Lecture 5: Innate Immune Sytem Flashcards
proteins of innate immunity recognize _______ common to many pathogens
patterns
local effects of inflammation
- heat
- redness
- pain
- swelling
clinical tests for inflammation test for ?
acute phase proteins
- the tests can indicate the presence of inflammation but not the etiology
physical barriers of the innate immune system
- skin
- epithelium
- cilia
molecular/chemical barriers of the innate immune system
lysozymes (tears, saliva, milk, GI mucus)
defensins, cathelicidins (antimicrobial peptides)
lactoferrin
lactoperoxidase
function of lysozymes in innate defense
destroys bacterial cell walls
function of Defensins, cathelicidins in innate defense
destroy microbial cell membranes
antimicrobial
function of lactoferrin in innate defense
sequesters iron
function of lactoperoxidase in innate defense
generate ROS
what is the role of non-cellular barriers to pathogen invasion
they protect all exposed surfaces
what is Latherin
protein in horse sweat that causes evaporative cooling and inhibits microbes
identify these physical barriers (A,B,C)
A: skin (keratinized squamous epithelium)
B: Mucus membrane (non-keratinized squamous epithelium)
C: GI tract (columnar epithelium)
what are the innate immune cells (cellular barriers)
- dendritic cells
- macrophages
- neutrophils
- NK cells
- eosinophils
- basophils and mast cells
innate immune cells that are primarily of myeloid lineage BUT can come from lymphoid precursors too
dendritic cells
subpopulations of dendritic cells are identified by their?
surface molecules
what are the professional antigen-presenting cells
- dendritic
- macrophages
- B-cells
what is the function of dendritic cells
they are professional antigen-presenting cells
T-cell activation (takes place in lymph node)
what 2 populations of classical dendritic cells (cDCs) activate helper T-cells
cDC1 and cDC 2
cDC1 - promote type I responses by producing IL-12 and activating Th1 cells
cDC2 - promote type II responses by producing IL-6 and IL-23, activating Th2 and Th17
what cell type links the innate and adaptive immune system
dendritic cells
macrophages are part of what system?
reticuloendothelial system (RES)
- destruction of foreign substances
- clean up dying/apoptotic or abnormal self cells/tissues
what are macrophages derived from
monocytes
what are the differentiations of macrophages in tissues
PIMPS - alveolar macrophages
Kupffer cells - liver
Peritoneal macrophages - abdominal cavity in peritoneal fluid
Microglia - CNS
splenic macrophages - white pulp of spleen
what structural feature of macrophages demonstrates the cells’ ability to synthesize lots of proteins
the presence of a rough ER
What are the 2 main functions of macrophages
Phagocytosis
– engulf foreign material/debris
– break down via lysosomal enzymes
Antigen Presentation
– uptake of an antigen
– processing of antigen
– presenting of antigen to T-cells
what is cellular input / output
cellular input: surface receptors
cellular output: cytokines and chemokines
what are the 3 main functions of neutrophils?
Degranulation
Phagocytosis
NETS (DNA expelled)
4 steps in phagocytosis
- chemotaxis
- adherence
- ingestion
- destruction
what do NK cells kill
- stressed cells
- cells lacking MHC-I
- Ab coated cells
- infected cells, tumor cells
NK cells activate macrophages via ____?
IFN-y
what are the two ways NK cell activation occurs
- loss of MHC-I on a target cell
- expression of stress-related protein on target cell
what are DAMPs
Damage (Danger) Associated Molecular Pattern
- endogenous indicators of cell damage or stress
= alarmins
what do PRR (pattern recognition receptors) recognize
PAMPs and DAMPs
PAMPs that signal through NOD-like receptors (NLR) generate what
multiprotein complexes called inflammasomes
what are inflammasomes and what is their function
A multi-protein complex that can form in cells such as macrophages in response to inflammatory stimuli (e.g. PAMPs and DAMPs)
Function: catalyze the maturation of pro-inflammatory cytokines IL-1B and IL-18
what are some known DAMPs
**Serum amyloid A
-HMGB1
-S100 proteins
- spliceosome-associated protein 130
-DNA
- ATP
- uric acid
what does activation of an inflammasome require
a PAMP and DAMP
what does activation of an inflammasome indicate
that microbial invasion and cellular damage have occurred
what pro-inflammatory cytokines do sentinel cells produce?
IL-1B and IL-18
innate response occur via?
pattern recognition receptors
what are the 3 ways macrophages can be activated
* Innate activation
– responds to TLR activation
* Classical activation
– become M1 cells by exposure to
microbial products and subsequent exposure to Th1 cytokines (IFN-γ)
*Alternative activation
– when exposed to Th2 cells, they become M2
what are the major sickness inducing cytokines?
IL-1
IL-6
TNF-alpha
HMGB1
what types of cells secrete cytokines
sentinel cells, dendritic cells, mast cells, macrophages
sickness symptoms caused by the hypothalamus
fever, anorexia, sleepiness, depression
sickness symptoms caused by the liver
increased synthesis of acute-phase proteins
iron sequestration
sickness symptoms caused by the bone marrow
increased white cell production
what changes might be seen on a CBC in response to inflammation (sickness)
- neutrophilia
- neutropenia
- changes to iron parameters
- “anemia of chronic diseases”
what are the main responses caused by the release of pro-inflammatory cytokines
local vasodilation
acute-phase response
endothelial cell activation
monocyte, neutrophil and dendritic cell activation
SIRS (systemic inflammatory response syndrome) results from?
the overexpression of multiple cytokines
what is one of the main shock oragns
kidney
what things occur from innate immunity that result in fever
increased NK cells (Cytotoxicity)
respiratory burst
release of neutrophils from bone marrow
what things occur from adaptive immunity that result in fever
an upregulation of T-cells
increased maturation of dendritic cells
increased release of macrophages, phagocytosis, NO, TLR2, TLR4, MHC I and II
normal microbiota can out-compete pathogens by…
preventing bacteria from adhering to surface of GI cells
where does T-cell activation take place?
lymph nodes
CD71 is a surface receptor that binds?
transferrin
iron sequestration
TLR2 and TLR4 are surface receptors that bind?
PAMPs (result from damaged cell tissue)
CD25 is a surface receptor that binds?
interleukin 2
what does Th17 make?
IL-17 whose function is to be a neutrophil chemoattractant
what is the role of IL-6?
promotes B cell differentiation
stimulates acute phase responses
endotoxin would be considered a ?
PAMP
example of a DAMP
serum amyloid A
What type of dendritic cell is of lymphoid origin
Plasmacytoid
What are the dendritic cell types from myeloid origin
Classical, follicular, langerhans
What is the main function of dendritic cells when they are in tissues (immature)
Antigen trapping / uptake
Sentinel function
What is the main function of dendritic cells when they are in lymphoid organs (mature)
Antigen presentation to T cells
High endothelial venules permit access to which cell type?
lymphocytes
