Ch2 - Innate Immunity

Question 1

What do Toll-Like Receptors (TLR’s) do?

Answer 1

• a major class of innate immune system receptors that recognise different microbial products including:
  - bacterial cell wall constituents
  - microbial nucleic acids
• expressed on plasma membranes and endosomal membranes of many cell types

Question 2

What are NOD-like receptor (NLR) family recognise?

Answer 2

• microbial cell wall lipoproteins
• products of damaged cells
• cytosolic changes typical of infection or cell injury

Question 3

How is IL-1 (cytokine interleukin-1) created in the active form?

Answer 3

• products of damaged cells and cytosolic changes typical of infection or cell injury
• forms multiprotein complex (inflammasome) –> this generates active form of IL-1

Question 4

What does IL-1 do?

Answer 4

regulates the immune and inflammatory responses to infections.

Question 5

What are the principle components of innate immunity?

Answer 5

• epithelial barrier cells in skin
• GI tract
• respiratory tract
• phagocytes
• dendritic cells
• mast cells
• NK cells
• cytokines
• plasma protien
• proteins of complement system

Question 6

What does epithelia do?

Answer 6

• provide physical barriers against microbes
• produce antimicrobial peptides (defesins and cathelicidins)
• contain lymphocytes that may prevent infections.

Question 7

What are principle phagocytes?

Answer 7

• neutrophil and monocytes/macrophages
• blood cells recruited to site of infection
• activated by engagement of different receptors
  - some destroy microbes and dead cells
  - others limit inflammation and initiate tissue repair

Question 8

What are innate lymphoid cells (ILCs)

Answer 8

• secrete cytokines that induce inflammation

Question 9

What do NK cells do?

Answer 9

• kill host cells infected by intracellular microbes

- produce cytokine interferon-y which activates macrophages to kill phagocytosed microbes

Question 10

What is the complement system and how does it work?

Answer 10

It is a family of proteins which are activated on encounter with some microbes (in innate immunity) and by antibodies ( humoral response of adaptive immunity)

• complement proteins coat (opsonize) microbes for phagocytosis, stimulate inflammation and lyse microbes

lysis = the breakdown of a cell caused by damage to its plasma (outer) membrane

Question 11

What do cytokines do and what type of immunity (adaptive or innate) are they?

Answer 11

Innate
stimulate inflammation (TNF, IL-1, IL-6, chemokines), activate macrophages (IFN-y) and prevent viral infections (type I IFNs)

Question 12

What happens when something is inflammed?

Answer 12

• phagocytes recruited from circulation to infection sites & tissue damage
• cells bind to endothelial adhesion molecules that are induced by cytokines TNF & IL-1
• cells migrate in response to soluble chemoattractants (including chemokines, complement fragments and bacterial peptides)
• leukocytes activated –> ingest and destroy microbes and damaged cells

Question 13

How does antiviral defence happen?

Answer 13

mediated by type 1 interferon –> inhibit viral replication
NK cells kill infected cells

type I interferon binds with a cell surface receptor called interferon-α/β receptor (IFNAR) while type II interferon binds with a specific receptor called IFN-γ receptor (IFNGR) complex

Question 14

Example of when innate and adaptive immunity work together?

Answer 14

innate provide signals that work with antigens to activate B and T lymphocytes

This causes, adaptive immunity to be evokes by microbes and not by nonmicrobial substances.

Question 15

Q - How does the specificity of innate immunity differ from that of adaptive?

Answer 15

Innate immunity is directed against common molecular patterns shared by different microbes and the products of damaged cells and is mediated by cell surface receptors and secreted proteins of limited diversity. Adaptive immunity uses an extremely diverse set of antigen receptors

Question 16

Q- What are examples of microbial substances recognized by the innate immune system, and what are the receptors for these substances?

Answer 16

Some examples of microbial substances recognized by the innate immune system include lipopolysaccharide recognized by Toll-like receptor-4 (TLR-4), flagellin recognized by TLR-5, microbial DNA recognized by TLR-9 and by cytoplasmic DNS sensors, viral RNAs recognized by TLR-3, -7 and -8, bacterial peptidoglycans recognized by NOD-like receptors, and mannans recognized by the mannose receptor, as well as by mannose-binding protein in

Question 17

Q- What is the inflammasome, and how is it stimulated

Answer 17

Inflammasomes are a multiprotein complex found in the cytoplasm of phagocytes, dendritic cells, and other cell types that respond to pathogens or cell stress by inflammatory cytokine secretion or cell death. One important type of inflammasome generates an enzyme that proteolytically cleaves a precursor of the cytokine interleukin-1β (IL-1β), producing an active proinflammatory form of IL-1β that is released from the cell. This inflammasome contains a NOD family molecule called NLRP3 and the proteolytic enzyme caspase-1. NLRP3 responds to many different stimuli that indicate cell infection or injury, leading to activation of caspase-1, which then cleaves the IL-1β precursor. Stimuli that activate the NLRP3 inflammasome include various microbial products, crystals such as sodium urate and cholesterol, reduced potassium concentration, and

Question 18

Q - What are the mechanisms by which the epithelium of the skin prevents the entry of microbes?

Answer 18

The skin provides a relatively impermeable multilayered physical epithelial barrier by virtue of a surface layer of keratin and by tight junctions between the epithelial cells, called keratinocytes. The intestinal tract is lined by a single layer of epithelial cells, also held together by tight junctions. Some of the intestinal epithelial cells secrete a layer of mucus which serves as a microbial barrier. Both skin and intestinal epithelial cells secrete antimicrobial peptide antibiotics, and both epithelial also contains protective intraepithelial lymphocytes.

Question 19

Q - How do phagocytes ingest and kill microbes?

Answer 19

Phagocytes express a range of receptors that recognize microbial carbohydrates and Fc receptors that recognize microbes coated (opsonized) by antibodies. Microbes that bind to these receptors are internalized into phagosomes, which fuse with lysosomes, where the microbes are destroyed by reactive oxygen and nitrogen species and lysosomal

Question 20

Q - What is the role of MHC molecules in the recognition of infected cells by NK cells and what is the physiologic significance of this recognition?

Answer 20

Natural killer (NK) cells express inhibitory receptors that recognize MHC class I molecules on healthy host cells and can then inhibit NK cell activation. In virally infected cells, MHC class I molecules may be downregulated and therefore fail to engage inhibitory receptors, and at the same time, ligands for activating NK cell receptors are expressed. As a result, NK cells are activated to kill these infected

Question 21

Q - What are the roles of the cytokines TNF, IL-12 and type 1 interferons in defence against infections?

Answer 21

Tumor necrosis factor (TNF) stimulates inflammation in part by activating endothelial cells that line blood vessels to express molecules that recruit neutrophils and monocytes out of the blood vessels and into sites of infection. IL-12 made by macrophages and dendritic cells contributes to NK cell and T cell activation. Type I interferons inhibit viral replication, thus inducing an antiviral state in infected and adjacent cells and also may enhance viral antigen display by infected cells for recognition by T cells.

Question 22

Q - How do innate immune responses enhance adaptive immunity?

Answer 22

Innate immune responses induce the expression of costimulators on dendritic cells that can provide signals for T cell activation that work together with signals produced by antigen recognition. Innate immune cells also make cytokines that promote the adaptive immune response. Complement activation as part of the innate immune response can lead to the generation of complement fragments that enhance B lymphocyte activation.