8-31 IMM Innate Immunity Overview

Question 1

How do innate and adaptive immunity work together?

Answer 1

Specific adaptive immune response with antibody and T cells can take days to weeks so innate response protects the body during this time

Question 2

A characteristic of _____ responses is that they remain unchanged however often the antigen is encountered

Answer 2

innate

Question 3

How does innate immune system distinguish between foreign and self?

Answer 3

Innate immunity occurs in response to motifs that are characteristic of microbes but not of mammalian cells (e.g. gram-negative lipopolysaccharaide (LPS) and viral double stranded RNA)

Question 4

Barriers to entry (4)

Answer 4

1) physical barriers - skin and mucous membranes
2) chemical agents - antimicrobial body excretions
3) physical actions - urinating reduces urethra colonization
4) microbiological barriers - normal microflora

Question 5

What is a neutrophil?

Answer 5

• also called polymorphonuclear leukocyte or PMN
• develop in the bone marrow
• are phagocytic and kill engulfed substances in vesicles called phagolysosomes using potent oxidative burst of reactive oxygen species
• average life span is <2 days

Question 6

What is a macrophage?

Answer 6

• when monocytes migrate into tissue spaces they differentiate into macrophages
• are phagocytic and use phagolysosomes
• serve to kill and degrade antigens and also to present peptides from those antigens
• therefore called “professional antigen presenting cells”

Question 7

What are dendritic cells?

Answer 7

• important in immunesurveillance
• very efficient at presenting antigen to T cell
• pick up antigens by endocytosis
• follicular dendritic cells are specialized cells of spleen and lymph nodes adept at trapping and presenting antigen to B cells

Question 8

What are natural killer (NK) cells?

Answer 8

• arise and mature in bone marrow
• contain granules (granzyme and preforin) and cell surface receptors for IgG
• destroy virally infected and malignant cells

Question 9

Microbial detection (what are PRRs and PAMPs)

Answer 9

• “pattern recognition receptors” recognize and react to components specific to microbes. Are either secreted and circulating proteins and peptides or transmembrane and intracellular signal-transducing receptors
• “pathogen-associated molecular patterns” are patterns specific to pathogens that PRRs recognize

Question 10

PAMP examples

Answer 10

• bacterial endotoxin, also called lipopolysaccharide (LPS)
• terminal mannose residues of bacterial glycoproteins
• double stranded ribonulceic acid in many viruses
• unmethylated CG-rich oligonucleotides in microbial DNA

Question 11

What are toll-like receptors (TLRs)?

Answer 11

• receptors specific for microbial proteins, lipids and polysaccharides on the cell surface
• receptors specific for nucleic acids are in endosomes where microbes are ingested

Question 12

TLR-2 recognizes

Answer 12

several bacterial and parasitic glycolipids and peptidogllycans

Question 13

TLR-3, TLR-7, and TLR-8 recognize

Answer 13

viral single-stranded and double-stranded RNAs

Question 14

TLR-4 recognizes

Answer 14

bacterial LPS (endotoxin)

Question 15

TLR-5 recognizes

Answer 15

bacterial flagellar protein called flagellin

Question 16

TLR-9 recognizes

Answer 16

unmethylated CpG DNA that is abundant in microbial genomes

Question 17

Why have microbes not adapted to avoid motifs recognized by innate immunity?

Answer 17

targets are indispensable to microbes

Question 18

Primary reactions of innate immune system

Answer 18

• acute inflammation

- antiviral defense

Question 19

What happens with acute inflammation?

Answer 19

recruitment and activation of leukocytes and plasma proteins at site of infection or tissue injury

Question 20

How does innate immunity initially defend against viruses?

Answer 20

by the interfeuron system

Question 21

Type I interfeurons

Answer 21

INF-alpha and INF-beta

Question 22

Type II interfeurons

Answer 22

INF-gamma

Question 23

How does the interfeuron system work?

Answer 23

• PRRs on plasmacytoid dendritic cells and macrophages detect viruses and make INF-alpha and INF-beta
• use TLR-7 and TLR-9 to detect viral RNA and DNA, which expresses proteins to slow viral replication

Question 24

Cytokines of innate immunity

Answer 24

• TNF (tumor necrosis factor)
• IL-1 (interleukin-1)
• IFN-gamma (interferon-gamma)
• IL-6 (interleukin-1)

Question 25

What is the chief stimulator of production of acute phase proteins?

Answer 25

IL-6

Question 26

Conditions that lead to acute phase responses include:

Answer 26

infection, trauma, surgery, burns, tissue infarction, various immunologically mediated inflammatory conditions, advanced cancer

Question 27

How is an acute phase protein defined?

Answer 27

one whose plasma concentration increases or decreases 25% or more during inflammatory disorders. Due largely to changes in their production by hepatocytes

Question 28

Role of C-reactive protein (CRP) in acute phase response

Answer 28

promote recognition and elimination of pathogens and enhance clearance of necrotic and apoptic cells

Question 29

Role of Serum Amyloid A (SAA) proteins in acute phase response

Answer 29

influence cholesterol metabolism

Question 30

Role of Haptoglobin and Hemopexin in acute phase response

Answer 30

antioxidants that protect against reactive oxygen species by removing iron containing cell-free hemoglobin and heme

Question 31

Role of Hepcidin in acute phase response

Answer 31

reduces serum iron by reducing intestinal iron absorption and impairing iron release by macrophages

Question 32

Role of Fibrinogen in acute phase response

Answer 32

helps wound healing by causing endothelial cell adhesion, spreading and proliferation

Question 33

Use of serum acute phase reactant (APR) levels in clinical setting

Answer 33

abnormalities generally reflect the presence and intensity of inflammatory process