Immunology Flashcards

1
Q

Azathioprine

A

MOA: Purine antimetabolite, impairs lymphocyte proliferation
Interacts with allopurinol and febuxostat 0> increased risk of bone marrow toxicity
Side Effects: Myelosuppression, mouth ulcers, oesophagitis, Hepatitis, photosensitivity, hypersensitivity syndrome (SJS/TEN, Pneumonitis), Interstitial Nephritis

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2
Q

Cyclophosphamide

A

MOA: Alkylating agent -> cytotoxic to lymphocytes by interfering with DNA cross linking

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3
Q

Immune response to live vaccine

A

Humoral and cellular response
High affinity antibodies with long term immune memory

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4
Q

Immune response to killed, subunit and toxoid vaccines

A

Response not as strong as live vaccines as pathogen can’t replicate. Primarily induce humoral response.

Need multiple doses to induce effective response, and boosters required.

Q fever vaccine can revert to wild type (exception to rule)

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5
Q

Immune response to conjugated vaccines

A

Polysaccharide + protein conjugate
T cell dependent response driven by conjugate

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6
Q

Vaccination and steroids

A

Live vaccines can be given if dose <20mg/day (or equivalent)
If given within one month of dose this high, risk of incomplete seroconversion.
After ceasing long term steroids (>2 weeks at >20mg/day), need to wait 1 month before vaccination

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7
Q

Management of accidental live vaccine administration to immunocompromised patient

A

Immunology input
IVIg to mop up vaccine

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8
Q

Mannose binding lectins

A

Pattern recognition molecules
Bind to mannose and N-acetyl glucosamine on microbes
Active complement cascade via lectin pathway

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9
Q

T cell negative selection

A

Removal of T cells at risk of causing autoimmunity by testing against self antigen by APCs

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10
Q

T cell positive selection

A

T cell receptors tested for ability to bind to MHC on APCs in thymus
If can’t bind to MHC, anergy triggered

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11
Q

MHC Class I

A

HLA-A, B, C
Present on all nucleated cells
Target for CD8+ cytotoxic T cells

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12
Q

MHC Class II

A

HLA- DR,DQ, DP
On antigen presenting cells
Target for CD4+ T helper cells

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13
Q

Immune response to intracellular pathogens, viral, bacterial infection

A

IL-12 and IFN-gamma release -> Th1 CD4+ T cell recruitment -> IFN-gamma and TNF-alpha release -> Macrophage recruitment

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14
Q

Immune response to Parasitic infection

A

IL-4 release -> Th2 CD4+ T cell recruitment -> IL-4, IL-5, IL-13 release -> Eosinophil recruitment

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15
Q

What type of infection are patients with asthma/atopy being treated with monoclonal antibodies at particular risk of?

A

Parasitic infection - most monoclonal antibodies block eosinophil activity

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16
Q

CD3

A

Present on all T cells

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17
Q

Role of C3a and C5a

A

Chemotaxis

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18
Q

Role of C3b

A

Opsonisation

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19
Q

Role of C5b

A

Formation of MAC alongside C6-C9

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20
Q

Triggers for alternative complement pathway

A

Endotoxins typically (lipopolysaccharides)

Others:
Aggregated Ig
Plant and bacterial polysaccharides
Radiographic contrast media
C3 nephritic factor
Some acute phase proteins

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21
Q

What protects host cells against complement?

A

DAF (Decay accelerating factor) and MCP (membrane cofactor protein): breakdown C3 convertase

HRF (Homologous restriction factor) C8 binding protein and CD59: prevent formation of MAC on host cells

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22
Q

NK Cell Regulation

A

Answer ####

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23
Q

Roll of Toll Like Receptors

A

Help a dendritic cell determine whether antigens are related to damage or foreign material, and thus whether they need to be presented

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24
Q

What is the key costimulation receptor for Dendritic Cells?

A

CD80/86 on DCs binds to CD28 on Naive Th cells in Lymph Node alongside interaction between MHC II and TCR

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25
Q

What chromosome are the genes for HLA on?

A

Chromosome 6

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26
Q

What is encoded as part of the HLA/MHC gene?

A

Class I: A, B, C, (E)
Class II: DP, DQ, DR
Class III: Complement C2 and C4, HSP70, TNF

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27
Q

What is required for MHC-I expression?

A

Beta 2 microglublin

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28
Q

What two receptors present on different immune cells have a very similar structure?

A

MHC-II and TCR

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29
Q

Where are the antigens presented by MHC-II predominantly found?

A

Extracellular/exogenous

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30
Q

Where are the antigens presented by MHC-I predominantly found?

A

Endogenous/intracellular/cytosol

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31
Q

What interleukin is released by naive Th cells to stimulate replication?

A

IL-2

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32
Q

What cytokines do Th1 cells produce?

A

IFN gamma, TNF-alpha

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33
Q

What cytokines to Th2 cells produce?

A

IL-4, IL-5

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34
Q

What cytokines do Th17 cells produce?

A

IL-17

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35
Q

What mechanisms do cytotoxic T cells use to induce apoptosis

A

Granzyme activity via Perforins

CD95L/CD95 interaction

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36
Q

What is the role of CTLA-4 and PD1/PDL1?

A

Bind to costimulatory receptors with greater affinity than their usual ligands to prevent activation of apoptotic signals

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37
Q

CD5

A

Present on B1 subset, do not produce memory cells, only produce IgM

38
Q

What is the costimulatory signal for B cells?

A

CD40 on B cells binds to CD40L on Th cells alongside MHC-II/TCR interaction

39
Q

What are the light chain gene segments of antibodies?

A

Kappa and Lambda. Two present in each antibody, but will both be the same type (i.e. either two kappa or two lambda)

40
Q

What Ig bind most efficiently to complement?

A

IgM, IgG3 > IgG1 > IgG2

41
Q

What is antibody affinity and avidity?

A

Affinity: strong binding
Avidity: lots of binding sites (e.g. IgM’s pentameric structure binds with high avidity, but low affinity)

42
Q

IgA

A

Two types:
IgA1: in serum
IgA2: forms dimeric structure and found in mucosal areas with protective secretory piece which protects it from enzymatic activity

43
Q

Type 1 Hypersensitivity

A

IgE mediated
Mostly immediate reactions
Th2 predominant environment - IL-4 mediates IgE production with help from IL-5
IL-5 primes eosinophils to migrate in response to chemotactic factors

Soluble antigen binds to neighbouring IgE on mast cells → crosslinking → mast cell activation → degranulation

Anaphylaxis, hay fever, hives, seasonal allergies, shellfish/peanut allergy, eczema

Most “allergic reactions” are type 1

44
Q

Type 2 Hypersensitivity

A

IgG mediated cytotoxic hypersentivity

Cell bound antigens

Antibody dependent cellular toxicity

IgG binds to surface antigen on target cell → T cell or complement mediated cell death
May be opsonic adherence via FcR, Complement mediated, also MAC

Examples: Red blood cell transfusion reaction with mismatched blood type; erythroblastosis faetalis; hyperacute graft rejection thyrotoxicosis

45
Q

Type 3 Hypersensitivity

A

Immune complex mediated

Soluble antigen

Deposition of antigen-antibody complexes in tissue → complement activation → neutrophil attraction → inflammation

Essentially the immune complexes can’t be phagocytosed when they are embedded in tissue, driving an inflammatory response

Examples: GN, RA, SLE

46
Q

Type 4 Hypersensitivity

A

T cell mediated

Soluble and cell bound antigens

Th1 cells sensitised to antigens → exposed to antigen → cytokine release → Macrophage and CD8+ T cell activation

IFN-gamma and GM-CSF key to response - Th1 environment

Clinical: Contact dermatitis, Tuberculin reaction, T1DM, MS, RA

> 80% of drug allergies are Type IV (SJS and TEN)

47
Q

Mechanism of Penicillin allergy

A

IgE mediated Type 1

48
Q

ACEi allergy mechanism

A

Bradykinin

49
Q

Mechanism of NSAID allergy

A

Type II hypersensitivity: cell bound antigen (don’t fully understand this mechanism)

50
Q

Tryptase for Anaphylaxis

A

Most specific diagnostic test for mast cell activity and thus anaphylaxis

Should be done 60-90 minutes post reaction, and okay in first 4 hours

Histamine drops too quickly to be useful, can du urinary histamine metabolites

51
Q

Gold standard test for food allergy

A

Oral food challenge

Skin prick testing has high NPV

52
Q

Types of Adverse Drug Reactions

A

Type A: pharmacological, i.e. related to drug action (80%)

Type B: hypersensitivity (10-15%)
- Majority T cell mediated, and thus not immediate. rash including SJS and TEN. DOn’t interact directly with drug, is mostly via haptens
- Immediate reactions IgE mediated: anaphylaxis, bronchospasm

53
Q

Key causes of DRESS

A

Carbamazepine, Allopurinol, Doxycycline, Phenytoin, Dapsone

Most common end organ involvement: Hepatic

54
Q

HLA associated with Allopurinol hypersensitivity

A

HLA-B58

55
Q

Key mediator of angioedema, the pthway activated and means of prevention

A

Bradykinin
Activates complement via classical pathway

56
Q

Hereditary Angioedema types, treatment

A

Problems with C1 esterase
C3 levels normal, C4 often low
Icatibant can be given - recombinant C1 inhibitor
FFP can also help

Key: loss of inhibition of C1 → unchecked complement activation

57
Q

Mechanism of ACEi angioedema

A

Blockade of ACE → reduced bradykinin degradation → accumulation → angioedema

58
Q

mTOR Inhibitors

A

Everolimus and Sirolimus
block mTOR (mechanistic target of rapamycin) kinase -> bloackade of cell cycle progression -> prevents cytokine induced B and T cell proliferation
Used to prevent solid organ transplant rejection and Tuberous Sclerosis

59
Q

Which cytokines are not upregulatory?

A

IL-10, TGF-beta

60
Q

General Effects of cytokines

A
  • upregulation of immune response
  • Induce cell growth
  • Affect T and B cells
  • Affect expression of cell surface molecules important in cell communication
  • interact via high affinity receptors on surface of cells
61
Q

Characteristics of cytokines

A

SOluble, intercellular messengers
Low molecular weight, secreted proteins
Produced by diverse range of cells
Act in autocrine, paracrine or distance manner
Effective at very low concentrations
Transient
Pleiotrophic

62
Q

IL-1 Function

A

Produced by macrophages and fibroblasts

Function:
- Proliferation of activated T and B cells
- Induction of IL-6, IFN-gamma, GM-CSF

63
Q

IL-2

A

Produced by T cells

Stimulates growth of activated T, B cells
Activation of NK cells

64
Q

IL-3

A

Produced by T cells and macrophases

Stimulates:
- Mast cell growth
- Growth and differentiation of haematopoietic precursor cells

65
Q

IL-4

A

Produced by T cells and Mast cells

Function:
- Isotype switch from IgG to IgE
- Characterises Th-2 subset of interleukins

66
Q

IL-5

A

Produced by Th2 subset T cells and Mast cells

Functions:
- IgM, IgA production
- Eosinophil and activated B cell proliferation

67
Q

IL-6

A

Produced by Macrophages, T helper cells, mast cells, fibroblasts

Function:
- Induction of acutephase proteins
- Growth and differentiation of haematopoietic stem cells

68
Q

GM-CSF

A

Produced by macrophages, T cells, endothelium, mast cells

Functions:
- Colony growth
- Activates macrophages, neutrophils, eosinophils

69
Q

TNF-alpha

A

Produced by macrophages, T cells

Functions:
- Activates macrophages
- Tumour cytotoxicity
- Cachexia

70
Q

TNF-Beta

A

Produced by CD4 T cells

Functions
- Induction of acute phase proteins
- Antiviral and anti-parasite activity
- Activation of phagocytes
- Induction of pro-inflammatory cytokines

71
Q

IFN-Alpha

A

Produced by leukocytes

Functions
- Antiviral
- Upregulated MHC-I

72
Q

IFN-gamma

A

Produced by T cells

Functions:
- Antiviral macrophage activation
- Upregulated MHC molecules
- Stimulates CTL differentiation
- Antagonises IL-4 effects
- Characterises TH1 subset

73
Q

What cell type has CD25?

A

Activated T cells

74
Q

Cell surface markers on Immature thymic cells

A

Tdt
Double positive CD4/CD8
Double negative CD3

75
Q

Cell surface markers on T cells

A

TCR, CD3, CD2
CD4 (Th, interacts with MHC-II)
CD8 (Tc, interacts with MHC-I)

76
Q

Cell surface markers on B cells

A

CD19, CD20
MHC- II
sIgM, or sIgG on memory B cells
Complement receptors: CD35, CD21

77
Q

Cell Surface Markers on Macrophages

A

MHC-II
CD35
CD32 (Fc receptor for IgG)
CD11b

78
Q

Cell surface markers on Dendritic Cells

A

MHC-II
CD11c/b
CD1a

79
Q

Cell surface markers on Neutrophils

A

CD35
FcR
Ly6C

80
Q

Cell surface markers on Mast cells

A

FcR for IgE

81
Q

CD45

A

Present on all leucocytes
CD45RA → naive T cell
CD45RO → memory T cell

82
Q

Immune response to viruses

A

Type 1 IFN produced early by innate immune system → limit viral replication
NK cells
Cytotoxic cells → IFN-gamma aids development
Neutralising antibodies

83
Q

Immune response to Bacteria

A

Phagocytosis - opsonisation by Ab and C components
CD4 T cell cytokines - aid Ab production, Ab class switching and memory development
Antibody mediated neutralisation of bacterial exotoxins

84
Q

Immune responses to Protozoa and worm infections

A

Mostly immunosuppressive
Immune system is cause of most host damage
High IgE (Th2) associated with worm infections
Can develop anaphylaxis if large quantities of Ag released, e.g. hydatid cyst rupture
Eosinophilia
No vaccines

85
Q

Immunisation prior to splenectomy

A

Encapsulated organisms key. Have polysaccharide antigen. Should have these vaccines at least 2 weeks prior to an elective splenectomy.

Strep pneumoniae
Neisseria meningitidis
Haemophilis influenzae

86
Q

Live attenuated vaccines

A

BCG, Sabin (polio), Measles, mumps

Never administered to immunocompromised individuals

87
Q

Predisposition to Atopy

A

HLA-Dw2
Environmental pollutants can increase IgE levels and inihibit T cell function + tolerance induction
Polymorphisms in IL-4 promoter region can lead to increase IgE production

88
Q

C3a and C5a anaphylotoxins

A

Can mimic a Type 1 hypersensitivty reaction, by also stimulating mast cell degranulation → same outcome as IgE cross linking on mast cells

However this is not Type 1 hypersensitivity

Some drugs can activate this - alternative complement pathway

89
Q

What Th subset is predominant in Sarcoidosis?

A

Th1

90
Q

What infections does complement deficiency predispose to?

A

Increased susceptibility to encapsulated gram negatives, particularly Neisseria as well as Haemophilis.

Severe pyogenic infecitons and immune complex disease common issues.

91
Q

Effects of T cell Deficiency

A

Poor response to fungal, viral and intracellular bacteria
Prolonged graft survival

Di George: failure in thymic development

92
Q

Effects of B cell deficiency

A

Increased susceptibility to pyogenic infections due to reduced opsonisation by antibodies and impaired phagocytosis
Impaired response to bacterial toxins

X gammaglobulinaemia (Bruton’s)
CVID