Lecture 5: The Innate Immune System Flashcards
What is the immediate response of the innate immune system
Send neutrophils to site
What are some local effects of the innate immune system
Heat, redness, pain, swelling
Describe the pathway of systemic effects of inflammation
Sentinel cells (mast cells, macrophages, dendritic cells) release cytokines that act on distant locations (hypothalamus, liver, and bone marrow) which results in an immune response
Why is the hypothalamus response to systemic inflammation
Fever, anorexia, sleepiness, depression
What is the livers response to systemic inflammation
Increased synthesis of acute phase proteins, iron sequestration
What is the bone marrows response to increased systemic inflammation
Increased WBC production
What are some possible changes to CBC indicating systemic inflammation
Neutrophilia, neutropenia, changes to iron parameters, anemia of chronic disease
What is an example of an acute phase protein
Serum amyloid A (SAA)
Why sequester iron
Bacteria needs iron so body will protect itself by storing it in liver
What is a consequence of iron sequestration
Anemia of chronic disease/inflammation
What is an indication of increased WBC production
Start seeing bands released which are immature WBC
Describe the cascade of events for conditions like systemic inflammatory response syndrome and multiple organ dysfunction syndrome
- Infection, 2. Recognized by PAMPS/DAMPS, 3. Release proinflammatory cytokines, 4. Local vasodilation resulting in hypotension and enemia, acute phase response resulting in thrombosis, activation of monocytes, neutrophils and DC’s, all ending with hypoxia and apoptosis and necrosis
Systemic inflammatory response syndrome
Results from overexpression of multiple cytokines. These cytokines trigger a series of events that result in widespread cell death and multiple organ failure
What effects does a fever have on adaptive and innate immune systems
Innate: increase neutrophils, increased NK cells
Adaptive: increase dendritic cells, macrophages, and T cells
What is an example of a clinical test for inflammation
Acute phase proteins- SAA
Function of lysozymes
Innate barrier in tears saliva, milk, GI, destroys bacterial cell walls, peptidoglycan
What do defending and cathelicidins do
Innate barrier to destroy microbial cell membranes
What does lactoferrin do
Sequester iron
What does lactoperioxidase do
Generates ROS
What is latherin
Protein in horse sweat that facilitates the evaporative cooling and inhibits microbes
Describe the maturation of dendritic cells
- Precursors begin in bone marrow
- Antigen uptake and processing in tissues
- Antigen presentation in lymphoid organs
What is the function of dendritic cells
Antigen presentation to T cells
CDC1 promotes what
Type I response by producing IL-12 and activating Th1 cells which recruit macrophages
What does cDC2 do
Promotes type 2 response by producing IL-6 and IL-23 and activates Th2 and Th17(recruits neutrophils)
Describe how dendritic cells link the innate and adaptive immune system
DC’s sense virus or bacteria with PRR’s, will present antigen to T and B cells, and they will migrate to infection site via guidance from cytokines
Where do macrophages derive from
Monocytes
What is the reticuloendothelial system
Macrophages are replenishing and replacing cells as basic maintenance and will clean up dying/apoptotic or abnormal self cells/tissues
What is a major structural feature of a macrophage
lots of RER because active therefore producing lots of proteins
Lysozymes filled with noxious substances for pathogen destruction
What is rhodococcus equi
Disruption of lysosome activity through VapA gene. PIMS will eat up pathogen in lung for lysosome to eat but VapA gene allows pathogen to live in lysosome
What are the three pathways in macrophage activation
Innate activation, classical, alterantive
what is innate activation of macrophages
Respond to TLR’s binding PAMP and will induced phagocytosis
What is the classical macrophage pathway
M1 cells exposed to microbial products and Th1 cytokines like INF-y and induce phagocytosis
What is the alternative activation of macrophages
Exposed to Th2 cytokines and become M2 cells- focus on repair
What are some common cellular input surface receptors on macrophages
PAMPs, transferrin (transport receptor) and cytokine receptors
Cyclic neutropenia in gray collies
Genetic disorder that affects neutrophil maturation resulting in recurrent infections
What do natural killer cells target
Stressed cells, cells lacking MHC I
What are DAMPS
Damage associated molecular pattern
Ex: SAA
What are examples of cytosolic PRR’s
NOD like receptors, Rig like receptors
What do NOD like receptors bind
Bacterial PAMPS
What do Rig like receptors bind
Viral RNA
What does PAMP signaling through these cytosolic receptors generate
Inflammasomes
Inflammasome
Multi protein complex that can form in cells like macrophages, function to catalyze maturation of pro-inflammatory cytokines
What are the major sickness cytokines
TNF-a, HMGB1, IL-1, IL-6
