STEP - Innate Immunity
What are key surface recptors of macrophages and what do they bind to?
CD14 -> LPS Fc -> Fc of Ab C3b -> duh MHC II -> CD4 B7 -> CD28 CD40 -> CD40L
What cell surface proteins do NK cells have?
CD16 -binds Fc of IgG to enhance killing ability -antibody dependent cellualr cytotoxicity CD56 (NCAM) -marker for NK cells
What are macrophages? What is their fx?
Guardians of innate immunity -has many names: kupffer cells, microglia, osteoclasts Fx -phagocytosis -cytokine production -antigen presentation
What does memory mean in immunology?
Adaptive immune system has faster response to second infection Innate immune system has same response
What charcteristics do eosionophils, mast cells, and basophils share?
All have granules of destructive enzymes -also triggered by IgE -useful for parasites -cause allergic disease
What are band forms? What is a left shift?
Band forms -immature neutrophils -more seen in bacterial infections (due to extra production) -this is a left shift
How do NK cells decide what to kill?
Bind to MHC Class I -found on most human cells, which also presents to CD8 T cells -activates adaptive immunity against intracellular pathogens Some viruses block MHC class I -NK cells destroy cells w/o MHC class I to get around
WHat does IL-1 and TNF-a do?
Both ^ synthesis of endothelial adhesion molecules -helps neutrophils enter inflamed tissue IL-1 -endogenous pyrogen (fever) -works on hypothalamus TNF-a -can cause vascular leak, shock -kills tumors by intravascular coagulation -can cause DIC
What are mast cells and basophils?
Both appear blue in Wright stain Basophils: blood stream Mast cells: tissue Both bind Fc of IgE -when a parasite cross links multiple IgE, they release histamine (vasodilation) and enzymes
What are cytokines? What are subtypes
Cell signalling proteins released by immune cells to stimulate inflammatory response Subtypes -chemokine: attracts cells -interleukins -TNF - alpha -transforming growth factor -interferons (interfere with viral replication
What is cluster of differnetiation (CD)?
Cellular surface molecules -found on many immune cells -can identify cell type
Wha do neutrophils react to?
Chemotaxins -IL-8 (from macrophages) -C5a Opsonin -IgG -only Ab that binds neutrophils Remember, they don't present antigens
How do innate immune cells recognize pathogens?
Don't use antigen presentation Recognize PAMPS (pathoge-associated molecular patterns) -use pattern recognition receptors (such as toll-like receptors) -these make cells secrete cytokines
WHat are PAMPs that innate immune cells can recongnize?
Endotoxin (LPS -binds CD14 on macrophages (TLR4) -release IL-1, TNF-a Peptidoglycan cell wall -receptors are intracellular Mannose Lipoteichoic acid (Gram+) dsRNA Unmethylated DNA
What is role of complement (very general)?
Form MAC complex to lyse foreign cells
What do IL-6/8/12 do?
Found in macrophages IL-6 -causes fever -stimulates acute phase protein production in liver IL-8 -attracts neutrophils IL-12 -promotes Th1 development
What are dendritic cells (Langerhans cells)?
Found in skin/mucosal membranes -pro antigen presenters Migrate to lymph nodes to activate T-cells
What is an eosinophil?
Innate immune cell that appears red in Wright stain Discharge contents onto parasites (IgE) Stimulated by IL-5 from Th2 Rise in count probably means helminth infection
What can key cytokines of macrophages?
Key: IL-1, TNF-a Others: IL - 6/8/12
What are roles of NK cells?
Kill human cells infected by viruses Produce IFN-gamma to activate macrophages
What family are NK cells in?
Lymphocytes -not in thymus -no memory -doesn't need antigen presentation
What are monocytes?
Macrophage precurosrs that circulate in blood for three days before entering tissues and becoming macrophages
What cells have TLRs?
Macrophages Dendritic Cells Mast Cells
How does phagocytosis work?
Macrophages engulf pathogens into phagosome -lysozome merges with phagosome -lysozome enzymes kill bacteria/virus
What is normal life cycle of neutrophil?
Made in bone marrow Circulates for 5 days and then die, unless activated If activated, they are drawn from blood to sites of inflammation -they provide extra phagocytic support ot macrophages
What can activate macrophages?
Major activators (via TLRs) -LPS -peptidoglycan -bacteria DNA Others -IFN-gamma (t-cells, NK cells) -also C5a
How do NK cells and eosinophils do antibody dependent cellular cytotoxicity?
NK cells -IgG binds to pathogen -CD16 on NK binds IgG Fc -NK cell kills cell Eosionphil -IgE binds to pathogens (paraties) -eosinophils bind Fc of IgE and relase toxic enzymes
What are granulocytes?
Neutrophil Basophil Mast Cell Eosionphil
What are cell types of innate immune system?
Phagocytes -macrophages -neutrophils Complement NK cels Eosinophils Mast cells Basophils
How do neutrophils show up on Wright stain?
Pink
WHat are deadly enzymes found in macrophage lysosomes?
Reactive oxygen species -superoxides from NADPH Oxidase (respiratory burst) -makes H2O2 and O2- Reactive nitrogen intermediates -combo of NO and O2- Enzymes -protease -nuclease -lysozymes (hydrolyzes peptidoglycan)
What are states of macrophages?
Resting state -debris removal Activated: more effective at phagocytosis
How do neutrophils exit blood stream?
Rolling -neutrophils have selectin ligand (SIalyl-Lewis X protein) -endothelial cells express E or P selectin (stimulated by IL-1 and TNF-a), which is bound by selectin ligand Crawling (tight binding) -neturophils express integrin (stimulated by LPS or C5a), which binds to ICAM on endothelial cells Transmigration -neutrophils bind PECAM-1 which is found between endothelial cells to get out Migration -neutrophils follow chemokines: C5a, IL-8
What granules do neutrophils have?
Small granules (secondary) -can either fuse with phagosome or be released outside cell Large granules (primary) -can only fuse with phagosomes
How do bacteria block phagocytosis?
TB modifies phagosome so it can't fuse with lysosome -then it proliferates inside macrophages
What is antibody dependent cellular cytotoxicity? ADCC
When Ab coat pathogen, which are destroyed by immune cells -not through phagocytosis Classic: NK cells and eosinophils
What is antigen presentation? Why does our body need it?
When pathogens are engulfed by antigen presenting cells, they are broken down and antigens are presented -this is only way T cells can be activated, because you want it to be very selective Innate system can be activated by free antigen
