BIO 343 Lecture Notes - Lecture 3: Antibody, Cytokine, Irf7
Immunology Chapter 3 Notes
Hayden Casassa
• Innate Immunity
o The induced response to infection
o Mechanism that takes ~4 hours to 4 days to develop
o Involves soluble and cellular receptors that detect infection, the synthesis of new molecules,
and the recruitment of leukocytes to do something about it
• Cell-surface receptors of innate cells that detet pathoges distiguish etee self ad o-self
o Receptors are able to distinguish microbial proteins, carbs, lipids, and other nucleic acids
o Each receptor can recognize multiple pathogenic species
o Same is true of NK cells as they can recognize pathogens
• Phagocytic Receptors
o All tissues contain resistant macrophages that express numerous phagocytic and signaling
receptors
o Phagocytic Receptors→ primarily recognize bacterial carbohydrates and lipids and trigger
macrophage phagocytosis
o Macrophages have two kinds of receptors
▪ One triggers the phagocytosis
▪ Other is signaling which causes those cells to produce cytokines
• Lectin Receptors recognize carbohydrates
o Mannose receptor recognizes specific terminal sugars on molecules like bacterial LPS and
polysaccharides
o Scavenger receptors and LPS receptor (CD14) recognize LPS and other specific structures on
molecules
o CR3 and CR4 recognize LPS on a variety of pathogens
o LPS→lipopolysaccharide
• Macrophage Phagocytosis
o Receptor mediated endocytosis and degradation
o Receptor causes pseudopods to come out and take in pathogen for degradation
• Toll-like Receptors
o Main Signaling receptors
o Present on innate cells such as macrophages, dendritic cells, and neutrophils
o Defense mechanism against pathogens
o Expressed on cell surfaces extracellularly and intracellularly
find more resources at oneclass.com
find more resources at oneclass.com
o You have toll receptors that recognize pathogens
▪ Some bind to LPS on bacteria or flagellum or things not found in humans
▪ They recognize viral RNA
▪ Signaling through TLRs which lead to inflammatory cytokines
• Promotes innate response and inflammation
• Promotes adaptive immune response
• TLR4 homodimer
o Ligands →LPS (lipopolysaccharide) on gram-negative bacteria
o Cells Carrying receptor→ Macrophages, Dendritic cells, mast cells, and Eosinophils
o Cellular location of receptor → Plasma membrane
• Macrophages Toll-Like Receptor
o Recognizes LPS and leads to the production of cytokines, adhesion molecules, and other
proteins necessary for inflammation
o Involves a complex of TLR4, MD2, and CD14
▪ LPS binds CD14
▪ TLR4 with MD2 protein binds CD14/LPS
▪ Cytoplasmic domain of TLR4 generates signal that leads to inflammatory cytokine
production
▪ Signaling involves adapter proteins and protein kinases for activation of transcription
factor Nuclear factor kB (NFkB)
• NFkB→ initiates transcription of cytokine genes
• Steps of production of cytokines from NFkB
o LPS and binds to macrophage surface and -----
o Signaling IKK from the cascade (inhibitor Kappa B kinase)
o This gets phosphorylated and interacts and phosphorylates IkB
o When this happens, IkB gets degraded and falls to pieces and the blue protein becomes free
▪ This blue protein is NFkB
o This now is the transcription factor and enters nucleus
o Binds to regulatory region of cytokine genes so cytokine production is turned on so then its
transcripted and translated to be secreted as soluble cytokines
• Without IKK (Inhibitor Kappa B Kinase), NFkB does not get activated so no cytokine production
o Kids are susceptible to bacterial infections because macrophages expressing TLR4 are not
activated
o NFkB can now never be activated to translocate into nucleus to initiate cytokine production
• Activated Macrophages release cytokines that promote inflammation
o Cytokines→ small soluble proteins secreted by cells that influence other cells by binding to a
specific surface receptor
▪ Cytokines can act locally or systematically
find more resources at oneclass.com
find more resources at oneclass.com
o Interleukin (IL) is a generic term used for cytokines made by leukocytes
• Macrophage pro-inflammatory cytokines
o Interleukin-1B, Il-6, Il-12, CXCL8, and TNF-a
▪ Combined effect is to induce state of inflammation
• Actions of Macrophage Inflammatory Cytokines
o Macrophage was signaled by Toll receptors to produce pro-inflammatory cytokines
o Looking at site of the infection
• IL-1B and TNF-a
o Cause vascular permeability/ vasodilation
o This enables effector cells and fluid containing soluble effector molecules to enter the infected
tissue
• TNF-a (in depth)
o Induces local inflammatory response acting on blood vessels and endothelium
o Helps with adhesion of leukocytes and blood clotting
o Whichever vessel is near infection you need to slow down the leukocytes
o In general, TNF-a produced is good, systematic response is dangerous
o Gram Negative bacteria can cause this and leads to septis which can kill you
• IL-6
o Induces fat and muscle cells to metabolize, make heat, and raise the temperature in infected
tissue
• CXCL8
o Recruits neutrophils from blood and guides them to infected tissue
o Example of chemoattractant cytokine called chemokine
o Has specificity for neutrophils to guide through tissue to infection
• IL-12
o Recruits and activates NK cells
o The NK cells in return secrete cytokines that strengthen macrophages response to infection
• Septic Shock
o Occurs in presence of gram negative bacteria which expresses LPS (endotoxin)
o Extensive # of macrophages in spleen become activated via TLR4 and secrete significant
amounts of TNF-a in bloodstream (systematically)
o Causes massive leak of fluid from vessels into tissues which causes drop in blood pressure
▪ TNF-a auses asodilatio ut if happes ssteatiall ou’re sreed
o This poor blood vessel leads to organ failure
• Pasteurella multocida
o Gram negative bacteria in cats mouth
o Dangerous→ starts with LPS triggering toll receptors on macrophages and TNF triggered so all
macrophages are told to secrete this cytokine
• Neutrophils
o Most audat WBC’s → Held in reserve in bone marrow
o Recruited by macrophages into tissues during infection
▪ First cell recruited during inflammatory response
o Major function is Phagocytosis and killing (contribute to pus after killing)
• Inflammatory cytokines recruit neutrophils from blood to inflamed tissues and involves adhesion
molecules
o Extravasation is the overall movement of cells from within capillaries into tissues over 4 steps
o Rolling Adhesion→ In presence of inflammatory cytokines (IL-1B, TNF-a, and CXCL8),
endothelium expresses selectin (adhesion molecule) that binds to sugar on neutrophil
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Innate immunity: the induced response to infection, mechanism that takes ~4 hours to 4 days to develop. Interleukin (il) is a generic term used for cytokines made by leukocytes: macrophage pro-inflammatory cytokines. Interleukin-1b, il-6, il-12, cxcl8, and tnf-a: combined effect is to induce state of inflammation, actions of macrophage inflammatory cytokines, macrophage was signaled by toll receptors to produce pro-inflammatory cytokines, looking at site of the infection. Il-1b and tnf-a: cause vascular permeability/ vasodilation, this enables effector cells and fluid containing soluble effector molecules to enter the infected tissue, tnf-a (in depth) Induces local inflammatory response acting on blood vessels and endothelium: helps with adhesion of leukocytes and blood clotting, whichever vessel is near infection you need to slow down the leukocytes. In general, tnf-a produced is good, systematic response is dangerous: gram negative bacteria can cause this and leads to septis which can kill you.
