Innate Immunity Flashcards

1
Q

Skin barriers

A

Longitudinal air flow
Fatty acids
Beta-defensins

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2
Q

Gut barriers

A

Longitduainl air flow
Low pH
Pepsin
Alpha-defensins

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3
Q

Lung barriers

A
Movement of cilia 
Pulmonary surfactant (chemical)
Alpha-defensins
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4
Q

Eyes/nose/oral cavity barriers

A

Tears/nasal cilia (mechan)
Lysozyme in tears
Beta-defensins

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5
Q

What do all surfaces share as a barrier?

A

Epithelial tight junction and normal microbia

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6
Q

How does lysozyme break down bacteria?

A

Can eat through peptidoglycan and exposes cell membrane …particularly effective for gram-positive

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7
Q

How do defensins work?

A

Electrostatically (positive charge) attracted to the membrane and brought into the lipid bilayer to form a pore

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8
Q

Defensins produced by

A

Epithelial cells and macrophages

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9
Q

TLRs on plasma membrane (subunits and what they recognize)

A

Diacyl lipopeptides (TLR2/TLR6)
Triacyl lipopeptides (TLR2/TLR1)
Flagellin (TLR-5)
LPS (TLR4)

Lipopeptides mostly be gram-positive bacteria
LPS mostly from gram-negative bacteria

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10
Q

Endosomal TLRs and what they recognize

A

dsRNA (TLR3)
ssRNA (TLR7)
ssRNA (TLR8)
CpG DNA (TLR9)

All viral except CpG which can also recognize bacteria

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11
Q

Plasma membrane TLR pathway

A

Dimers form when PAMP encountered…MyD88 binds to receptor…IRAK4 recruited (kinase that phosphorylates stuff)…NFkB activated (regulatory unit removed and complex made of p65 and p50 now free)…goes to nucleus and transcirbe cytokine genes

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12
Q

Which doesn’t use MyD88

A

TLR 3

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13
Q

TLR 3 pathway

A

Eventually uses IRF3 that induces type 1 interferon genes

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14
Q

All of TLR endosomal pathway except TLR 3

A

Uses MyD88…Activates IRF7 and goes induces type 1 interferon genes

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15
Q

NOD proteins

A

Activated when it binds to intracellular bactera…NFkB moves to nucleus and increases cytokine production

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16
Q

NLRP proteins

A

Type of NOD protein

Activated by toxins that cause efflux of potassium ions

Form inflammasome…activates caspase 1…that activates IL-1B and IL-18…these are acute phase proteins that involved in sepsis and activation of immunity

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17
Q

RIG-like receptors

A

Recognize uncapped RNA with 5’-triphosphate group…recognized by RIG or MDA-5…produce IRF-3 and NFkB activation (type 1 interferon and cytokines)

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18
Q

STING receptor

A

In ER

Recpgnizes c-di-GMP and c-di-AMP from bacteria…dowstream effect is IRF3 (type 1 interferon)

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19
Q

TNF source and target

A

Macrophages and T cells

Endothelial cells, neutrophils, hypothal (fever), fat (cachexia) and many cell types (apoptosis)

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20
Q

IL1 source and target

A

Macro, endo, some epithel

Endothel, hypothal, liver, T cells (TH17 differentiation)

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21
Q

IL1 activated by

A

Inflammasome

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22
Q

IL 6 source and target

A

Macro, endo, T cells

Liver, B cells, T cells (TH17 differenatiation)

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23
Q

IL 12 source and target

A
Macro, dendritic 
T cells (TH1 differentiation), NK cells and T cells (interferon gamma synthesis, increased CD8 activity)
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24
Q

Type 1 interferons source and target

A

IFN alpha and beta
source - alpha - macro, plasmacytoid dendritic cells
beta - fibroblasts

Act on - all cells (increase MHC class 1 expression for viruses ), activate NK cells

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25
Q

Chemokine type receptor and example

A

IL-8

G-protein domain

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26
Q

SCID mutation

A

X-linked mutation in gamma hematopoietin receptor

27
Q

Cytokine receptors

A

2 chains using JAK-STAT pathway…STAT moves to nucleus to initiate gene trascription

28
Q

Macrophage receptors

A

Mannose - bacteria
Dectin-1 - for fungal B-glucans
Fc receptors - antibodies

29
Q

Phagosome binds

A

Lysosome or neutrophils

30
Q

Macrophage and neutrophil similarities

A

Low pH
NO
ROS
Lysozyme

31
Q

Macro and neutro differences

A

Macro - cathelicidins
Neutro - defensins and cathelicidins

Neutrophil have lactoferrin inhibitor and B12 binding protein

32
Q

Neutrophil process of engulfment and digestion

A

fMLF receptor activates Rac2…eventually NADPH oxidase gets ROS in phagolysosome…influx of ions and breakdown bacteria

33
Q

Dying neutrophils form

A

Extracellular traps that trap bacteria and prevent them from moving

34
Q

Cytokine effect in blood vessels

A

Causes dilation and upregulation of adhesion molecules…blood clotting takes place and prevents movement of infection

35
Q

Monocyte binds to

A

Integrin on the vascular endothelium and pulled in to become macrophage

36
Q

Sepsis summary

A

TNF-alpha secreted into the bloodstream and there is systemic edema…leads ot decreased blood volume and collapse of blood vessels

37
Q

IL-1B/IL-6 and TNF-alpha act on

A

Liver, bone marrow, hypothal, fat/muscle, dendritic cells

38
Q

IL-6 effect on liver

A

Acute phase proteins including CRP and MBL

CRP opsonizes

MBL activates complement cascade

39
Q

IFN-alpha and Beta

A

Interferons

Increase MHC class 1 expression
Activate dendritic cells and macophages
Activate NK cells to kill viral cells
Induce chemokines to recruit lymphocytes

40
Q

NK cells induced by what and produce what

A

Induced by IL12

Produce interferon gamma, perforin, granzyme

41
Q

Time of onset after viral infection

A

Quickly - interferons, TNF alpha and IL12
Later - NK mediated killing (3 days)
Latest - T cell killing (7 days)

42
Q

MHC class 1 mechanism

A

MHC 1 receptor is on all cells and inhibitory for NK cell…when infected, will not express…NK cell will come and kill by 1 of 2 methods

Granzyme and perforin

NK cell TRAIL binds to DR4 and DR5 and activates caspase 8 for apoptosis

43
Q

Chediak-Higashi dz

A

Recurrent infections and pigmentation defects…bleeding

Lymphocyte proliferation…fever, liver nad spleen enlargement, reduced WBC, platelets and RBC (pancytpenia)

Caused by defect in intracell vesicle causes failure of phagosome to fuse with lysosome…inability of vesicle for melanocyte and nervous system cell function as well

44
Q

Chronic granulomatous dz

A

Frequent infections during 1st year of like (aspergillus, staph, klebsiella, E coli)…pneumonia, lymph node infection, absecesses

Mutation in NADPH oxidase complex

45
Q

LAD

A

Recurrent infection and gingivitis

Neutrophils and monocytes trappen in blood stream

Deficiency of CD18…common B chain of LFA-1(CR3), Mac1, and gp150,95 (CR4)

46
Q

Neutropenia

A

Recurrent and severe bacterial infection

Brought on by immunosuppression

47
Q

IRAK4 def

A

Recurrent pyogenic bacteria

Intermediate in TLR and IL1R signaling

48
Q

Nucleic acid PAMPs

A

ssRNA - virus
dsRNA - virus
CpG - virus, bactera

49
Q

Protein PAMPS

A

Pilin and flagellin - bacteria

50
Q

Cell wall lipid PAMPS

A

LPS - gram -

Lipoteichoic - gram +

51
Q

Carb PAMPS

A

Mannan - fungi and bacteria

Glucans - fungi

52
Q

NOD protein pathway starts with

A

NLRP proteins

53
Q

What activates STING pathway?

A

dsDNA from viruses or bacteria

54
Q

IL-8 major function

A

Chemoattractant of neutrophils

55
Q

Hematopoietin receptor subfamily with gammac chain and why its important

A

IL-2, 7, and 15 which are important for lympho development…x-lined SCID is caused by mutation in this

56
Q

IL-1 local vs. systemic

A

Local - vascular endothelium, activates lymphocytes, local tissue destruction

Systemic - fever and production of IL-6

57
Q

TNF-alpha local vs system

A

Local - vascular endothelium and permeability

Systemic - fever, mobilize metabolites, shock

58
Q

IL-6 local vs system

A

Local - lympho act and increased antibody production

Systemic - fever and acute-phase proteins

59
Q

Hoqw does neutrophil work?

A

Produce phagosome that fuse with granules and dump contents that kill organisms

60
Q

Sepsis common in

A

Gram-negative bacteria

61
Q

How does MBL start complement pathway?

A

Binds C1q

62
Q

What do NK cells recognize?

A

When MHC class 1 is down-regulated, will kill

63
Q

Neutrophil numbers high in

A

Chronic granulomatous dz

64
Q

CD18 is common chain for

A

CR3 and CR4