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Immunology > A2: Innate Immunity > Flashcards

A2: Innate Immunity Flashcards

1
Q

How does the innate immune system distinguish self from nonself?

A

By recognition of motifs that are shared by microbes but not present on host cells, including pathogen-associated molecular patterns (PAMPs)

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2
Q

Are the pattern recognition receptors of the innate immune system clonally distributed or non-clonally distributed?

A

They are non-clonally distributed (identical receptors are expressed on all cells of a particular type; differs from adaptive immune system)

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3
Q

What are the 3 main reasons why the innate immune system does not react against self?

A
  1. Receptors of innate immunity are specific for microbial structures and damaged cells
  2. Pattern recognition receptors are in cellular compartments such as endosomes so healthy cells are excluded
  3. Normal cells express regulatory molecules that prevent innate immune reactions
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4
Q

What are the major receptors on innate immune cells (macrophages, dendritic cells, etc) that recognize PAMPs and DAMPs?

A

Toll-like receptors

NOD-like receptors

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5
Q

Which Toll-like receptors are present on the cell surface and which are present in endosomes?

A

Cell surface = 1,2,4,5,6

Endosomes = 3,7,8,9

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6
Q

What is the significance of the location of the TLR when compared to cell surface and endosomes?

A

Cell surface TLRs recognize bacterial and parasitic glycolipids
Endosomal TLRs recognize viral DNA and RNA products

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7
Q

What TLRs recognize bacterial lipopeptides? Which recognize lipopolysaccharide (LPS)? Which recognize bacterial flagella?

A

TLR 1 and 2 recognize lipopeptides (and TLR 6)
TLR 4 is specific for bacterial LPS
TLR 5 recognizes bacterial flagella

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8
Q

What TLRs recognize viral single stranded and double stranded RNAs? What recognizes unmethylated CpG DNA?

A

All of these are endosomal; TLR 3,7,8 recognize ss and dsRNA; TLR9 recognizes unmethylated CpG DNA

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9
Q

What are the two outcomes of TLR engagement?

A
  1. NF-kB activation which promotes expression of various cytokines and 2. interferon regulatory factors (which produce antiviral cytokines and type I interferons)
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10
Q

What are the 3 most important NOD-like receptors, and what do they do?

A

NOD 1 and 2 recognize bacterial peptidolgycans and activate NF-kB.
NLRP-3 enhances production of IL-1B via the inflammasome

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11
Q

What 3 components make up the inflammasome, and what is the goal of the inflammasome?

A

NLRP-3 (sensor)
Adaptor protein
Caspase-1
Goal of which is to make biologically active IL-1B

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12
Q

What causes the inflammation of gout?

A

Deposition of urate crystals causes inflammation via inflammasome and IL-1B production

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13
Q

What 3 components make the epithelial barrier a protection against microbes?

A
  1. Physical barrier to infection
  2. Locally produces antibiotics called defensins
  3. Intraepithelial lymphocytes kill microbes
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14
Q

What two chains make up the intraepithelial lymphocytes?

A

gamma and delta chains (compared with alpha and beta chains of the majority of T lymphocytes)

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15
Q

What are the 2 main types of circulating phagocytes?

A

Monocytes and neutrophils

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16
Q

Which cytokines stimulate the production of neutrophils?

A

Colony-stimulating factors

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17
Q

What are two phagocytic receptors that are on the cell surface of macrophages?

A

Mannose receptors and scavenger receptors

18
Q

What are the 2 ways that macrophages are activated?

A

Classical Activation: Innate immune signals from TLRs and IFN-gamma allows macrophages to destroy microbes
Alternative Activation: IL-4 and IL-13 induce macrophages to begin tissue repair and terminate inflammation

19
Q

What is the main goal of dendritic cells?

A

Initiate inflammation and stimulate adaptive immune responses

20
Q

What activates mast cells?

A

Microbial products binding to TLRs or via antibody-dependent mechanism

21
Q

What do mast cells do?

A

Release histamine to cause vasodilation.

Synthesize and secrete prostaglandins and cytokines (eg TNF) to stimulate inflammation

22
Q

What is the difference between an innate lymphoid cell and true lymphocytes?

A

Innate lymphoid cell do not express T cell antigen receptors (TCRs)

23
Q

What is the main role of natural killer cells?

A

Recognize infected cells and kill them and secrete IFN-gamma

24
Q

What is the interplay between natural killer cells and macrophages?

A

Activated NK cells secrete IFN-gamma which activates macrophages.
Activated macrophages produce IL-12 after ingesting microbes which activates NK cells

25
Q

What 3 cytokines activate natural killer cells?

A

IL-15 (important in maturation of NK cells)
type I interferons
IL-12 (Type I IFN and IL-12 important to enhance killing by NK cells)

26
Q

What cells are the principal mediators of antibody-dependent cellular cytotoxicity, and how does it occur?

A

Natural killer cells. Occurs via CD16 receptor on NK cells that recognizes IgG antibodies on cells.

27
Q

What are the 2 main activating receptors of NK cells?

A 
NKG2D: recognizes MHC class I proteins
CD16: recognizes IgG antibodies and kills via antibody-dependent cellular cytotoxicity
28
Q

How do the activating receptors of NK cells work?

A

Activating receptors have ITAMs on their cytoplasmic tails. ITAMs that are phosphorylated promote tyrosine kinases. Tyrosine kinases lead to cytotoxic granule exocytosis and production of IFN-gamma.

29
Q

What are the two main inhibitory receptors for NK cells?

A

Killer cell immunoglobulin-like receptors (KIRs), CD94+NKG2.

30
Q

How do inhibitory receptors of NK cells work?

A

Contain ITIMs which when they bind to class I MHC become phosphorylated. ITIMs then promote tyrosine phosphatases which inactivates tyrosine residues and prevents ITAMs action

31
Q

What are the types of T cells that are present in the epithelial?

A

the gamma/delta subtypes of T cells

32
Q

What are the 3 pathways of activation for the complement protein system?

A

Classical pathway: antibodies that bind to microbes activate complement system (adaptive)
Alternative pathway: proteins are activated directly from microbial surfaces (innate)
Lectin pathway: Activated when mannose-binding lectin binds to mannose residues on microbes (innate)

33
Q

What is the first step of the complement pathway? What are subsequent steps?

A

C3 is cleaved to make C3a and C3b. C3b goes on to activate more of the complement system.

34
Q

What are the 3 roles of the complement system?

A
  1. Opsonization (via C3b)
  2. Inflammation (via C5a and C3a)
  3. Cell lysis (via membrane attack complex)
35
Q

What are 3 key functions of TNF and IL-1?

A
  1. Main chemoattractant (activates endothelium)
  2. Activate liver to produce acute-phase proteins
  3. Induce fever via action at hypothalamus
36
Q

What are the 3 steps to leukocyte migration? What molecules mediate each step?

A
  1. Leukocyte rolling (selectins)
  2. Leukocyte adhesion (integrins)
  3. Leukocyte chemotaxis (chemoattractants)
37
Q

What is a key enzyme that is involved in oxidative burst, and what disease results if it is deficient?

A

Phagocyte oxidase converts molecular oxygen to superoxide anion and free radicals. This is key in destroying microbes via phagocytosis. Deficit in this enzyme results in chronic granulomatous disease

38
Q

What are the key molecules that act as antivirals, and what is the main cell that releases these molecules?

A

Type I interferons (interferon-alpha and interferon-beta). Mainly released by a dendritic cell called a plasmacytoid dendritic cell when activated by TLRs that recognize viral nucleic acids

39
Q

Why are adjuvants sometimes administered along with vaccines?

A

Vaccines administer the antigen without the actual microbe, so the adaptive immune system may need microbial products in order to provide the microbe-dependent secondary signals

40
Q

What two signals are needed in order to properly induce activation of the adaptive immune response?

A

Costimulators: expressed by dendritic cells when activated by microbes or IFN-gamma produced by NK cells).
IL-12, IL-1, and IL-6: secreted by dendritic cells and macrophages stimulate differentiation of naive T cells into effector cells

41
Q

What other signal does a B cell need when its antibody binds to an antigen in order to become active?

A

C3d. C3d is a product of C3b proteolysis that binds to the microbe. B cells recognize the antigen and the C3d molecule and induce proliferation of that B cell.

Immunology (25 decks)

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