Term
| What are the three components of Innate Immunity? |
|
Definition
1) Physical barriers
2) Cellular Components
3) Non-cellular components |
|
|
Term
Compare/contrast Innate and Adaptive Immunity concerning the following:
a) response time
b) specificity
c) memory |
|
Definition
a) Innate=immediate, adaptive=delayed
b) innate=no, adaptive=yes
c) innate=no, adaptive=yes |
|
|
Term
| Is acute inflammation in response to innate or adaptive immunity? Chronic? |
|
Definition
-acute= innate
-chronic= adaptive |
|
|
Term
| True or False: Aside from physical barriers, most components of the innate immune response are found in the blood. |
|
Definition
|
|
Term
| Why is it important that most components of the innate immune response are found in the blood? |
|
Definition
| -because it is always near the potential pathogens and it is a quickly recruited source |
|
|
Term
| Give a few examples of places in the body that directly interact with the outside world. |
|
Definition
-ailamentary tract
-respiratory tract
-urogenital tract |
|
|
Term
| Give some examples of organs that indirectly interact with the outside world |
|
Definition
|
|
Term
| How do organs that are in no way exposed to the outside world get an infection? |
|
Definition
|
|
Term
| What is the first line of defense in physical barriers? |
|
Definition
|
|
Term
| True or False: Most organisms cannot penetrate the intact skin. |
|
Definition
|
|
Term
| In what ways is skin the first line of defense? |
|
Definition
-wounds heal quickly to keep out pathogens
-sweat has an acid pH and sebaceous glands produce lysozyme and fatty acids that inactivate microorganisms
-upper skin layer is dead and will constantly desquamate, removing and carrying away pathogens in the process |
|
|
Term
| In what ways are the mucosa of the Respiratory tract, Alimentary tract, and Reproductive/Urinary tracts defended? |
|
Definition
-resp: hair, turbinates, cilia, mucus, coughing, sneezing
-alimentary: saliva, acid pH, bile
-repro/urinary: acidic pH, urination |
|
|
Term
| Name an organisms that will grow in bile. |
|
Definition
|
|
Term
| How do normal microflora prevent pathogens from establishing themselves on skin and mucous membranes? |
|
Definition
| -they compete for nutrients and space |
|
|
Term
| What is a common clinical situation in which normal microflora get destroyed? |
|
Definition
|
|
Term
| What happens in atrophic rhinitis in pigs? |
|
Definition
| -toxins go into turbinates and tells osteoclasts to killosteocytes and deactivates osteoblasts=> eventually destroys turbinates=> taken away physical barriers and loses filtering |
|
|
Term
| What are the two types of sentinel cells? |
|
Definition
-mast cells
-mononuclear phagocytic system: macrophages |
|
|
Term
| What is the role of sentinel cells? |
|
Definition
| -they hang out on surveillance, looking for insults (things that do not belong) |
|
|
Term
| Which Pattern Recognition Receptors recognize gram-negative bacteria? Gram-positive? |
|
Definition
-Toll-like Receptor 4
-Toll-like Receptor 2 |
|
|
Term
| Where are neutrophils produced? |
|
Definition
|
|
Term
| Where are neutrophils usually found? |
|
Definition
| -remain in circulation until needed |
|
|
Term
| True or False: Once neutrophils leave the blood vessels, they go back into the circulation. |
|
Definition
| FALSE, they never go back into the circulation, they die fighting |
|
|
Term
| What is the most prominent type of cells in most animals? In ruminants? |
|
Definition
|
|
Term
| What type of cells are the first line of defense in the fight against bacterial infection? |
|
Definition
|
|
Term
| Before neutrophils can phagocytose bacteria, they must first be summoned by _______ produced by sentinel cells. |
|
Definition
|
|
Term
| What happens when neutrophils are summoned by cytokines produced by sentinel cells? |
|
Definition
-they leave or emigrate out of the blood vessels into the infected tissue
-they capture and destroy bacteria and foreign antigens through phagocytosis only |
|
|
Term
| Definition: Extravasation |
|
Definition
| -the process by white immune cells leave the bloodstream when called for an immune response |
|
|
Term
| What are the 3 steps of extravasation? |
|
Definition
1) Margination and rolling
2) adhesion and diapadesis
3) Chemotaxis |
|
|
Term
|
Definition
| -the directional migration of a cell along a concentration gradient |
|
|
Term
| What do Slex's on neutrophils do? |
|
Definition
| -they recognize selectins on the surface of the epithelial cells |
|
|
Term
| What are the two types of selectins on the surface of the epithelial cells? |
|
Definition
-P-Selectins: P standing for platelets: pre-packaged and ready to go
-E-Selectins: product of transcription/translation |
|
|
Term
| What is the main functional difference b/n P-Selectins and E-Selectins? |
|
Definition
| -E-selectins take hours to respond |
|
|
Term
| What are the components of firm adhesion of neutrophils to endothelial walls? |
|
Definition
| Firm adhesion= S-lex+ integrins+ ICAMS+ conf change induced by chemokines from Sentinel cells |
|
|
Term
| Explain how neutrophils roll along endothelial walls. |
|
Definition
-roll via weak connections to S-lex, thus many interactions bind and break
-to get strong adhesion, use beta integrins on neutrophils on the surface of endothelial cells (beta integrins bind weakly to ICAMS, but iva chemokines secreted by sentinel cells will switch to strong binding) |
|
|
Term
| What is the purpose of CD31? |
|
Definition
| -platelet endothelial cell adhesion molecule (PECAM): creates nooks and crevices that facilitates the pseudopodia of neutrophils can grab onto in the intracellular gaps b/n the endothelial cells to get through |
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|
Term
| Once in tissue, neutrophils will start migrating towards chemotactic molecules- this directed migration is termed ________. |
|
Definition
|
|
Term
| Is there any pattern to neutrophils migration? |
|
Definition
| -yes, they migrate to the area with the highest concentration of chemotactic molecules |
|
|
Term
| Neutrophils are activated during migration by _______ (produced by Macrophages), by _______ (produced by NK cells), and by C5a |
|
Definition
|
|
Term
| What happens when chemokine receptors are activated? |
|
Definition
| -they cause breakdown and reassembly of cell's cytoskeleton so that it can have directional movement towards where the concentration gradient of the chemokines is |
|
|
Term
| What are the bacterial products of chemotaxis? |
|
Definition
-N-fMLP
-C5a: component of complement
-LTB4: pdt of arachodonic acid pathway |
|
|
Term
| Once the neutrophil encounters a bacterium, it must adhere to it. This can occur ONLY if the bacterium is __________. |
|
Definition
|
|
Term
| True or False: Neutrophils have both Fc receptors (CD32) and complement (CR) receptors for C3b (CD35). |
|
Definition
|
|
Term
| As the opsonins contact the receptors, the cytoplasm of the neutrophils (________) flows over the bacterium, engulfing the bacterium into a cytoplasmic vacuole called a _________. |
|
Definition
|
|
Term
| What are the two integral enzymes in oxygen dependent killin? |
|
Definition
-NADPH oxidase (catalyzed first rxn)
-Myeloperoxidase (in neutrophils) |
|
|
Term
| What is the gist of oxygen dependent killing? |
|
Definition
| -take oxygen, use cascade rxn to shove electrons onto it |
|
|
Term
| Myeloperoxidase in neutrophils prefers _________ and the myeloperoxidase in eosinophils prefers _________. |
|
Definition
|
|
Term
| What are the 4 main components of oxygen-independent killing? |
|
Definition
-bacterial permeability increasing protein
-lysozyme
-defensins
-lactoferrin |
|
|
Term
| Describe cationic proteins. |
|
Definition
-innate immune response
-no specificity
-like to poke holes in membranes |
|
|
Term
| What does Lactoferrin do? Why can it sometimes cause problems? |
|
Definition
-sequesters Fe so that microorganisms cannot use it
-can ometimes keep Fe away from our own cells, thus when patients have chronic inflammation, will cause anemia (due to lack of iron to make RBCs) |
|
|
Term
| What is Neutrophil elastase? |
|
Definition
| -enzyme that degrades lots of things (broad spectrum activity) |
|
|
Term
|
Definition
-breaks down the carcasses of stuff
-inactive unless in an acidic pH |
|
|
Term
| What type of cells are the first to reach and attack pathogens? |
|
Definition
|
|
Term
| What functionally happens when neutrophils die? |
|
Definition
| -in dying, they attract blood monocytes to the area |
|
|
Term
| Neutrophils have a limited reserve of energy. When are they most active? When do they die? |
|
Definition
-most active immediately upon release from bone marrow
-they rapidly get exhausted and can undertake only a limited number of phagocytic events |
|
|
Term
| True or False: Neutrophils do not process Ag: they do not present Ag to Th cells or CTL via MHC. |
|
Definition
|
|
Term
| Describe the nuclei of eosinophils. |
|
Definition
|
|
Term
| Eosinophils are abundant at sites of _______, _______, or _______/________. |
|
Definition
-allergic
-parasitic
-yeast/fungal disease |
|
|
Term
| What is the most abundant protein in the eosinophilic granule? |
|
Definition
|
|
Term
| What is the purpose of eosinophils? |
|
Definition
| -neutralization of mast cell derived mediators (histaminase, arylsulfatase) |
|
|
Term
| Cytology of canine mast cell tumors will contain ________. |
|
Definition
|
|
Term
| Macrophages start as ________ in bone marrow and enter the blood as _________. |
|
Definition
|
|
Term
| Macrophages circulate for a few days and then leave circulation to become __________ and __________. |
|
Definition
-Sentinel cells
-responding cells in inflammatory rections |
|
|
Term
| Different macrophage names: When circulating, called ________ and when in tissue called _________. |
|
Definition
|
|
Term
| What are the 5 functions of macrophages? |
|
Definition
1) sustained phagocytic activites
2) process and present antigen
3) amplify and modulate specific immune responses by secreting cytokines
4) repair and heal damaged tissue by removing damaged and dead cells
5) control inflammation |
|
|
Term
| True or False: Neutrophils serve as link between innate and adaptive immune response. |
|
Definition
|
|
Term
| Do macrophages die immediately after they complete their job? |
|
Definition
|
|
Term
| Describe the receptors on macrophages. |
|
Definition
1) PRRs
2) Fc receptors and C3b receptors
3) receptors (MHCII) and coreceptors necessary for their role in antigen presentation |
|
|
Term
| What is the function of C3b receptors on macrophages? |
|
Definition
| -opsonizing component of the complement pathway |
|
|
Term
| Monocytes and resting macrophages are effective phagocytes, their phagocytic activity is greatly enhanced when activated by the cytokine _______ produced by NK cells and Th cells. |
|
Definition
|
|
Term
| What is the major function of IFN-gamma? |
|
Definition
|
|
Term
Activation of Macrophages accompanied by which of the following:
a) enhanced phagocytic activity
b) decreased amts of cytoplasmic lysosomes
c) increased expression of Ab and Complement receptors
d) increased secretion of proteases
e) increased amount of cytoplasmic lysosomes |
|
Definition
|
|
Term
| If macrophages are activated further by bacterial products such as LPS and mannose, they become ___________. |
|
Definition
|
|
Term
| The transition from normal macrophages to activated macrophages is accompanied by what 3 principal changes? |
|
Definition
1) increase in size, movement, and phagocytic activity
2) they can engulf whole cells
3) increased expression of MHC class II molecules and coreceptor molecules |
|
|
Term
| In persistent chronic infections, activated macrophages are known as _________ which can fuse into _________. |
|
Definition
-epitheloid cells
-giant cells |
|
|
Term
| How long do giant cells stick around? |
|
Definition
| -they are completely insult-driven, thus as soon as the intigens are gone, everything quits |
|
|
Term
| Definition: IFN famma-interleukon 12 loop |
|
Definition
-macrophages receive signals from interfeuron gamma to ramp up their level of activation
-in response to IFN gamma, they send message back to helper cells to tell them to keep it coming via interleukon 12 |
|
|
Term
| How does NO relate to macrophage function? |
|
Definition
-macrophages produce large amounts of NO
-sustained production of NO permits macrophages to efficiently kill bacteria, fungi, protozoa, some helminthes, and more importantly, tumor cells |
|
|
Term
| True or False: Macrophages are necessary for proper healing of wounds. |
|
Definition
|
|
Term
| Why are macrophages necessary for wound healing? |
|
Definition
-secrete proteases which break down CT
-regulate collagenase and fibroblast activity through IL-1 secretion
-once damaged tissue is removed, macrophages secrete growth factors for collagen synthesis by fibroblasts, and for growth of new vessels |
|
|
Term
| What are natural killer (NK) cells? |
|
Definition
| -large granular lymphocytes that make up 10-15% of circulating leukocytes (they are CD56+) |
|
|
Term
|
Definition
| -they contain enzymes that destroy virus infected cells, cancer cells, and cells infected with intracellular protozoa and bacteriia |
|
|
Term
| NK cells are activated by _____ and _____ which are manufactured by viral infected cells. |
|
Definition
|
|
Term
| How are IFN-alpha and IFN-beta manufactured? |
|
Definition
| -when TLRs (3 &7) recognize any viral nucleic acid, they stimulate the cell to start pumping out IFN-alpha and IFN-beta |
|
|
Term
| NK cells are also activated by cytokines released by macrophages, especially _____ and _____. |
|
Definition
|
|
Term
| What are the 4 receptors that NK cells have are associated with killing? |
|
Definition
1) activating Rc: natural cytotoxic receptors that recognize changes in cell surface proteins caused by metabolic stress or intracellular infection2) Inhibiting Rc: receptors that recognize MHC I molecules on cells surface
3) receptors (CD16) for the Fc protion of the Ab: these recognize cells opsonized by Ab (for ADCC)
4) Fas ligands (FasL) receptors: recognize trimerized Fas molecules on stressed immune cells |
|
|
Term
| True or false: Inhibiting Rc signals will always override the Activating Rc signals o NK cells. |
|
Definition
|
|
Term
| Describe the activating receptors of NK cells. |
|
Definition
| -the natural cytotoxic receptors (NCRs) recognize a wide variety of glycoproteins on normal cells- they can somehow know from their distribution and quantity if these cells are stressed (cancer, infection, old age) |
|
|
Term
| Describe the inhibitory receptors of NK cells. |
|
Definition
| -the inhibitory receptors recognize MHC class I molecules on the surface of cells |
|
|
Term
| Describe the pathway by which NK cells kill. |
|
Definition
-after NK cells have attached, they secrete perforin
-perforins aggregate to form powes in the cell membrane similar to the MAC formation by complement
-next, NK cell secretes granzyme that enter the cell through the pore
-the granzyme binds to cell proteins (death proteins) inducing programmed cell death (apoptosis) |
|
|
Term
| How do NK cells recognize their prey? |
|
Definition
-activating and inactivating Rc- inactivating Rc always overrides
-Fc Rc for Ab thaht opsonize target |
|
|
Term
| What is the name of the pathway by which NK cells kill? |
|
Definition
| -perforin-granyzme pathway |
|
|
Term
| The complement system is the branch of the innate immune system response that is key in protecting hosts against _________. |
|
Definition
|
|
Term
| What are the two things that complement proteins recognize? |
|
Definition
1) structural molecules: present only on the surface of pathogens (ex: sugars)
2) opsonized pathoges: Fc ob both IfM and IgG are recognized |
|
|
Term
| True or False: Complement is very specific and therefore only recognizes a narrow range of pathogens. |
|
Definition
| FALSE, complement is non-specific and recognizes a broad range of pathogens |
|
|
Term
| What is the defining characteristics of the complement system that makes it a part of the innate immune system? |
|
Definition
| -complement proteins are everywhere in the entire body and are nonspecific, thus they respond quickly and without memory |
|
|
Term
| What are the main 4 characteristics of the complement cascade? |
|
Definition
1) they are always readily available in the blood and tissues
2) circulate in inactive forms
3) become activated in microseconds
4) are activated sequentially in a cascade fashion |
|
|
Term
| What are the 3 pathways of complement? |
|
Definition
-Alternate Pathway
-MBL (Lectin) Pathway
-Classical Pathway |
|
|
Term
| Generally describe the complement chart. |
|
Definition
| classical pathway+lectin pathway+ alternative pathway= complement activation= recruitment of inflammatory cells+ opsonization of pathogens+ killing of pathogens |
|
|
Term
| Which pathway of complement links the adaptive immune system to the innate immune system? |
|
Definition
|
|
Term
| Briefly, how does the classical pathway of complement work? |
|
Definition
-C1 is the first protein and it recognizes the Fc region Igm and IgG that have attached to the surface of pathogens
-then lots of cutting happens until C3 convertase is deposited on the pathogen surface to opsonize it for phagocytosis by macrophages |
|
|
Term
| to be activated, C1 must be bound to ___ IgM(s) and ___ IfF(s) in the ________ pathway of complement. |
|
Definition
|
|
Term
| What is the function of C3 convertase? |
|
Definition
-to cleave as many C3 ocmpleent proteins as possible into C3a and C3b
-binds to surface of pathogens to opsonize it for phagocytosis of macrophages |
|
|
Term
| ___ is the most abundant complement protein in the blood and tissues. |
|
Definition
|
|
Term
| True or False: C3 spontaneously and continually breaks down into C3a and C3b. |
|
Definition
|
|
Term
| True or False: C3a is very reactive and will bind avidly to any amino and hydroxyl groups which are plentiful on the surface of pathogens. |
|
Definition
| FALSe, C3b is very reactive and will bind avidly to any amino and hydroxyl groups which are plentiful on the surface of pathogens. |
|
|
Term
| How is C3 convertase forms? What does it do? |
|
Definition
-when C3b binds to a pathogen, protein B attaches too it to form C3 convertase (C3bBb)
-C3 convertase cleaves all C3 in the vicinity into C3a and C3b |
|
|
Term
| Briefly, how does the MBL Pathway work? |
|
Definition
| -MBL bind to mannose on pathogens to activate serine protease which causesC3 convertase formation |
|
|
Term
|
Definition
| -Mannose Binding lectin (MBL) |
|
|
Term
| How do normal cells prepare themselves agains C3bBb? |
|
Definition
-have Factor proteins on their surface that bind C3bBb and inactivate it
-Facotr I in plasma also binds to and inactivates C3bBb |
|
|
Term
| True or False: Although iC3b is inactivated and cannot activate the terminal pathway, it is still an opsonin |
|
Definition
|
|
Term
| How does complement cause an inflammatory response? |
|
Definition
-small complement fragments (anafalatoxins) are released and bind to mast cells, causing them to release histamine
-most active: C5a, followed by C3a |
|
|
Term
| What are the 3 pro-inflammatory cytokines that activated macrophages secrete? |
|
Definition
| -Il-1, IL-6, and TNF-alpha |
|
|
Term
| What do pro-inflammatory cytokines (IL-1, IL-6, and TNF-alpha) do? |
|
Definition
| -they induce the synghtesis and secretion of acute-phase proteins by the liver |
|
|
Term
| What are 5 types of acute-phase proteins? |
|
Definition
-fibrinogen
-C-reactive proteins
-MB-lectins
-Iron-binding molecules
-Serum amyloid A |
|
|
Term
| How does Fibrinogen behave as an acute-phase protein? |
|
Definition
| -acts as a temporary scaffold for wound repair |
|
|
Term
| How do c-reactive proteins behave as acute-phase proteins? |
|
Definition
-bind both bacteria and phagocytic cells
-they behave as opsonins and activators of complement |
|
|
Term
| How do MB-lectins behave as acute-phase proteins? |
|
Definition
| -bind mannose on bacteria and activate Complement |
|
|
Term
| How do iron-binding molecules behave as acute-phase proteins? |
|
Definition
| -bind iron in the blood and make them unavailvable to bacteria, thus inhibiting bacterial replication |
|
|
Term
| What is the clinical significance of acute phase proteins? |
|
Definition
| -they are used as serum markers of inflammation |
|
|
Term
| What do acute phase proteins grossly do when you are sick? |
|
Definition
-tell brain to raise body temp: fever
-promote the release of sleep-inducing molecules: lethargy
-also suppress appetite: anorexia |
|
|
Term
| How do acute phase protiens induce catabolism of proteins? |
|
Definition
-during systemic infections, protein catabolism occurs via skeletal m digestion to supply AAs needed to feed inflammatory response
-controlled by TNF/IL-1 |
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