EK B2 Ch4 Immune System COPY Flashcards
immune system 1
- Constant pathogen exposure to respiratory, digestive, urinary epithelia
- Immune system protects against disease-causing pathogens
- Two branches of immune system
- Innate immunity is nonspecific, meaning helpful for anything** that comes at us
- Adaptive immunity is specific, meaning our response is specific to the kind of pathogen* we would respond differently to virus causing measles v. COVID
Pathogens are harmful microorganisms =
= viruses, bacteria, fungi, protozoa any kind of harmful microorganisms** exposed to them all the time!
innate immune system 1
super important, first line of defense; all good defenses regardless of pathogens! first response and general, happens immediately, lots of things get knocked out and never get to step 2 pretty good!
- Mechanical and chemical barriers to infection
- Skin prevents entry of pathogens- mechanical barrier
- Nasal hairs filter out pathogens**
- Mucus traps many pathogens in respiratory tract
- Stomach acidity and digestive enzymes inactivate many pathogens
- Tears and mucus contain lysozyme, which lyses bacteria cell wall
- Cytokines, inflammation, and complement are important
- Macrophages and neutrophils can eat bacteria
- Basophils and mast cells can release histamine and promote inflammation
lysozyme
• Tears and mucus contain lysozyme, which lyses bacteria cell wall
Macrophages and neutrophils
• Macrophages and neutrophils can eat bacteria
Basophils and mast cells
can release histamine and promote inflammation
cytokines 1
secreted proteins, signaling molecules of immune system*** they are important for innate immune system and adaptive immune system* acquired immunity and adaptive immunity are the same thing*
- Cytokines are secreted proteins, signals for immune system
- Important for both innate and acquired immunity
- Interferons inhibit viral replication
- Interleukins signal between lymphocytes, key for B and T cell activation interleukins- how B and T cells talk to each other, cytokines in general are throughout everything we talk about as signaling molecules*
inflammation and fever 1
- Inflammation triggered by leukocytes → cytokines and histamine release → vasodilation
- Inflammation yields increased plasma outflow from capillaries = edema
- Cells, antibodies, fluid enters interstitial fluid
- Fever = raised temperature to inhibit pathogen growth
inflammation and fever 2 chain of events
when think of local inflammation get a cut, wounded tissue releases signaling molecules -capillary dilates, fluid and some leykocytes can migrate out into interstitial area, and that is what makes are swollen* can see nuetrophils and macrophages can go and eat up debris, white blood cells go out there* and eat up whatever the pathogen is** but there is all of this signaling that makes the blood vessel dilate in the first place* lot of signaling molecules involved, that allow the fluid and the cells to get out there an do their job* innate immune response happens immediately! always there
why fevers are great actually
inflammatory response is contained in one area if have scratch!
usually if have a system wide inflammatory response =a fever is a big hallmark of that, fever represents body raising its temperature everywhere to inhibit the growth of the pathogen*** It turns out that at slightly higher temperature makes it slightly harder for many or most pathogens to grow slows down their life cycle** to this day still counter intuitive, when have fever not suppose to reach for advil a fever helps you its an adaptive thing*
adaptive immune response
slower! bt benefit if go through the whole adaptive immune response end up with memory cells, meaning if exposed to same pathogen again we can respond faster and also more robustly*
2 parts B cells and T cells
Adaptive immunity is specific to a particular pathogen
Characterized by a delay in response to pathogen exposure (1–3 wks)
“Memory” provides for a robust response on second exposure to antigen
Second exposure elicits rapid response (few days)
Antibody mediated immunity (B cells)
Cell mediated immunity (T cells)
B cells
Antibody mediated immunity (B cells), humoral response
Their name comes from the name of the place they were discovered, the Bursa of Fabricius. The Bursa is an organ only found in birds.
T cells
Cell mediated immunity (T cells)
If fight off virus with innate immune system…..
exposed, but never amounted an adaptive immune response wil not have antibodies! could be they fought it off so quickly* or ppl with asymptomatic cases may never have mounted an adaptive immune response to virus at all*
antigen 1
- ANYTHING that triggers an immune response*** Antigen is a molecule that triggers an immune response
- Antigen can be a protein, lipid, sugar can be ANYTHING
- During active immunity, immune response is highly specific for antigen, during adaptive immune response* we make antibodies directed against the antigens* but antigens can be big, like can say entire covid particle would be an antigen
- antibodies recognize certain cites on an antigen* so if exposed to COVID can make 6 differnet antibodies against it able to bind to different places on antigen, part on antigen where antibody actually binds is called epitope
- Cell-mediated immunity also directed against antigens- T cell side
- Presence of antibodies indicates prior exposure to antigen (e.g., HIV, Herpes) means person was previously exposed* can have antibodies against something and not be currently sick with that thing, just means exposed to it at some point*
Epitope
= part of the antigen that is recognized by an antibody
B and T lymphocytes
- In category of white blood cells, we have lymphocytes like all WBC generated in bone marrow
- Lymphocytes are generated specifically in red bone marrow
- B cells mature into plasma cells that secrete antibodies
- T cells mature in the thymus and are critical for cell-mediated immunity
B cell
- very distinctive Y shaped receptor!
- a particular B cell will have 1 receptor for the antigen, we are born with a repetiore of B cells, many many different B cels with receptors so we have the potential to recognize a very wide range of antigens*
- B cells are generated in the bone marrow
- Reside in secondary lymph organs (spleen, lymph nodes, tonsils)
- Each B cell has only ONE type of transmembrane antigen receptor on its surface
- Each antigen receptor is specific for one antigen
- Humoral immunity
B cell receptors!
- C constant regions
- each receptor has 2 binding sites specific for hte same antigen**
- V= variable regions* when we say we have a repetoire of B cells that can potentially recognize thousands and thousands of differnt viruses or bacteria, the difference if you were to compare the B cell receptors would differ in variable regions, what allows them to bind all different antigens
- constant regions= basically 5 types of constant regions that represent our different B cells* so there are some variety among constant regions, but relatively constant compared to variable regions which are extremely diverse
- why if can study someone’s B cells can see wide variety of pathogens they could respond to would be, why novel pathogens can be so dangerous, ppl do not have in repetoire to fight, if something been in population for a long time kids born in that environment will have B cells, passed down so if you ancestors have seen a pathogen for years adn years, born with B cells with atnigen binding site can recognize that thing, totally novel pathogen results from mixing and matching results from some animal covid virus, or some crazy scenario some virus came from outer space we would be screwed becuase no one has that in repeitore or ability to bind to that thing if look across B cells*
B cell 2
- B cells recognize pathogen and bidn to pathogen extracellular =meaning if a little bit of virus is floating around in the blood, or its in lymph of intersitital fluid, that is when a B cell receptor would connect with it vs T cell which deals with pathogens that have already weasled their way inside cells*
- B-cells can connect to antigens right on the surface of the invading virus or bacteria. This is different from T-cells, which can only connect to virus antigens on the outside of infected cells.
what happens when B cell …… clonal selection
- top row shows 3 diff B cells with purple, blue or green receptor, purple rceptor can bind incoming pathogen so we make lots and lots of copies of that prticular type of b cell** so its ability to bind to that pathogen is suddenly very important, so we do not want a small number of cells with this binding ability, we want lots so the cell starts making clones!
- some of those clones will differentiate into memory cells so have the same memory cells incase this same antigen comes around again, others of clones keep developing into cell type called plasma cells*
- plasma cells = secrete antibodies which are the receptor**
- so what plasma cell does, B cells differentiate into plasma cells and plasma cell starts synthesizing receptor without transmembrane region, which is the part of protein that makes it stick in membrane so these Y shape receptors go out into blood, intersitital fluid or lymph and at that point we call them antibodies* this is pretty smart because these receptors were able to bind to the pathogen in teh first place, so antibody should be able to bidn to whatver triggered this whole thing in first place* antibodies floating free of cell gives it more range releasing fighters from mother ship*
antibody action
antibodies cannot directly themselves lyse pathogens or destroy them
- can neutralize a pathogen, meaning bind to it soit cannot do its job
- they can also cross link and basically create big clumps of pathogen so macrophages can come and clean up the mess, think of it as trapping the pathogen but not quite destroying it yet, and macrophages come adn eat everythign up**
- activation of complement system and pore formation, say membrane of bacterial cell, foreign cell of some kind; orange antigen boudn to upside down Y represent antibodies, then there is this big ballooning thing on top bound to stem of Y, variable region of Y binding to bacterial cell the antigen, and then the constant region or stem of the Y is binding to complement proteins* so basically what is happenign is when antibody binds to antigen that can activate complement protein, which is hte hit man of the system** the complement protein goes and creates a pore in the membrane, which causes the bacterial cell to lyse
IMPORTANT TO REMEMBER FOR ANTIBODIES*
antibody not directly lysing foreign cell, activating complement protein which then lyses the cell** all targeting extrcellular pathogens, so bacterial/foreign cell in blood stream or interstitial fluid, not somethign insdie one of our cells yet!
antibodies 2
five classes of antibodies
also called = immunoglobulin = Ig
Five classes of antibodies differ in the Fc region: IgG, IgM, IgA, IgD, IgE
if rearrange them spell MADGE**
different categories of antibodies, IgG is the main antibody we have in the blood, so if want ot know if someone has main antibodies against a disease, main thing will be looking for is IgG**
IgA= type find in muscus, tears, saliva and breast milk
IgE= associated with allergic reactions and inflammation* sometimes if describe a research study that has to do with allergy, the outcome measure that research on allergy sometimes looks at is presence of IgE* if someone has a lot of IgE means havign allergic reaction, if doign study can document spike in IgE is enough to say have allergic reaction can stop it dont need to go into an. shock can establish having an allergic reaction*
IgG is
IgG is main soluble antibody in blood
T cell receptor
- just like B cells born with many many of these receptors, generate whole repetoire through process of mixing and matchign DNA to end up with when we are born a big range of different receptors which will hopefully be enough to deal with pathogens we encounter in our lvies, what a T cell receptor looks like
- not Y shape, 1 binding site per antigen per receptor, same idea if have one particular T cell its good for recognzing a pretty small range pretty specific for recgonzing specifc pathogen*
- if bidns to antigen, makes copies of itself… trying to respond to antigen that has already gotten inside of cells, a little bit more ot the mechanism*
T cell receptor 2 image
T cell binding to antigen fragment
- why T cell system called cell mediated immune sytem, only sees and binds to antigen being presened by one cell n body presented on this MHC flagpole
- 2 ways pathogens can get inside cell of body= if imagine host cell is an immune cell like a macrophage, eats it up, then when it presents a fragment of the antigen on its MHC* it is really giving a heads up to the rest of the immune system that there is an infection underway* so the macrophage isnt in trouble but it is giving an SOS, alert to the rest of the immune system, type of T cell that will come is a Helper T cell
- Helper T cell will then boost the response of B cells and other T cells
- Immune cells have a type of MHC called class 2 MHC* so helper T cells will bind to antigen presented on class two MHC*
- way 2- infecting us, gets inside cell by infecting us, getting inside our respiratory lining or stomache cell infected; when pathogen inside host cell not because host cell’s job is to eat pathogen but because host cell is in trouble
for scenario 2- when gets inside cell by infecting us, getting inside our respiratory lining or stomache cell infected
- steps are the same but now cytotoxic T cells–Killer T cell– to respond want T cell to destroy infected cell and get lysed
- want cytotoxic t cells to come around and destroy cells ifnected, we DO NOT want them destroying macrophages presenting antigen*** to get immuen response
- so this is the point of two different classes of MHC, most cells of body have class 1 MHC so cytotoxic t cells recognize antigen presented on class 1 MHC*, for ifnected cells…. how we avoid killing our own immune cells
2 scenarios why have 2 different MHC classes
Steps involved for scenario 2 in which pathogen gets inside of cell, one is because its what we want, eating pathogen dont want to destroy macrophage wants to let immune system know what is going on, what helper T cells are doing- cass 2 MHC
versus pathogen infecting host clel, then we want that cell, because viruses need host cells to replicate, so great strategy if cell gets infected to kill it so that prevents cell/ virus to replicate*
-identical twins same MHC< but then every individual has a pretty unique set of MHC, pretty identifiying and signature for the person*
Helper T cell binding
- big purple cell is macrophage, will phagocytosis orange pathogen, then gets chopped up into fragments
- then fragments get posted onto MHC class 2 kind of flagpole they have** cell starts waving flag of orange antigen fragment
- so becuase Class 2 helper T cell responds, binds to the receptor of hte helper T cell, the purple thing sticking up from helper T cell recognizes that antigen fragment
- so helper T cell with right receptor variable region to recognize this particualr antigen fragmetn* close up of binding*
- then helper T cells do this sort of signal boost for immune system, lookign at all those arrows with dots called cytokines, cytokines are signaling molecules of immune system so when a helper T cell realizes that a macrophage has phagocytosed a certain kind of virus, part of helper T cell job is to let everyone else know* what cytokines are about* arrows with green pluses, B cells being alerted, T cell being alerted, cant get full B cell response with all the steps unless confirmation adn green light of helper T cell, amplifies everything we have talked about with B cells and T cells, necessary for full B cell response
- one hallmark of immune system tehse guys are talking to eachother a lot, say person exposed to measles virus the B cell may recognzie and bind to the measles antigen* but then also hears from Helper T cell, same thing phagocytosed virus cell, checks andbalance, bfore B cell mounts whole immune response and sends out all these antibodies from all these clones needs to be confirmation adn green light from helper T cell- so heads up to humoral immune system and then the rest of immune system to get cytotoxic T cells activated as well, really cranking otu cell medaited immunity part of this*
Helper T cells and also cytotoxic T cells after doing all this, full adaptive immune response to some infection*….
- like what we said with B cells, when cell with certain receptor binds to an antigen, really needed in that moment, cell makes lots and lots of copies of itself, some of those copies/clones help with prsent fight and others differentiate into memory cells to be called into action really qucikly if same antigen comes around in future
- so person shoudl end up with, memory cytotoxic T cells, memory T helper Cells, memory B cells**= 3 main types of lymphocytes, after doing all of this person should have memory cells for all three, meaning this whole thing can be rebooted more quickly and more strongly in future if necessary*
people get what is called a cytokine storm…
means cytokines get released in such an itnense way, get B cells adn cytotoxic t cells amped up to such an aggressive level that the person ends up suffering more from friendly fire, immune response becomes the problem, get massive inflammation too much immune activity
with COVID, all these ppl seem to be having all these autoimmune type symptoms after they recover from infectionl; ppl getting antibodies attacking brain and causing brain fog condition, or in diabetes 2 attacking insulin cells, virus in some ppl who are younger and healthier strong immune response, but for some ppl immune system gets cranked up too high, one way that can happen is cytokines are too active, shouting at B and T cells to do more and more, gets out of hand*
immune system overview
- exposed by antigen, engulfed by entigen present cell like macrophage, can see that that activates a Helper T cell
- antigen independly comes into contact with B cell, then helper T cell goes to right, gives signal boost to B cell, then B celld oes its thing and makes lots of copies of itself, someof the copies differentiate into memory B cells, some straight down become plasma cells which then secrete antibodies**
- antigen presenting cell mashes together two categories can be affective cell or immune cell posting antigen fragment
- infected cell recognzied by cytotoxic T cell, helper T cell recognizes immune cell antigen being presented by immune cell like a macrophage* then cytotoxic t cell recognizes antigen presented by infected cell* when say in this image two kinds can present antigen
- helper T cell sends cytokines over to the right signal boosting cytotoxic t cells, which then become activated, so going down from cytotoxic t cells, you get lots and lots of clones or copies of that particular T cell, right receptor for this particular infecton, some clones become active cytotoxic t cells going to lyse infected T cells, other differentaite into memory cytotoxic t cells*
- active cytotoxic t cells lyse infectd T cells- also great at recognizing cells that look wrong in some way, on path to cancer, to cytotoxic T cells are a realy good defense against cancer** lots of immuno therapies getting a lot of atention right now are training T cell system to recognize hallmarks of cancer* boosting immune system can be a dangerous game
immune system overview 2
- you are really poking the beast when crank up immune system, need to thread the needle carefully*
- can really damage the self also* so be careful*
- where says antigen 2nd exposure, if measles comes back or exposed to the same thign agian* then all 3 types of memory cells get activated, adn then can go right from memory B cells to plasma cells or right from memory cytotoxic T cells to active, immune response is faster adn stronger to* in this case*
antibody structure
Antibody structure is Y shaped
Each antibody has two identical heavy chains and two identical light chains
Disulfide bonds connect heavy chains, and light chains to heavy chains
Each arm of the Y is an antigen binding site = Fab
TWO antigen binding sites per antibody for the SAME antigen
Antigen binding site is highly variable
Tail of antibody is a constant region = Fc
Fc is effector region, allows complement binding, phagocytosis, mast cell binding
Five classes of antibodies differ in the Fc region: IgG, IgM, IgA, IgD, IgE
Each arm of the Y is an antigen binding site
Each arm of the Y is an antigen binding site = Fab
Tail of antibody is a constant region =
Tail of antibody is a constant region = Fc
i =
= O allele at locus yields no antigen = type O blood
image of O- no Rh factor!
Blood type and blood groups chart
Rhesus (Rh) antigen
- Rh antigen is another blood antigen
- Important for mother-fetus interactions
- During birth, fetal blood often comes in contact with mother
- If fetus is Rh+ and mother is Rh–, mother will develop antibodies to Rh antigen
- If second baby is Rh+, mother’s anti-Rh antibodies can cross placenta, attack fetal RBCs
- Maternal antibodies can lead to fetal RBC lysis, anemia, and death
- Today, anti-Rh antibodies (Rhogam) are injected into mother
- Rhogam destroys any fetal RBCs before mother can mount immune response
ELISA Assay
Enzyme Linked ImmunoSorbent Assay
- Can detect how much antigen is in a sample
- Antigen sticks to surface OR to a specific antibody bound to a surface
- Detect antigen with a second antibody
Rh antigen 2
why astrix with O as universal donor and AB universal acceptor**
- ppl are either Rh antigen plus or not, so plus if make the Rh antigen and a minus next to their blood type if they do not make this particular antigen
- it is just a marker on blood cells, same as A antigen is a marker, its surface decoration!!! It doesn’t have a function just characteristic pattern you would find on surface of red blood cells or not, its a pattern either there are not*
- decorative protein
- ppl think about this because blood types have to be matched, so if you have a negative AB- designatons but with a negative, do not want blood that has anything positive, if AB- do not want AB+ blood becuase make antibodies against the Rh factor in that case**
- so if O- is the true true universal donor, “O neg” bags*
- if AB- cannot be given O+** *has to be O-*
Rh antigen 3
- if mother Rh - and gets pregnant with baby Rh+, during pregnancy no mixing of materanl and fetal blood, during childbirth there is some mixing of blood when placenta separates* for mother to be exposed to fetal blood and she will make antibodies then against Rh factor* if she is negative and the fetus is positive
- that is actually ok for that kid, immune responses take 1-3 weeks baby born at that point
- but if that same mother who now has active immunity against Rh factor, gets prengant with another baby can make antibodies against it can destroy fetuses red blood cells, cause of miscarriage and babies being born that are severely anemic on verge of death anemic, so makes antibodies against red blood cells of kid and kills kids red blood cells**
- so there is a drug called rogam basically suppresses mother’s immune response to Rh factor and its not always know what blood type fetus is, any women going into labor is gloing to be given this drug to make sure would nto make antibdoies against Rh factor* preventative measure truly life savign no memory cells against Rh factor she will not put another Rh positive baby at risk* breast feeding should not be an issue*
How do B cells become plasma cells?
When a B-cell receptor connects to its specific antigen, a Helper T-cell releases chemicals that tell that B-cell to divide many times. This makes an army of B-cells with the perfectly shaped B-cell receptor to connect to the invader in your body.
Many of these B-cells quickly turn into plasma cells. Plasma cells make and release antibodies that connect to the same antigen as the original B-cell receptor.
Plasma cells make thousands of antibodies per second, which spread throughout your body, trapping any viruses they see along the way.
antigens 2
Q25. All of the following are true regarding a type O individual EXCEPT:
a. they donate blood to a type O or type A person
b. they can accept blood from any type blood donor
c. they can generate antibodies to type B blood
d. they lack genes encoding type A and B blood antigens
answer is b. they can accept blood from any type blood donor
think of an antigen as a protein, foreign protein on surface of bacterial cell sometimes it is a carbohydrate, can be lipid can be different categories but basically a foreign thing of something that comes in and triggers immune system aka virus , bacteria as a whole category considered antigens, peanut is an antigen* if you are allergic to peanuts your immune system has defined peanuts as an antigen
antigen a marker on the surface of the RBC< so say A anting a in a person with type a blood and then again it is just a molecule on surface doesnt have any functional or clinical significance type B blood not healthier than ppl with type A blood, A antigen and B antigen are not doing anything decorative protein, but trigger for immune system if put B cells antigen into a person never seen before who has type a blood bad, just like the Rh factor that is just another protein can be present or absent on the surface of a person’s red blood cells depending on what their genotype is produce protein maybe maybe they do not, if they do they are Rh+ and if you don’t they are RH-**
person with A+ blood is b/c of Rh antigen on cells**
those antigens are not doing anything important for cell, only important in terms of their effect on transfusion, who can get what blood can go crazy if give someone wrong kind of blood
blood what do you mean lacks antigens- not a bad thing, if have a person with no A or B antigen in this RBC no RH (or RH factor same thing) can say this person is type 0 negative, completely fine to not have any of these. remember it really doesn’t matter in terms of your health if you retype A, B or O ONLY matters if you need a transfusion you have to make sure whatever new blood cells coming in will not trigger a huge immune response because the incoming blood you are reciting contains an antigen never seen before
