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Innate Immunity Flashcards

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1
Q

How long does it take for the innate immune response to respond to a pathogen?

A

The innate immune response is almost immediate, initiating within 0-4 hours

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2
Q

Barriers, anti-microbial peptides, complement, soluble mediators, phagocytes and granulocytes belong to which type of the body’s immunity?

A

They belong to the innate immune response.

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3
Q

Where are anti-microbial peptides and proteins found?

A

They are often present in secretions such as sweat, mucus, tears, or saliva.

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4
Q

What is the role of anti-microbial peptides/ proteins?

A

They disrupt microbial membranes, activate lytic, and inhibit DNA/RNA protein synthesis, causing target lysis within minutes.

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5
Q

What is complement?

A

A large group of soluble inactive proteins that, upon recognition of a microbial cell, initiate a sequential cascade of proteolytic activation, ultimately resulting in cell lysis.

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6
Q

How does complement recognize microbial cells?

A

Recognition is mediated by binding of complement directly to the microbial cell surface, or by binding to antibodies that have already coated the target cell.

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7
Q

What are three types of soluble mediators?

A

Interferons, cytokines, and chemokines.

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8
Q

What triggers the release of soluble mediators?

A

Activated immune cells and infected cells will trigger the rapid release of soluble mediators.

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9
Q

What do interferons do?

A

Interferons induce a general anti-viral state along with a fever.

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10
Q

What do cytokines and chemokines do?

A

They increase the production of white blood cells (leukocytes) and recruit immune cells to sites of infection.

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11
Q

What does it mean if cells are non-clonal?

A

Contrary to intuition, it means that all cells of that type are identical.

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12
Q

What role do phagocytes and granulocytes play in the innate immune response?

A

After being activated immediately upon target recognition, these cells often directly kill target cells through phagocytosis or the release of toxic compounds.

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13
Q

Does the innate immune system recognize specific pathogens?

A

No, the innate immune system simply differentiates between self and non-self.

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14
Q

How does the innate immune system differentiate between self and non-self?

A

Using Pathogen Associated Molecular Patterns (PAMPS). These could include dsRNA, flagella, formylated peptides, etc.. The innate immune system can also recognize targets tagged with soluble components (complement and opsonization).

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15
Q

What is opsonization?

A

Part of the immune response where foreign pathogens are tagged to be eliminated via phagocytosis with the assistance of opsonins.

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16
Q

Does the innate immune response form memory cells?

A

No, since innate cells aren’t pathogen specific, there is no benefit to forming memory cells. This means that subsequent infections with the same pathogen will result in the same immune response, no better or faster.

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17
Q

What are the three broad types of barriers the body uses to defend itself in the innate immune system?

A

Mechanical, chemical, and microbiological barriers.

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18
Q

What is the epithelium?

A

The thin outer layer of cells lining the outside of the body along with the hollow structures within the body.

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19
Q

How does the epithelium protect against pathogens?

A

The epithelium acts as a physical barrier between the external environment and the host.

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20
Q

What are examples of epithelium in humans?

A

The skin, the GI tract, the respiratory tract, and the genitourinary tract.

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21
Q

What are epithelial tight junctions?

A

Connections formed by protein complexes that hold adjacent cell membranes together. These tight junctions are so dense that they will not even let ions pass through.

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22
Q

How does the skin epithelium remove pathogens?

A

It acts as a conveyor belt that runs skin cells through different stages until they are shed, removing pathogens in the process.

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23
Q

What is sloughing?

A

The process of shedding dead skin cells from the body.

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24
Q

What are cilia?

A

Hairlike projections lining the airway epithelium which sweep and propel mucus out of the respiratory tract.

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25
What is the role of goblet cells?
They are the cells that produce mucus
26
What is the function of mucus?
Mucus protects the underlying epithelium from pathogens, trapping dust, particulate matter and pathogens. Mucus also protects from digestive and antimicrobial molecules.
27
How does the innate immune system recognize pathogens?
PAMPs, Pathogen-Associated Molecular Patterns.
28
What is the mechanism that TLRs (using MyD88), found in dendritic cells and macrophages, use to recognize and target pathogens?
PAMPs activate TLRs, forming a dimer (homo or hetero). Facilitates binding of MyD88 and MAL, leading to binding of IRAK and subsequently TRAF6 and TRICA 1. This creates a scaffold leading to the recruitment and activation of TAK1, which is phosphorylated to produce IKK. IKK is phosphorylated into IkB, which is degraded and releases NFkB into the nucleus for transcription and translation of soluble mediators such as cytokines.
29
What is the mechanism that TLRs (using TRIF), use to recognize and target pathogens?
PAMPs activate TLRS, forming a timer. This allows for the binding of TRIF, subsequently causing binding of TBK1 and IkKe to TRIF. These two kinases become phosphorylated, activating them and leading to the phosphorylation of IRF3, which translocates to the nucleus and transcribes target genes, leading to the production of interferons.
30
How do TLRs initiate different immune responses (viral, bacterial, fungal)?
Location of the TLRs, either within the cell membrane or in the endosome, leads to the recognition of different PAMPs. The magnitude of the signal, the number of receptors involved, and the duration of the TLR signal can vary. Other signalling adaptors, MyD88 vs TRIF also result in different cellular responses.
31
What are NOD-like receptors? What is the mechanism that NOD-like receptors, found in monocytes and dendritic cells, use to recognize and target pathogens?
Cytoplasmic receptors that can be grouped into families based upon amino-terminal structural motifs, NOD family has n-terminal CARD. Binding of PAMPs to NOD results in dimerization, recruiting cytoplasmic kinase RIPK2 to the CARD domain of NOD. RIPK2 phosphorylates TAK1, which phosphorylates IKK, which phosphoylates IkB, which degrades and releases NFkB.
32
What is the mechanism that formylated peptide receptors (FPRs), found in neutrophils, use to recognize and target pathogens,
FPRs recognize bacterial formylated peptides, activating Ca2+ IP3 and cyclic AMP, creating gradients which mobilize the neutrophils towards the bacteria in a process known as chemotaxis.
33
Where do pluripotent hematopoietic stem cells come from?
The majority originate in the bone marrow.
34
What are pluripotent hematopoietic stem cells?
They give rise to all blood cell lineages as they pass through different stages of differentiation.
35
What are common progenitor cells?
Pluripotent hemaopoietic stem cells in the intermediate stages of differentiation.
36
Where are monocytes and macrophages found?
Monocytes are present in the blood, and upon entering tissues, they differentiate into macrophages.
37
Through what mechanism do monocytes and macrophages kill pathogens?
Phagocytosis.
38
How are monocytes and macrophages different?
Macrophages are much larger, have an increased phagocytic ability, and secrete a variety of soluble factors (cytokines) that help with tissue repair.
39
What do macrophages do?
Detect pathogens using PAMPs, clear infections via phagocytosis, activate the adaptive immune system by forming an MHC complex and presenting antigens to T cells, and release cytokines.
40
Dendritic cells do not lyse pathogens, are they still phagocytes?
Yes, they sample pathogens via phagocytosis.
41
What is the role of dendritic cells?
With high levels of MHC (major histocompatibility complex), after sampling pathogen, dendritic cells express antigen and migrate to lymphatic system to help activate naive T-cells.
42
Are neutrophils lymphocytes?
No, they are phagocytes and granulocytes.
43
What is the lifespan of neutrophils?
Very short, 1-2 days. As a result, they do not need their DNA to replicate, they instead use it to make NETS (neutrophil extracellular traps).
44
Do neutrophils have a circular nucleus?
No, they are characterized by their multi-lobed nucleus.
45
What are the effector mechanisms of neutrophils?
Phagocytosis, degranulation, oxidative bursts, cytokines, and NETs.
46
What are neutrophils, eosinophils, basophils, and mast cells?
They are all granulocytes.
47
What are the characteristics, physical and chemical, of mast cells?
They are granulocytes coated with IgE antibodies which, upon activation, leads to the release of granular contents to fight the pathogen. However, mast cells are often associated with overreactions which are cause allergies.
48
Are natural killer (NK) cells lymphocytes?
Yes, they are the only lymphocyte that is categorized into the innate immune response.
49
What are characteristics of NK cells?
They are large granular lymphocytes that are non-clonal. They can kill target cells (usually infected or tumor cells of the body) without prior immunization based on regulation by a balance of activating and inhibiting receptors.
50
How do NK cells attack target cells?
If there is no inhibitory signal, NK cell will bind to activating receptor which will cause the NK cell to release granule contents, inducing cell apoptosis.
51
What are the five major innate immune mechanisms?
Phagocytosis, cellular recruitment, inflammation, oxidative burts, and NETs.
52
What is the effect of inflammation?
Increased vascular permeability, cellular recruitment, and cell proliferation/ metabolism (activity) at the site of infection. This results in leukocytes and plasma proteins migrating to the infection site, increased blood flow, increased ability for antibodies to enter tissue, and increased lymph. There is also increased drainage of waste.
53
What mediates inflammation?
Cytokines and chemokines.
54
What are cytokines?
Small proteins released by cells inducing a response in a target cell. The specific response is based on the specific cytokine, which will bind to the appropriate cytokine receptor. This can result in activation, repression, inflammation and anti-inflammatory responses.
55
What are chemokines?
Chemokines are chemoattractant cytokines, inducing cellular adhesion or directional cell migration in response to a gradient of the chemokine.
56
Through what process do leukocytes, which circulate the entire body, navigate to a specific site of infection, from the blood into the tissue, and target pathogens?
The 5-step Leukocyte Recruitment Cascade.
57
What are the 5 steps of the Leukocyte Recruitment Cascade?
Tethering, Rolling, Activation, Adhesion, and Transmigration.
58
What occurs in the tethering step of the Leukocyte Recruitment Cascade?
In the activated endothelium of the bloodstream, Selectins (receptors) bind mucin-like cell adhesion molecules (mucin CAMs), which are molecules containing sialyl Lewis x residues.
59
What occurs in the rolling step of the Leukocyte Recruitment Cascade?
Following initial tethering, weak attractions between Selectins and mucin CAMs causes constant attaching and letting go as the leukocyte is pushed through the blood stream. This serves to slow down the leukocyte.
60
What occurs in the activation step of the Leukocyte Recruitment Cascade?
The slow rolling cell can sample molecules on the endothelium. If chemokines bind to the appropriate receptor, the leukocyte becomes activated, inducing a conformational change in other adhesion molecules in the cell, integrins.
61
What occurs in the adhesion step of the Leukocyte Recruitment Cascade?
Following chemokine-mediated activation of the leukocyte integrins, the cell can firmly adhere to the endothelium. Integrins bind their ligands on the endothelium (Ig-superfamily CAMs). This causes the leukocyte to flatten out and crawl along the endothelium looking for a way out of the vessel.
62
What occurs in the transmigration step of the Leukocyte Recruitment Cascade?
Adherent leukocytes squeeze between endothelial cells to enter the tissue below. This process is tightly regulated such that transmigration does not causes any blood plasma to leak into tissue. The leukocyte then continues to follow the initial chemokine gradient towards the site of infection.
63
Why don't all leukocytes get recruited to a site of infection by the Leukocyte Recruitment Cascade?
Differential expression of adhesion molecules and differential expression of chemokine receptors.
64
Describe the process of phagocytosis.
Phagocytes (macrophages, dendritic cells, and neutrophils) enclose pathogen into a membrane-bound vesicle known as the phagosome. The phagosome is then fused with another vesicle containing anti-microbial peptides and cytotoxic enzymes, the lysosome. This results in the formation of the phagolysosome. Immune functions of the phagocyte depend on the contents of the lysosome.
65
How do phagocytes target pathogens?
Receptors on the phagocytes recognize pathogen-derived molecules, such as PAMPs, or host-derived molecules, such as antibodies or complement which serve as opsonins.
66
What are the general contents of lysosomes?
Acid phosphatase, nucleases, protein/ lipid/ carbohydrate digesting enzymes, and defensins.
67
Why are lysosomes not harmful to the phagocyte?
Harmful enzymes are made in the endoplasmic reticulum, but are not active at normal physiological conditions (ph 7). The mature lysosome, however, is acidic, which activates the enzymes.
68
How do specific proteins navigate to the lysosome?
Proteins are tagged with a mannose-6-phosphate (M6P) residue, which binds to an MP6 receptor in the ER, budding off and fusing into lade endosomes. Late endosomes lower their pH by pumping in H+ ions, causing the enzymes to detach from M6P, activate, and the M6P is recycled bback to the ER.
69
How do phagocytes deal with pathogens resistant to lysosomal contents?
Phagocytes generate reactive oxygen and reactive nitrogen species which will react with and disrupt the function of the pathogen almost instantly.
70
What are oxidative bursts?
The result of the formation of reactive oxygen and reactive nitrogen species (ROS and RNS).
71
How do oxidative bursts occur?
Following phagocytosis, NADPH oxidase complex forms in the phagolysosome membrane, resulting in the generation of superoxide (O2-) which is released into the vesicle. O2- is highly reactive and extremely short-lived and will react with all parts of the pathogen, effectively lysing it.
72
What are NETs (neutrophil extracellular traps)?
NETs are composed of extracellular DNA (decondensed chromatin from the nucleus of neutrophils covered in histones which are highly charged) which can ensnare and kill pathogens due to their high cytotoxicity.
73
What type of barrier is the low pH skin, salty sweat, low pH stomach acid, and high pH intestine?
These are all examples of chemical barriers.
74
What type of barrier is lysozyme?
It is an enzymatic barrier.
75
What is the function of lysozyme, and where is it found?
Present in tears, saliva, and milk, lysozyme, which is produced by neutrophils and stored in granules, catalyzes the breakdown of peptidoglycan in bacterial cell walls.
76
What type of barriers are alpha-defensins, beta-defensins, and antibodies?
They are collectively known as molecular barriers.
77
What are defensins?
Small peptides produced as an inactive pro-peptide that must be proteolytically cleaved to be activate, and once activated, will result in the activation of leukocytes.
78
What are alpha-defensins?
These defensins are produced by either paneth cells in in the small intestine to be released into the gut or neutrophils which store them in granules. These alpha-defensins are used to direct anti-microbial activity.
79
What are beta-defensins?
These defensins are produced by skin epithelial cells and are stored in lipid-rich lamellar bodies, creating a water-proof barrier for the skin that is resistant to microbes.
80
Where are beneficial bacteria found within the body?
Most barriers are coated in non-pathogenic commensal bacteria which occupy space to prevent attachment of pathogenic microorganisms and also stimulate defensin and IgA production to maintain immune tolerance.

Immunology (7 decks)

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