Innate Immunity Protection Flashcards
Definition of innate immunity
Non specific defense mechanisms that a host uses immediately/within several hours after exposure to an antigen (0-96hours)
Definition of complement
Series of proteins that circulate in blood and tissue fluids.
Synthesised in response to inflammation in the liver
Definition of cascade
1 product induces the formation of the next
Definition of opsonization
A molecule that enhances phagocytosis by marking an antigen for an immune response or marking dead cells for recycling
Definition of immunogenic
A protein that further escalates the immune response
Definition of pleotropic
Many cytokines and chemokine can exert similar actions
What is the innate immune system and what is made up of?
What processes does it precede?
1st part of the immune system
- Epithelial barriers to infection
- Components that are induced upon infection (cells, secreted compounds)
Precedes adaptive and specific immune response
Characteristics of the innate immune system
Born with it
V fast, within hours
Ancient evolution, found in invertebrates, snails, fruit flies
Same response every time
Molecules used to recognize infection
Induces, directs acquired/adaptive immune response
What are the physical/mechanical/anatomical components of the innate immune system
Skin
GI tract
Resp tract
Mucosal epithelia
What are the secreted compounds in the innate immune system
Antibactreial
Complement
Natural antibodies
Cytokines
What are the cellular compounds in the innate immune system
Phagocytes
NK cells
How does the skin attempt to prevent entry of pathogens into the body
Keratin
Antimicrobial compounds
-Psoriasin kills Ecoli
-Burn patients more likely to get Ecoli infections
How does the respiratory tract attempt to prevent entry of pathogens into the body
V tight junctions, cells cannot be penetrated easily
Motile cilia waft pathogens out
-Primary ciliary dyskinesis, pathogens can’t be moved out
Mucus traps bacteria and wafted away
How does the GI tract attempt to prevent entry of pathogens into the body
Peristalsis
HCl , low pH activates acid hydrolases which can digest bacteria
How do mechanical and secretory methods attempt to prevent entry of pathogens into the body
Blinking
Crying, lysozymes break down cell walls
How does microbial competition prevent entry of pathogens into the body
Friendly bacteria will compete against them for
Light
Space
Nutrients
How are pathogens recognised
Cannot recognize all possible antigens
Recognizes a few highly conserved molecular structures in many different microorganisms
PAMPS (pathogen associated molecular patterns)
What is the criteria for a PAMP
Must be present in the microbe and not the host
Must be essential for the survival of the pathogen
-Genetic material can mutate under stress
PAMPs in gram -ve bacteria
Lipopolysaccharide LPS
Made up of an O polysaccharide and lipid A
PAMP = lipid A
Type of gram -ve bacteria = O polysaccharide
PAMPs in gram +ve bacteria
Lipoteichoic acid
Found in all gram +ve bacteria cell walls
How are pathogens recognized?
What are the types and where are they found?
PRR (pattern recognition receptors)
Collecting, in serum
Toll like receptors, in membrane
Nod like receptors, in cytoplasm
Describe how collectins work
What are collectins made up of
Collagen like + lectin region
Collagen interacts with effector parts of immune system
Lectin binds to sugar molecules on pathogen surface (mannose, fucose)
-Spacing is also considered
Describe how Toll like receptors work
Each TLR on the cell surface recognizes specific molecules
Found on membrane bound surface and vesicles in cells
What TLR recognizes gram +ve bacteria?
TLR 1 and 2
What TLR recognizes gram -ve bacteria?
TLR 4
What TLR recognizes flagelli?
TLR 5
What TLR recognizes double stranded RNA
TLR 3
What TLR recognizes single stranded RNA
TLR 7 and 8
What TLR recognizes unmethylated GpG DNA
TLR 9
What TLR recognizes mycoplasma
TLR 2 and 6
How doe NOD like receptors work (nucleotide oligomerization domain)
Which NOD like receptors recognize what?
In cytoplasm, recognize components of gram +ve, -ve bacteria
- NOD1, y glutamyl diaminopimelic acid
- NOD2, muramyl dipeptide
What are the effector mechanisms of the innate immune response
Complement
Phagocytosis and killing
Cytokines
Activation of adaptive immunity
What is a complement and how does it work?
Series of proteins that circulate in blood and tissue fluids
Synthesised in response to inflammation in liver
Operates via cascade
All lead to formation of C3, activated by C3 convertase
What are the 3 pathways that lead to C3 converts activation
Classical, antigen antibody complex
MB lectin, mannose on pathogen
Alternative, pathogen causes spontaneous activation
What happens when C3 converts is activated?
C3 =C3 convertase=> C3a + C3b
What does C3a do
Diffuses away from site of inflammation
Binds to C3a receptors on macrophages, neutrophils
Activated cells recruited to site of infection
What does C3b do
C3b sits on pathogen surface (opsonization)
More likely to be phagocytosed by neutrophils and macrophages
What do the terminal components (C5b, C6, 7, 8, 9) do?
Form the MAC (membrane attack complex)
Form a pore that disrupts osmotic potential, pathogen cell lyses
What happens if you have a genetic C3 deficiency?
Have frequent bacterial infections
Describe the properties of monocytes/macrophages
Mature from circulating monocytes
In large nos in GI, lung, liver, spleen
Relatively long life span
Describe the properties of neutrophils
Found in blood but can enter tissues when signal from inflammation received
Shorter lifespan than monocytes/macrophages
Describe the process of phagocytosis
Recognition of pathogen
Chemotaxis and adherence towards pathogen
Pseudopodia engulf pathogen into vesicle/phagosome
Phagosome decreases in pH, recruitment of molecules on phagosome surface signals for lysozomes to fuse with the phagosome
Phagolysozome pH activates hydrolytic enzymes, digests microbe
Exocytosis of waste materials
Immunogenic proteins are presented on cell surface to activate further immune response
What are the 2 killing mechanisms of macrophages and neutrophils
Generation of reactive oxygen radicals (more in neutrophils)
Generation of reactive nitrogen intermediates (more in macrophages)
How are reactive oxygen radicals generated
Following phagocytosis, increase in O2 uptake, respiratory burst
O2 reduced by NADPH oxidase => hydroxyl radicals + hypochlorite
Causes DNA damage and alternations in bacterial membranes, must be controlled
How is damage to the neutrophil/macrophage limited
When resting, the NADPH oxidase complex is separated
2 parts of complex in membrane
Other components in cytoplasm
When there is a respiratory burst, increase in microbes and inflammatory mediators, NADPH complex activated
Complex comes together on phagosome membrane
2O2 => 2O2 -
NADPH => NADP+ + H+
2O2 - => H2O + O2
Assembly is on phagosomal membrane, near pathogen
How are reactive nitrogen intermediates generated
iNOS, NOS2 induced by cytokines and bacterial components (interferon y, tumor necrosis factor)
Activates iNO synthetase
O2 + L-arginine =tetrahydrobiopterin=> NO + citrulline
Causes DNA damage and alterations in bacterial membranes
What are cytokines and what do they do
Proteins, intercellular messengers
Bind to specific receptors
Can activate and deactivate
What are the activating cytokines
IL 1 (interleukin 1) IL 6 (interleukin 6) TNF a (tumor necrosis factor a)
What are chemokines
Type of cytokine with chemoattractant properties
Particular arrangement of cysteine residues
Not specific to 1 receptor
Chemokine receptors bind to more than 1 receptor (pleiotropic)
Attracts cells to site of infection
What are the types of chemokines
CXC
CC
CX3C
XC
What chemokine is produced by macrophages and endothelium and what do they do
IL 8
Encourages neutrophils to come to site of inflammation
What are the types of interferons
Type 1
-IFa, IFb, both made in innate response to a viral infection. Activates NK cells
TYpe 2
-IFy, activate macrophages for antimicrobial killing mainly made by T cells in the adaptive immune response
Describe the function of NK cells
Kill virally infected cells, tumor cells
Respond to TNFa, IL12, IFNa, IFNb
Produce IFNy which activates macrophages, unregulated MHC
IFMy, IL12 stimukates differentiation of CD4 TH1 cells
How is the adaptive immune response activated
Signal 1
-Pathogen fragments from phagocytosis presented on APC surface with MHC
Signal 2
- Pathogen recognized by PRR
- Signal sent to nucleus to unregulated costimulatory signal production
Both these signals can activate Naive T cells => Effector T cell
Cytokines released by APC dictate what type of Effector T cell forms
What are the antigen presenting cells (APC)
Macrophages
B cells
Dendritic cells
How do the dendritic cells mature
Immature cells have MHCs but they are not displayed on the surface
They display many PRRs
When PRR recognizes a pathogen, dendritic cells mature
Mature dendritic cells display many MHCs and costimulatory molecules
