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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
Role of NK cells
``` 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
Chemokines role
Release from tissue sites, direct movt of leukocytes | 4 chemokine families -CXC,CC,C,CX3C
27
Chemokine in HIV
HIV R5 strains use CCR5 and CD4 for entry into cell X4 strains use CXCR4 Patients with CCR5 mutation- resistant to HIV
28
Leukocyte adhesion deficiency
``` Failure of leukocyte migration Delayed seperation of umbilical cord Recurrent bacterial infections Severe gingivitis,periodontitis Poor wound healing ```
29
Which are primary lymphoid tissues
Thymus and bone marrow
30
Which are secondary lymphoid tissues
Tonsils, lymph nodes, spleen, MALT
31
Manifestation of MBL deficiency
Increased risk of bacterial, fungal, viral and protozoal organisms
32
Disease caused by mutation in Fox p3
IPEX (Immune dysfunction, polyendocrinopathy, enteropathy X linked
33
Disease caused by mutation in AIRE
APECED
34
PAMPS expressed by gram positive bacteria
Peptidoglycan ,DNA, lipoteichoic acid Gram negative bacteria -Lipopolysaccharide RNA virus -dsRNA Yeast -Mannan
35
Recurrent infections with which organism is characteristic of CGD
Coag neg Staph and fungi | Diagnosis to test activity of granulocyte -NBT test
36
Molecular defect in X linked SCID
Deficiency of cytokine receptor gamma common chain | AR SCID-Deficiency of JAK 3,IL7R alpha, ZAP 70,CD3
37
Protein shared by alternate and classical pathway
C3
38
Immunoglobulin that fixes alternate complement pathway
Ig A
39
Types of dendritic cells
Conventional (CDc), plasmacytoid (pDC) | pDC expresses TLR7 (RNA virus), TLR9 (DNA virus) in endosomes, induces rapid anti viral state
40
First cell to deal with pathogen that crosses epithelial barrier
Macrophage
41
Component of immune function most likely associated with gingivitis
Neutrophils
42
Characteristic of IgG4 MOLPS
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
Organs affected by IgG4 MOLPS
Autoimmune pancreatitis Lacrimal and salivary gland (Micklulicz disease) Retroperitoneal fibrosis IgG4 associated nephropathy
44
Mechanism of escape of HSV from APC
Produces TAP inhibitor protein that prevents transport of peptides onto MHC
45
Mechanism of escape of adenovirus
Produces protein that anchors MHC in ER, prevent surface expression of MHC
46
Mechanism of escape of CMV from APC
Accelerates transport of peptides out of ER, reduces chance of binding to MHC
47
MOA of mycophenolate
MMF->mycophelonic acid - reversible inhibitor of IMP dehydrogenase ->G1 arrest
48
MOA of tacrolimus
Binds to FK506 binding , inhibits IL-2
49
MOA cyclosporin
Calcineurin inhibitor. Inhibits IL-2 generation, decreases clonal proliferation of T cells
50
MOA Rapamycin
Inhibits response to IL-2 | Blocks B and T cell activation
51
Component of bacteria that is T cell dependent
Protein
52
Interaction that leads to septic shock in G-ve sepsis
Binding of TLR4 to bacterial LPS
53
NOD like receptor involved in gout
NLRP3
54
First cell of immune system that deals with pathogen that has crossed epithelial barrier
Macrophage
55
Role of NFkB
TLR signalling via IRAK4 to NFkB -> Interferon production
56
Disorders due to TLR related deficiency
TLR3 deficiency -> HSV encephalitis IRAK-4 deficiency -> Recurrent pyogenic infections Defects in NKfB1 or 2 -> CVID (some)
57
IL responsible for acute phase response
Monokines -TNF, IL-1,IL-6 | Act on liver to release proteins -MBL,CRP,Alpha1AT, fibrinogen
58
Nucleic acid sensors in cytoplasm
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
Molecular defect in CGD
Deficiency of NADPH oxidase 1-4 subunits , X chr | Responsible for respiratory burst in neutrophils
60
Most potent APC
Dendritic cell | Activated by engagement of PRR by foreign antigens
61
What are epithelial alarmins
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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