Innate Immunity Flashcards
Immediate innate immune response time frame
0-4 hrs
*can have removal of infectious agents with no symptoms of infection
Early induced innate immune response time frame
4-96 hrs
*recognition of PAMPS, inflammation
Adaptive immune response time
greater than 96 hrs
*transport of Ag to lymphoid organs
Physical barriers
skin, mucus membranes
Humoral barriers
Complement system
Cellular barriers
Phagocytes, NK cells
Skin, cilia in respiratory tract, peristalsis in GI tract, washing by tears/saliva, and thick mucus are all types of _______ defense
Mechanical
Chemical factors in the innate immune response
Fatty acids (sweat)
lysozyme and phospholipase (tears/saliva)
low pH (sweat/gastric fluids)
Surfactants (lungs)
Normal flora on the skin and GI tract is an example of what type of defense?
Microbiological
Toxic oxygen-derived products involved in protecting the host during pathogen elimination
Superoxide O2- H2O2 O2 hydroxyl radical OH+ hypohalite OCl-
Toxic nitrogen oxides involved in protecting the host during pathogen elimination
Nitric oxide NO
Antimicrobial peptides involved in protecting the host during pathogen elimination
Defensins
Cationic proteins
Beta-lysine produced by platelets has bactericidal effects against ______ during coagulation
Gram + bacteria
Role of lactoferin and transferin
Bind Fe++ so bacteria can’t grow
Role of lysozyme
digests bacterial cell wall
Role of interferons
inhibit infection and replication of VIRUSES
Role of interleukin 1
increase temperature during inflammation and induce acute phase proteins (bactericidal)
PMN cells that phagocytose microorganisms
neutrophils
Phagocytic cells that ingest microorganisms and infected cells, and can act as Ag presenting cells
macrophages
Role of NK and LAK cells
kill infected or tumor cells
Cells that participate in eliminating parasites
eosinophils
What are the 4 most important cell types in innate immunity?
Neutrophils
Macrophages
Dendritic cells
Natural Killer cells
2 types of granules neutrophils have that are required for the intracellular killing process?
Azurophilic and Secondary
Azurophilic granules in neutrophils contain…
Defensins - kill bacteria
Enzymes - elastase and cathepsin G - degrade bacterial proteins
Lysozyme - degrades bacterial cell wall
Myeloperoxidase - generation of bactericidal subst.
Secondary granules are only found in mature neutrophils and contain…
Lysozyme
Lactoferin
NADPH oxidase - production of toxic radicals
Expression of CD14, CD11b or F4/80 is used to identify what cell?
Macrophages
Macrophages contain _____ that kill intracellular pathogens
lysosomes
Signals that induce chemotaxis of macrophages toward sight of microbe entry
N-formyl-methionine - bacteria
Peptides - coagulative system
Complement
Cytokines - secreted by macrophages
4 types of receptors phagocytes use to bind microorganisms
Fc
Complement
Scavenger
Toll-like (TLR)
Fc regions of ______ bind Fc receptors on ______
antibodies, phagocytes
What happens when an Ab that is bound to an Ag binds to the Fc receptor on a phagocyte?
Phagocytosis begins
*only works if Ab for a certain Ag are already present
In complement mediated phagocytosis, C3b binds the ____, then binds its receptor (CR1) on the _____, which leads to activation of phagocytosis.
Antigen, Phagocyte
_____ receptors sense Ag in the vicinity of macrophages and bind polyamines on their surface to mark them for phagocytosis
Scavenger
When macrophages bind Ag through their ________ they secrete cytokines in preparation for an ______ reaction.
Toll-like Receptors, inflammatory
3 main roles of phagocytosis?
Detect and destroy. Remove damaged cells and foreign objects.
Induce production of cytokines to initiate inflammatory reactions.
Process and present antigens to induce lymphocytes.
Steps of phagocytosis in macrophages
Chemotaxis
Detection and Binding of target (release of cytokines)
Endocytosis
Enclosure in the phagosome
Phagosome fuses with lysosome (phagolysosome)
Contents of lysosome are released into phagolysosome to kill target
Digestion of target
2 killing pathways in neutrophils, macrophages and monocytes
Oxidative - dependent on ROS and RNS
Non-oxidative - dependent on ulysosomes
During phagocytosis, the increase in use of oxygen and glucose is called ____ ____.
Respiratory Burst
In oxygen-dependent intracellular killing, respiratory burst leads to the formation of ____ ____ ____, which are toxic to microorganisms.
Reactive Oxygen Species
Azurophilic granules contain myeloperoxidase, which uses H2O2 and Cl- to produce the killing agent, _____
Hypochlorous acid HClO
Superoxide anion (O2-) can interact with Nitric oxide (NO) to produce the RNS ______
peroxynitrite
Oxidation of NO generates the RNS _____
nitrogen dioxide
Why is NO not always a beneficial method of killing microorganisms?
It is not only harmful to microorganisms, but to the host cell itself, killing everything in the vicinity of the phagocyte. Can cause tissue damage.
The non-oxidative intracellular killing pathway is dependent on the toxic substances present in ______
Lysosomes
*Ex: peptides, proteins, enzymes
Mechanism of action of cationic proteins
damage bacterial cell wall
Mechanism of action of lysozyme
damages mucopeptides in bacterial cell wall
Mechanism of action of lactoferrin
Binds free Fe++ to inhibit bacterial growth
Mechanism of action of proteolytic and hydrolytic enzymes
digest murdered bacteria
Pattern Recognition Receptors (PRR) recognize _____
PAMPs
5 classes of PRRs
Toll-like receptors TLR NOD-like receptors NLR RIG-like receptors RLR C-type lectin receptors CLR Peptidoglycan-recognition proteins PRGP
What are the major PPRs, located on all host cell membranes or within host cells that signal the presence of invaders?
Toll-like receptors
TLR3 binds double stranded RNA and targets _____
viruses
TLR7 and TLR8 bind _____ _____ ___ and target viruses
single stranded RNA
TLR9 Targets
Bacterial DNA and some herpes viruses
The endpoint of signaling through TLRs is production of _____ _____
Pro-inflammatory cytokines
NOD-like receptors are found _____ the cell and detect pathogens in the _____.
inside, cytoplasm
NOD1 recognizes _____
NOD2 recognizes______
NOD1 - bacterial peptidoglycans
NOD2 - muramyl dipeptides
As with TLRs, the endpoint of signaling through NLRs is ______
expression of pro-inflammatory cytokines
As well as recognizing PAMPs, NLR can also recognize ____
DAMPs
RIG-like receptors are found in the ______, detect _______ and produce ______
cytoplasm, viral RNA, pro-inflammatory cytokines
C-type lectin receptors bind ______ and are involved in recognition of _____ pathogens
carbohydrates, fungal
Peptidoglycan-recognition proteins are located in the large granules in neutrophils in most species, but in the ____ are located in the skin, bone marrow, and intestines.
Pig
PGRPs detect peptidoglycan on G+ and G- cell walls, and induce production of ______
antimicrobial peptides (Defensins)
Changes in serum proteins during infection is known as ____ ____ _____
Acute phase response (APR)
Examples of APR (acute phase response) proteins are
complement system proteins
C-reactive proteins (CRP)
Most APR proteins are synthesized in the _____
Liver
Synthesis of APR proteins in the liver is induced by _____ ______
Pro-inflammatory cytokines
C-reactive proteins (CRP) bound to the surface of a microbe promote ______ and activate ____ _____ ____.
phagocytosis, complement-mediated attack
Acute phase response protein that recognizes mannose on microbes, but not vertebrate cells.
Mannose-binding lectin
