1.2 Innate Immune System Flashcards
What are the sites of infection on the extracellular part of cell?
Interstitial spaces, blood, and lymph
Epithelial surfaces
What are the sites of infection in intracellular parts of the cell?
Cytoplasmic and vesicular
What are the pathogenic mechanisms of tissue damage?
Exotoxin release
Endotoxin release
Direct cytopathic effect
How is lymph created?
Interstitial fluid leaks out of capillaries and into the tissues, washing cells of body with the liquid, and now that it’s out of capillaries it’s called lymph
Steps of the alternative pathway
C3 is cleaved into C3b and C3a
- Cleavage of it exposes the thioester bond and nucleophilic attack occurs at the bond
- The attack can be facilitated by water and results in soluble C3b
OR
- The attack can be facilitated by an R group and results in C3b bound to pathogen surface
What does the C3b bound to bacteria trigger?
Opsonization (C3b is tagged as foreign object) which enhances phagocytosis
- C3b is englufed by endocytosis, creates a phagosome, and lysosomes kill the pathogen
The C3b complex can also activate ___
C5
What happens when C5 is activated?
C5 attaches to C3b complex –> splits C5 into C5b and C5a –> C5b forms a pore on the surface of the pathogen
- It forms a membrane attack complex
Does the membrane attack complex (MAC) affect host cells?
No
- Protects from C9 pore forming
Complement compounds increase ___ ___
Vascular permeability
- Complements flow out of blood vessels
Defensis are what?
Antimicrobial peptides
- they’re secreted on mucosal surfaces to kill invaders
What’s cell is the main source of defensis in the intestine?
Paneth cells
- They produce antimicrobial peptides
What brings the defensin into the lipid bilayer?
Electrostatic attraction and the transmembrane electric field
- all defensins poke a hole in the membrane and form a pore
What are TLRs?
- Recognize conserved pathogen molecules
- Type of pattern recognition receptor (PRR) that recognize molecules that are broadly shared by pathogens
- allows the immune system to recognize and attack non-self molecules
Innate immune receptors recognize ___ ___
Microbial structures
Recognition of microbial products through what?
Toll-like receptors
TLR binding stimulates ___ production
Cytokine
Describe cytokines
- Small secreted proteins released by host cells that act on other host cells
- Act over short distances and short time span and at low concentration
Define chemokines
They’re cytokines that attract leukocytes to infection cites
Define interferons
They’re cytokines that have antiviral activity
Localization of ___ production is important
Cytokine
- local infection is good
- systemic infection is bad
Describe the process of cytokine recruitment of neutrophils:
Neutrophils roll along the surface and binds to various ligands and interacts with LFA-1 and ICAM-1, causing tight binding
If there’s an IL8 receptor that interacts with IL8, it triggers diapedesis
- Attracts neutrophils from bone marrow to tissues where IL8 is being produced by macrophage eating bacteria
What is IL6 effect on the liver?
Induces the liver to make mannose-binding lectin, fibrinogen, C-reactive protein
What does C-reactive protein do?
It binds phosphocholine on bacterial surfaces and acts as an opsonin and as a complement activator
What does mannose-binding lectin do?
it binds to carbohydrates on bacterial surfaces, acting as an opsonin and as a complement activator
Process for mannose binding lectin activating complement
Mannose activating serine protein (MASP-2) cleaves C4 to C4a and C4b
Activated MASP-2 cleaves C2 to C2a and C2b
C2a binds to C4b forming C4b2a
C4b2a binds C3 and cleaves it to C3a and C3b
C3b binds covalently to microbial surface
Antibody specific for a microbe can stimulate ___ to break down ___ and ___
C1
C4
C2
Natural Killer cell receptors recognize what
Virally infected cells and kill them
What’s the process for innate viral protection?
Once a virus infects a cell, it induces a transcription factor that’s called IRF3
Transcription factor’s activated
Comes in and binds DNA and induces NF(delta)B and makes interferons which can have a paracrine effect on other cells or autocrine effect on itself on IRF7 which would produce IFN-2
Process for NK cells to eliminate infected cells
Virus infection of cells triggers interferon response
Interferons drive the proliferation of NK cells
NK cells activate
NK cells induce apoptosis of infected cells
What’s the process for innate NK activation?
Macrophages produce cytokines that recruit and stimulate NK cells
NK cell and macrophage form a pair with a synpase and IL-12 and IL-15 activate the NK cell
NK cell is stimulated to divide and macrophages are stimulated to be activated
NK cells secrete interferons
Interferons bind to its receptors on macrophages and activates them to increase phagocytosis and secretion of inflammatory cytokines
Process for phagocytic killing of microbes
Neutrophils bind bacteria, engluf them and destroy them with the toxic contents of the neutrophil granules
What raises and lowers the pH in the phagocytic killing of microbes?
NADPH = raises
2H+ = lowers
What are the cells of adaptive immunity?
NK/T cell precursor B cell T cell Plasma cell Effector cell NK cell
What are the cells of innate immunity?
Neutrophil Basophil Eosinophil Monocyte Dendritic cell Macrophage Mast cell NK cell
Function of dendritic cells
Process antigen material and present it on the cell surface to T cells
