Immunology Flashcards

1
Q

BTK

A

Bruton’s Tyrosine Kinase
Crucial in B Cell maturation
Deficiencies cause X-linked agammaglobulinemia (no mature B cells)

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2
Q

TDT

A

Terminal Deoxynucleotidyl Transferace

Responsible for junctional diversity (during VDJ recombination)

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3
Q

AID

A
Activation Induced (Cytidine) Deaminase
Involved in Somatic Hypermutation
Class switching (IgM -> IgG)
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4
Q

RAG

A

Recombination Activating Genes

Enzyme for rearrangement of receptors (VDJ recombination) during developmental stages.

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5
Q

Th1

SIGNAL & FUNCTION

A

SIGNAL:
IL-12

PRODUCES:
IL-2
IFN-γ
LT/TNF

FUNCTION :
Macrophage Activation (IFN- γ)
B Cell activation – IgG antibody (IFN- γ)
Neutrophil Activation (LT/TNF)

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6
Q

Th2

SIGNAL & FUNCTION

A

SIGNAL:
IL-4

PRODUCES:
IL-4
IL-5
IL-13

FUNCTION:
Macrophage activation (IL-4/IL-13)
Mast Cell / Eosinophil activation (IL-5)
B Cell activation - IgE (IL-4)

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7
Q

Th17

SIGNAL & FUNCTION

A
SIGNAL:
IL-6
IL-21
IL-23
TGFβ
PRODUCES:
IL-17A
IL-17F
IL-6
IL-21
IL-22

FUNCTION:
Neutrophil recruitment

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8
Q

Treg

SIGNAL & FUNCTION

A

SIGNAL:
TGFβ

PRODUCES:
TGFβ
IL-10

FUNCTION
Dampen immune response and maintain tolerance, regulation of anti-self responses

nTregs - derived from thymus during T cell development
iTregs - derived following activation of naiive CD4 T cells in presence of TGFb

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9
Q

TFH

SIGNAL & FUNCTION

A

SIGNAL:
IL-6

PRODUCES:
IL-21
CXCR5

FUNCTION
Combine necessary signals to get B cells activated (proliferation and differentiation) - maintenance of germinal centres

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10
Q

Complement - Alternative

A

C3 tickover, Factor B, Factor D

C3bBb = C3 convertase

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11
Q

Complement - Classical

A

Antibody Mediated, C1, C4, C2

C4bC2b = C3 Convertase

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12
Q

Complement - Mannose Binding Lectin

A

MASP-2, C4, C2

C4bC2b = C3 Convertase

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13
Q

B Cell stimulation (stimulated by cytokines from CD4 T Cells)

A
SIGNAL:
CD40L & CD40
TCR & MHC II + pathogen (peptide)
IFN-γ
IL-4
TGFβ
EFFECT:
IFN-γ - IgG
IL-4 - IgE
TGFβ - IgA
Affinity Maturation
Memory Cell Production
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14
Q

CD4 T Cell Activation (by APC following ICAM-1 & LFA-2 adhesion)

A

SIGNAL:
MHC II + pathogen (peptide) & TCR
CD80/86 & CD28
(cytokine signal)

EFFECT:
Express CD40L
Express IL-2R
Secrete IL-2
Express CTLA-4 (higher affinity for CD80/86 than CD28)
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15
Q

TNFα / LTα

A

Inflammatory & Pyrogenic
Principal Source: Macrophages, T Cells
Endothelial Cells: activation (inflammation, coagulation)
Neutrophils: Activation & Migration
Hypothalamus: Fever, Prostaglandin Synthesis
Liver: synthesis of acute phase proteins
Muscle & Fat: catabolism (Cachexia)
Many cell types: Apoptosis
Increase cell migration, expression of adhesion molecules, collagen synthesis

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16
Q

TGFβ

A
Regulatory & Suppressive
Principal Source: T Cells (Treg), Many Cell Types
Inhibition of inflammation
Fibroblast migration,
Treg & Th17 differentiation,
IsoType switch to IgA
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17
Q

IL-1

A

Inflammatory & Pyrogenic
Principal Source : Monocytes/macrophages, DCs, endothelial cells, some epithelial cells, fibroblasts, keratinocytes, hepatocytes
Endothelial Cells : activation (inflammation, coagulation)
Hypothalamus : Fever, Prostaglandin syhtnesis
Liver : synthesis of acute phase proteins (CRP, complement, fibrinogen)

Vasodilation expression of adhesion molecules, collagen synthesis
Increases Bradykinin-1 receptors
Increases COX-2 and PLA2

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18
Q

IL-2

A

Survival Signal
Principal Source : T Cells
CD8 T cell activation
T cells: proliferation and differentiation into effector and memory cells; promotes regulatory T cell development, survival, and function NK cells: proliferation, activation

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19
Q

IL-4

A

Principal Source : T Cells (Th2), Mast Cells
B Cells : Isotype switch to IgE
T Cells : Th2 differentiation
Macrophages : Alternative activation and inhibition of IFN-γ classical activation

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20
Q

IL-5

A

Principal Source : T Cells (Th2)

Eosinophiles : Activation, increased generation

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21
Q

IL-6

A

Principal Source: Macrophages, Endothelial Cells. T Cells (Th17)
Liver: synthesis of acute phase proteins
B cells: proliferation of antibody producing cells
Marrow: stimulation of megakaryocytes
Fever, prostaglandin synthesis by hypothalymus,

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22
Q

IL- 8 (CXCL8)

A

Released by macrophages/epithelial cells/endothelial cells

Chemotactic gradient for recruitment of WBCs (primarily neutrophils)

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23
Q

CCR5

A
Chemokine receptor
Important in HIV infection
- CCR-5 delta32 mutation confers resistance to infection
- Moderately pathogenic
- used early in phase of infection
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24
Q

CCR7

A

Chemotactic towards lymph

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25
IL-9
Source: CD4 T Cells | Mast cells, B cells, T cells, and tissue cells: survival and activation
26
IL-10
Regulatory & Suppressive Principal Source: Macrophages, DCs, T Cells (Treg) Macrophages & DCs: Inhibition of IL-12 production, reduced expression of co-stimulators and MHC Class II Suppression of Th1 proliferation, reduction in inflammation
27
IL-12
Stimulatory Principal Source: Macrophages, Dendritic Cells Stimulate T-Cells and NK Cells: IFN- γ production, increased cytotoxic activity T cells: Th1 differentiation
28
IL-13
Principal Source: Th2, NKT Cells, Mast Cells B cells: isotype switching to IgE Epithelial cells: increased mucus production Fibroblasts: increased collagen synthesis Macrophages: alternative activation
29
IL-15
Principal Source: Macrophages NK cells: Proliferation T Cells: Proliferation and survival
30
IL-18
Principal Source: Macrophages | NK & T Cells: IFN- γ
31
IL-17
Principal Source: T Cells, other cells T Cell: Differentiation to Th17 Endothelial cells: increased chemokine production Macrophages: increased chemokine and cytokine production Epithelial cells: increased defensin GM-CSF and G-CSF production
32
IL-21
Principal Source: T Cells (Th17) | B cells: activation, proliferation, differentiation Th17 cells: increased generation TFH cells: development
33
IL-22
Principal Source T Cells (Th17) Epithelial cells: production of defensins, increased barrier function Hepatocytes: survival Enhances antimicrobial defence and epithelial repair and barrier entegrity - important in GI immune response
34
IL-23
Principal Source: Macrophages, CDs | T cells: increased stability and inflammatory activity of IL-17 producing T cells
35
IL-27
Principal Source: Macrophages, CDs | T cells: inhibition of Th1 cells NK cells: IFN-γ synthesis
36
IL-33
``` Principal Source: DCs, Epithelial cells, Endothelial Cells Stimulation of basophils (release IL-4) T cells: IL-5, IL-13 expression Mast cells: activation Eosinophils: activation ```
37
INF-α/β
Antiviral Principal Source α : DCs & Macrophages, β : fibroblasts Cause antiviral state, increased MHC Class I expression Activation of NK Cells Bind neighbouring cell and block translation of viral mRNA
38
IFN-γ
Principal Source : NK Cells, T Lymphocytes (Th1, CD8) Stimulates macrophage pathogen killing (classical activation) Stimulation of some antibody responses B Cell Isotype switching to IgG Increased expression of MHC class I and II Increased antigen processing and presentation to T Cells
39
LT
Lymphotoxin, neutrophil activation
40
PECAM-1 (CD31)
Platelet Endothelial Cell Adhesion Molecule for leukocyte diapedesis
41
Hypersensitivities
I - IMMEDIATE IgE, Mast Cells, IL-4, Th2, low dose Ag Asthma & anaphalaxis. II - ANTIBODY MEDIATED IgM and IgG against cell-bound or ECM Ag Myasthenia Gravis, Rheumatic Heart Disease, Graves, Drugs bound to RBCs, Rh newborn, Goodpastures III - IMMUNE COMPLEX IgM and IgG immune complex deposition Systemic Lupus Erythematosus, Vasculitis, Glomerulonephritis, Arthritis IV - DELAYED CD4(Th1) mediated, CD8, persistant antigenic stimulation TB / Mantoux, Celiac
42
Mast Cell Secrections
``` IMEMDIATE: 30-45seconds Histamine Heparin Tryptase +- chymase TNF-alpha ``` RAPID: 10-30 minutes Prostaglandins Leukotrienes SLOW (transcriptional) IL-3, IL-4, IL-5, IL-13, TNF-alpha
43
Goodpasture's Syndrome (basic immuno)
Type II Hypersensitivity Antibodies to Collagen type IV (basement membranes) Cause glomerular disease
44
Graves Disease (basic immuno)
Type II Hypersensitivity Antibodies bind to TSH Rc on thyroid cells stimulating thyroid hormones (negative feedback to pituitary is circumvented) Hyperthyroidism
45
Type III Hypersensitivity Factors
Excessive production of immune complexes Inefficient clearance Size (larger are better at activating complement and binding to RBCs -> spleen) Low affinity antibodies (don't form large complexes) Excessive antigens
46
MadCAM1
Mucosal Cell Adhesion Molecule 1 Exists on endothelial cells in mucosal tissue Allows lymphocytes to home to vascular endothelium of mucosal surfaces
47
GI immunity
``` Commensals IL-22 &TGFb Treg MALT TLR5 basolateral (so only invasive pathogens stimulate response) ```
48
Obesity & inflammation
``` Chronic Low Grade Inflammation TNFalpha, IL-1, IL-6, IL-17 decrease in Tregs desensitisation of insulin receptor and leptin receptor increased epithelial permeability ```
49
Inflammasome
SIGNAL 1 TLR -> NF-kb -> pro-IL-1b SIGNAL 2 potassium efflux, membrane perturbation, viral RNA, etc. Formation of inflammasome (active caspase-1) cleavage of pro-IL-1b and pro-IL-18 and secretion
50
ICE
Interleukin-1-converting enzyme A.K.A active caspase-1
51
CD40L
Expressed on activated T Cells Required for B Cell isotype switching, affinity maturation, differentiation to memory cells (w/o get hyper-IgM) Required for Macrophage activation (and respiratory burst) Required for CD8 activation
52
Multiple Sclerosis
Degeneration of CNS leading to paralysis CD4 cells specific for myelin promote inflammatory response Th1 and Th17 responses are detrimental (IFN gamma, IL-17) Th2 associated with remission Dysregulation of Tregs HLA-DR15, HLA-DQ6
53
Eamples of T cell mediated Autoimmunity
``` Insulin dependent diabetes mellitus (IDDM) Multiple Sclerosis (MS) ```
54
Examples of B Cell mediated Autoimmunity
``` Graves Disease (stimulating Ab) Myasthenia Gravis (inhibitory Ab) SLE (immune complex deposition) ```
55
CTLA4
binds CD80/86 more avidly than CD28 and delivers inhibitory signals to activated T cells Important in suppressing autoimmunity
56
AIRE
Autoimmune Regulator of Expression Ectopic expression of peripheral tissue proteins in thymic medulla People without AIRE get multiple organ systemic autoimmune disease
57
B-Cell maturation & receptor
BONE MARROW Heavy D-J rearrangements on both chromosomes Heavy V-DJ rearrangement on first chromosome (second if failure) * RAG - cleavage * TDT - junctional diversity Light κ rearrangement on first chromosome Light κ rearrangement on second chromosome Light λ rearrangement on first chromosome Light λ rearrangement on second chromosome Express μκ or μλ BTK required for maturation ``` SECONDARY LYMPHOID Express μκ & δκ or μλ & δλ Antigen binding Isotype Switching Somatic hypermutation (AID) Clonal Selection (for antigen based on affinity) ```
58
T-Cell maturation & receptor
Encoded by rearranging TCR α and TCRβ genes α - VJC region β - VDJC region ``` Pro-T cell Double Negative T Cell (β rearrangement) Double Positive (α rearrangement) Single Positive Thymocyte (based on MHC recognition & positive/negative selection) ```
59
Autoimmune Polyglandular Syndrome 1
Loss of thymic tolerance to peripheral antigens Results from mutations to AIRE gene Multiple immune disorders (addison's, hypoparathyroidism, mucocutaneous candidasis, type 1 diabetes)
60
IPEX (Immune Dysfunction, Polyendocrinopathy, Enteropathy, X-Linked)
Mutation of FoxP3 (controls Tregs) Approx 80% with syndrome develop diabetes Bone marrow transplant can reverse
61
Passive Immunisation
Passive immunisation with Ig antibodies from blood plasma Short lived Potentially hazardous (can cause serum sickness w/ repeat injections)
62
Living Immunising Agents | - Unattenuated (different host or route)
Cow pox to prevent smallpox (vaccinia) Rotavirus (monkey and bovine) Respiratory adenovirus given by mouth
63
Living Immunising Agents | - Empirically attenuated
Don't know why they are less virulent Grown under conditions they don't like, causes adaptation, hopefully no longer grow well in humans polio (Sabin OPV), measles, mumps, rubella, varicella-zoster, rotavirus (Rotarix), yellow fever* BCG, Typhoid (Ty21a - doesn't have vi antigen due to attenuation) *Need to give to mother BEFORE she becomes pregnant
64
Living Immunising Agents | - Rationally attenuated
no current vaccines avaiable CVD 103-HgR Live oral cholera vaccine w/ deleted gene for cholera toxin and mercury label
65
Living Immunising Agents | - Reassortants
Take existing living vaccine (e.g. typhoid), and clone genes that are virulence factors for other pathogens (e.g. E. Coli adhesins, ETEC colonisation factors) Rotavirus (RotaTeq) Influenza
66
Non-Replicating Immunising agents | - Inactivated pathogen
Polio (Salk IPV), influenza, Hep A, Jap Encephalitis, Rabies Oral cholera, thyphoid, pertusses (whole cell), Q fever
67
Non-Replicating Immunising agents | - Component
Hepatitis B (recombinant DNA of surface antigen) HPV acellular pertussis (3 or 5 components - less sides than whole cell, less effective) toxoids: diptheria, tetanus capsular polysaccharide: - unmodified: 23vPPV (pnemococcal), Vi (S. typhi) - modified: Hib, 10vPCV, 13vPCV, MenCCV, 4vMenCV
68
CXCR4
Chemokine receptor Important in HIV infection - highly pathogenic - used late in phase of infection
69
TRIM5a
Cellular Enzyme Causes destabilization of viral capsid Prevents uncoating and interferes with the reverse transcription Degrades virus&capsid through proteasome Possible medical use to inhibit HIV infection
70
APOBEC3G
Cellular Enzyme Assembles within virus during step of reverse transcription it interacts with ssDNA and causes deamination of cytosine to uracil = lethal hyper-mutation of virus (HIV-Vif binds APOBEC3G and targets it for death through proteosome)
71
Tetherin
Cellular Enzyme Inhibits virus release (HIV-Vpu antagonises tetherin and allows virus to excape)
72
Interferon α/β | Type I Interferons
Produced by infected epithelial cells and macrophages Induces influx and activation of NK Enhances MHC-I expression Bind neighbouring cells and block translation of RNA (antiviral state) Induces Protein Kinase R (dsRNA dimerises and this causes deactivation of eIF2α, thereby halting protein translation)