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Foundations Test 4 > Innate Immunity > Flashcards

Flashcards in Innate Immunity Deck (64):
1

Skin barriers

Longitudinal air flow
Fatty acids
Beta-defensins

2

Gut barriers

Longitduainl air flow
Low pH
Pepsin
Alpha-defensins

3

Lung barriers

Movement of cilia
Pulmonary surfactant (chemical)
Alpha-defensins

4

Eyes/nose/oral cavity barriers

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

5

What do all surfaces share as a barrier?

Epithelial tight junction and normal microbia

6

How does lysozyme break down bacteria?

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

7

How do defensins work?

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

8

Defensins produced by

Epithelial cells and macrophages

9

TLRs on plasma membrane (subunits and what they recognize)

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

10

Endosomal TLRs and what they recognize

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

All viral except CpG which can also recognize bacteria

11

Plasma membrane TLR pathway

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

12

Which doesn't use MyD88

TLR 3

13

TLR 3 pathway

Eventually uses IRF3 that induces type 1 interferon genes

14

All of TLR endosomal pathway except TLR 3

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

15

NOD proteins

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

16

NLRP proteins

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

17

RIG-like receptors

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

18

STING receptor

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

19

TNF source and target

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

20

IL1 source and target

Macro, endo, some epithel
Endothel, hypothal, liver, T cells (TH17 differentiation)

21

IL1 activated by

Inflammasome

22

IL 6 source and target

Macro, endo, T cells
Liver, B cells, T cells (TH17 differenatiation)

23

IL 12 source and target

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

24

Type 1 interferons source and target

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

25

Chemokine type receptor and example

IL-8

G-protein domain

26

SCID mutation

X-linked mutation in gamma hematopoietin receptor

27

Cytokine receptors

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

28

Macrophage receptors

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

29

Phagosome binds

Lysosome or neutrophils

30

Macrophage and neutrophil similarities

Low pH
NO
ROS
Lysozyme

31

Macro and neutro differences

Macro - cathelicidins
Neutro - defensins and cathelicidins

Neutrophil have lactoferrin inhibitor and B12 binding protein

32

Neutrophil process of engulfment and digestion

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

33

Dying neutrophils form

Extracellular traps that trap bacteria and prevent them from moving

34

Cytokine effect in blood vessels

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

35

Monocyte binds to

Integrin on the vascular endothelium and pulled in to become macrophage

36

Sepsis summary

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

37

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

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

38

IL-6 effect on liver

Acute phase proteins including CRP and MBL

CRP opsonizes

MBL activates complement cascade

39

IFN-alpha and Beta

Interferons

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

40

NK cells induced by what and produce what

Induced by IL12
Produce interferon gamma, perforin, granzyme

41

Time of onset after viral infection

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

42

MHC class 1 mechanism

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

Chediak-Higashi dz

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

Chronic granulomatous dz

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

Mutation in NADPH oxidase complex

45

LAD

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

Neutropenia

Recurrent and severe bacterial infection
Brought on by immunosuppression

47

IRAK4 def

Recurrent pyogenic bacteria

Intermediate in TLR and IL1R signaling

48

Nucleic acid PAMPs

ssRNA - virus
dsRNA - virus
CpG - virus, bactera

49

Protein PAMPS

Pilin and flagellin - bacteria

50

Cell wall lipid PAMPS

LPS - gram -
Lipoteichoic - gram +

51

Carb PAMPS

Mannan - fungi and bacteria
Glucans - fungi

52

NOD protein pathway starts with

NLRP proteins

53

What activates STING pathway?

dsDNA from viruses or bacteria

54

IL-8 major function

Chemoattractant of neutrophils

55

Hematopoietin receptor subfamily with gammac chain and why its important

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

56

IL-1 local vs. systemic

Local - vascular endothelium, activates lymphocytes, local tissue destruction

Systemic - fever and production of IL-6

57

TNF-alpha local vs system

Local - vascular endothelium and permeability

Systemic - fever, mobilize metabolites, shock

58

IL-6 local vs system

Local - lympho act and increased antibody production

Systemic - fever and acute-phase proteins

59

Hoqw does neutrophil work?

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

60

Sepsis common in

Gram-negative bacteria

61

How does MBL start complement pathway?

Binds C1q

62

What do NK cells recognize?

When MHC class 1 is down-regulated, will kill

63

Neutrophil numbers high in

Chronic granulomatous dz

64

CD18 is common chain for

CR3 and CR4