EK B2 Ch4 Immune System Flashcards
1
Q
immune system 1
A
- 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
2
Q
Pathogens are harmful microorganisms =
A
= viruses, bacteria, fungi, protozoa any kind of harmful microorganisms** exposed to them all the time!
3
Q
innate immune system 1
A
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
4
Q
lysozyme
A
• Tears and mucus contain lysozyme, which lyses bacteria cell wall
5
Q
Macrophages and neutrophils
A
• Macrophages and neutrophils can eat bacteria
6
Q
Basophils and mast cells
A
can release histamine and promote inflammation
7
Q
cytokines 1
A
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*
8
Q
inflammation and fever 1
A
- 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
9
Q
inflammation and fever 2 chain of events
A
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
10
Q
why fevers are great actually
A
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*
11
Q
adaptive immune response
A
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)
12
Q
B cells
A
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.
13
Q
T cells
A
Cell mediated immunity (T cells)
14
Q
If fight off virus with innate immune system…..
A
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*
15
Q
antigen 1
A
- 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
- 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*
16
Q
Epitope
A
= part of the antigen that is recognized by an antibody
17
Q
B and T lymphocytes
A
- 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
18
Q
B cell
A
- 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
19
Q
B cell receptors!
A
- 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*
20
Q
B cell 2
A
- 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.
21
Q
what happens when B cell …… clonal selection
A
- 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*
22
Q
antibody action
A
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
23
Q
IMPORTANT TO REMEMBER FOR ANTIBODIES*
A
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!
24
Q
antibodies 2
five classes of antibodies
A
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*
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IgG is
IgG is main soluble antibody in blood
26
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\*
27
T cell receptor 2 image
28
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
29
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
30
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\*
31
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\*
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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\*
33
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\*
34
immune system overview
1. exposed by antigen, engulfed by entigen present cell like macrophage, can see that that activates a Helper T cell
2. 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\*\*
3. antigen presenting cell mashes together two categories can be affective cell or immune cell posting antigen fragment
4. 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
5. 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\*
6. 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
35
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\*
36
B Lymphocyte activation
B cell receptor encounters antigen and internalizes it via receptor mediated endocytosis
Antigen is broken down into peptide fragments
Antigen peptide fragments are displayed on B cell surface
Helper T cell “sees” antigen on B cell surface
Helper T cell gives B cell a “handshake” and activates B cell (via ligand, cytokines)
Activated B cells proliferate and differentiate into plasma cells
Plasma cells secrete antibody with same antigen specificity
A few activated B cells remain in the body and are “memory” B cells
Memory B cells enable robust immune response upon second antigen exposure
37
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
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Each arm of the Y is an antigen binding site
Each arm of the Y is an antigen binding site = Fab
39
Tail of antibody is a constant region =
Tail of antibody is a constant region = Fc
40
IgA
IgA present in mucus, tears, saliva and milk
41
IgE
IgE can be bound by mast cells, causing histamine release
42
antibody mechanism
* B cells and antibodies provide humoral immunity
* Humoral immunity defends against extracellular pathogens and toxins
* Two binding sites allow crosslinking of antigen complexes
* Antibody does not directly destroy antigen
* Antibody can neutralize virus/ bacteria by blocking surface proteins used in cell entry
* Phagocytic cells can bind Fc region, leading to phagocytosis and clearing
* Complement proteins can bind Fc region and trigger pathogen lysis
* what does corsslinking of antigen complexes? cross linking= means grab one and grab another in a blob, big thing that antibodies do
* if think abotu how there are two binding sites one antibody can bind two molecules of antigen can grab one on each site of arms cannot be free to float away, dumb down image what this leads to is creating a blob of antigens a whole bunch of antibodies are holding down a whole bunch of antigen molecules, then macrophages come and eat it all up, so basically creating a cluster, clump of antigen molecules that will be easier for macrophages to come get rid of /however antibody binding to antigen, and holding onto it and one antibody is holding tow antingens\* so they become a clump and then get another antibody that can combine to two antigens so start to get a blob\*
43
complement system
Complement proteins enable antibodies to remove pathogens
Activated by antigen-antibody complexes
Can cause cell lysis of antibody coated cells (e.g., bacteria)
Can coat antigen and aid in phagocytosis, clearing from body
Also promotes histamine release and inflammation
44
Antibody generation and diversity
Genetic mechanism involving DNA recombination gives antibody diversity
Encode antibody in DNA with three pieces
Have lots of different versions for each piece
Mixing and matching gives lots of combinations (e.g., 100 × 500 × 1000)
Each combination is specific for a different antigen
Similar process generates different T cells
45
T lymphocytes
T cells are generated in the bone marrow and migrate to the thymus for maturation
Each T cell has only ONE type of T cell receptor (TCR) on its surface
Each T cell is specific for one antigen
Two T cell types, helper and killer
Cell-mediated immunity
46
T cell activation
Pathogen-infected cells display pathogen antigens on their cell membrane
Helper T cells is activated when it “sees” foreign antigens on cell surface
Activated T cell proliferates and produces cytokines
Helper T cell activates B cells and killer T cells with cytokines and cell interactions
Killer T cell is cytotoxic, can kill cells with ONE specific foreign antigen
Killer T cell “sees” pathogen infected cell, gets a second signal from helper T cell
Activated killer T cell sees foreign antigen on infected cell surface and kills
Memory cells for all T varieties: helper T, cytotoxic T
47
Killer T cells
Killer T cell is cytotoxic, can kill cells with ONE specific foreign antigen
Killer T cell “sees” pathogen infected cell, gets a second signal from helper T cell
Activated killer T cell sees foreign antigen on infected cell surface and kills
born with repetoire of whole different receptors, with variable regions which really differ from each other and have capacity to bind to whole range of pathogens\*\*
48
Memory cells for all T varieties:
=helper T, cytotoxic T
also for B cells, so three types memory cells!\*
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Major Histocompatibility complex (MHC)
MHC is a cell surface protein
Critical for leukocytes to “see” foreign antigens
Class 1 MHC: present on most cells, recognized by CD8 on cytotoxic T cells
Class 2 MHC: present on antigen-presenting cells, like macrophages, and recognized by CD4 on helper T cells
Each person has a (relatively) unique set of MHC genes
50
Class 1 MHC
present on most cells, recognized by CD8 on cytotoxic T cells
51
Class 2 MHC
=present on antigen-presenting cells, like macrophages, and recognized by CD4 on helper T cells
52
Lymphocyte homing
Cytokines act as signals for lymphocytes to home in on an infection
Interleukins signal between lymphocytes
53
secondary immune response
Second exposure to antigen elicits rapid and robust immune response
Memory B and T cells remain after first exposure
Rapid expansion of specific B and T cells confers immunity
Accounts for immunity to certain diseases (e.g., chickenpox)
More antibodies, higher affinity for antigen
really when the memory cells are called to do their thing!
- get a faster and more robust immune response, this accounts for our immunity to certain diseases once we have had them can ammount such a fast response so do not get sick the second time we are exposed\* very interesting thing seeing in real time with COVID\< some diseases get once and memory cels are so strong that you will never get that disease again in your life, other things where that is not true soo much\* in theory can be such a robust response never get sick again from that in your life, can last 10-20 years but not forever\*
54
acquired immunity: active
**Active immunity results from exposure to antigen or vaccine**
**Active immunity is long lasting and has memory**
-basically anything situation in which you have memory cells, can activately make memory cells you need nad active cells need to fight pathogen in future; one way to get active ommunity is to have an infection\* if get measles as a kid, vaccines etc also give ppl active immunity, giving them a chance to build memory cells without having to suffer through the whole illness\*
55
acquired immunity: passive
**Passive immunity results from acquisition of antibodies from another source**
**Passive immunity protects against pathogens, but is not long lasting**
Baby obtains antibodies from mother’s milk
Someone gets an injection of gamma globulin blood fraction
- ex breast feeding great example of this, lots of antibodies in mother's milk that gives ppl's passive immunity, great protection while antibodies are circulating, but antibodies are just proteins and will not last that long, can circulate for a few weeks but not lifetime protectioN!! no memory cells so baby still has to learn how to make antibodies itself\*
medically valuable when we talk about ppl getting convalescent serum trying to give patients antibodies from other patients who have recovered from the disease, still helpful\* thats big strategy endorsed by world health organization for ebola, world health organization was suggesting taking blood from people that had ppl who had recoverd from Ebola, very tricky to be advocating for blood transfusions in africa talked about blood supply but some of the american providers who came back handle americans came down with ebola doing work in africa, network around them where they were sharing blood, donating blood to help the next wave of people\*
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Vaccines 1
* **Vaccines are often attenuated or killed pathogens**; need to give someone exposure to do make meory cells, go through a whole fire drill even though there isn't actually a fire, so the idea is to spur all of those steps to take place, the traditional way of doing that is to expose someone to a dead version of the pathogen\* dead version of bacteria that causes whooping cough, or a very weakened version of the virus\*
An attenuated vaccine is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable. Attenuation takes an infectious agent and alters it so that it becomes harmless or less virulent. These vaccines contrast to those produced by "killing" the virus.
* **Attenuated/killed pathogens elicit specific B and T cell responses**
* **Attenuated/killed pathogens are safe**
* **Can generate an attenuated virus by passing it through tissue culture or another animal**
* **Purified or recombinant protein from pathogens are also used**
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ABO blood groups
ABO blood antigens are encoded by a single locus, expressed on RBC surface
Four blood types: A, B, AB, O
IA = A allele at locus yields A antigen = type A blood
IB = B allele at locus yields B antigen = type B blood
i = O allele at locus yields no antigen = type O blood
A and B alleles yields both A and B antigens = type AB blood
Antibodies are present for non-self antigens (e.g., type A blood has anti-B antibodies)
- three alleles at this locus, A, B and O, ex. of two more alleles for particular genetic locus\*; Ia and IB are both dominant, co dominant alleles and both dominant to little i\*
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Type AB blood =
= UNVERSAL ACCEPTOR (no antibodies to A or B)
person has both A and B so both would not be recognized as foreign\*
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Type O blood =
= UNIVERSAL DONOR (O blood cells lack A and B antigens)
- type O blood can be recognized by everyone, wouldn't trigger any other type to make antibodies\* if a markers on blood cells, but exposed to B make antibodies against B, anything not native to you you will make antibodies against\*
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A and B
A and B alleles yields both A and B antigens = type AB blood
Antibodies are present for non-self antigens (e.g., type A blood has anti-B antibodies)
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IA =
= A allele at locus yields A antigen = type A blood
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IB
= B allele at locus yields B antigen = type B blood
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i =
= O allele at locus yields no antigen = type O blood
image of O- no Rh factor!
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ABO transfusion with wrong blood type...
Transfusion of wrong blood type will lead to reaction with antibodies
Reaction with antibodies leads to clumping = agglutination
Agglutination will lead to histamine release, vasodilation, shock, and death
For donor blood, centrifuge cells to remove donor antibodies
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aggulination 1
=Reaction with antibodies leads to clumping
Agglutination will lead to histamine release, vasodilation, shock, and death
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Blood type and blood groups chart
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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
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transplants and immunosuppression
MHC loci are highly polymorphic- plants flag poles, if cells have been infected by a virus\* but fact we all have unique set of MHC genes and unique set of markers therefore on surface of cells that is actually how our immune system identifies self versus nonself\*- so its really about MHC genes and MHC proteins\* why when we are getting a transplant, the absolute ideal would be to get transplant from identical twin with matching MHC\* so rarely possible, ppl talk about trying to find a good match btw donor and receptient, good match is dependent on how much of MHC is similar\*- what physicians are looking at quantiatively, MHC genes are big but certain loci of MHC get matched or paired how similar are they between receptive donor and receptient\*
Each human being has a unique combination of MHC genes
Only identical twins have identical combinations of MHC genes
Identical twins can provide 100% compatible transplants
In non-identical transplants, closet match is better
Donor tissue is recognized as foreign and triggers an immune reaction = rejection
Immunosuppressive drugs allow transplants (block T cell activation & proliferation)
Immunosuppression results in higher susceptibility to infection
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self vs. nonself, autoimmunity
* Normal immune system only attacks foreign antigens
* But, all kinds of B and T cells are born (can recognize self and non-self antigens)
* Self-reactive B and T cells are eliminated by cell suicide (apoptosis)
* Defects in suicide process can lead to autoimmunity, if issues with that process, process of apoptosis didn't work well may still be cells like B cells that can generate antibodies that attack the bodies own cells\* one way to get autoimmune diseases\*
* Autoimmunity also triggered by mimicry (e.g., bacterial antigen similar to host protein)
* Perfect autoimmune system only attacks foreign cells and great at differentiating, being able to tell when an unknown is a pathogen or not but we also said that we are born with lots of different kinds of B and T cell receptors produced through genetic recombination mixing and matching, Y shaped receptors on B cells all variable regions made through process of shufflign DNA through devleopment and that could randomly generate some receptors i.e. future antibodies that may bind to something on body's own cells, maybe MHC or somethign definitely don't want so early in development self reactive B and T clels supposed to be represse dand autopsosd, killing off the ones that might react against the bodies own tissue\*
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allergic reactions
Allergic reactions = hypersensitivity to immune reaction, IgE mediated
* Allergen causes mast cell activation, histamine release
* Histamine release promotes vasodilation, exit of plasma into interstitial fluid
* Severe allergic reaction can lead to circulatory shock
* Can rescue with epinephrine, which promotes vasoconstriction
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ELISA Assay
**_E_**nzyme **_L_**inked **_I_**mmuno**_S_**orbent **_A_**ssay
* 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
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helper T cells like...
Paul Raver need to call attention to B cells and killer T cells!
immune cells have Class 2 MHC\*\*\*
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acellular vaccines
1. take proteins form surface of bacteria or virus to deterime which parts of bacterial or virus surface genrerates best immune response; epitophes part of antigen immune systemr eally responds to and expose ppl to a cocktail that exposes just those proteins\*
2. those vaccines tend to produce fewer side effects, but dont necessarily confer as long lasting immunity\*
3. think about what on this virus would immune system recognize, think a bout what is on the surface will be seen by immune system and trigger immune system and present immune system with those paritcular triggers
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whooping cough case study for acellular vaccines
1. caused by bacterium, usually inject patients sludge of dead bacterial cells, messy brew that ppl got but has saved so many thousands and thousands of lives because it is very effective but caused such a strong immune response ppl would have in rare cases high fevers or surgers, side effects are part of what kicked off antivaccine movement in US
2. then US switched in 2000 to an acellular vaccine, just atke 3-5 proteins from the surface of original whooping cough bacterium and put that in a vaccine, and ppl make antibodies to that and that vaccine has way fewer side effects, whooping cough outbreaks- the real reason huge whooping cough outbreaks was because some of those kids\* kid who got that vaccine born in year 2 thousand when they were 15-17 and childhood shoosts wore off huge outbreaks on college campuses, so part of that is the antivax propaganda but part of it was the not working anymore
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PFizer and Moderna mRNA vaccine
1. mRNA so reactive, so unstable, so hard to deliver, why storage requirements
2. all because of OH group\* why ppl need ot buy these crazy cold refridgerator units, when someone receives vax own cells make protein, have antibodies and all the subsequent things
3. research litearture- dna vaccines another idea out there make mrna, protein, and immune reaction against it, mRNA way safer, dna can integrate weirdly cause cancer, ppl doing those experiments know all of that can't get very far, issue is always mRNA is so unstable have to start with dna instead in order to effectively deliver the nucleic acid, but last year has proved that isn't true\* we do not have reverse transcriptase only if infected with HIV, HIV brings its own reverse transcriptase, a tool HIV needs ot complete its own life cycle\* our host cell cannot provide that\*
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ex of codominance
blood type- person expresses A and expresses B as markers on surface of red blood cells, so they would be Ia and Ib\*
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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, i**ts 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-\*
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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\*
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transplants and immunosuppression 2
* if get kidney have to take immunorepressant drugs for their rest of their life anyway becuase their immune system will attack the transplanted organ if have different MHC
* why geting kdiney transplant also means having to be on drugs that suppress immune system forever, suppressing immuen system can make person much more susceptible to a million other infections
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autoimmunity 2
* sometimes you can be infected with a bacterial cell that has some protein on its surface, that is similar to a protein in eukartoic cells or on surface of eurkaryotic cells, lots of things conserved in nature, somehow something on surface of htis particular abcterium makign antibdoies against is just a little too similar to something on own cells; all antidboeis made ot attack bacteiral cell are made to also hit our own cells
* ties into the idea that if we mount a very large or strong immune response to bacterial or viral infection and just have usch a huge number of antibodies, evne if cross reactivity with our own cells isn't very high, liek those antibodies are really suspecific and well tooned to attacking our own body cells, fact so many fo them even if weak or lose binding in aggregate do some damage to our own cells
* so ppl who think about autoimmunity risk whne ru system is in overdriv efor any region, another reason inflammation thought ot be so dangerous, create conditions where body can be our own worst enemy against it\*
* ex of ppl getting long covid that is persisting months and months after original infection, some cases its becuase virus itself damaged someone's heart or kidney, but in other cases some kind of autoimmune thing going on where immune response to virus became so strong that some of it ended up directed against cells of host body in a way that is causing damage\*
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allergic reaction 2
* immune response to someting not in and of itself dangerous but its the immune response that causes problems for us! cat hair, piece of shrimp, peanut, nothign inherently dangerous abotu that for us, but if our immune system for whatever reason are sensitive and amoutn huge immune response that immune response can cause us real harm\*
* **talked about that in terms of histamine causing vasodilation, circualtory shock, if you have massive vasodilation, fluid leaves the blood vessels, blood pressure crashes that is circualtory shock and tht cna be fatal**
* epi pen- causes constriction of peripheral blood vessels, why using epipen early in one of these early reactions can be life saving causes blood vessels ot constrict and then all that lfuid doesnt leave the blood stream\* why ahve ot administer an epi pen early once there ha sbeen massiv efluid loss from vessels and person's blood pressure has crashed maybe other things a person can do if in ER but its too late to use an epi pen\*
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ELISA ASSAY 2
* allows you to detect how much antigen is in a sample!
* use labeled antibodies to detect antigens, can have antigen sticking to substrate, use antibody to detect hte antigen, fluorescently labeld antibody\* so basically idea is that you are using antibody to detect antigen, bottom row showing a slightly fancy, more accurate and expensive wy to do this, use antibody on bottom, allow antigen to bind, allow more fluorescently labeled antibody to bind poitn is tryign to get fluroescently labeled body to bind to anigen to gage how much antibody is antigen is present in sample\*
* if sample and want to know if high concentration of antigen and low cocnentration of antigen--\> can stick sample onto substrate\* so antigen on the substrate\* and then you use antibodies specific for that antigen, wash some antibodies over the antigen, and let antibody bind ot antigen\* then based on how much binding has occured you can say how much antigen you had\* reason can detect how much binding there is is make antibodies fluorescent, so if more bind get stronger fluroescent signal\*
* bottom row is really the same concept, instead of just putting antigen onto substrate put down layer of antibody first\* and then you have antigen come on\* then bring more antibodies so sandwich surrounding antigen\*
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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.
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Q3. Which of the following statements concerning macrophage function is correct?
a. each macrophage recognizes one and only one antigen
b. macrophages originate in the yellow marrow of bone
c. the macroiphage engages in endocytosis of many pathogens
d. mature macrophages differentiate into plasma cells that secrete antibody
**c. the macroiphage engages in endocytosis of many pathogens**
macrophages are nonspecific they considered part of innate immune system, nonspecific all purpose garbage go around and chop things up cells, in contrast to adaptive parts of immune system b cells adn t cells that do recognize and interact with only specific antigens\*
remeber WBC come from red bone marrow
fat is in yellow bone marrow
a. each macrophage recognizes one and only one antigen= no false they eat everything!
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Q10 Which of the fllowing is NOT a true statement?
a. The antingen present on the protein coat of a virus may shift over time as a result of mutaiton
b. Each B cell can adapt to recognize a variety of foreign proteins
c. an antigen that binds to a B cell causes that B cell to produce clones
d. All of the above are true
a - THIS IS a strategy some viruses have where they have a group of genes that codes for surface proteins, and when they are under selective pressure and immune system has gotten really good at responding to a certain version of the virus they can switch it up\* like putting on a disguise, can start making surface proteins using different genes and then their surfaces do not look familiar to the immune system anymore, often a certain drug is being used to fight a pathogen the pathogen can sort of respond by switching up what it looks like\* big part of how viruses evolved to evade immune system\* where selection pressure is where virus mutates\*
## Footnote
**b no we have other ones to adapt and recognize others, but one b cell reocniges one angtien, answer is b!!! ONLY ONE that is why we have so many that regonize so many**
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Q15. Antibodies would be least likely to:
a. neutralize secreted bacterial toxins
b. lyse infected host cells
c. block receptors on teh surface of a virus
d. cross-link antigenic molecules
b. lyse infected host cells
## Footnote
cross linking= means grab one and grab another in a blob, big thing that antibodies do
if think abotu how there are two binding sites one antibody can bind two molecules of antigen can grab one on each site of arms cannot be free to float away, dumb down image what this leads to is creating a blob of antigens a whole bunch of antibodies are holding down a whole bunch of antigen molecules, then macrophages come and eat it all up, so basically creating a cluster, clump of antigen molecules that will be easier for macrophages to come get rid of /however antibody binding to antigen, and holding onto it and one antibody is holding tow antingens\* so they become a clump and then get another antibody that can combine to two antigens so start to get a blob\*
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Q18. Which of the following is NOT true of cytotoxic T Cells?
a. they bind to an infected cell
b. by lysing the host clels, they may make pathogenic molecules more vulnerbale to cells of the humoral system
c. They bind to bacterial cells that are dissovled in blood plasma
d. they can destroy more than one cell before dying
c. They bind to bacterial cells that are dissovled in blood plasma
## Footnote
everything else is true, cytotoxic t cells kill more than one cell before dying
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antigens 2
## Footnote
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
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one antibody-antigen complex has.....
one antibody has 1 binding type specific for the same antigen\*
one natibody has to have one binding shape specific for one antigen and both shapes have to be hte same for that specific natibody bindign site
