L2- Innate immunity Flashcards
How does the skin, respiratory tract, GI, tears, sweat, saliva and microbiome prevent entry?
SKIN: dry, outer, protective layer. Hard for pathogens to penetrate. Fatty acid production inhibits microbes on the skin.
RESPIRATORY TRACT: cells are tightly joined. Tight junctions act as a physical barrier by sealing gaps between cells so pathogens cannot enter. Cillia clear debris. Mucus contains antimicrobial substances (AB and enzymes) to neutralise and destroy microbes. Trapped pathogens are moved by cillia towards the throat to be coughed out or swallowed.
GI: peristalsis. Moves trapped pathogens through the digestive system. Mechanical defense so pathogens cannot stick to the intestinal wall. Produces HCL so low PH to hydrolysed bacteria.
SWEAT,TEARS,SALIVA: contain lysozyme to destroy the bacterial cell wall.
MICROBIOME: microbial competition with pathogens for space and nutrients so prevent microbe growth.
2 examples of specific microbes?
SKIN- staphyllococcus aureus
GI TRACT- Lactobacilli: produce lactic acid for low PH and competes with bacteria
Secreted components of the innate immune system?
Series of proteins circulating in blood and tissue fluids. Operate via a cascade.
An example of a secreted components ?
C3- activated by C3 convertase.
The 3 pathways are: Classical, MB-LECTIN and Alternative.
How do the 3 pathways to activate C3 convertase work?
CLASSICAL: Activated by a antigen-antibody complex producing C1q,C1r,C1s,C4 and C2. C1 cleaves C4 into C4a and C4b. C4b binds to the pathogen surface to recruit C2. C1 cleaves C2 into C2a and C2b. C2a and C4b bind to form C4bC2a (C3 convertase).
MB-LECTIN: activated via mannose on pathogen surface binds to mbl (an accute phase protein). produces MBL,MASP,C4,C2. MASP cleaves C4 into C4a and C4b + C2= C4bC2a
ALTERNATIVE: activated by pathogen recognition directly. cleaves C3 into C3,B,D= C3 convertase (more on this in L3)
What does C3 convertase do?
Cleaves C3 into C3a and C3b. C4a,C5 and C3a are required for recruitment of phagocytosis. C3b is required for oponisation- coates pathogens with oponins such as AB or complement proteins to enhance recognition so therefore, enhance phagocytic abilities.
C3b is also required for formation of terminal components: C5b, C6,7,8,9. Forms the membrane attack complex so responsible for pathogen lysis.
what does C3 convertase do?
cleaves C3 into C3a and C3b. C3b is required for oponisation- the coating of pathogens with opsonins such as ab or complement proteins so enhanced recognition of pathogens so increase phagocytic activity. C3a,C4a and C5a are involved in recruiting immune cells for phagocytosis. c3b involved in the creation f C5b required for MAC formation along with C6,C7,C8,C9 for cell lysis.
how does recognition of pathogens occur?
Innate IS recognises conserved molecular structures called PAMPS- pathogen associated molecular patterns.
examples of PAMPS?
Lipopolysaccharide in gram negative bacteria and lipoteichoic acid from gram positive bacteria.
what are the receptors of PAMPS?
PRR- pathogen recognition receptors.
examples of PRRs?
TOLL-LIKE RECEPTOR: present on immune cells like macrophages, dendritic cells, neutrophils, mast cells, some t cells and b cells. membrane-bound on csm and vesicular membranes.
COLLECTINS: proteins in solution. have a collagen-like region- interacts with effector parts of immune system and lectin region- binds to sugar molecules on surface of pathogen e.g: mannose by mannan-binding lectin.
THESE ARE EXTRACELLULAR PRRS
INTRACELLULAR: NOD-LIKE RECEPTORS, RIG- LIKE RECEPTORS CYTOSYLIC DNA SENSORS.
TLR examples and their ligands?
TLR-4: ligand= LPS (gram negative bacteria) on macrophages, mast cells, eosinophils, apc.
TLR-5: flagellin (bacteria)
TLR-9: DNA with methylated CPG (bacteria and herpes viruses)
TLR-3: double stranded RNA (viruses), poly 1:C
TLR-1: TLR-2 heterodimer and TLR-2: TLR-6 heterodimer: lipo mannans (mycobacteria), lipoproteins, lipoteichoic acid (gram positive bacteria), cell wall beta glucans in bacteria and fungi, zymosan.
where are neutrophils and macrophages?
neutrophils- blood, short lived.
macrophages- liver, lung, gi tract, spleen. long lived.
killing mechanism of neutrophils?
REACTIVE O2 INTERMEDIATES (NEUTROPHILS): following phagocytosis there is an increase in o2 uptake called respiratory burst. NADPH oxidase assembles onto the phagocytic membrane. O2 is reduced by NADPH oxidase into toxic OH- radicals. Toxic Hypochlorite radicals are are rapidly converted to harmless compounds tp not harm the host. Causes DNA damage and alterations in bacterial membranes so bacteria are unable to replicate and cellular processes are disrupted.
killing mechanism of macrophages?
REACTIVE NITROGEN INTERMEDIATES: catalysed by inducible nitric oxide synthetase (INOS, NOS2) induced by cytokines and bacterial components. INOS is an enzyme that produces NO from L-arginine (L-arginine plus inos gives you no plus L-Citrulline). Inferion gamma (IFN-Y) upregulates INOS. IFN-Y is cytokine by T and NK cells that activate macrophages and promote adaptive immunity. bind to receptors on immune cells to increase INOS expression. causes DNA damage and alterations in bacterial membranes.
