Week 2: Innate Immunity Flashcards
1
Q
What evokes a response to an infection?
A
When a pathogen breaches our anatomical barriers, innate immune mechanism immediately
2
Q
What are involved with humoral innate immune response?
A
- Antimicrobial enzymes and peptides
- Complement
3
Q
What are involved with cellular innate immune response?
A
Innate effector cells
Macrophages
Granulocytes
NK cells
4
Q
What is the function of macrophages and granulocytes in innate immunity?
A
Recognize, ingest, and destroy pathogens with adaptive response
5
Q
How fast is innate immunity?
A
Immediately or quickly induced when the host is attacked by a pathogen
6
Q
What is innate immunity?
A
- second line of defense are triggered by cell surface or intracellular receptors that recognize microbial carbohydrates, lipids, proteins, and nucleic acids
7
Q
Where are innate receptors located?
A
Macrophages, NK cells, and other innate immune cells
8
Q
What does innate receptors recognize?
A
Stress and infected self cells
9
Q
What occurs after phagolytic receptor activation?
A
Lead to phagocytosis and degradation of the pathogen
10
Q
What occurs after signaling receptor activation?
A
The recruitment of additional innate cells to the infected tissues
11
Q
What makes innate immunity non-specific?
A
Exresses many different types of receptors depending on the type of cell
Macrophages recognizes diverse groups of ligands
12
Q
What are pattern recognition receptors (PRRs)?
A
Recognize patterns on microbes and of cellular damage
13
Q
What are PRRs found?
A
Innate immune cells (Mac, DC, neu) and on adaptive immune cells (T and B)
14
Q
What are the types of innate receptors?
A
- C-Type Lectin Receptors (CLRs) (phagocytic receptors)
- Toll-Like Receptors (TLRs) (signaling receptors)
- NOD-Like Receptors (NLRs) (signaling receptors)
- Rig-I-Like Receptors (RLRs) (signaling receptors)
15
Q
What are (PAMPs)?
A
pathogen-associated molecular patterns: Broad structural motifs present on microbes PRRs bind to
16
Q
What is the difference between surface and intracellular PRRs?
A
S: Recognize and bind to extracellular pathogen PAMPs
I: Located in enodsomes/lysosomes and recognize PAMPS that have been endocytose or in the cytosol
17
Q
Where are PRRs located?
A
Extracellular or intracellular
18
Q
What are DAMPs?
A
present on cells that are damaged due to damage, stress or transformation and recognized by PRRs (Damage-associated molecular patterns)
19
Q
What are TLRs?
A
Toll-Like Receptors recognize and bind PAMPs and DAMPs causing immune cells activation
20
Q
Why is cellular location of TLRs important?
A
Allows them to respond to particular ligands
21
Q
What is the difference between extracellular and intracellular TLRs?
A
Extracellular TLRs respond to PAMPS from extracellular pathogens.
Intracellular TLRs primarily respond to viral PAMPs
22
Q
What does activated TLRs induce?
A
Intracellualr signalling pathways that activate transcription factors in producing cytokines and chemotactic factors
23
Q
What pathways are activated by TLRs?
A
- NF-κB transcription factor activation
- Interferon regulating factor (IRF) pathways
24
Q
What is the function of NF-κB transcription factor activation?
A
- Stimulate production of antimicrobial proteins, peptides, and enzymes
- Production of pro-inflammatory cytokines (interleukin-1b (IL-1b) and tumor necrosis factor (TNF-a)
- NOD-like receptors also signal through this pathway resulting in IL-1b production
25
What is the function of Interferon regulating factor (IRF) pathways?
Pathways used by intracellular TLRs responding to viral PAMPs
Produce and secrete type 1 interferons
Inhibit the replication of viral infected cells
26
What activates NF-κB transcription factor activation and Interferon regulating factor (IRF) pathways other than TLRs?
mitogen-activated protein kinases (MAPK) pathway downstream transcription factors such as activator protein 1 (AP-1)
27
What is the function of NF-KB and AP-1?
Induce expression of pro-inflammatory cytokines and chemokines initiating its production
28
What are cytokines?
Small soluble proteins that the cells use to affect the behaviors of nearby cells
29
What are chemokine?
Type of cytokine that act as chemoattractant
30
What is the function of cytokines?
Secreted from the cytokine producing cell and work by binding to the cytokine receptor on the target cell
31
What are the 3 responses of cytokines?
1. Autocrine (short distances from the cell)
2. Paracrine (neighboring cells)
Both limited by distance and life span from collateral damage
3. Endocrine: more stable cytokines and larger distant cells by entering circulation
32
How does cytokines and chemokine produce a response?
When an infection is detected in a tissue, resident macrophages become activated, secrete cytokines to induce inflammation and chemokines that recruit other immune cells to the area
33
What are the pro-inflammatory cytokines?
IL-1, IL-6 and TNF-a
34
What are the biological effects of IL-1, IL-6 and TNF-a release?
1. Raise in body temperature
2. Microbes grow slower
35
What is the function ofIL-1, IL-6 and TNF-a on liver?
Acute-phase proteins, CRP, MBL to activate complement opsonization
36
What is the function IL-1, IL-6 and TNF-a on bone marrow?
Neutrophil mobilization by phagocytosis
37
What is the IL-1, IL-6 and TNF-a on the hypothalamus?
Increased body temp decreasing viral and bacterial replication
38
What is the IL-1, IL-6 and TNF-a on fat and muscle?
Protein and energy mobilization to generate increased body temp decreasing viral and bacterial replication
39
What iInduces the Acute Phase Response in the Liver Increasing the Supply of Recognition Molecules of Innate Immunity?
IL-6
40
How are acute phase proteins formed?
Increased response to cytokines produced to infection
41
What are CRPs?
Causes opsonination of the pathogen by phagocytic cells, act similar to complement proteins by binding to surfaces on bacteria, fungi, yeast, and parasites
42
What is the clinical use for CRP?
1. Diagnostic indicator of infection
2. Inflammation
3. Tissue damage
43
What acute phase proteins recognize pathogens?
1. C-reactive protein
2. Mannose binding lectin
3. Lipopolysaccharaide binding protein
44
What acute phase proteins eliminatates pathogens?
Complement components C3, C4, C9, factor B
45
What acute phase proteins creates inflammatory response?
Cranulocyte colony-stimulating factor, serum amyloid A, secreted phospholipase A2
46
What acute phase proteins causes coagulation?
Fibrinogen, plasminogen, tissue plasminogen factor
47
How Do Leukocytes Get to the Site of Infection?
1. Chemokines (IL-8) produced by macrophages recruit neutrophils and other leukocytes to the infected tissue.
2. Cytokines (IL-1 and TNF-a) increase the expression of adhesion molecules on the endothelium to help move leukocytes from the circulation into the tissues by extravasation.
3. Neutrophils migrate to the site of infection by following the chemokine (IL-8) gradient.
48
What are the first responders at a site of an infection?
Neutrophils
49
What is the most abundant leukocyte?
Neutrophils
50
Where do neutrophils come from?
recruited from the blood and bone marrow to the infected tissue by inflammatory cytokines
51
What is the function of TNF-a and IL-1B?
Increase the permeability of the endothelium allowing neutrophils to access tissues
52
What is the difference between neutrophils and macrophages?
N: Short-lived
M: Long-lived
53
What is the function of macrophages?
1. Raise the alarm that an infection is present
2. Produce inflammatory cytokines and chemokine that bring neutrophils to infected area
54
What happens after neutrophils phagocytose microbes?
Forms pus, dies and swallowed by macrophages
55
What are the anti-microbial granules in neutrophils?
Primary, secondary, tertiary
56
What are primary granules?
Contains substances that disrupt and digest the microbe
57
What are secondary granules?
Contain components needed to carry out enzymatic reactions that produce hydrogen peroxide
58
What are tertiary granules?
Contain gelatins that restricts the growth of bacteria by sequestering iron
59
What is the function of a virus?
Uses the host cell to replicate, transcribe, and translate their genome resulting in a viral nucleic acids in the cytoplasm of human cells
60
What are RIG-I-like receptor (RLRs) and endosomal TLRs?
Detect viral RNA/DNA
61
What happens if RIG-I-like receptor (RLRs) and endosomal TLRs are activated?
Leads to production of cytokines, specifically type 1 interferons
62
What are the inferno responses?
1. Induce resistance to viral replication in all cells
2. Increase expression of ligands for receptors on NK cells
3. Activate NK cells to kill virus-infected cells
63
Where are plasmacytoid dendritic cells (pDC) located?
Blood and lymphoid tissues
64
What are plasmacytoid dendritic cells (pDC)?
1. Detects viral infections through TLR7 and TLR9 (intracellular)
2. Secrete large amounts of type 1 interferon (IFN-a and b) upon TLR induced activation
65
What is the function of IFN?
Travels in the blood and lymph and serves to prevent a systemic infection
66
What are the Main Circulating Lymphocyte?
NK cells
67
What are NK cells?
large and active lymphocytes that respond rapidly to infection, cancer, and cellular stress
68
What is the purpose for NK cells?
contribute to the defense against both intra- and extracellular pathogens
69
What is the main functions of NK cells in innate immunity?
1. Kill cells infected with virus
2. Maintain or increase inflammation in infected tissue
70
How does NK cells kill infected cells?
1. Prevent viral replication
2. Prevent the spread of the virus to neighboring cells
71
How does NK cells maintain or increase inflammation?
1. Production of inflammatory cytokines
2. Activate macrophages to secrete cytokines and increase phagocytosis of viral particles
72
What is secreted by infected epithelial cells in response to infection?
IFN-a and IFN-b
73
What does IFN-a and IFN-b induce?
induce NK cells to proliferate and differentiate into cytotoxic NK cells that will then kill the virally infected cells
74
What does NK cells induce?
Induce infected cells to undergo apoptosis by releasing the contents of their granules containing lytic enzymes that cause the infected cell to undergo apoptosis.
75
What happens to apoptotic cells?
Cleaned up by macrophages
76
Describe how NK cells and macrophages activate each other?
1. Activated macrophages secrete chemokines that lure NK cells to the site of infection and activate those NK cells.
2. NK cells can reside in the tissues and enter infected area from the blood following the chemokine gradient.
3. The macrophage and NK cell form a synapse and IL-12 and IL-15 released from the macrophage cause the NK cell to proliferate and differentiate into an effector NK cell
4. Effector NK cells then secrete interferon-g (IFN-g)
5. IFN-g induces macrophages to increase phagocytosis of virus particles and virus infected cells that have been killed by NK cells
6. IFN-g (type II interferon) is a potent cytokine secreted by NK cells.
7. Increases phagocytic activity of macrophages.
77
What is the outcome of an innate response?
Stimulation of NK cells
78
What is the outcome of an adaptive response?
Stimulation of T cells
79
What is the interact between DCs and NK cells during an immune response?
DCs take up pathogens by phagocytosis or become infected by the pathogen.
Induces cell-surface receptor changes on DC that are recognized by NK cells
80
What can NK cells recognize?
Pathogen induced changes on DCs
81
What does NK cells bind to?
DC and leads to the secretion of IL-15 by the DC
82
What is the function of IL-15?
1. induces NK cell to proliferate, differentiate and survive
83
What occurs do to the increase of NK cells?
lead to cytotoxic killing of pathogen infected DC
84
What occurs due to the increase in DC numbers?
leads to movement of DC to the lymph node to active T cells to initiate adaptive response
85
Resident macrophages are responsible for activating what induced innate responses?
1. Secrete inflammatory cytokines (IL-1, IL-6 and TNF-a) and chemokines (IL-8)
2. Induce an acute phase response in the liver
3. Recruit neutrophils, monocytes and NK cells from blood into the tissues
4. Clean up dead neutrophils at the site of infection
86
What are the cell types that secrete type 1 interferons in response to a viral infection?
1. pDC secrete largest amount of type 1 interferons
2. NK cells are activated by type 1 interferons, become cytotoxic NK cells that cause infected cells to die by apoptosis
3. Macrophages induce NK cells to differentiate into effector NK cells that secrete interferon-g
4. DC and NK interaction will determine if adaptive immune response is activated
