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Innate Immunity Flashcards

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1
Q

How does immediate innate immunity respond to infection?

A

Recognizes infection through pre-formed, non-specific and broadly specific effects

These remove infectious agents

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2
Q

How does early induced innate immunity respond to infection?

A

Recruits effector cells

Recognize infection by PAMPs then activating effector cells and inflammation

These remove infectious agents

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3
Q

How does adaptive immunity respond to infection?

A

Transport antigen to lymphoid organs

Recognition by naive B and T cells

Clonal expansion and differentiation of effector cells

Removal of infectious agents

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4
Q

Name 2 physical barriers to infection

A

Intact skin = when cut or burnt microbes can infect more easily

Mucus and cilia

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5
Q

What order are layers of the skin found?

A

Epidermis > dermis > hypodermis

From top to bottom layer

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6
Q

Role of mucus

A

Physical barrier to infection

Prevents pathogen colonization

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7
Q

What synthesizes and secretes mucus?

A

Goblet cells

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8
Q

What happens in cystic fibrosis?

A

Defective gene causes production of unusually thick and sticky mucus

Frequent lung infection because more difficult to get rid of pathogens so they colonize

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9
Q

Name chemical barriers to infection

A

Anti-microbial enzymes

Microbe-binding molecules

Acidic pH

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10
Q

Examples of anti-microbial enzymes

A

Phospholipase A2

Antimicrobial peptides

Lysozymes

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11
Q

Lysozyme mechanism of action?

A

Cleaves peptidoglycan bonds in bacterial cell walls

Cell wall is needed for bacteria to survive

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12
Q

Phospholipase A2 mechanism of action?

A

Enzyme able to insert into bacterial membrane and break it

The outside components can enter the cell = causing cell to burst

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13
Q

Name a microbe-binding molecule and its mechanism of action

A

Pulmonary surfactant = produced by alveolar type II cells

Binds to pathogen but is NON-specific

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14
Q

Antimicrobial peptides’ mechanism of action against virus?

A

Hindering virus attachment and virus-cell membrane fusion

Disrupting virus envelope

Inhibition of virus replication by interacting with viral polymerase

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15
Q

Name 3 anti-microbial peptides

A

Defensins

Cathlicidins

Histatins

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16
Q

What are the two defensin classes?

A

Alpha

Beta

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17
Q

Defensin mechanism of action?

A

One end positively charged other negatively

Bacterial cell membrane = negative so positive end of defensin is attracted and inserts itself

Then negative ends are hydrophobic so cluster together pulling membrane apart

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18
Q

Defensin functions in the body

A

Maintian a healthy gut= balancing gut microbiota

Modulate inflammation

Attract immune cells to site of infection

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19
Q

Cathelicidins action against microbes?

A

Damage microbial membrane

Inhibit bacterial DNA and protein synthesis

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20
Q

What are Histatins?

A

Anti-microbial peptides

Small and cationic

Hisitidine-rich peptides in human saliva

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21
Q

What microbe do histains fight against?

A

Anti-fungal activity

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22
Q

What feature does the microbiome demonstrate?

A

Competitive exclusion = microbiome occupies our body surface so that the pathogen find it hard to colonize

Compete for resources and space

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23
Q

What does clostridium difficile infection do to the body?

A

Diarrhea

Colitis = an inflammation of the colon)

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24
Q

What compounds does the microbiome produce?

A

Compounds toxic to pathogenic bacteria

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25
What does the microbiome help mature?
Need microbiome when mucosal structure and immunity is not fully developed or established
26
Where are paneth cells found and what is their function?
Highly specialized secretory epithelial cells Located in the small intestinal crypts of Lieberkühn.
27
What do paneth cells do?
Highly specialized secretory epithelial cells = secrete antimicrobial peptides Located in the small intestinal crypts of Lieberkühn.
28
Where are M cells found?
Found overlying GALT lymphoid follicles, such as Peyer's patches in the ileum
29
What do M cells do?
Microfold cells sample antigens Clathrin-coated endocytic vesicles for larger antigens Or via fluid phase pinocytosis for smaller antigens
30
What is the structure of an M cell?
Short microvilli or none Allows antigens to come in close proximity to apical surface Basolateral invagination allows for positioning of APCs and lymphocytes = close to lumen
31
M cells and antigen interaction?
M cells acquire antigens through apical surface Antigens pass through M cells via vesicular transport to basolateral membrane They are released from basolateral membrane APCs uptake antigens and process them for presentation to T cells and other lymphocytes
32
What do absorptive endothelial progenitor cells do?
Secrete cytokines
33
What is the role of tight junctions?
Blocks movement of bacteria and PAMPs into lamina propria
34
What are germ-line encoded?
Pattern Recognition Receptors?
35
What does germ-line encoded mean?
Means that the information for PRRs is inherited = they have an innate ability to recognize certain patterns in pathogens
36
What is required for adaptive immunity activation?
Activation of innate immunity
37
Name 5 PRRs
Toll-like receptors NOD-like receptors RIG-I-like receptors Mannose receptors Phagocytic receptors
38
How many TLRs are there in humans vs mice?
10 in humans and 12 in mice
39
What is the ligand of TLR-3?
dsRNA
40
What is the ligand of TLR-4?
Lipopolysaccharide
41
What is lipopolysaaccharide?
Cell-wall component of gram-negative bacteria = sensed by TLR4
42
What is the ligand of TLR-5?
Flagellin
43
What is the ligand of TLR-7 and TLR-8?
ssRNA
44
What is the ligand of TLR-9?
CpG-ODN
45
What is CpG-ODN?
C linked to D oligodeoxynucleotides = single strand
46
Where are TLRs found?
Both on the cell membrane and in the endosome
47
What is the structure of TLRs?
Leucine rich repeat motif Cysteine rich flanking motif TIR domain
48
What part of the TLR sites in the cytoplasm?
TIR domain = tail
49
What is the TLR4 signalling pathway to activate gene expression of IL-6, TNFalpha etc?
When LPS is bound the receptor will dimerize TIR domains are brought together = activating the domain TIR domains recruits MyD88 = no enzyme activity IRAK1/4 binds MyD88 at Death domain IRAK1/4 go to activate MAPK and NFkB
50
What is the TLR4 signalling pathway to activate IFN-beta gene expression
When LPS is bound, the receptors will dimerize TIR domains are brought together = activatingthe domain TIR domains recruits TRIF TRIF activates both kinases = IKK and TBK1 Which then activate IRF3 and NFkB
51
What two domains does MyD88 have?
TIR and Death domains TIR binds to TLR4s TIR domain
52
Where are NOD-like receptors expressed?
Cytoplasm because they detect intracellular bacteria
53
What form are NOD proteins found in?
Inactive form
54
What is the structure of NOD-like receptors?
LRR NOD CARD
55
What are the differences between NOD1 & NOD2?
NOD1 has 1 CARD domain but NOD2 has 2 NOD NOD1 activation triggered by iE-DAP in gram-negative bacteria NOD2 activation triggered by MDP in both gram-positive and -negative bacteria.
56
What does NLR activation ultimately lead to?
Nuclear Factor kappa B (NFkB) activation by removing the inhibitor (IkB)
57
What happens when bacterial ligand binds to NOD protein?
Either iE-DAP or MDP binds RIPK2 recruited and binds the CARD domain TAK is phosphorylated by RIPK2 TAK is activated and then phosphorylates IKK IKK phosphorylates IkB leading to its ubiquitination and subsequent degradation by the proteasome NFkB is free to act as a transcription factor
58
Where are NOD2 strongly expressed?
In Paneth cells found in the small intestine
59
What does NOD2 induce?
Alpha-defensin expression
60
What mutation can cause Crohn's disease?
Loss of function mutation in NOD2 = less anti-microbial production More bacterial growth causing chronic gut inflammation
61
What mutation can cause Blau syndrome?
Gain of function mutation in NOD2 = activates signalling in absences of infection Spontaneous inflammation in joints, eyes and skin
62
Where are RIG-I-like receptors found and why?
Expressed in cytoplasm because important to detect viral infection
63
What are the two types of RIG-I-like receptors?
RIG-I and MDA-5
64
What do the two RLRs recognize?
1. RIG-I = unmodified 5’-tiphosphate end of ssRNA 2. MDA – 5 = recognize dsRNA
65
What is the structure of RIG-I-like Receptors?
Repressor Domain Helicase CARD

Immunology (8 decks)

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