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Immunology Flashcards

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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
What chromosome are the genes for HLA on?
Chromosome 6
26
What is encoded as part of the HLA/MHC gene?
Class I: A, B, C, (E) Class II: DP, DQ, DR Class III: Complement C2 and C4, HSP70, TNF
27
What is required for MHC-I expression?
Beta 2 microglublin
28
What two receptors present on different immune cells have a very similar structure?
MHC-II and TCR
29
Where are the antigens presented by MHC-II predominantly found?
Extracellular/exogenous
30
Where are the antigens presented by MHC-I predominantly found?
Endogenous/intracellular/cytosol
31
What interleukin is released by naive Th cells to stimulate replication?
IL-2
32
What cytokines do Th1 cells produce?
IFN gamma, TNF-alpha
33
What cytokines to Th2 cells produce?
IL-4, IL-5
34
What cytokines do Th17 cells produce?
IL-17
35
What mechanisms do cytotoxic T cells use to induce apoptosis
Granzyme activity via Perforins CD95L/CD95 interaction
36
What is the role of CTLA-4 and PD1/PDL1?
Bind to costimulatory receptors with greater affinity than their usual ligands to prevent activation of apoptotic signals
37
CD5
Present on B1 subset, do not produce memory cells, only produce IgM
38
What is the costimulatory signal for B cells?
CD40 on B cells binds to CD40L on Th cells alongside MHC-II/TCR interaction
39
What are the light chain gene segments of antibodies?
Kappa and Lambda. Two present in each antibody, but will both be the same type (i.e. either two kappa or two lambda)
40
What Ig bind most efficiently to complement?
IgM, IgG3 > IgG1 > IgG2
41
What is antibody affinity and avidity?
Affinity: strong binding Avidity: lots of binding sites (e.g. IgM's pentameric structure binds with high avidity, but low affinity)
42
IgA
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
Type 1 Hypersensitivity
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
Type 2 Hypersensitivity
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
Type 3 Hypersensitivity
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
Type 4 Hypersensitivity
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
Mechanism of Penicillin allergy
IgE mediated Type 1
48
ACEi allergy mechanism
Bradykinin
49
Mechanism of NSAID allergy
Type II hypersensitivity: cell bound antigen (don't fully understand this mechanism)
50
Tryptase for Anaphylaxis
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
Gold standard test for food allergy
Oral food challenge Skin prick testing has high NPV
52
Types of Adverse Drug Reactions
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
Key causes of DRESS
Carbamazepine, Allopurinol, Doxycycline, Phenytoin, Dapsone Most common end organ involvement: Hepatic
54
HLA associated with Allopurinol hypersensitivity
HLA-B58
55
Key mediator of angioedema, the pthway activated and means of prevention
Bradykinin Activates complement via classical pathway
56
Hereditary Angioedema types, treatment
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
Mechanism of ACEi angioedema
Blockade of ACE → reduced bradykinin degradation → accumulation → angioedema
58
mTOR Inhibitors
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
Which cytokines are not upregulatory?
IL-10, TGF-beta
60
General Effects of cytokines
- 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
Characteristics of cytokines
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
IL-1 Function
Produced by macrophages and fibroblasts Function: - Proliferation of activated T and B cells - Induction of IL-6, IFN-gamma, GM-CSF
63
IL-2
Produced by T cells Stimulates growth of activated T, B cells Activation of NK cells
64
IL-3
Produced by T cells and macrophases Stimulates: - Mast cell growth - Growth and differentiation of haematopoietic precursor cells
65
IL-4
Produced by T cells and Mast cells Function: - Isotype switch from IgG to IgE - Characterises Th-2 subset of interleukins
66
IL-5
Produced by Th2 subset T cells and Mast cells Functions: - IgM, IgA production - Eosinophil and activated B cell proliferation
67
IL-6
Produced by Macrophages, T helper cells, mast cells, fibroblasts Function: - Induction of acutephase proteins - Growth and differentiation of haematopoietic stem cells
68
GM-CSF
Produced by macrophages, T cells, endothelium, mast cells Functions: - Colony growth - Activates macrophages, neutrophils, eosinophils
69
TNF-alpha
Produced by macrophages, T cells Functions: - Activates macrophages - Tumour cytotoxicity - Cachexia
70
TNF-Beta
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
IFN-Alpha
Produced by leukocytes Functions - Antiviral - Upregulated MHC-I
72
IFN-gamma
Produced by T cells Functions: - Antiviral macrophage activation - Upregulated MHC molecules - Stimulates CTL differentiation - Antagonises IL-4 effects - Characterises TH1 subset
73
What cell type has CD25?
Activated T cells
74
Cell surface markers on Immature thymic cells
Tdt Double positive CD4/CD8 Double negative CD3
75
Cell surface markers on T cells
TCR, CD3, CD2 CD4 (Th, interacts with MHC-II) CD8 (Tc, interacts with MHC-I)
76
Cell surface markers on B cells
CD19, CD20 MHC- II sIgM, or sIgG on memory B cells Complement receptors: CD35, CD21
77
Cell Surface Markers on Macrophages
MHC-II CD35 CD32 (Fc receptor for IgG) CD11b
78
Cell surface markers on Dendritic Cells
MHC-II CD11c/b CD1a
79
Cell surface markers on Neutrophils
CD35 FcR Ly6C
80
Cell surface markers on Mast cells
FcR for IgE
81
CD45
Present on all leucocytes CD45RA → naive T cell CD45RO → memory T cell
82
Immune response to viruses
Type 1 IFN produced early by innate immune system → limit viral replication NK cells Cytotoxic cells → IFN-gamma aids development Neutralising antibodies
83
Immune response to Bacteria
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
Immune responses to Protozoa and worm infections
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
Immunisation prior to splenectomy
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
Live attenuated vaccines
BCG, Sabin (polio), Measles, mumps Never administered to immunocompromised individuals
87
Predisposition to Atopy
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
C3a and C5a anaphylotoxins
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
What Th subset is predominant in Sarcoidosis?
Th1
90
What infections does complement deficiency predispose to?
Increased susceptibility to encapsulated gram negatives, particularly Neisseria as well as Haemophilis. Severe pyogenic infecitons and immune complex disease common issues.
91
Effects of T cell Deficiency
Poor response to fungal, viral and intracellular bacteria Prolonged graft survival Di George: failure in thymic development
92
Effects of B cell deficiency
Increased susceptibility to pyogenic infections due to reduced opsonisation by antibodies and impaired phagocytosis Impaired response to bacterial toxins X gammaglobulinaemia (Bruton's) CVID

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