4/5 Innate Immunity and Complement Flashcards
(47 cards)
Innate immune system function
First line of defense: identify/ initiate inflammation, eliminate and repair, and activate and regulate adaptive immunity.
Characteristics of innate immunity
No memory or specificity, (no protective immunity) rapid response
3 barrier types of the innate immune system:
Anatomical barriers (skin and mucous membranes)
Physiological barriers: chemical-mediated, involves microflora and the enzymes they produce
Phagocytic barriers: cell-mediated, using macrophages and neutrophils
Chemical defensive barriers
Lysozyme, stomach acid, defensins (microbes can kill organisms like them who compete for resources) and lactoferring (prevents iron-scavenging of infectious bodies)
Types of phagocytic barriers
Monocytes (bloodstream) and macrophages (all connective tissue and organs)
Neutrophils (polymorphonuclear leukocytes/ PMNs)
Recognition of foreign particles
- Pattern recognition receptors
—> conserved, found on PHAGOCYTIC cells including antigen-presenting dendritic cells, recognize PAMPs and DAMPs
Function of phagocytosis
Uptake of particulate material from the local environment by specialized cells (Macrophages, neutrophils, and dendritic/ antigen-presenting cells)
—> engulfment and internalization of materials for their clearance and destruction
Steps of the phagocytic process
- Antigen binds to PRRs on membrane evaginations called pseudopodia
- Antigen is ingested, forming phagosome
- Phagosome fuses with lysosome
- Antigen killed and digested by low pH-activated lysosomal enzymes (lysozymes) which include reactive oxygen and nitrogen species
- Digestion products are released from the cell
What are PAMPs? Two examples:
Pathogen associated molecular patterns (epitopes not present on host cells). These target cells for clearance and shortens response time.
Examples: Viral RNA, or bacterial cell wall peptidoglycan
What are PRRs?
Pattern recognition receptors: found on phagocytic cells and recognize PAMPs and DAMPs
Four most common types of PRRs
Toll-Like Receptors (TLRs)
C-type lectin receptor (CLR)
RIG-I-like receptor (RLR)
NOD-like receptors (NLR)
Toll-Like Receptor; location on the cell, and to what types of molecules do they bind?
Found on surface and within cells (to recognize both extracellular and intracellular PAMPs)
Different TLRs recognize different PAMPs
(Extracellular: Gram + and - Bacteria, parasites, fungi, flagella)
(Intracellular: viral components and some bacterial DNA)
TLR activation pathways
Activates transcription factors to stimulate expression of cytokines, enzymes etc
C-type lectin receptors: location and recognition types
Extracellular pathogens (located on membrane) recognizes carbohydrate components of fungi, viruses, mycobacterium, parasites and allergens. Transcription factors activated promote expression of proinflammatory cytokines (IL-1B, TNF, IL-23)
NOD-like Receptors: cell location and primary targets
Located intracellularly, and recognize components of cells walls (muramic acid), NOD1 and NOD2 bind to these PAMPs, while NLRP-3 binds microbial products and DAMPs. Induces expression of antimicrobial proteins and peptides, and can initiate autophagy by forming autophagosomes that fuse with lysosomes to kill bacteria.
RIG-I-like receptors, cell location and primary targets
Work in the cytosol and recognize viral double-stranded RNAs, which is bound by the RLR helicase domain. Triggers the pathway to activated interferons to trigger antiviral interferon responses
Killing Mechanism of phagocytosis
Kill with enzymes: lysozyme and acid hydrolase’s to dissolve/ digest, lactoferrin and Vitamin B12-binding protein to sequester nutrients pathogen would need to grow, and defensins and cationic proteins to direct antimicrobials to site of infection.
Also use reactive oxygen and nitrogen species that are directly toxic to bacteria
When phagocytic cells encounter invading microbes, name one transcription factor that is activated
NF-kB
5 signs of inflammation, and what is responsible for each sign
Redness, pain, swelling, warmth (fever), loss of function
Vasodilation causes local edema (swelling) and increases the temperature, and causes redness
Bradykinin triggers release of prostaglandins which bind to free nerve endings, causing pain (and edema broadly)
Swelling can cut off mobility and function to a region
Step 1 of inflammation
Tissue damage and pathogen introduction begins the release of inflammatory mediators.
- Damage cells and local immune cells release chemokines that activate capillary dilation and attract more phagocytes
- Bradykinin is one of these chemokines and also causes cascade leading to swelling, rise in temperature, and pain
Stage 2 of Inflammation
Phagocytes normally roll casually down the vessel endothelium using L-selectins. Cytokines produced by macrophages lead epithelium to display E-selectins which bind to phagocyte’s integrin receptors, causing rolling to stop at “door” of infection. Phagocytes squeeze between endothelial cells into interstitial fluid (diapedesis). Phagocytes then migrate to the site of injury, moving along a chemokine gradient. When arrived, phagocytes destroy pathogen or cause of tissue damage, and removes dead and damaged host cells.
Margination
The process by which phagocytes stick to the lining of blood vessels at site of infection using E-selectins, as opposed to rolling casually using endothelial L-selectins
Diapedesis
Cytoskeleton of phagocytes reorganizes and flattens out along endothelium, allowing the phagocyte to squeeze through the endothelial cells into the interstitial fluid
Phagocytic extravasion
How phagocytes migrate to the site of injury. When in the interstitial fluid, they move along a chemokine gradient, like a hound dog following a stronger and stronger scent.
