A2 innate immunity Flashcards
innate immune system
innate vs adaptive
innate
-inherited (germ-line coded)
-recognition of common microbial motifs
adaptive
-random generation of recognition
-generates diversity of cells, can respond too very specific parts of pathogens
components of innate immune system
anatomical barriers
inflammation
complement
wbc
-macrophages, neutrophils, basophils, eosinophils, mast cells, nk cells
anatomical barriers (mechanical)
skin, gut, lungs, eyes/nose
-epithelial cells joined by tight junctions
skin and gut
-longitudinal flow of air or fluid
lungs
-movement of mucus by cilia
eyes/nose
-tears, nasal cilia
anatomical barriers (chemical)
skin, gut, lungs
-antibacterial peptides
skin
-fatty acids
gut
-low pH
-enzymes (pepsin)
eyes/nose
-enzymes in tears (lysozyme)
anatomical barriers (microbiological)
skin, gut
-normal flora
inflammation
recognition of pathogen associated molecular patterns (PAMPS) binding to pathogen recognition receptors (PRRs)
-TLR, CLR, NOD
activation of innate cells
-macrophages and mast cells
release of inflammatory mediators that recruit innate cells and lymphocytes
pattern recognition
innate immune system detects molecules from pathogens or damaged cells
-PRRs
many pathogens use similar mols that are distinct from eukaryotes
-pathogen associated molecular patterns (PAMPs)
-damage associated molecular patterns (DAMPs)
examples of pattern recognition receptors
toll-like receptors (TLRs0
-protein
-recognise leucine repeats
-virusus, bacteria, fungi, damaged cells
c-type lectin receptors (CLR)
-recognise carbohydrates
-viruses, bacteria, fungi, parasites, cancer
NOD-like receptors (NLR)
-recognise peptidoglycans
-bacteria
consequence of TLR stimulation
-often cell activation
-causes cell to secrete chemokines and cytokines
(recruitment of more phagocytes and inflammation)
-allows cell to increase phagocytosis and intracellular killing
1. macrophage expresses receptors for many bacterial constituents
2. bacteria binding to macrophage receptors initiate the release of cytokines and small lipid mediators of inflammation
what cells carry out phagocytosis
innate cells
-PMN, macrophages, dendritic cells
-termed phagocytes
step names of phagocytosis
-recognition
-pseudopod formation
-ingestion
-phagosome
-phagosome/lysosome fusion
digestion
stages of phagocytosis (detail)
- chemotaxis and adherence of microbe to phagocyte
- ingestion of microbe by phagocyte
- formation of phagosome
- fusion of phagosome with lysosome to form phagolysosome
- digestion of ingested microbe by enzymes
- formation of residual body containing indigestible material
- discharge of waste materials
what do phagocytes need in order to start destruction
recognition requires receptors on cell surface of phagocyte to bind pathogen
sometimes opsonisation
eg PRRs such as TLRs
recruitment of cells- rolling
adhesion of mols slow blood cells
using selectins binding to lectins on target cell
diff combinations of selectins- selective recruitment of cells
recruitment of cells- extravasation
-once leukocyte has slowed down, other adhesion mols can allow attachment
-integrins (LFA-1) and cell adhesion mols (CAMs, ICAM)
-allows cell to stick and axtravaste
(ie passes through endothelial cells lining the blood vessel)
recruitment of cells- chemokines
migration influences by chemokines
small proteins that control cell movement- chemotaxis
different chemokines recruit different cells to different tissues
-ie IL8/CXCL8
complement summary
collection of serum proteins
activated by a number of factors
causes serial activation of proteases
several functional outcomes
classical pathway
antigen antibody complex
complex activation
recruitment of inflammatory and immunocompetent cells
lectin pathway
lectin binding to pathogen surfaces
complement activation
opsonisation of pathogens
alternative pathway
pathogen surfaces
complement activation
killing of pathogens
cell recruitment & activation and opsonisation stages
-bacterium is coated with complement by the alternative and MBL pathways
-when only C3b binds to CR1, bacteria are not phagocytosed
-C5a can activate macrophages to phagocytose via CR1
direct killing of bacteria stages
-C5b binds C6 and C7
-C5b67 complexes bind to membrane via C7
-C8 binds to comp and inserts into cell membrane
-C9 mols bind to the comp and polymerize
-10-16 mols of C9 bind to form a pore in membrane
inflammation pillars
calor- heat
rubor- redness
tumor- swelling
dolor- pain
functi olaesa- loss of function
what bridges innate and adaptive systems
breakdown of pathogens generates lots of antigens
these represent fragments of the various proteins expressed by pathogen
can be recognised by adaptive immune system
(covid mutating and changing)
