Immunology Lec 2 - Innate Immunity Pt1 Flashcards
acute inflammation
-doubling time of microbes
-what is accute inflammation
-designed for what
-also used for
-what can happen as a result of inflammation thats bad
-microbes have very short doubling times, 1 microbe can propagate into ~500 million in only 24 hours
-need a system that can respond very rapidly to prevent an organism from getting overwhelmed by a pathogen
-acute inflammation is a mechanism that rapidly recruits molecules and cells of the innate immune system
-designed to protect against microbial invasion
-the same system is also used to repair tissue damage
-note that inflammation is a relatively blunt tool; it can cause off target damage especially at its peak of if excessive
initating an immune response - PAMPs information
-pathogens have conserved structural features
-e.g; the cells walls of gram negative, gram positive, and acid fast bacteria
-these molecules can serve as pathogen-associated molecular pattern (PAMPs)
-PAMPs are recognized by pattern-recognition receptors (PRRs)
-by recognizing molecules conserved across a wide range of pathogens, a relatively limited repertoire of PRRs can provide an efficient way to monitor the body for infections
-lipopolysaccharide is a gram negative bacteria which is a type of PAMP
initiating an immune response; danger associated molecular patterns (DAMPs)
-another name for it
-also called damage associated molecular patterns or alarmins
-DAMPs are induced by injury to tissues
-this can be by physical disruption, or the consequence of an infection (e.g. cytopathic effect of viruses)
-known these two commonly studied DAMPs:
- HMGB-1 = high mobility group box-1. a hallmark of immunogenic death
- HSP = heat shock proteins. induced by things like fevers, some have direct anti-viral/bacterial effects
cytopathic effect; what is it, what does it mediate, important for interpreting what
-CPE for short
-cyto refers to cell, pathic effect refers to killing so its a cell-killing effect
-other things can mediate CPE, including bacteria (especially intracellular), drugs, etc (anything that kills cells)
-its a way for virologists to determine if replication-competent viruses (as opposed to replication incompetent or “dead” cell viruses) exist in samples
- important concept when interpreting diagnostic test results for viral infections
high mobility group box-1 (HMGB1)
- functions
functions of the alarmin HMGB1 released from damaged cells
-activates many cells associated with inflammatin
-triggers systemic responses to tissue damage
-in large enough quantities it can cause septic shock (overstimulation of immune system)
-associated with immunogenic cell death (ICD), as opposed to quiescent apoptosis as part of physiological development
sentinel cells
-beginning of what
-location and distribution
-intercept and detect
-expression and activation
-primary types
-beginning of an immune response
-systemtically distributed
-strategically located at common microbe entry sites (in skin, just under mucosal surfaces)
-intercept and respond to microbial invasion
-also detect tissue damage
-express diverse array of pattern recognition receptors (PRR) to detect PAMPs and DAMPs
-are activated by PAMPs and/or DAMPs
-these cells trigger inflammation
-3 primary sentinel cells are dendritic cells, macrophages, mast cells
-other cells (epithelium, endothelium and fibroblasts) can function as sentinel cells under certain circumstances
what are the three primary sentinel cells
dendritic cells, macrophages, mast cells
pattern recognition receptors; initiation, location, impact
- An immune response is initiated
when PAMPs/DAMPs bind to PRRs in/on sentinel cells - The location of this binding tells the immune system the nature of the pathogen (i.e., intra‐ versus extra‐cellular)
- This impacts qualitative aspects of the immune response
toll like receptors (TLRs) and the PAMPs they recognize
-TLR3 recognizes dsRNA viruses
-TLR4 recognizes LPS-expressing (gram negative) bacteria
-TLR7/8 recognizes ssRNA viruses
-TLR9 recognizes dsDNA viruses
equine aural plaques and imiquimod: translating knowledge of innate immunology into novel treatments; what is it, what is an imiquimod
-equine aural plaques: papillomas that grow in the ears of horses. caused by papilloma viruses
-imiquimod: a synthetic drug, a TLR7 agonist (simulates ssRNAs). induces an innate anti-viral response
-generic imiquimod is available in Canada as a cream and can be dispensed for off label vet use
linking recognition of PAMPs/DAMPs to inflammation; binding, cascade result, inflammatory cytokines, activation
- Binding of a PAMP or DAMP to a PRR generates a signaling cascade inside a sentinel cell
- The cascade results in activation of one or more transcription factors:
- MAPK: mitogen‐activated protein kinase
- NF‐κB: nuclear factor kappa‐light‐chain‐ enhancer of activated B cells
- IRF3: Interferon regulatory factor 3
- MAPK and NF‐κB activate the genes for the three major cytokines associated with inflammation:
- IL‐1, IL‐6, and TNF‐α
- IRF3 activates the genes for the antiviral cytokines known as type I interferons, of which IFN‐β and IFN‐α are the most common
IL-1; effects
every cytokine has a broad range of function and effect
IL-1 can affect the brain. induces things like fever, drowsiness, sickness behaviour
TNF-a: name, what can it mediate
tumor necrosis factor alpha
activates cells, toxic effects, enhances, promotes inflammation
what are the three major cytokines associated with inflammation
IL-1, TNF-a and IL-6
IL-6; when is it produced, what is it a mediator for, what other role can it have
- Produced in response to tissue damage (including in muscles after exercise) and severe infections
- A major mediator of septic shock
(covered in detail in a later lecture) - Can have an anti‐inflammatory role in some contexts (Therefore, also an important immunoregulatory cytokine)
- Neutrophils dominate the early stages of inflammation
- Macrophages dominate the later stages of inflammation
…IL‐6 regulates this transition
