in chapter 22 we're going to talk about innate non-specific human um or host resistance and we'll basically focus on humans so we resist parasitic relationships because we're using both non-specific and specific uh mechanisms so non-specific resistance this is um is what we're going to talk about in this particular chapter and we need to look at the discussion of immunity the cells the organs all of those that are involved in the human immune response the mechanisms of cell cellular immunity are presented in this chapter um we'll talk about inflammation and the details of inflammation we're going to look at the physical barriers of innate respon um resistance and discuss the tissues and organs again then we're going to look at the the details um complement cytoines acute phase proteins things of that sort so when we look at the overview of host response to establish an infection a pathogen must cross the defense barrier and if a pathogen does succeed the immune system is going to offer protection so our immune system is made up of a variety of cells tissues and organs that are going to recognize the foreign material and the microorganisms and you want to be able to define the terms so immunity is the ability of the host to resist a particular disease and immunology is the science that deals with human responses so when we're looking at immunity we've got two different types we have non-specific immune responses that are also called innate or natural immunity and um this is a general resistance mechanism that we inherit as part of our innate structure and function and um all organisms have a form of innate immunity so animals plants have immunity uh again we're going to talk mainly about humans with this innate immunity does lack memory and um this is a non-specific response so it occurs the same time uh the same way with each encounter um with specific immunity this is also known as acquired or adaptive um this is a specific immune response so resistance to a particular foreign agent or an antigen by the immune response is going to produce antibodies or specific response to antigens this is um it improves on re uh repetition of exposure and there are bridges that help to connect innate and adaptive adaptives does produce memory and uh the bridges that connect these two um are several of our white blood cells but we'll talk a lot about dendritic cells so antigens is uh any entity any um molecule substance um that is going to elicit an immune response so our immune system can differentiate between self antigens and foreign antigens and this is very important um so this is what's going to enable our immune system to um handle the variety of things we're exposed to so antigens and u the self antigen and and foreign antigen this is going to enable the immune system to rid the host of foreign invaders and also eliminate cancer cells if the ability is lost if the person is not able to recognize the difference then that's going to lead to allergic responses and autoimmune diseases so when we think about the barriers that are associated with um innate immunity um the skin is an important barrier [Music] um tear saliva the mucus um our normal biota um the pampant cells lysosymes antimicrobial peptides so so much here are considered barriers in that first line of defense so think back to the structure of your uh skin and um this again is a one of our barriers um thinking about the structure so you have the epidermis and the dermis and of course the subcutaneous is not shown here and then the different layers of the epidermis but the skin is going to provide an effective mechanical barrier to microbial invasion uh because it is densely packed and it's thick um cells um thick layer of cells and we consistently shed those layers you're also going to notice that there is um acidity and um salt concentration that will help with um being a barrier if the pan uh pathogen does penetrate tissue under the skin then it's going to encounter the skin associated lymphoid uh tissue what we call salt and once that happens uh the langangerhans cells um these are specialized uh dendritic cells that will fagocytosa antigen and um these cells will migrate to the lymph nodes and differentiate into um dendritic cells that will um continue to help recognize the antigen and um these dendritic cells are antigen presenting cells they're going to help to activate t-c cells they'll interact with activated b cells and then help to induce humoral immunity then the intra epidermal lymphocytes that are going to help with um uh recognizing antigen they're going to function as tea cells and help to destroy the antigen mucous membranes uh these are going to secrete mucus and form a protective covering that's going to have antibacterial uh substances lysosymes um lactoeren lacto peroxidase so uh these antimicrobial peptides and um also there is the mucosal associated lymphoid tissue or malt and there are several types that um we'll include with these the gut associated and bronchial associated so and balt with those um malt is going to operate by the action of m cells in the mucous membrane so m cells will fagocytose antigen and transported either to a pocket in the m cell containing b cells and macrofasages or to the lympoid follicles containing b cells and so um this you see with the respiratory system uh the aerodynamics uh are going to help with the filtration so um you could see the celia escalator here the mucosiliary escalator so the aerodynamics are going to filter deposits that organisms have u made on the mucosal surface and microbes are going to be entrapped in the mucus and um that um muccoiliary again um escalator will help to um the activity of these siliated epithelial cells are going to help to transport microbes away from the lungs and so you'll go through coughing sneezing uh salivation and that will all help remove microbes um the alvear macrofasages are um macrofasages that are in the alvei of the lungs and they're there to help destroy pathogens that do get into the alvei the gi tract um the gastric juices so the um very acidic stomach juices are going to kill a lot of the microbes in the intestines there's pancreatic enzymes bile intestinal enzymes again uh paristalysis the normal biota that we have loymes um antibacterial peptides all of these are going to help to destroy uh the pathogens in that area the genito urinary tract um the kidneys urtors urinary bladder these are all sterile due to multiple factors so the ph uh the flushing capability the vagina is going to produce a glycogen and this um which is fermented by the lactobacilli to lactic acid and that's going to help lower ph and then um so again you'll notice um with the distance of the male urethra and the um female urethra again there will be more um infections or infections are more common in female um infections versus male so some of the chemical mediators that we have in the innate system so um again gastric juices salivary glyoproteins loymes um the oleic acid on skin ura all of these are important in um helping with our inate immunity and the antimicrobial peptides like the cationic peptides these would damage bacterial plasma membranes through uh electrostatic interactions the cathidin uh this is a group of linear alpha helical peptides so there's 12 to 80 amino acids that are produced by a variety of cells like neutrfils respiratory epithelial and we also have um defensins uh this is more of a diverse group um of dulfide linked openended peptides so about 29 to 42 amino acids long these are found in a variety of cells like neutrfils and the intestinal uh panis cells and then uh histatins these are larger peptides with um a regular structural repeat in those um sequence so when we get into the compliment system uh the compliment system is a set of series of pro uh serum proteins that play a major role in our immune response so compliment has three major physiological activities um so they're defending against bacterial infections they're bridging innate and adaptive immunity and they're getting rid of waste materials so during optinization uh the microorganism is coated with antibodies and um the manon binding protein and or compliment proteins um this is going to help promote and uh recognize fagocytosis so you're going to increase the opportunity for fagocytosis compliment is also going to be activated um it's going to work in a cascade effect and the complement proteins are produced in an inactive form and then they're going to be activated by one [Music] um and the activation of one of them is when um the protein is cleaved and so then that leads to this cascade effect so there's three pathways that we'll talk about there's the alternative the lectin and then the classical pathway so the alternative pathway is uh in response to intravascular invasion by bacteria and some fungi it involves interaction of compliment with the surface of the pathogen uh that's forming the mac uh complex so the membrane attack complex and you can see here these are all uh complement proteins and they're forming a pore a hole in that uh plasma membrane so they're activating c3 and then of course um you start adding these proteins to form mac lectin and classical pathways of the lectin complement is also called the man and binding lectin pathway and this is going to occur when macrofasages stimulate liver cells to release acute phase proteins like manos binding protein which is lectin and um then it can activate complement in the alternative pathway or the classical pathway the classical pathway is going to result from antigen antibbody interaction and so this one is going to happen during a specific immune responses so when we're looking at cytoines these are soluble proteins or glyoproteins that are released by one cell population and they act as intracellular med mediators so there are um different types of cytoines there are interlucans cheocyines interferons colony stimulating factors and tumor necrosis factors so acute phase proteins uh so the macrofase will activate uh be activated by bacteria then uh cytoines will be released the liver will be stimulated and then acute phase proteins will be produced so this is going to help to assist in the uh prevention of blood loss with a microbial invasion and it does include the c reactive protein manos binding protein and surfactant proteins that will help bind bacterial surfaces and then of course increase uh oxinization so when we are looking at the different cells of innate um innate immunity luccoytes are our white blood cells that come from the plur potent stem cells in bone marrow and they're going to migrate to other body sites and they'll mature and perform their functions uh they do include um the cells monocytes and macroof macrofasages uh granular sites mass cells dendritic cells lymphocytes um the um or the innate lymphoid cells uh natural killer cells so there's a a wide range of cells that we will talk about with this section and in this figure you want to be comfortable with the um different cells of the immune system the blood cells um their function and their progenitor where do they come from okay so be comfortable with this figure so mass cells are found in our connective tissue uh they have granules that have histamine and other chemicals this is going to contribute to our immune response and mass cells play an important role in uh allergies and hypersensitivities granulosytes are also known as polymorphuclear luccoytes um we'll talk about basoils eocinophils and neutrfils so basoils are nonfagocitic uh when they're stimulated they're going to release chemicals like histamine and prostaglandins these chemicals are going to impact blood vessels so vasoactive and basopils play an important role in allergic reactions eocinophils are mobile cells that are going to migrate from the bloodstream into tissue spaces they're going to protect against prozzoal and um helment parasites they also may have a role in allergic responses neutrfils are highly fagocitic cells they rapidly migrate to sites of tissue damage and infection monocytes and macrofasages uh these are also highly fagicitic cells that um constitute uh the monocy macrofase system so monocytes are monuclear fagocitic cells they're going to circulate in the blood for a very short period of time and they can migrate to tissues where they're m where they will mature into macrofasages macrofasages are larger than monocytes they have more organels and possess receptors that allow them to discriminate self from non-self so their surface molecules are going to help recognize common components of pathogens like the lps of a gram negative bacterial cell wall and they're also going to respond to oxinization so have a chemical enhancement to fagocytosis and dendrrenic cells are fagocitic um cells they're going to fagocytos microorganisms and kill viruses by secretreting inter interferon alpha u mature dendritic cells are going to migrate to the bloodstream or the lymphatic system where they're going to interact with b cells and natural killer cells and present antigen to tea cells so these are very important cells we find them in skin mucous membranes of the nose lungs and intestines so they're very important when we think about the innate uh lympoid cells um these are common lymphoid progenitor cells they're going to give rise to um again the innate lymphoid cells and natural killer cells and lymphoid tissue inducer cells these are not going to express antigen specific receptors uh they lack receptors um so they are going to respond to the pathogens lti are found in lymph nodes and fire patches and ilc's are basically divided into three functional groups so ilc1 is going to help to activate macrofasages uh ilc2 is going to trigger vasoddilation um these are going to release more mucus and macrofase activity in response to extracellular pathogens and il3 are responding to the normal microbiota biota in addition to microbial pathogens so it helps to maintain uh barrier function in our mucous membranes uh helps to stimulate antimicrob antimicrobial peptides and then also to prevent the immune response against our normal biota so microbial stimulus intracellular pathogen uh activating a natural killer cell and um an innate lympoid cell so what is happening here what kind of activity is happening so this is going to kill the infected cell and then macrofasages are activated parasites um impacting or um stimulating the ilc2 so you'll get mucus secretions vasoddilation macrofase will be activated and then thermmorreulation extracellular pathogens or microbiome um stimulating ilc3 so this is going to help to um for oxinization promote fagocytosis uh release the antimicrobial peptides and epithelial cell survival natural killer cells are large nonfagocitic granular lymphocytes that destroy malignant cells and cells that are infected with microorganisms so they recognize and target two ways uh antibbody dependent cell mediated cytotoxicity and um these receptors on the natural killer cells are going to link them to the antibbody coded target cells and if the natural killer cell binds class one mhc molecule uh there's which that's of course a self antigen on our cells u killing is going to be inhibited so if there's no class one mhc on a target cell uh maybe the cell's been infected with a virus or it's a malignant tumor cell then killing will occur uh there will be the poor forming proteins and cytotoxic enzymes to help destroy that cell so the two ways that you get recognition uh or um activity from your um natural killers so we've got the natural killer cell uh here's the mhc and adhesion um receptors and proteins so this is the target cell once that's been uh recognized um the cytokeleton is going to rearrange uh you get an attachment of the natural killer cell to the target cell and then you're going to release the uh granules into the target cell uh once they're inside they're going to um perforate and lice the cell the target cell and then eventually that target cell will die this is showing you antibodies that are going to bind to the viruses that are attached to a um an infected cell so antibbody receptors on natural killer cells when that target cell is infected uh the virus now then can recognize the um antigen and so this is going to increase oxinization or um not really oxinization but um recognition of that target cell so now the receptors on the natural killer cell are going to recognize the antibbody attached to the target cell release the granules and uh again kill that target cell similar to what we saw here okay so now we want to get into uh the secondary lympoid tissue and the organs so our um when we think about the first looking at the primary lymphoid tissue primary lymphoid tissue is where the lymphosytes are going to mature and differentiate and um secondary lymphoid tissue is where we're going to get exposed to antigen so here you can see um the primary lymphoid organs and secondary lymphoid organs so thymus and bone marrow um this is where b cells are going to mature in the bone marrow t cells are going to mature in the thymus and then our secondary lymphoid tissue tonsils lymph nodes spleen um the pyrus patches um the lymph vessels so all of these you recognize from uh mentioning them earlier secondary lymphoid organ tissue um the spleen is going to filter uh blood and trap bloodborne microorganisms um and antigens so these the spleen contains macrofasages and dendritic cells that are going to present antigen to the tea cells lymph nodes are also going to filter they're going to filter the lymph fluid and trap microorganisms and antigens they also contain macrofasages and dendritic cells and present antigen to tea cells te-c cells are going to release cytoines and stimulate differentiation and proliferation of b cells in antibbody producing plasma cells and memory cells some of the lympoid tissue is closely associated with certain tissue such as uh salt malt bault and g that we talked about earlier so again skin associated lympoid mucosa associated um lipoid tissue so there's some of these are going to um be in association to other tissues so when we look at salt this is um where we would um have microbial invaders so here are the antigens coming in to the tissue uh the longer hans the longer hans sales i mentioned those earlier in the video uh these are going to let's move that out of the way oops so um these cells are going to um be specialized dendritic cells that are going to fagocytosis the uh microbe that penetrates the skin once it is in the lymph tissue it will present the antigen to the um t- helpper cell and then through differentiation and match or differentiation and activation then in turn it can activate b cells and um plasma cells and um the additional specialized cells are the intraepidermal dermal lymphocy so this again is a very specialized uh here's the t-c cell the intradermal lymphocy that you find mock move back down um mock is um specialized lymphoid tissue and the mucosal so these are gut associated the g and bronchial associated with the bault and so this is the m cell here and you can see the macrofase is engulfing or fagocytosing the antigen processing that and then of course then it can be um presented to uh b cells and then the lining of the intestine so um secrettory iga uh this is a really good um antibbody that's going to help protect against um infections of course of the intestines so things we eat um drink that type of thing okay so we want to talk about fagocytosis and this is a process of cell eating so u in fagocytosis a fagocitic cell is going to um engulf through endoccytosis um an organism and uh it's a process where the invader is going to be recognized ingested and killed uh some of the cells that are fagic cells are monocytes tissue macrofasages which is that's their name once they go into the tissue dendritic cell neutrfil so they're very important um when you're thinking about how we how um cells macrofasages are recognizing um the infected cell or the damaged cell we've got to think about pathogen recognition uh to help with this so um your micro associated molecular patterns uh we'll talk about these as pamps pathogen associated uh microbial um are just referred to as any of the microbes that's not present in a host of these receptors so lps on uh gram negative bacteria like ecoli and then pepidoglycan uh that you would find in the grand you know thicker in the grandpositive bacteria so maps are going to be recognized by pattern recognition receptors or prrs and this is important so that the fagocitic cell will know what to fagocytosse receptors are prrs and they act exclusively as signaling receptors that are going going to bind to pamps which are pathogen associated ated molecular patterns or maps which are micro associated molecular patterns and they're going to communicate with the cell nucleus to get the appropriate response to different classes of pathogen so recognition of maps by prrs so toe to toe like receptors that we find on the surface of the host cell these are non-specific and so they're going to recognize for example lps um the triricolated lipopeptides the diacolated lipopeptides flagagulin from fleella one so this is signal transduction um those of you that have had cellto cell communication chapter 11 and intro to cell that's this those of you that haven't realize that for a cell to respond to a signal we have to have a receptor and we have to have a liand so these lians bind to the receptors whichever receptor it is and the first change would be or the first signal would be the receptor and liand with transduction what's happening is all of this this is the cascade effect so as this receptor is signaling the next protein the next molecule then that molecule is signaling the next just like a relay race the same concept as a relay race so they're passing the baton to the next protein until we get to the nucleus where we're going to have a specific response we're wanting either to produce uh chemicals to destroy this antigen here uh we may want to or in addition in addition to produce chemicals that will signal more uh response to the antigen so in signal transduction in cellto cell communication this micro cell is communicating with the host cell by receptor and liand and then a cascade effect of signal transduction pass on to the next to the next to the next until we get to the nuclear level a dna level and then in the dna we're going to turn on the [Applause] genes signal the genes to produce whatever material we need to respond to the pathogen or the antigen intracellular digestion respiratory burst uh when you're looking at this u this is where the microbe is going to be able to be internalized so the prr on the fagocitic cell is recognizing the maps or pamps it's engulfing the bacteria when that happens then um the lysosome is going to fuse with the fagosome by doing that we're going to be able to break down the uh components of the bacteria or the pathogen and then you get intracellular digestion so these litic enzymes are going to break down uh the specific parts um of the pathogen and then you get uh the toxic oxygen products so the ros are going to respond to that and this is going to help to kill the microbe and so debris is going to be released out and then um excreted autophagy this is such a neat concept so autophagy is self-killing so this is a very conserved process it's going to tag microbes for destruction uh the ubiquitin protein is going to label it you have a fagosome um or they the faggoaphor um so the autofagosome is going to fuse with the loone and break down the contents inside so this is a way that a cell can recognize that uh there's proteins damaged or the dna is damaged or the cell has been damaged um and autophagy is is an intracellular digestion that takes place exocytosis uh this is where the antigenic remains of invaders can be expelled from the cell like neutrfils or further process for antigen presentation to the lymphosytes on the cell surfaces so macrofasages and dendritic cells do this so um neutrfils are going to um expel out the debris and macrofasages and dendritic cells are going to help to present antigen to um that broken down debris to um lymphocytes to help further um handle that material okay now we want to get into inflammation so inflammation is a non-specific response to tissue injury uh it's characterized by redness heat pain swelling and if uh possible altered function of the tissue so that's the four cardinal rules are redness pain heat and swelling the altered function is an additional one uh potentially so in inflammatory response injured tissue cells are going to release chemical signals that'll activate cells in the capillaries um so the interaction of selectins on the vascular endothelial surface and integr surfaces are going to promote neutrfil extravasation uh neutrfils are going to attack the pathogen more neutrfils and luccoytes are going to be attracted to the sight of the tissue damage and help destroy the uh microorganism so that's with that chemotaxis so this is a good figure to look at um so the marginization the diaps diapetus and extraation so um you can see with the capillary here we have um neutrfils uh this is the marginization where they're going to travel into the damaged tissue area the di the diapet the diapetus um moving through this is where it is forming like the um like a foot looking structure where it's moving through where it's pushing through so the marginization is getting the um cells the umosal cells kind of separated and then uh the dietis is uh moving through where it's actually moving into extra vasation again is to get um uh the dilation so you can get the cells into that damaged tissue area so in um inflammation sometimes the tissue is um killed uh it's damaged or uh it'll be it'll um potentially die out uh the calocrine this is an enzyme that's going to help to catalyze the formation of the brady kynan and bradyanin is going to help bind capillary walls causing the movement of the fluid and the luccoytes into tissue and the production of prostaglandins so this is what's going to cause the pain and of course when you're moving u material into that area into that tissue area there's your swelling um then you're going to have mass cells that will bind causing uh histamine and other inflammatory u mediators to be produced and released so here's your histamine histamine is going to promote the movement of more fluid lucasytes bradyanine and the um calocrine into that tissue area chronic inflammation is characterized by a long duration so it's a dense filtration of lymphosytes and macrofasages and the formation of granulomaas in some cases so a granuloma is a walled off area and so this takes care of chapter 22 let me know if you have any questions