Innate Immunity Flashcards
what are the 3 overall aspects of the innate immune response (+ hrs)
- Intrinsic barriers (prevent entry)
- Immediate response (0-4h)- recognition of microbes or alarmins by broadly specific receptors
- Early induced innate response (4-6h)- Leukocytes are recruited from the blood into tissues and provide key innate responses
How does the epidermis and dermis act as a barrier
epidermis- Tightly packed desmosomes, top layers composed of dead cells w low water content and no receptors
Dermis- Sebacecous glands produce a low pH environment
how does the mucus membrane act as a barrier
- Epithelial cells tightly packed by tight junctions
- lamina propria contains various immune cells
- Goblet cells secrete mucans which traps particals from entry
where is the mucocillary escalator found and what does it do
-found in respiratory areas with epithelial cells with cilia that beat in synchronized rythm to move musus up and out
what is dysbiosis and examples (2) `
Alteration in the normal constituents of tissue microbiota
- C diff–> associated w antibiotic use
- Bac vaginosis–> gardnerella vag> lactobacilli spp.
what are AMPs
Released by immune/tissue cells to trigger immune respone/ kill microbes
What are 4 examples of AMPs
- Lysosome- degrades peptidoglycan (gram pos bac)
- Defensins- + charged peptides that form pores on microbial cell membranes (causing eflux)
- Surfactant pros- act as oposins (phago beacons)
- Complement pros
What do complement proteins lead to (3)
- Inflamation + chemotaxis
- Opsonization of microbes
- Disruption of microbial membranes
what happens in the compliment protein classical path, lectin path and alternative path
Classic- C1q binds directly to pathogen surface
Lectin- lectins(MBL) bind to mannone on pathogen
Altern- Spontaneous activation of compliment pro 3 on path
What happens when c1q/lectin bind to the pathogen surface + what is made in the end
Serine pros are activated which break down compliment pros
All pathways produce an important structure called C3 convertase**
what does c3 convertase make and what do they do
C3a,C5a- promote inflamation/chemotaxis
C3b- opsonin
C5b,c6,7,8,9- membrane attack complex (make pores so int contents of microbe leak out)
What type of pathogen is most susceptible to actions of complement pro
Bacteria and fungi
What type of cells initiate the intermediate immune response and how do they detect it
tissue resident cells found @ the site of injury
- using broadly non specific receptors called pattern recognition receptors (PRRs)
What 2 things do PRRs recognize
PAMPs (found on microbes; LPS/dsRNA/RNA virus)
DAMPS/alarmins (due to damage; intracellular structures)
examples of DAMPS
- Free DNA, histone pros
- Heat shock pros
- Uric acid
- HMGB1
- S100 pros
What are the inflammatory PRRs and what do they do
- Toll like receptors
- RAGE
-cell signaling cascade that results in activation of proinflammatory genes+ mediators +interferons
What do embeded TLRs sense compared to endosomal TLRs
embeded membrane- ext microbe structures
Endosomal- recognize int microbe structures
What TLR receptor recognizes: DAMPs, peptidoglycan/zymosan, dnRNA, LPS, ssRNA, Flagelin, CPG DNA
DAMPS- TLR2+4 pep/zym- TLR 1+2 DsRNA- TLR 3 LPS- TLR4 ssRNA- TLR 7+8 Flagenlin- TLR5 CPG DNA- TLR9
Examples of cytokines that inflamatory PRRs release
IL1 TNFa IL6 IL8 IL12 type 1 interferons
what are the type 1 interferons and wht do they do
-IFNa and IFN b
- induce resitence to viral replication in cells not affected
- increase MHC class 1 (for t cell function)
- Activate dendridic cells and macrophages and NKcells
what is the physiological roles of acute inflamation
- antimicrobial responeses for regen + repair
- Fever- triggers body temp increases and increases phagocyte activity, heat shock pros and inhib of microbe growth
Other than inflammatory PRRs what is the other PRR + exmaples (3)
Phagocytic PRRs
- Mannose receptor
- Scavenger receptors
- complement receptor
- if ant of these receptors bind its associated ligand phagocytosis occurs
How do phagosomes destroy phagocytized material
phagosome fuses with lysosome forming phagolysosome (has hydrolytic enzymes + low ph, increased prod of ROS/RNS and antimicrobial peptides)
What starts the induced innate response and what is its goal
Inflammatory mediators produced as a result of recognition of PAMPS/DAMPS
-Facilitates extravasion of leukocytes and blood components into injured area
what are the steps that proinflammatory mediators do to facilitate extraversion
- Edothelia activation (icams/selectins)
- Capillary endothelial cell tight junctions weaken making blood vessels leakier
- Arteriole smooth muscle relaxes (vessel dialation)
What happens in rolling adhesion
E selections on membrane binds to slex on blood leukocytes that roll along vessel wall
What happens in firm adhesion
Integrens on leakucytes bind to ICAM molecules on endothelial cells; anchors them firmly
What happens in diapedesis and migration
diapedesis- leukocytes squeeze between epithelial cells
Migration- Chemokines (IL8) attract leukocytes to site of injury
What are the 3 main antigen presenting cells
cDCs
macrophages
B cells
