1.2 Flashcards

1
Q

what is the defense for Intracellular viruses, listeria and protozoa?

A

NK cells

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2
Q

what is the response for intracellular mycobacteria, cryptococcus, and trypanosomes?

A

activated macrophages

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3
Q

what is the defense for organisms on epithelial surfaces?

A

antimicrobial peptides

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4
Q

what is an example of an exotoxin release disease?

A

cholera

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5
Q

what is an example of an endotoxic release disease?

A

plague

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6
Q

lymphatic capillaries pick up the interstitial fluid called _____. this travels through the lymph nodes and returns to the blood by the lymphatic ducts

A

lymph

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7
Q

complement system

A

has alternative pathway, lectin pathway, classical pathway. complement activation leads to cleavage of C3

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8
Q

what happens when C3b covalently binds to the surface of a pathogen?

A
  1. recruitment of inflammatory cells
  2. opsonization of pathogens, killing by phagocytes
  3. perforation of pathogen cell membranes
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9
Q

steps of fixation to complement

A
  1. C3 cleaved to C3a and C3b
  2. C3b attaches to bacterium and tags it for destruction
  3. C3a recruits phagocytes
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10
Q

activity of C3b on microbial surface

A
  1. C3b + B = C3b B
  2. D cleaves end of B off, now C3b + Bb
  3. C3b + Bb convertase can cleave free C3, making more C3b
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11
Q

C3b Complement deposition leads to opsonization

A
  1. C3b on bacterial cell surface
  2. CR1 on macrophage binds to C3b on bacterium
  3. endocytosis of bacterium
  4. membranes fuse, creating membrane bound vesicle (phagosome)
  5. lysosome + phagosome = phagolysosome
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12
Q

C3b can also activate _____

A

C5

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13
Q

how does C3b activate C5?

A

C3b2Bb cleaves C5 into C5a and C5b

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14
Q

What does C5b activation do?

A

forms pores in pathogen (MAC) , insides leak out

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15
Q

on human cells, ______ binds to the C5b678 complex to keep C9 from recruiting and forming the pore

A

Cd59

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16
Q

_______ act on blood vessels to inc vascular permeability

A

anaphylatoxins

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17
Q

increased permeability allows what?

A

fluid leakage from blood vessels with complements, plasma proteins, increased migration of monocytes and neutrophils into blood

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18
Q

C3b

A

coats pathogens and promotes killing

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19
Q

innate immunity complement activation (3 actions)

A

recruitment of inflammatory cells, opsonized microbial cells, formation of MAC

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20
Q

Inhibition of microbial proteases

A
  1. protease sees bait and enters a2-macroglobulin
  2. protease cleaves bait and causes conformational change
  3. a2 enshrouds protease and is covalently bonded to it
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21
Q

__________ make antimicrobial peptides

A

paneth cells

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22
Q

_______ & ______ bring the defensin into lipid bilayer

A

electrostatic attraction, transmembrane electric field

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23
Q

________ recognize molecules that are broadly shared by pathogens, called _______-

A

TLRs
pathogen-associated molecular patterns (PAMPS)

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24
Q

the macrophage expresses several receptors that are specific for bacterial constituents. All of them recognize _______ molecules and trigger ________

A

different, phagocytosis

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25
Q

bacteria binding triggers _____ and/or ______

A

phagocytosis, cytokine production

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26
Q

Toll like receptors sense microbial products inside and outside human cells. Some examples of these are:

A

TLR4 (homo)
TLR3 (homo)
TLR1:TLR2 (hetero)

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27
Q

Ligand for TLR4:TLR4 homodimer:

A

lipopolysaccharide

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28
Q

which microorganisms do TL4:TL4 homodimers recognize?

A

gram-negative bacteria

29
Q

How can TLR binding stimulate cytokine production? (4 Steps)

A
  1. LPS binds with CD14 and stimulates TLR4
  2. stimulation triggers a cascade down various kinases
  3. ends with NFkB
  4. NFkB goes into host, is a transcription factor that activates genes for inflammatory cytokines
30
Q

______ are small secreted proteins released by host cells that act on other host cells

A

Cytokines

31
Q

which 3 actions can cytokines have?

A

autocrine
paracrine
endocrine

32
Q

_____ are cytokines that attract leukocytes to infection sites

A

chemokines

33
Q

______ are cytokines with antiviral activity

A

Interferons

34
Q

Local effects of cytokine production

A

resident macrophages secrete inflammatory cytokines at the site of infection

35
Q

what does IL-6 cytokine do?

A

induce fat and muscle cells to metabolize (raising temp)

36
Q

what does CXCL8 (IL8) cytokine do?

A

recruit neutrophils from the blood

37
Q

why is localization of cytokine production important?

A

if it were all over the body it would result in:
low blood volume, low blood pressure, collapsed blood vessels and systemic edema
ultimately septic shock

38
Q

what does the cytokine TNF-a do?

A

induce blood vessels to become more permeable

39
Q

local infection with gram-neg bacteria

A
  1. macrophages activated to secrete TNF-a
  2. increased release of plasma proteins, influx of phagocytes, and lymphocytes into tissue
  3. phagocytosis of bacteria, containment of infection, antigens drain
40
Q

Neutrophils can roll along the vascular endothelial surface due to ______-

A

selectin-mediated adhesion

41
Q

As the neutrophil rolls along the membrane, the _____ binds to the ______ and makes a tight bond. the membrane then opens and lets in the neutrophil to look for the pathogen. If there is a receptor that interacts with _______, diapedesis is triggered and the neutrophil enters the membrane

A
  1. LFA-1
  2. ICAM-1
  3. IL8
42
Q

what systemic innate cytokine activities do IL-1/IL-6/TNF-a cytokines trigger?

A
  • neutrophil mobilization
  • inc body temp
  • inducing acute phase proteins which activate opsonization pathway
43
Q

what effect does IL-6 have on the liver?

A
  1. acts on hepatocytes to induce synthesis of acute-phase proteins (mannose binding lectin, fibrinogen, C-reactive protein)
  2. C-reactive protein binds phosphocholine on bacterial surfaces, acting as an opsonin and a complement activator
  3. mannose-binding lectin binds to carbs on bacterial surfaces and acts as an opsonin and complement activator
44
Q

explain mannose-binding lectin complement system

A
  1. MASP-2 cleaves C4 (C4a and C4b), C4b binds to surface
  2. MASP-2 cleaves C2 (C2a and C2b)
  3. C2a binds to surface C4b making CONVERTASE C4b2a
  4. C4b2a now can break down C3
45
Q

what systemic effects can IL-6 have?

A
  • induces acute phase proteins from liver
  • fever
46
Q

Alternative pathway

A
  1. C3 cleaves to C3a /C3b → C3b tags bacterium for destruction, C3a recruits phagocytes → B binds to C3b → D cleaves B into Bb/Ba → Ba leaves, Bb + C3b convertase which can now cleave other C3 into C3a/C3b
47
Q

How does C-reactive protein activate complement system? (Classical pathway)

A
  1. C-reactive protein binds C1 and they bind to the ANTIGEN on the pathogen
  2. C4 gets cleaved
  3. C4 interacts with C2 to form C2a/C4b
  4. C4b/C2a complex acts on C3 to make C3b
  5. C3b activates C5→C5b to MAC
48
Q

Mannose binding lectin binds first because of ______

A

affinity

49
Q

Antibody binding is the ______ to act. why?

A

last, because it takes like 2 weeks to make antibodies

50
Q

alternative pathway uses only _____

A

C3 and the interaction to carbohydrates, but still activates complement system

51
Q

Natural Killer cell receptors recognize _________

A

changes at the surface of human cells that are caused by infections

52
Q

When a virus enters a cell it induces a transcription factor called _______. This then binds to IFN-B which makes _______. These have a paracrine or autocrine effect. This causes IFN-a to be made

A
  1. IRF3
    1. Interferons
53
Q

What do IFN-a and IFN-b do?

A
  1. induces resistance to viral replication
  2. increases expression of ligands for receptors on NK cells
  3. activates NK cells
54
Q

order of responses to viral infection

A
  1. Production of IFN-a, IFN-b, TNF-a, and IL-12
  2. NK cell killing
  3. T cell killing
55
Q

how does a NK cell eliminate virally infected cells?

A
  1. virus effects cells and makes interferons which goes and bind an NK Cell
  2. NK cells proliferate
  3. NK cells get activated
  4. NK cells induce apoptosis in virus infected cells
56
Q

_______ tells NK cell that a cell is infected and needs to be killed

A

MIC ligand

57
Q

the level of nk cells (part of the innate system) has a role in regulating ______

A

the adaptive immune system

58
Q

how do macropghages and NK cells differ in what they recognize?

A
  • Macrophage receptors recognize cell-surface carbohydrates of bacterial cells but NOT those of human cells
  • NK cells recognize changes at surface of human cells caused by viral infection
59
Q

How do neutrophils kill microbes?

A
  1. neutrophils have receptors for many different bacterial/fungal constituents
  2. neutrophils bind bacteria, engulf them, and destroy with toxic contents
60
Q

neutrophils and macrophages both make granules, but the granules arent active due to the _____

A

pH of the cell

61
Q

neutrophil/macrophage granules are activated by what?

A

when the granules are brought into the vacuole, and the pH of the phagosome RISES. this pH change activates the granules to kill the bacteria

62
Q

whats the difference in the granules between neutrophils and macrophages?

A
  • Neutrophils: only have a certain amount of granules. when they run out they die
    • Macrophages: can make more granules, and eat dead neutrophils
63
Q

one of the major mutations in the human genome is with ______, and what happens?

A

NADPH oxidase, cant kill bacteria inside a phagolysosome (chronic granuloma)

64
Q

what causes the pH to change in a phagolysosome?

A

enzymatic reactions including NADPH and O2

65
Q

______ lowers pH and _____ raises pH

A

hydrogen peroxide, H+

66
Q

classifications of immune system cells?

A

Phagocytes: neutrophil, dendritic, macrophage

lymphocytes: neutrophil, basophil, monocyte, dendritic, macrophage, mast

WBC/leukocyte; Everything except RBC

67
Q

adaptive vs innate cells

A

adaptive: B cell, T cell, plasma cell, effector T, dendritic
innate: neutrophil, basophil, eosinophil, dendritic, macropahge, mast

NOTE: dendritic is involved in both

68
Q

what is the immune response at 0-4 hours?

A

complement activation, start of inflammation, if that doesnt take care it we move on to the next step

69
Q

what is the immune response at 4hours -4 days?

A

macrophages and neutrophils come in, acute phase proteins being produced, some tissue damage