency

SCID
- Most common is autosomal recessive adenosine deaminase (ADA) deficiency

109
Q

Relationship between exercise-induced asthma and allergy

A

Almost everyone who has exercise -induced anaphylaxis has wheat- dependent exercise-induced anaphylaxis
- If you eat even a small amount of wheat and then exercise, they can develop anaphylaxis

110
Q

Indication for neutrophil function testing?

A

Chronic granulomatous disease

111
Q

Different types of hereditary angioedema

A

Type 1 - deficiency of C1 inhibitor
Type 2 - dysfunction of C1 inhibitor
Type 3 - normal levels C1 inhibitor; rare, usually related to genetic mutations including factors XII

112
Q

What is mechanism of action of icatibant?

A

Bradykinin B2 receptor antagonist
- Use in treatment of acute hereditary angio-oedema AKA HAE

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