Lec 18-Microbial Recognition By Innate Immune System Flashcards
What is inflammation?
- Occurs everytime there is an immune response
- Strong when innate immune sys is activated, starts when bacteria first comes into skin—first alarm
- Nonspecific rxn to noxious stimuli
- Characteristics: Redness, swelling, pain, and heat at infection site
- A few innate immune cells are always around, they react first. These immune cells recruit cytokines, lipids, histamines, and chemokines to draw other immune cells/WBCs to inflammation site
- Is a GOOD thing, works in our favour
Pillars of inflammation
- Redness: increase in circulation
- Swelling: recruitment of immune cells=water coming out from base
- Pain: cytokines and swelling
- Heat: all of these things combined
Acute vs chronic affects of inflammation
Acute:
- Short term effects
- Fight infection and heal it
- Eg. Local tissue damage
Chronic
- Long term effects that don’t resolve
- Initiate inflammation, but immune cells can’t clean them up
- Eg. arthritis, inflammatory bowel disease
Example of local acute inflammation
- Tissue damage
- First patrolling innate immune cell recognizes damage, releases cytokines and chemokines
- Cells from circulation in capillaries release liquid to clear bacteria
- Phagocytosis and neutrophil migration work to destroy bacteria
- Immune sys begins healing process
Example of systemic acute inflammation
- Pathogen is not resolved locally, bacteria has spread
- Pro-inflammatory cytokines (pyrogens are fever-causing cytokines) are released to raise body temp, cause a fever
- Fever increases circulation rate, making a bigger alarm for the body to recruit leukocytes. It is also beneficial bc some pathogens can’t survive high body temp. Fever also increases transferrins which keep iron away from pathogens and limit their growth
- Cytokines go to hypothal receptors that produce inflammatory lipid formation (prostaglandin) which can change our body temp and BP, improving migration of immune cells
Relation of systemic inflammation and septic shock?
- Widespread inflammation can lead to septic shock by decreasing BP (they dont receive oxygen) which can damage organs. First thing that fails is kidney
- Gram-neg bacteria is dangerous bc it has lipopolysaccharides (LPS) which trigger pro-inflammatory cytokine response from WBCs, leading to cytokine storm that can be fatal
- Anything that is uncontrolled can cause damage
What do regulatory processes do?
Enhance or inhibit innate and inflammatory responses
What is the role of innate immune response?
Plays essential role in elimination of infection, but can be harmful when not adequately controlled
ALL innate immune cells:
- Are part of primary response
- Patrol interstitial space, tissue, dermis
- Can recruit more innate immune cells if detection of foreign substance
- Can initiate reaction
- Have PRRs (some adaptive immune cells do too!)
What are PAMPs?
- Pathogen associated molecular patterns: pathogens have structures/molecs not found in or on host cells (eg. Peptidoglycan, flagellin, dsRNA)
- Innate immune cells (i.e. leukocytes) recognize molecules that are typical of pathogens that we don’t have in our body using PRRs (pattern recognition receptors)
Differences between innate immune cell receptors (PRRs) and adaptive immune cell receptors
Memorize table on slide 14
What organisms have PRRs?
- Vertebrates, invertebrates, and plants have PRRs
- Originally discovered in fruit fly—has been around for millions of years meaning it is very good
How are pathogens detected? Give 2 egs
- PAMPs can be carbs, proteins, lipids, etc. PRRs can recognize PAMPs based on strucutre
- PRRs trigger a signal transduction cascade to activate the best immune response for that cell
- Eg. If PRR is activated on macrophage, macrophages are good phagocytic cells so they will phagocytose pathogen
- Eg. If PRR is activated on neutrophil, neurophils can secrete granules, do phagocytosis, or do NETosis
Eg of PAMP-PRR interaction
- PAMP binds to TLR (toll like receptor) and peptidoglycan activates it
- TLR promotes intracellular signalling to promote transcription of genes involved in processes like phagocytosis
Toll-like receptors (TLRs)
- There are a few TLRs in our genome, each recognizes diff PAMPs
- All have same structure: extracellular region interacts with PAMP, intracellular TIR domain activates signalling to produce a gene to support a specific immune response
