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Immunology (Miller) > #11 Innate Immunity 01.29 > Flashcards

#11 Innate Immunity 01.29 Flashcards

1
Q

what happens if you have neutropenia or NK deficiency?

A

you lack innate immunity and probs will die

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2
Q

name some examples of chemical components of innate immunity

A 
fatty acids, lactic acid, sebum (skin)
low pH/acidity (gut)
enzymes, like pepsin and proteases (gut)
salivary and tear enzymes, like lysozyme 
antibacterial peptides, like definsins
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3
Q

name a example of microbiological innate immunity

A

natural flora (skin and gut)

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4
Q

name some examples of mechanical components of innate immunity

A 
epithelial cells joined by tight junctions (skin)
longitudinal flow of air or fluid 
movement of mucus by cilia
perspiration (skin)
sloughing off of cells (skin)
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5
Q

what is a definsin?

A

human antimicrobial peptide

active against bacteria, fungi, many enveloped/unenveloped viruses

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6
Q

what aa is a definsin rich in?

A

arginine residues

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7
Q

what makes a definsin special?

A
  • its ampiphatic character, which also puts + charge on hydrohillic side
  • hydophillic residues create channel in bacterial membrane
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8
Q

what is the 2* structure of a definsin?

A

alpha helical

beta sheet

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9
Q

what make definsins?

A

neutrophils
macrophages
effector cells

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10
Q

what are the main source of definsins in the intestine?

A

paneth cells, which live in crypts of gut lumen and secrete definsins

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11
Q

what are two human antimicrobial peptides?

A
  1. definsins

2. cathelicidins

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12
Q

what is a cathelicin?

A
  • 2* structure also alpha helical and beta sheet
  • macrophages, neutrophils
  • epithelial cells
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13
Q

when thinking about the complement cascade, you are always making what?

A

complements

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14
Q

what is the production of complements (cascade) a response to?

A

trick question!

nothing. NOT a response to infection, bc you are always making them

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15
Q

what by-product of the complement cascade is a recruiter for effector cells?

A

anaphlotoxins (the small bits)

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16
Q

generally describe the sequence of events for an infection in terms of innate and acquired response

A
  1. ubiquitous response of innate immunity
  2. induced response of innate immunity (amplified if early response overwhelmed)
  3. adaptive response
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17
Q

what pathway is part of the innate response and can most always take care of an infection?

A

the Alternative Pathway of complement activation

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18
Q

what do phagocytes recognize on bacteria/viruses?

A

pattern recognition receptors (PAMPS), aka general features of bacteria

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19
Q

do innate phagocytic responses to bacteria result in long lasting protective immunity?

A

no, they have the same response every time and it never improves

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20
Q

what are pattern recognition receptors (PRRs)?

A

host cell receptors that bind to common features of pathogens aka PAMPS

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21
Q

what are the initiators/mediators of neutophil rolling?

A

adhesion molecules

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22
Q

what acts as a “danger signal”?

A

PAMPs

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23
Q

what does PAMP recognition initiate?

A

phagocytosis
inflammatory cytokine production
expression of B7.1 and B7.2 on APCs

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24
Q

what are the 3 categories of PRRs?

A
  1. endocytotic PRRs
  2. signaling PRRs
  3. secreted PRRs
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25
Q

what are endoctotic PRRs?

A

promote phagocytosis of microorganisms by phagocytes without relaying an intracellular signal

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26
Q

what do endoctotic PRRs recognize?

A

carbohydrates

Ex: mannose, glucan, scavenger receptors

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27
Q

what are the two kinds of singaling PRRs?

A
  1. toll-like receptors (membrane)

2. NOD-like receptors (cytoplasm)

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28
Q

what are toll-like receptors?

A
  • membrane bound**
  • recognize microbial CONSTITUENTS
  • mediate signaling that initiates cytokine production
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29
Q

what are NOD like receptors?

A
  • cytoplasm**
  • affinity for microbial PRODUCTS
  • initiate signaling that results in production of inflammatory cytokines
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30
Q

toll-like receptors: gram + bacteria

A

TLR2:6 heterodimer

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31
Q

toll-like receptors: double stranded viral DNA

A

TLR3

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32
Q

toll-like receptors: gram - bacteria

A

TLR4:4 homodimer

33
Q

toll-like receptors: flagellin

A

TLR5

34
Q

toll-like receptors: single stranded viral RNAs

A

TLR7

TLR 8

35
Q

toll-like receptors: bacteria and viruses

A

TLR 9

36
Q

toll-like receptors: bacteria and parasites

A

TLR1:2 heterodimer

37
Q

toll-like receptors: bateria

A 
TLR1:2 heterodimer
TLR2:6 heterodimer
TLR4:4 homodimer
TLR5
TLR9 (bac and virus)
38
Q

toll-like receptors: viruses

A

TLR3
TLR7
TLR8

39
Q

toll-like receptors: TLR10

A

who the fuck knows

40
Q

what are secreted PRRs? examples?

A

PRRs secreted from host cells

Ex: c-reactive protein (CRP) and mannose binding protein

41
Q

what complement cascade can mannose binding protein start?

A

Lectin Complement Cascade

42
Q

what complement cascade can c-reactive protein (CRP) start?

A

Classical Complement Cascade

43
Q

what is the order of binding in the CRP-indced classical complement cascade?

A

CRP binds phosphocholine

C1 binds to CRP

44
Q

C1 : CRP :: C1 : ____

A

IgM pentameric or 2+ IgG

45
Q

what cytokines are responsible for fever?

A

IL-6
IL-1-beta
TNF- alpha

46
Q

what fever-inducing cytokine upregulates production of a co-pyrogenic cytokine?

A

IL-1-beta induces production of IL6

47
Q

what cytokines activate vascular endothelium?

A

TNF-alpha
IL-1-beta
(this activating inflammation and movement of phagocytes into site of inflamm)

48
Q

what cytokine activates NK cells? what do the NK cells produce?

A

IL-12

Nk cells produce IFN-gamma

49
Q

what cell produces IL-6, IL-1-beta, TNF-alpha, IL-12?

A

macrophages

50
Q

what coordinates innate response to microbial presence? how?

A

macrophages

by releasing cytokines

51
Q

who produces acute phase response proteins?

A

liver

52
Q

what induces the liver to produce actute phase proteins?

A

IL-6 especially

IL-1, TNF-alpha too

53
Q

what are the 2 prominent acute phase proteins?

A

CRP

mannose-binding lectin

54
Q

effects of IL-1, IL-6, TNF-beta

A
  1. liver producing acute phase proteins –> activation of complement opsonization
  2. neutrophil mobilization in bone marrow and endothelium –> phagocytosis
  3. increased body temperature via hypothalamus –> decreased viral and bac replication
  4. use protein and energy to generate increased body temp in muscle and fat —> “
    4.
55
Q

adaptive immune response is more efficient at ___ temperature

A

higher/elevated

56
Q

what is acute phase response?

A

innate immune response that occurs soon after initiation of infection that involves the synth of acute phase proteins by the liver, which are secreted into the blood

57
Q

what do acute phase proteins do?

A

amplify innate immune responses

CRP and MBP

58
Q

what is an important feature od acute phase response?

A

induction of fever

59
Q

CRP is structurally similar to ___ and :: can bind to phophocholine on bacteria

A

C1q

60
Q

TNF-alpha does what? when can this be bad?

A
  • contracts capillaries to restrict distribution of infection
  • in sepsis, when it is systemically produced, it can shut down organ function
61
Q

what are B1 B cells?

A
  • B cells that are innate
  • ## no clonal expansion or affinity maturation
62
Q

what do B1 B cells respond to? what do they do when activated?

A
  • they are cross linked by T independent type 2 antigens (TI-2), which semi-activates them
  • they produce IgM and a little IgG
63
Q

what Ab do activated B1 B cells produce?

A

IgM and a little IgG

64
Q

is there class switching in B1 B cells?

A

yes, just a little to IgG

65
Q

what do B1 B cells recognize?

A

repeating carbohydrate markers

66
Q

how old is the host when B1 B cell innate response is finally developed?

A

5 YO

this means that those < 5 are more susceptible to encapsulated infections

67
Q

what do virus infected cells produce?

A

type 1 interferons
IFN- alpha
IFN-beta

68
Q

what do type 1 interferons do in innate immunity?

A
  • they are produced by cells that are virally infected
  • help to make adjacent cells less susceptible to infection
  • upregulate MHC I
  • activate NK cells
69
Q

what is the role of NK cells in the innate immune response?

A

they “buy time” by killing infected cells to limit viral replication whilst acquired immune system has time to develop response

70
Q

what do NK cells produce?

A

inflammatory cytokines that promote development of Th1 type response wh

71
Q

name two processes that activate NK cells in acquired immunity response

A

type-1 interferons:
IFN-alpha
IFN-beta

macrophage cytokine release:
IL-12

72
Q

what cells produce IFN-gamma?

A

innate:
NK cells
NK T cells

acquired:
Helper T cell/CD4
CTL T cell/ CD8

73
Q

NK cells detect the imbalance of inhibitory and activating _____ on _____ cells via what kinds of receptors?

A
  • ligands
  • host
  • Ig-like receptors
    lectin-like receptors
74
Q

NK response is innate or acquired?

A

innate

75
Q

NK cells are programmed to kill any cell without ____

A

MHC I

76
Q

can an NK cell ever clear an infection? what can? why?

A
  • no
  • CTLs
  • CTLs recognize early viral replication :: few infected cells, whereas NK cells only recognize late viral replication and spread the contents when it kills cell
77
Q

CTLs kill cells with ____

A

MHC I

78
Q

MIC proteins are

A

stress proteins produced late in infection

dont present antigen

79
Q

will an NK cell kill a host cell expressing MIC? is there an exception to this rule?

A
  • yes
  • yes, if there is enough MHC I to “hide” the MIC the NKC cell will pass over

(think of MHC I covering the MIC like the lambs blood keeping the baby boys safe from the shadow of death)

Immunology (Miller) (4 decks)

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