Block 2 Flashcards
What is the function of lymphnodes?
facilitates interaction between dendritic cells and antigen-sensitive T and B lymphocytes
What are characteristics of white pulp?
- rich in lymphocytes
-where immune induction occurs
What is the primary functions of the spleen?
filters blood for blood-borne antigens, cellular debris and aged blood cells
stores RBCs, PLTs, and recycles iron
What is innate immunity?
- Non specific
- Fast
- No memory
Present @ birth
protects body from infection without prior contact w infectious agent
Physical Barriers (skin, MM)
Humoral Barriers (complement system)
Cellular Barriers (Phagocytic, NK cells)
What is adaptive immunity?
- Specific
- Delayed response
- Memory present
What is the first line of defense?
Physical barriers- Skin, mucus membranes, chemicals
What is the 2nd line of defense?
Phagocytosis, complement, interferons, inflammation, fever
What is the 3rd line of defense?
Adaptive immunity
Lymphocytes and antibodies
What are the mechanical factors associated with physical barriers of innate immunity?
- Skin
- Ciliary movement (resp. tract)
- Peristaltic movement (in SI + LI)
- Washing (by tears + saliva)
- Mucus layer
All of theses defend body by mechanically removing infectious agents and preventing entry
What are the chemical factors associated with physical barriers of innate immunity?
- Fatty acids- SWEAT inhibits bacteria growth
- Lyzozyme + Phospholipase (in tears/sweat)
- Low pH of sweat
- Surfactants (Opsonins in lungs! Enhances phagocytosis)
What are the microbiological factors associated with physical barriers of innate immunity?
Normal biota on skin and digestive tract prevents infection by secreting inhibitory substances
What is the most important humoral factors of innate immunity?
- Complement system!
- Coag system
- Lactoferrin and transferrin
- Lysozyme
- Interferons
- Interleukin 1
What is the coag system responsible for in innate immunity?
a Humoral barrier
if activated, leads to coagulation at damage site
some molecules act as CHEMOTACTIC FACTORS that attract other cells to site of damage
Beta-lysine made by platelets has bacteriocidal effects on gram + bacteria
What does Beta-Lysine do?
made by PLTs
Kills Gram + bacteria during the coagulation process
What does lactoferrin and tranferrin do?
binds iron so bacteria cant grow
Interleukin 1
Humoral barrier of innate immunity
increases temp during inflammation and induces acute phase proteins that are bacteriocidal
What cells are part of the cellular barrier of innate immunity?
- Neutrophils
- Macrophages
- NK cells
- Eosinophils
What are the most IMPT cells on innate immunity?
- Neutrophils
- Macrophages
- Dendritic cells
- NK cells
What are the vital cells of the phagocytic system?
Neutrophils and macrophages
Which granules do neutrophils require for intracellular killing?
- Azurophilic granules
- Secondary granules
Azurophilic granules
Granules found in neutrophils
Contains:
1. DEFENSINS that kill bacteria
- PROTEOLYTIC ENZYMES like ELASTASE and CATHEPSIN G
- LYZOZYMES that degrade bacteria cell wall
- MYELOPEROXIDASE for generation of bactericidal substances
Secondary granules
Granules found in neutrophils
Contains:
1. LYZOZYMES that degrade bacteria cell wall
- LACTOFERRIN that binds iron so bacteria cant grow
- NADPH oxidase that produces toxic radicals
What is the function of proteolytic enzymes?
Degrades bacterial proteins
Found in azurophilic granules in neutrophils
Ex: Elastase and Cathepsin G
Neutophils are identified by expression of _________
CD66 on cell surface
Macrophages are identified by expression of __________
CD14
CD11b
F4/80
Which cell does NOT pocess granules but has lysosomes that contain factors required for killing
Macrophages
Macrophages react to ______ generated at sites of pathogen entry
Danger signals (SOS)
Ex:
1. N-formyl-methionine
2. Peptides
3. Complement system
4. Cytokines
What are danger signals?
signals that alert and induce chemotaxis of macrophages to site of pathogen entry
- N-formyl-methionine
- Peptides
- Complement system
- Cytokines
What receptors do phagocytes possess to bind microorganisms?
- Complement receptors
- Scavenger receptors
- Fc receptors
- Toll-like Receptors (TLRs)
What are TLRs?
receptors on phagocytes that recognize PAMPs
located on the host cell membranes OR within the host
signals presence of invaders
What happens when macrophages bind antigens through TLRs?
They become activated and secrete cytokines like:
- IL-1
- 1L-6
- TNF
in prep for inflamm. rxn
What are Fc receptors?
Found on macrophages, ass. w phagocytosis
Only used when antibodies are available, for example in a recurrent infection
enhances activity of phagocyte
What is the purpose of phagocytosis?
- Detect and destroy pathogens
- Produce cytokines req. for inflamm rxn
- Present antigens to induce immune response by lymphocytes
What are the steps of phagocytosis?
- Chemotaxis
- Phagocytes detect and bind to target
- They surround the captured target w pseudopodia and engulf through endocytosis
- Endocytosed object becomes enclosed in phagosome
- Phagosome fuses w lysosome = phagolysosome
- Contents of lysosome released into phagolysosome
- Digestion begins
What killing pathways are used for neutrophils, monocytes and macrophages?
- Oxidative pathway (ROS, RNS)
- Non-oxidative pathway
What is the oxidative pathway of killing?
dependent on ROS and RNS
Oxygen and glucose increases (respiratory burst)
Generation of ROS
- Glucose metabolized through pentose-phosphate leads to NADPH
- Cytochrome oxidase activates NADPH
- NADPH uses O2 to produce SUPEROXIDE ANION
- Superoxide anion reduces to H2O2 and O2
OR superoxide anion reacts with H2O2 to produce hydroxyl (OH-) and ions
What are some important ROS species?
H2O2
OH-
Superoxide anion
NADPH
Myeloperoxidase
released during fusion of azurophilic granules with the phagosome
uses H202 and Cl- to make hypochlorous acid
Generation of RNS
Superoxide anion interacts with NITRIC OXIDE to make PEROXYNITRITE
NITRIC OXIDE can also undergo oxidation to make RNS nitrogen dioxide
TNF alpha
induces expression of inducible nitric oxide synthetase (iNOS)
What does iNOS do?
Oxidises L arginine to yield L citrulline and nitric oxide (NO)
** NO highly toxic to bacteria
What induces iNOS?
TNF alpha and and IFNy
What are non oxidative mechanisms of killing?
- Cationic proteins
- Lysozymes
- Lactoferrin
- Proteolytic and hydrolytic enzymes
Cationic proteins
a non oxidative way of killing
damages the bacterial cell wall
Lysozyme
a non oxidative way of killing
damages mucopeptides in bacterial cell wall
Lactoferrin
a non oxidative way of killing
sequestrates iron so bacteria cant grow
Proteolytic and hydrolytic enzymes
a non oxidative way of killing
digests killed bacteria
Which are sentinel cells?
- Macrophages
- Mast cells
- Dendritic cells
they use PRRs to sense PAMPS and DAMPs
Pattern recognition receptors (PRRs)
they recognize PAMPs and DAMPs in the innate immune system
PAMPs
repetitive motif molecules expressed by microbial pathogens and not found on host tissues
Ex of PAMPs:
1. Lipopolysaccharides
2. Peptidoglycans
3. Lipoteichoic acids
DAMPs
endogenous molecules released from damaged cells
What are some of the different classes of PRRs?
- TLRs
- NLRs
- RLRs
- CLRs
- PGPs
What TLRs detect bacterial parasites?
TLR1 and TLR2
What TLRs detect gram + bacteria and fungi?
TLR2 + TLR6
What TLRs detect gram NEG bacteria?
TLR4
What TLRs detect flagellated bacteria?
TLR5
What TLR detects intracellular viral dsRNA (double stranded RNA)?
TLR3
What TLRs detects intracellular viral ssRNA (single stranded RNA)?
TLR7 + TLR8
What TLR detects intracellular bacterial DNA elements?
TLR9
How does signaling by TLRs occur?
All TLRs are signaled by MyD88
except TLR3 which signals through TRIF
End point of signalling is to produce proinflamm. cytokines
What is a NLR?
A type of TLR, found INSIDE cells
Detects INTRACELLULAR pathogens in the cytoplasm
NOD1 detects bacterial peptidoglycans
NOD2 detects muramyl dipeptides
activated by non-microbial danger signals released by DAMPs
What happens when NOD-like receptors detect PAMPs?
leads to activation of transcription factor NF-KB
NF-KB
activated when NOD like receptors detect PAMPs
leads to transcription of genes responsible for expressing pro-inflamm. cytokines
NOD like receptors signal through _______ leading to production of _____________
IRF3/7
Type 1 interferons
What are RLRs?
Type of TLR
Expressed in cytoplasm (intracellular)
detects viral RNA (single and double)
induces production of antiviral cytokines like IFNs and inflamm. cytokines
What are CLRs?
Type of TLR
Fungal recognition and modulates innate immune response
has receptors that bind to CARBS in CALCIUM DEPENDENT manner
expressed by most cells (macrophages, dendritic cells)
PGRPs
localized in the large granules of NEUTROPHILS
detects peptidoglycan which induces production of antimicrobial peptides like defensins
alternating NAG and NAMs found on Gram + and - bacteria
Where are PGRPs in pigs expressed?
In the skin, bone marrow, and intestines
What is the endpoint of TLR signalling?
Production of pro inflamm. cytokines like:
PGEs, NO, TNFa, IL-1b, IL-6
Peyers patches are are considered PRIMARY lymphoid organs in what species?
Dogs, ruminants, pigs, rabbits
similar function to Bursa of Fabricius
Peyers patches undergo involution in what species?
Rodents and rabbits
GALT/MALT
Inductive site- immune response induced
Effector site- where cytolytic cells carry out the killing
What are enzymes involved with ROS?
- superoxide anion
- H2O2
- O2
- -OH (hydroxyl radical)
- OH-
What enzymes are involved in RNS?
- Superoxide anion
- Nitric oxide
- Peroxynitrite
- nitrogen dioxide
