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Flashcards in Immunology Deck (72)
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1
Q

BTK

A

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

2
Q

TDT

A

Terminal Deoxynucleotidyl Transferace

Responsible for junctional diversity (during VDJ recombination)

3
Q

AID

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

RAG

A

Recombination Activating Genes

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

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)

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)

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

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

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

10
Q

Complement - Alternative

A

C3 tickover, Factor B, Factor D

C3bBb = C3 convertase

11
Q

Complement - Classical

A

Antibody Mediated, C1, C4, C2

C4bC2b = C3 Convertase

12
Q

Complement - Mannose Binding Lectin

A

MASP-2, C4, C2

C4bC2b = C3 Convertase

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
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)
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

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
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

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

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

20
Q

IL-5

A

Principal Source : T Cells (Th2)

Eosinophiles : Activation, increased generation

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,

22
Q

IL- 8 (CXCL8)

A

Released by macrophages/epithelial cells/endothelial cells

Chemotactic gradient for recruitment of WBCs (primarily neutrophils)

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
24
Q

CCR7

A

Chemotactic towards lymph

25
Q

IL-9

A

Source: CD4 T Cells

Mast cells, B cells, T cells, and tissue cells: survival and activation

26
Q

IL-10

A

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
Q

IL-12

A

Stimulatory
Principal Source: Macrophages, Dendritic Cells
Stimulate T-Cells and NK Cells: IFN- γ production, increased cytotoxic activity
T cells: Th1 differentiation

28
Q

IL-13

A

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
Q

IL-15

A

Principal Source: Macrophages
NK cells: Proliferation
T Cells: Proliferation and survival

30
Q

IL-18

A

Principal Source: Macrophages

NK & T Cells: IFN- γ

31
Q

IL-17

A

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
Q

IL-21

A

Principal Source: T Cells (Th17)

B cells: activation, proliferation, differentiation Th17 cells: increased generation TFH cells: development

33
Q

IL-22

A

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
Q

IL-23

A

Principal Source: Macrophages, CDs

T cells: increased stability and inflammatory activity of IL-17 producing T cells

35
Q

IL-27

A

Principal Source: Macrophages, CDs

T cells: inhibition of Th1 cells NK cells: IFN-γ synthesis

36
Q

IL-33

A
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
Q

INF-α/β

A

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
Q

IFN-γ

A

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
Q

LT

A

Lymphotoxin, neutrophil activation

40
Q

PECAM-1 (CD31)

A

Platelet Endothelial Cell Adhesion Molecule for leukocyte diapedesis

41
Q

Hypersensitivities

A

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
Q

Mast Cell Secrections

A
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
Q

Goodpasture’s Syndrome (basic immuno)

A

Type II Hypersensitivity
Antibodies to Collagen type IV (basement membranes)
Cause glomerular disease

44
Q

Graves Disease (basic immuno)

A

Type II Hypersensitivity
Antibodies bind to TSH Rc on thyroid cells stimulating thyroid hormones
(negative feedback to pituitary is circumvented)
Hyperthyroidism

45
Q

Type III Hypersensitivity Factors

A

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
Q

MadCAM1

A

Mucosal Cell Adhesion Molecule 1

Exists on endothelial cells in mucosal tissue

Allows lymphocytes to home to vascular endothelium of mucosal surfaces

47
Q

GI immunity

A
Commensals
IL-22 &TGFb
Treg
MALT
TLR5 basolateral (so only invasive pathogens stimulate response)
48
Q

Obesity & inflammation

A
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
Q

Inflammasome

A

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
Q

ICE

A

Interleukin-1-converting enzyme

A.K.A active caspase-1

51
Q

CD40L

A

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
Q

Multiple Sclerosis

A

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
Q

Eamples of T cell mediated Autoimmunity

A
Insulin dependent diabetes mellitus (IDDM)
Multiple Sclerosis (MS)
54
Q

Examples of B Cell mediated Autoimmunity

A
Graves Disease (stimulating Ab)
Myasthenia Gravis (inhibitory Ab)
SLE (immune complex deposition)
55
Q

CTLA4

A

binds CD80/86 more avidly than CD28 and delivers inhibitory signals to activated T cells

Important in suppressing autoimmunity

56
Q

AIRE

A

Autoimmune Regulator of Expression
Ectopic expression of peripheral tissue proteins in thymic medulla
People without AIRE get multiple organ systemic autoimmune disease

57
Q

B-Cell maturation & receptor

A

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
Q

T-Cell maturation & receptor

A

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
Q

Autoimmune Polyglandular Syndrome 1

A

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
Q

IPEX (Immune Dysfunction, Polyendocrinopathy, Enteropathy, X-Linked)

A

Mutation of FoxP3 (controls Tregs)
Approx 80% with syndrome develop diabetes
Bone marrow transplant can reverse

61
Q

Passive Immunisation

A

Passive immunisation with Ig antibodies from blood plasma

Short lived

Potentially hazardous (can cause serum sickness w/ repeat injections)

62
Q

Living Immunising Agents

- Unattenuated (different host or route)

A

Cow pox to prevent smallpox (vaccinia)
Rotavirus (monkey and bovine)
Respiratory adenovirus given by mouth

63
Q

Living Immunising Agents

- Empirically attenuated

A

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
Q

Living Immunising Agents

- Rationally attenuated

A

no current vaccines avaiable

CVD 103-HgR
Live oral cholera vaccine w/ deleted gene for cholera toxin and mercury label

65
Q

Living Immunising Agents

- Reassortants

A

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
Q

Non-Replicating Immunising agents

- Inactivated pathogen

A

Polio (Salk IPV), influenza, Hep A, Jap Encephalitis, Rabies

Oral cholera, thyphoid, pertusses (whole cell), Q fever

67
Q

Non-Replicating Immunising agents

- Component

A

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
Q

CXCR4

A

Chemokine receptor
Important in HIV infection
- highly pathogenic
- used late in phase of infection

69
Q

TRIM5a

A

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
Q

APOBEC3G

A

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
Q

Tetherin

A

Cellular Enzyme
Inhibits virus release
(HIV-Vpu antagonises tetherin and allows virus to excape)

72
Q

Interferon α/β

Type I Interferons

A

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)