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Immunology > Innate immunity > Flashcards

Innate immunity Flashcards

1
Q

Role of PRR

A

Target highly conserved structures shared by groups of microorganisms (which are essential for survival of the organism)
Can be soluble, membrane bound, intracellular

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2
Q

What are PAMPs

A

Pattern associated molecular patterns
In bacteria - toxins,flagellin,peptidoglycan,LPS,RNA,DNA
Virus -RNA,DNA,M2protein
Fungus -beta-glucans,hyphae,mannan,zymosan
Protozoa- hemozoin

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3
Q

Role of DAMPs

A

Danger associated molecular patterns
Self derived- ATP,HMGB1,Cholesterol crystals,monosodium urate,CPPD
Enviornment -Alum,asbestos,silica,alloy particles,UV radiation,skin irritants

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4
Q

What are soluble PRR

A 
Antimicrobial peptides(AMP)-
      Defensins(alpha and beta), cathelicidins
Complement activators 
  Classical -CRP, C1q
  Lectins - MBL,Ficolin
  Alternate -foreign surface
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5
Q

Which are membrane bound PRR

A

Toll like receptors(TLR)

C-type lectins

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6
Q

What are the intracellular PRR

A

Endosomal - TLR

Cytosolic - Nod-like receptors(NLR), Rig-I-like receptors(RLR),AIM2-like receptors (ALR)

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7
Q

MBL

A

Acute phase protein
Activates lectin pathway of complement
Cleaves C4 and C2
Acts as opsonin
MBL deficiency - increased susceptibilty and severity
to infections, esp in immunocompromised patients

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8
Q

TLR and septic shock

A

G -ve microbes release LPS into circulation
LPS recognised by TLR4 -Signals via NK-kB
Widespread systemic cytokine release -> shock

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9
Q

TLR s clinical significance

A

TLR signalling in B cells promotes auto antibody formation -may explain targeting of nucleic acids in lupus
TLR3 deficiency - predispose to HSV encephalitis
IRAK-4 deficiency - Distal to TLR4,7,8and 9
Recurrent pyogenic infections

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10
Q

Dectins and fungal infections

A

Dectin 1 and 2 -major receptors for fungae

Direct APC to stimulate Th17 differentiation

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11
Q

Role of inflammasomes

A

8 of NLR involved in inflammasome complexes
Inflammasomes sense PAMPs and DAMPs
Activate caspase-1 -> activate and release IL-1 and IL-18

Central to inflammation in gout
Crystals activate NLRP3 inflammasome

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12
Q

Role of IL-1

A 
Induces inflammatory response
'endogenous pyrogen'
Reduces viral replication
Stimulates IL-6 production 
Anakinra is IL-1 inhibitor
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13
Q

Role of IL-6

A 
Fever, acute phase response
Stimulates hemopoiesis
Activates osteoclasts
Lymphocyte activation
B cell activation and antibody formation
T cell differentiation -Th17
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14
Q

TNF

A

Transmembrane protein -cleaved and released to act as cytokine
Acts on TNFR1 and II
Activates endothelium,increases vascular permeability,fever

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15
Q

NALP3 mutations

A 
Autoinflammatory syndromes (gain of function)
Familial cold urticaria syndrome
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16
Q

NALP1 SNPs related conditions

A

Associated with vitiligo and related autoimmune disorders-thyroid,SLE,RA,T1DM

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17
Q

Associations of NOD2 mutations

A

Crohn’s disease
Lack of inflammatory response to MDP
Lack of basal IL-10 production

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18
Q

RIG like receptors

A

Detect RNA of virus in cytoplasm
Cytoplasmic location in dendritic cells
Respond by releasing Type1 INF

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19
Q

Role of INF in infection

A

Released from cells in response to viral infection
INF-alpha,INF-beta
Plasmacytoid dendritic cells -potent source
INF acts on its receptors to induce resistance to viral replication
Increase MHC-1 expression and antigen presentation ain all cells
Activate DC,NK cells

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20
Q

Role of ILC

A

Generated in marrow and fetal liver
Present in skin,liver,small intestine,lung
Amplify signals from macrophage and DC
Produce cytokines

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21
Q

Group 1 ILC effects

A

Like TH1 cells
Make INF gamma
Classical NK cells
Kill target cells (virus)

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22
Q

Group 2 ILCs

A

Make IL-4,5,9,13

Immunity against helminths, allergy

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23
Q

Group 3 ILCs

A

TH 17 cells
Make IL-17,IL-22
Lymphoid tissue inducer necessary for lymphoid tissue formation

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24
Q

ILC and disease

A

Involved in asthma,allergic rhinits,eosinophilic esophagitis,atopic dermatitis

IL 33 activation underlies what makes an allergen

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25
Q

Role of NK cells

A 
BM derived, in response to IL-15
Kill virally infected cells
Elimination of tumour cells
Respond to cytokines INF alpha,IL-12,15,18
Express and make INF gamma
26
Q

Chemokines role

A

Release from tissue sites, direct movt of leukocytes

4 chemokine families -CXC,CC,C,CX3C

27
Q

Chemokine in HIV

A

HIV R5 strains use CCR5 and CD4 for entry into cell
X4 strains use CXCR4
Patients with CCR5 mutation- resistant to HIV

28
Q

Leukocyte adhesion deficiency

A 
Failure of leukocyte migration
 Delayed seperation of umbilical cord
 Recurrent bacterial infections
 Severe gingivitis,periodontitis
 Poor wound healing
29
Q

Which are primary lymphoid tissues

A

Thymus and bone marrow

30
Q

Which are secondary lymphoid tissues

A

Tonsils, lymph nodes, spleen, MALT

31
Q

Manifestation of MBL deficiency

A

Increased risk of bacterial, fungal, viral and protozoal organisms

32
Q

Disease caused by mutation in Fox p3

A

IPEX (Immune dysfunction, polyendocrinopathy, enteropathy X linked

33
Q

Disease caused by mutation in AIRE

A

APECED

34
Q

PAMPS expressed by gram positive bacteria

A

Peptidoglycan ,DNA, lipoteichoic acid
Gram negative bacteria -Lipopolysaccharide
RNA virus -dsRNA
Yeast -Mannan

35
Q

Recurrent infections with which organism is characteristic of CGD

A

Coag neg Staph and fungi

Diagnosis to test activity of granulocyte -NBT test

36
Q

Molecular defect in X linked SCID

A

Deficiency of cytokine receptor gamma common chain

AR SCID-Deficiency of JAK 3,IL7R alpha, ZAP 70,CD3

37
Q

Protein shared by alternate and classical pathway

A

C3

38
Q

Immunoglobulin that fixes alternate complement pathway

A

Ig A

39
Q

Types of dendritic cells

A

Conventional (CDc), plasmacytoid (pDC)

pDC expresses TLR7 (RNA virus), TLR9 (DNA virus) in endosomes, induces rapid anti viral state

40
Q

First cell to deal with pathogen that crosses epithelial barrier

A

Macrophage

41
Q

Component of immune function most likely associated with gingivitis

A

Neutrophils

42
Q

Characteristic of IgG4 MOLPS

A

Serum Ig G4 elevated
IgG4 positive plasma cells infiltrate in involved tissues
Mass forming lesions with fibrosis
Good response to steroids
No positivity of SSA/SSB in organs affected

43
Q

Organs affected by IgG4 MOLPS

A

Autoimmune pancreatitis
Lacrimal and salivary gland (Micklulicz disease)
Retroperitoneal fibrosis
IgG4 associated nephropathy

44
Q

Mechanism of escape of HSV from APC

A

Produces TAP inhibitor protein that prevents transport of peptides onto MHC

45
Q

Mechanism of escape of adenovirus

A

Produces protein that anchors MHC in ER, prevent surface expression of MHC

46
Q

Mechanism of escape of CMV from APC

A

Accelerates transport of peptides out of ER, reduces chance of binding to MHC

47
Q

MOA of mycophenolate

A

MMF->mycophelonic acid - reversible inhibitor of IMP dehydrogenase ->G1 arrest

48
Q

MOA of tacrolimus

A

Binds to FK506 binding , inhibits IL-2

49
Q

MOA cyclosporin

A

Calcineurin inhibitor. Inhibits IL-2 generation, decreases clonal proliferation of T cells

50
Q

MOA Rapamycin

A

Inhibits response to IL-2

Blocks B and T cell activation

51
Q

Component of bacteria that is T cell dependent

A

Protein

52
Q

Interaction that leads to septic shock in G-ve sepsis

A

Binding of TLR4 to bacterial LPS

53
Q

NOD like receptor involved in gout

A

NLRP3

54
Q

First cell of immune system that deals with pathogen that has crossed epithelial barrier

A

Macrophage

55
Q

Role of NFkB

A

TLR signalling via IRAK4 to NFkB -> Interferon production

56
Q

Disorders due to TLR related deficiency

A

TLR3 deficiency -> HSV encephalitis
IRAK-4 deficiency -> Recurrent pyogenic infections
Defects in NKfB1 or 2 -> CVID (some)

57
Q

IL responsible for acute phase response

A

Monokines -TNF, IL-1,IL-6

Act on liver to release proteins -MBL,CRP,Alpha1AT, fibrinogen

58
Q

Nucleic acid sensors in cytoplasm

A

RNA -viral RNA detected by RIG-1 helicase receptors
located in cytoplasm of pDC –> INF A and B
DNA - AIM2 inflammasome –>cGAS via STING–>INF1

59
Q

Molecular defect in CGD

A

Deficiency of NADPH oxidase 1-4 subunits , X chr

Responsible for respiratory burst in neutrophils

60
Q

Most potent APC

A

Dendritic cell

Activated by engagement of PRR by foreign antigens

61
Q

What are epithelial alarmins

A

IL-33,TSLP (Thymic stromal lymphopoietin)
Present in skin, liver, lung, small intestine
Sense distress signals from DCs/mo activated by PAMP/DAMP
Produce cytokines -INF -G,IL-4/5/9/13,IL-17/22/GM-CSF

Immunology (11 decks)

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