The Innate Immune System & Inflammation Flashcards
what is the innate immune system
rapid non specifc inflammatory response that responds to signals from the PRR
PAMPs
conserved molecular structures of bacteria, virus and pathogens that bind to PRR
Role of the innate immune system
controling infections during the first 7 days after an infection
How is the adaptive immune system activated
Most cells in the innate immune systen release cytokines or interact with each other directly in order to activate the adaptive immune system
Cells that are not antigen presenting
The delta gamma t cells and NK cells are not APC. They are considered innate cells with some similarities to effector lymphocytes
Functions of the innate immune system - 3
- Initial response to eliminate and control infections
- Recognise and eliminate dead and damaged cells
- Modulate the adaptive immune system to be more effective
The most important defense
mucous membrane and skin
how does the innate immune system differentiate between self and non self - 3
- Recognition of pathogen associated immunostimulants on the pathogen but absent on the host
- Stimulate inflammatory responses of phagocytosis by macrophages and neutrophils
- Microbes have some stuctures that are not seen on mammalian cells
Example of this difference - 7
- Prokaryotic translation initiation differs from eukaryotic
- Fmet in bacteria other than the normal fmet and is on the first AA
- Fmet on the N-terminus must be of bacterial origin
- Fmet serves as a chemosttractant for neutrophils which migrate quickly to the source
- Bacteria has shorter DNA sequences
- CpG motifconstist of unmethylated dinucleotide CpG flanked by two 5’ purines and two 3’ pyrimidines
- More common in bact DNA and it activates macrophages, stimulate inflammatory response and increase the production of antibodies by B cells
fMet is recognized as
as a PAMP, and can therefore be detected by PRR
what are PRR
proteins that are capable of recognizing molecules frequently associated with pathogens
what do PRRs recognize
PAMPs and DAMPs
Soluble PRR - 5
- Ficolin
- Collectin
- Pentraxin
- Natural antibodies (IgM)
- Complement proteins
Cell associated PRR
- TLR - plasma membrane
- NLR - cytoplasm
- CLR - cytoplasm
- RLR - plasma membrane
- Scavenger - plasma membrane
- N-formyl met-leu-phe - plasma membrane
two CLASSES of PRR
- endocytic/phagocytic - found on the surface of phagocytes and promote the attachment of microbes to the PRR for their engulfment and destruction
- signalling - binding of the microbial PAMPs to the PRR promotes infammatory cytokines, chemotatic factors, antimicrobial peptides, cytokines such as type 1 inteferons
Activation of the downstream signalling pathway - 6
- Recruit and release cytokines, hormones, gf and chemokines
- Chronic inflammation
- Inflammatory micro environment
- Maintain a balanced microecology
- Initiate innate immune killing and subsequent acquired immunity
- Eliminate dead and mutate cells
TLR (MUTT OT)
- Membrane bound
- Up to 10 functional tlrs are in humans and 12 in mince
- TLR 1,2,4,5,10 are on the surface of immune cells in the form of h/h and they recognize lipids, proteins and lipoproteins (of B/F)
- TLR 3,7,8,9 are homodimers and they recognize nucleic acids of microorganisms (viral)
- Transmembrane type 1 are composed of extracellular, intracellular, transmembrane domains
- The transmembrane domain has LRR which recognise specific ligands and perform extracellular pattern recognition
NLR
- growth cycle of microorganisms or pathogens involves infection of the cytoplasm
- Nuclotide binding domain - nucleic acid binding and oligomerization
-LRR- C terminus, used to identify gaps - NED - protein interaction domain
RIG- I like receptors - VRBR
- Viral nucleic acids detected by tlr 7 and 9 but most types are recognized by RLR to induce antiviral immune responses
- Recognize RNA of different viruses through LRD
- Both RIG-1 and MDA-5 recognize dsRNA and the recognition depends on the length of the dsRNA
- RLR recognize viral products or particles in the cytosol
C- type lectins - PRAEDA
- Phagocytotic PRR
- Recognizes pamps through prr and places the pathogen in cytoplamsic vesicles for direct digestion and elimination for infection control
- A class of receptors that recognize carbohydrates on the surface of microorganisms with the participation of Ca2+ mediated by CRD
- Expressed on macrophages, dendritic cells and other tissue cells
- DCA 1 and 2 interact with glycans
- Abnormal glycosylation is usually associated with malignant tumors and antagonising this may be treatment of human infectious and malignant diseases
AIM-2 receptors - RIP
- Recognize intracellular DNA
- Promote the formation of inflammasomes and the maturation and release of IL-1B and IL-18
- Participate in innate immune response and regulate apoptosis
Extracellular Soluble PRR - FERI
- Free receptors with antibacterial effects in serum
- Extracellular soluble PRR include complement, collectins, pentraxin, ficolins
- Recognize various pathogenic factors and eliminate them through complement activation, opsonization, aggregration, neutralization o inflammatory regulation
- Interact with cell related PRRs and joinly regulate innate immune response
3 main types of molecules invlolved in signal transduction
- protein kinases
- adaptor proteins
- transcription factors
Major signalling pathway of the innate immune system
nfkB
Transcription of pro-inflammatory genes results in - 3
- cytokine secretion
- anti apoptotic genes (stops immune cells from dying)
- leukocyte recruitment (chemotaxis) `1
2 PRR agonists
- Imiquimod - TLR 7
- Selgantolimod - TLR 8
Imiquimod
induces the production of TNFa, IFNa and IL6 regulating immunity and controlling tumors
Selgantolimod
Elicit cytokine responses in individuals with chronic hepatitis B infection
Inflammation - 3
- Tissue response to pathogen invasion, injury or allergy intended to be protective
- It sets the stage for tissue repair
- Bacterial infections can result in mass of leukocytes, bacterial cells and damaged tissue called pus
Vasodilation - 5
- Increased BF
- Increased Protein permeability of venules
- Diffusion of protein to the interstitial fluid
- Diapedisis of neutrophils and filtration of fluid into the interstital space
- Clottin of fluid in the interstitial spaces
Chemotaxis
Migration of granulocytes and monocytes from the venules into the IF of the affected area
swelling of the tissues
Destruction of bacteria and necrotic tissue
phagocytosis and oxidative burst of resident macrophages and neutrophils
Tissue repair
Fibroblasts - cells found in connective tissue, divide rapidle and secrete large quantities of collagen.
Blood vessels proliferate (angiogenesis)
