8-31 IMM Innate Immunity Overview Flashcards
How do innate and adaptive immunity work together?
Specific adaptive immune response with antibody and T cells can take days to weeks so innate response protects the body during this time
A characteristic of _____ responses is that they remain unchanged however often the antigen is encountered
innate
How does innate immune system distinguish between foreign and self?
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)
Barriers to entry (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
What is a neutrophil?
- 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
What is a macrophage?
- 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”
What are dendritic cells?
- 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
What are natural killer (NK) cells?
- arise and mature in bone marrow
- contain granules (granzyme and preforin) and cell surface receptors for IgG
- destroy virally infected and malignant cells
Microbial detection (what are PRRs and PAMPs)
- “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
PAMP examples
- 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
What are toll-like receptors (TLRs)?
- receptors specific for microbial proteins, lipids and polysaccharides on the cell surface
- receptors specific for nucleic acids are in endosomes where microbes are ingested
TLR-2 recognizes
several bacterial and parasitic glycolipids and peptidogllycans
TLR-3, TLR-7, and TLR-8 recognize
viral single-stranded and double-stranded RNAs
TLR-4 recognizes
bacterial LPS (endotoxin)
TLR-5 recognizes
bacterial flagellar protein called flagellin
TLR-9 recognizes
unmethylated CpG DNA that is abundant in microbial genomes
Why have microbes not adapted to avoid motifs recognized by innate immunity?
targets are indispensable to microbes
Primary reactions of innate immune system
- acute inflammation
- antiviral defense
What happens with acute inflammation?
recruitment and activation of leukocytes and plasma proteins at site of infection or tissue injury
How does innate immunity initially defend against viruses?
by the interfeuron system
Type I interfeurons
INF-alpha and INF-beta
Type II interfeurons
INF-gamma
How does the interfeuron system work?
- 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
Cytokines of innate immunity
- TNF (tumor necrosis factor)
- IL-1 (interleukin-1)
- IFN-gamma (interferon-gamma)
- IL-6 (interleukin-1)
What is the chief stimulator of production of acute phase proteins?
IL-6
Conditions that lead to acute phase responses include:
infection, trauma, surgery, burns, tissue infarction, various immunologically mediated inflammatory conditions, advanced cancer
How is an acute phase protein defined?
one whose plasma concentration increases or decreases 25% or more during inflammatory disorders. Due largely to changes in their production by hepatocytes
Role of C-reactive protein (CRP) in acute phase response
promote recognition and elimination of pathogens and enhance clearance of necrotic and apoptic cells
Role of Serum Amyloid A (SAA) proteins in acute phase response
influence cholesterol metabolism
Role of Haptoglobin and Hemopexin in acute phase response
antioxidants that protect against reactive oxygen species by removing iron containing cell-free hemoglobin and heme
Role of Hepcidin in acute phase response
reduces serum iron by reducing intestinal iron absorption and impairing iron release by macrophages
Role of Fibrinogen in acute phase response
helps wound healing by causing endothelial cell adhesion, spreading and proliferation
Use of serum acute phase reactant (APR) levels in clinical setting
abnormalities generally reflect the presence and intensity of inflammatory process
