innate immunity Flashcards
(32 cards)
outline the characteristics of innate and adaptive immunity, highlighting their differences.
innate
- inherited (normal)
- acts rapidly hours/days, vital to triggering initial adaptive responces
- triggered by threat / damage
activated by general microbial patterns and damage
- canhave come immunilogical memory
adaptive
- acquired (learned)
- relatively sloe days/weeks
- triggered by exposure to specific antigen
- very focused, targets specific pathway
- excellent rapid immunilogical memory
what cells are involved in innate immunity
- neutrophil
- eosinphil
- macrophage
- monocyte
- granulocyte
- NKT cell
- DC
- NK cell
outline the main difference between how extracellular and intracellular pathogens replicate.
- extracellular - replicate outside host cells
- intracellular - replicate inside host cells
what abnormalities is the innate immune system able to recognise and define the molecular patterns used with each one?
- microbial nonself (microorganisms or their components which are foreign, not the bodies own, eg bacteria, viruses, fungi, pathogens) - pathogen associated molecular patterns (PAMP)
- consequences of infection or injury - innate immunity activated as it identified foreign or damaged cells - damage associated molecular patterns (DAMP)
- missing self - target cells that are missing complex molecules (MHC)
by what strategy are pathogens recognised?
- pattern recognition receptors
- these detect pathogens in fluids, cell surfaces and compartments as well as intracellularly
outline how pattern recognition receptors sence pathogens.
- detect PAMS - these are molecular structures unique to microbes and absent in host cells
- also recognise DAMP - signals released by host cells during stress or injury
name the 6 overlapping mechanisms of innate sensing.
- PAMP
- effector-triggered immunity
- recognition of absent self
- recognition of altered self
- damage recognition
- surveilance
outline what is meant by diapedesis.
the movement of neutrophills and other wbc from the lumen of a blood vessel into the surrounding tissues to travel to the area of infection / damage / foreign microbes ect
outline the steps involved in the pathway of innate immunity from pathogen discovery to cytotaxis.
- PAMPS and DAMPS bind to PRRs which activates cytokine release from mast cells and damaged tissue
- cytokines and chemokines activate endothelial cells, causing them to express e-selectin and p-selectin
- it also causes the endothelial cells to contract making them leaky
- leukocytes attach to the selectin on the endothelial rolling along the endothelial cells due to weak interactions between selectins and their ligands (CD15)
- leukocytes become activated from cytokines, causing the upregulation of integrins on the leukocyte surface which binds to selectins on endothelial cells
- diapedesis - leukocytes move through endothelial cell junctions into the tissue - integrins on leukocytes undergo confirmational change allowing them to interact strongly - PECAM-1 and CD31 fascilitate movement through junctions as well as selectins and integrins
- chemotaxis - chemokines released by injured tissue creating a gradient - guides leukocytes towards the source of injury
- this is a positive ffedback loop because wbc release TNFa and IL-1which leads to more secretins being projected by the endothelial cells
- it also promotes the neutrophills to move from the selectin to the PCAM to move through the endothelial cells
during extravasation, adhesion molecules circulate immune cells and endothelial cells, name the 3 catagories of adhesion molecules.
- selectins
- integrins
- immunoglobin family - ICAM
whats the role of selectins in extravasation and what tissue are they on?
- bind carbohydrates, initiates leukocyte-endothelial interactions
- activated endothelial cells and platelets
whats the role of integrins in extravasation and what tissue are they on?
- bind to cell-adhesion molecukes and extracellular matrix
- monocytes, neutrophills, macrophages, NK cells, dendritic cells, T cells
- example is CD31
whats the role of the IMg family (ICAM-1) in extravasation and where are they found?
- various roles - ligand for integrins (CD31)
- found on activated and resting endothelium, activated leukocytes and dendritic cells
outline the process of phagocytosis
The process of phagocytosis involves several phases:
- detection of the particle to be ingested
- activation of the internalization process
- formation of a specialized vacuole called phagosome
- maturation of the phagosome to transform it into a phagolysosome
what cells are phagocytes?
- neutrophills and macrophages mainly but also:
- immature dendric cells
- monocytes
- eosinophills
- osteoclasts
how are microbes or apoptotic cells recognised for phagocytosis?
- opsonic receptors on the immune cells detect opsonins which are bound to the target
- non-opsonic receptors on immune cells identify distant molecular patterns on target
name a few examples of opsonic receptors.
- Fc receptors (FcR) bind IgG or IgA
- Complement receptors (CR) bind activated complement components (e.g. iC3b)
name a few examples of non-opsonic receptors.
- C-type lectins (e.g. dectin)
- Lectin-like molecules (e.g. CD169)
- Scavenger receptors (e.g. SR-A, MARCO, CD36)
an immune cell has located its target microbe to phagocytose, it is deciding which mechanism of internalisation to uptake the cell, what sort of things does this depend on?
- particle size
- multiplicity of receptor-ligand interactions
- involvement of the cytoskeleton
outline the PH of the early and late phagosome and the phagolysosome.
- early phagosome - PH 6.1 - 6.5
- late phagosome - PH - 5.5 - 6.0
- phagolysosome - PH = 5.0 - 5.5
outline the steps and overall process of phagocytosis.
- cells membrane surrounds particle and pinches off to form a phagosome (vesicle)
- Early Phagosome: Contains the ingested material, is mildly acidic, and fuses with early endosomes, making it more acidic.
- Late Phagosome: More acidic, fuses with lysosomes, and begins degradation.
- Phagolysosome: A highly acidic vesicle where the pathogen is fully degraded by lysosomal enzymes and ROS.
- multiple things then occur to digest the pathogen, however the only thing which cant be digested is the antibodies
- macrophages will present these on its cell membrane and neutrophills wont they will exocytose them
name some mechanisms that the phagocytes use to eliminate the microbe after its been engulfed. (microbial killing)
- acidification
- toxic oxygen-derived products - free radicals create oxidative damage to dna and lipids
- antimicrobial peptides
- toxic nitrogen oxides - dna, protein and lipid damage
- enzymes - lysosomes
- competitors
many successful pathogens have evolved multiple strategies to prevent and / or inhibit phagocytosis, name some of these stratagies.
- prevention of phagocytosis by secreting damaging toxins which cause necrosis
- interference of phagosome maturation by inhibiting acidification
- resistance to phagolysosome contents by expressing OatA
- physical escape from phagolysosome - fuses the phagosome with the plasma membrane releasing it from the cell alive
how does the innate immune system help initiate adaptive immunity?
- dendritic cells phagocytose or endocytose pathogens
- this causes the upreg of MHC molecules and stimulatory molecules (b7 ligands)
- dendritic cell then migrates to lymph node where it presents antigens to naive T cells
- naive T cells then become activated and undergo clonal expansion and differentiate into effector T cells
