Term
|
Definition
| different species - like mice and men |
|
|
Term
|
Definition
| same species, different alleles, like people (except for identical twins) |
|
|
Term
|
Definition
| all the same alleles (except x & y) - like identical twins |
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|
Term
|
Definition
| same individual - like a how a tissue relates to you |
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|
Term
|
Definition
| different at a small region - small group of genes - happens b/c of a crossover event |
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Term
|
Definition
| different at 1 gene mutation (mutation at 1 gene) |
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|
Term
| describe innate immunity - specificity, response, function, prevalence |
|
Definition
- 1st line of defense,
-broadly specific - recognizes patterns but not specifics (like a car vs truck)
- response is the same every time, although it can respond differently to different threats
- present in every healthy person
- alerts the adaptive system |
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|
Term
| Adaptive immunity - rapidity of response, recognition specificity, cells produced |
|
Definition
- slower to respond, but the 2nd exposure is much more rapid
- very specific
- activation creates memory and effector cells that do the killing |
|
|
Term
| what are the major players in innate and adaptive immunity? |
|
Definition
innate = barriers (skin, etc), phagocytes, complement, NK cells
adaptive = T cells (effector), B cells (ABs) |
|
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Term
| What are the 2 types of adaptive immunity? Describe them. |
|
Definition
humoral -
mediated by ABs made by B cells
extracellular response - the ABs eliminate microbes and toxins by binding to them and marking them, but can't get into the cell itself
cell-mediated - mediated by T cells - eradicates intracellular microbes by getting into infected cells |
|
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Term
| Name the anatomic and physiological barriers of the innate defense system |
|
Definition
anatomical - skin (mechanical), mucous membranes (normal flora compete with microbes for attachment, mucus traps foreign objects, cilia propel upward)
physiological - low pH, dry, salt, lysosomes, interferon, complement, phagocytic barriers, inflammation barriers
digestive- stomach acid (low pH) |
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Term
| How do some microorganisms get around the innate defense |
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Definition
| surface modifications like fimbriae or pili - like gonorrhea - allows for firm attachment to cells |
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Term
| How does the innate defense system respond if an invader gets past the external barriers? |
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Definition
| Different responses for different invaders - the cells of innate defense have receptors that recognize common patterns in microbes - they produce chemicals that signal the presence of danger - which type indicates the nature of the threat and stimulates the appropriate response |
|
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Term
| What are cytokines? Who makes them? Give 3 examples. |
|
Definition
Chemical signals that are released by a cell that affect another cell of the host defense(usually)
- the cells of the host defense make them
- IL's, lymphokines, monokines |
|
|
Term
| What is an opsonin? Function? Example? |
|
Definition
a serium protein that normally circulates in the inactive state, gets activated
- it coats the particle and acts like a handle to make it easier for a phagocyte to eat
- an example is complement |
|
|
Term
| What are the classic signs of inflammation? What is the overview of inflammation? |
|
Definition
| [image]
- increased vascular dilation, increased vascular permeability, accumulation of leukocytes |
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Term
| Describe T and B cells - what they respond to, have on their surface, other characteristics |
|
Definition
- all ASRs on a cell are the same - they are the basis for AG specificity & the binding of AG is the 1st signal needed for activation of the immune response
B cells - express membrane forms of Ig (AB) on their surface - these recognize soluble AG or ones bound on the surface of cells - B's recognize intact AG
T cells - express ASR - only recognize AG bound to an MHC on APCs |
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|
Term
| What are the 3 types of T cells |
|
Definition
CD4+ - Th - helps activate B cells to make ABs, helps phagocytes destroy microbes
CD8+ - Tc - kill cells harboring microbes
NK - involved in innate immunity - no CD, but they do kill cells |
|
|
Term
| What are the microbes, responding lymphocytes, effector mechanisms, and functions of the 2 types of adaptive immunity? |
|
Definition
|
|
Term
| How do you transfer cell mediated and humoral immunity? |
|
Definition
humoral - give a non-immune animal the serum from an immune animal
cell-mediated - give the non-immune animal the cell fraction of the blood |
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|
Term
| What happens during B cell activation? |
|
Definition
The naive B cell sees an AG that matches its AB - it binds, causing the B cell to proliferate and differentiate into memory cells and plasma cells
plasma cells make ABs in a form that can be secreted, they have little surface bound AB |
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Term
|
Definition
1) bind to AG and link several together, making them easier to phagocytize
2)activating the complement system
3)can neutralize toxins or foreign material by coating them so they can't bind to host cells |
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|
Term
| What happens during T cell activation? |
|
Definition
The naive T cell recognizes an AG bound to an MHC. Th cells interact with AG-MHC II, which activates them-->they release cytokines, which
1) activate B cells
2) activate Tc cells and macrophages
the Tc cell under the influence of the cytokines, recognizes the AG-MHC I complex and proliferates and differentiates into cytotoxic cells, killing the infected cells |
|
|
Term
| Describe active and passive immunity. |
|
Definition
Passive -
- maternal immunity
- short-lived - transfer of pre-made components (gamma globulin)
- your body doesn't actually mount a response, you're getting the response pre-formed
-can give gamma globulin shots to boost immunity
Active
- get through natural exposure or vaccines
- long-lived, sometimes lasting a lifetime |
|
|
Term
| Describe clonal selection theory. |
|
Definition
How B and T cells are made and "educated."
- l'cyte clones mature in generative organs (bone marrow, thymus) without any exposure to AGs
- mature l'cyte clones go to lymphoid organs and are exposed to a variety of AGs
- what the ASR binds to is a random event
- during maturation, cells that don't recognize AG or can't distinguish self are destroyed
- AG binding causes them to proliferate and differentiate - the memory cells created ensure a better response to the next exposure |
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|
Term
| Name and describe the 5 phases of adaptive response. |
|
Definition
Recognition - naive cells locate and recognize AG
Activation - clonal expansion - proliferation and differentiation
Effector - effector cells and their products kill the microbes
Decline - most of the activated cells die by apoptosis
Memory - surviving memory cells are left |
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|
Term
| What does the curve look like for 1st and second exposures in adaptive immunity? |
|
Definition
| The 1st response is low and has a lag time when the cells are proliferating and differentiating - the 2nd response to the same AG is much bigger b/c you have memory cells left from the original exposure (like 10-20 P&D instead of 1) |
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Term
| Are the innate and adaptive systems independent of each other? Give examples. |
|
Definition
the 2 are not separate - they interact
- microbe/macrophage interaction (innate) give off soluble proteins that alert the adaptive system - m'phages can also secrete cytokines that can direct adaptive reponses
- the adaptive system produces signals that enhance the innate system - i.e. activated T cells can secrete cytokines that increase m'phage's ability to kill microbes or can mark microbes for attack by complement |
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|
Term
| What characteristics are necessary for a cell to be an AG presenting cell? What types of cells are typically APCs? |
|
Definition
have to express MHC II molecules on their membranes AND be able to deliver a costimulatory signal to Th cells
- macrophages/monocytes, B cells, and dendritic cells |
|
|
Term
| Innate response - how does it respond? What line of defense is it? What happens when it does and does not work? |
|
Definition
- Responds the same way every time to a particular insult, but can respond differently to different insults
- 1st and 2nd lines of defense
- does work: no disease
- doesn't work: disease, induction of adaptive system |
|
|
Term
| Adaptive response - how does it respond? what happens if it works? Fails? |
|
Definition
- Response is slow the 1st time and faster the second - very specific response to a particular AG
- 3rd line of defense
- works: recover, resistant to re-infection
- fails: death |
|
|
Term
| What are the 2 signals needed for l'cytes to respond? |
|
Definition
1) AG binding
2) B cells - signal from innate system. T cells - costimulatory signal from APC |
|
|
Term
| Give the relative binding strengths of a phagocyte to a microbe when the following are present: nothing, complement C3b, antibody, AB and complement. |
|
Definition
- nothing - binds ok
- C3B ++
- AB ++
- AB+C3b ++++
works better with both |
|
|
Term
| What happens in hypersensitivity? |
|
Definition
| innappropriate response to an innocuous agent - like allergies |
|
|
Term
| What happens in autoimmune disorders? |
|
Definition
| you respond to self - can't distinguish self from non-self - special case of hypersensitivity |
|
|
Term
| What happens to grafts (normal reaction)? |
|
Definition
|
|
Term
| What causes immunodeficiencies? |
|
Definition
| Missing or low amounts of a particular component |
|
|
Term
| What cell do all cells of the immune system originate from? |
|
Definition
|
|
Term
| Name all the cells that are generated from the myeloid and lymphoid progenitor cells. |
|
Definition
|
|
Term
| Give some characteristics of stem cells - regneration, self replication, differentiation. |
|
Definition
the stem cell can self replicate - a true stem cell can turn into anything, a hemopoeitic stem cell can turn into any type of blood cell
- as the cells mature and become committed, they lose the ability to self-replicate and the ability to become other things |
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|
Term
| What are progenitor cells? What does progenitor committment depend on? |
|
Definition
these are cells that have lost the self renewal capacity and are committed to becoming a particular cell lineage, like eosinophil progenitors, etc
-progenitor committment depends on the acquisiton of responsiveness to particular growth factors and cytokines |
|
|
Term
| What is a colony forming unit? A colony stimulating factor? Examples of important CSFs? |
|
Definition
CFU - a precursor cell; the "cell that will become something"
CSF - pushes cells in a particular direction - cytokines
- acidic glycoprotein - has the ability to induce formation of distinct hematopoeitic stem cell lines
- erythropoeitin - cytokine that regulates terminal development and production of RBCs |
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|
Term
| Starting the bone marrow stem cell, go through the differentiation of macrophages. |
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Definition
| Stem cell-->blood monocyte-->tissue macrophage-->microglia, Kupffer cells, alveolar macrophages, osteoclasts |
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Term
| When macrophages are activated, what happens to their function? |
|
Definition
| -increases their ability to do things - better phagocytic ability, better able to kill ingested material, better able to activate T cells, secrete cytotoxic proteins, and MHC II, therefore making them better APCs |
|
|
Term
| What are the monoblast and promonocyte stages? Why is knowing lineage importantin lymphomas and leukemias? |
|
Definition
monoblast - 1st committed stage to only mononuclear phagocytes
promonocyte - 1st stage identifiable as a mononuclear phagocyte (found in bone marrow)
- knowing lineage is important b/c it can give you info for treatment - aggressiveness, etc |
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|
Term
| Characteristics of the monocyte/macrophage: function, stickiness, movement. |
|
Definition
function: phagocyte, APC (enhanced by exposure to cytokines)
stick: will stick to glass and plastic (useful for separating)
movement: don't swim - they crawl - can be directed by chemotaxis |
|
|
Term
| Describe phagocytosis, including the enzymes |
|
Definition
bacteria is eaten by phagocytosis, the phagosome fuses with the lysosome to become the phagolysosome
- in the PL, there are 3 enzymes that get activated: phagocyte oxidase (converts O2 to superoxide anion and free radicals), inducible NO synthase (catalyzes conversion of arginine-->NO, and lysosomal protease- breaks down microbial proteins
- the peptides get associated with MHC II molecule
-phagolysosome fuses with the membrane again and releases the MHC-AG, which is now on the surface |
|
|
Term
| Name 7 things that are on the surface of most monocytes/macrophages |
|
Definition
-Fc receptors - grabs AB that has grabbed something else (responds to Ig)
- complement receptors
-MHC II
-cytokine receptors (IL2R, IL4R, IFNgamma)
- pattern recognition-MFR (mannose fructose receptor-TLR
-AG markers
-biochemical markers - peroxidase and nonspecific esterase |
|
|
Term
| How do you identify surface markers that aren't associated with function? |
|
Definition
| with an antigenic marker - it's like a hood ornament - allows distinction between cells |
|
|
Term
| Define (FNC def) APC. List the APCs and who they present to. |
|
Definition
- facilitates contact betwene the AG and ASR on the lymphocyte
-dendritic cells - initiation of T cell response
- macrophages- initiation and effector phase of CMI
-follicular dendritic - display AG to B cell in humoral immune responses |
|
|
Term
| Why do we use macrophages as APCs experimentally? |
|
Definition
| they are phagocytes, hace MHC class II, secretes IL-1, and B7 |
|
|
Term
| Where are dendritic cells found? Are they good APCs? |
|
Definition
-aka Langerhan's cells in skin, found in tissue and lyphoid organs
- they are better APC b/c they express high MHC II and co-stimulatory factors - the immature ones eat and process AG, the mature ones present to T cells |
|
|
Term
| What are the characteristics of follicular dendritic cells (surface, who they present to) |
|
Definition
| low in MHC II, high in CR and FcR, present to B cells |
|
|
Term
| What are the characteristics of B cells in terms of cell markers, who they present to |
|
Definition
| high in MHC II, present to T cells |
|
|
Term
| Give the family tree for dendritic cells, starting from the hemopoeitic stem cell |
|
Definition
SC-->myloid and lymphoid progenitor
myloid-->Langerhan cell, interstitial dendritic and monocyte
monocyte- myloid dendritic
lymphoid- lymphoid dendritic |
|
|
Term
| Name the 3 types of granulocytes, What's the other name for them? WHat is this based on? |
|
Definition
Eosinophils, basophils, neutrophils
-polymorphonuclear leukocytes
-based on staining characteristics of granules |
|
|
Term
| Neutrophils - life span, arrival order, % of WBC, % of granulocytes |
|
Definition
short life span - circulate 7-10 hours, migrate into tissues and live a few days
-usually 1st to arrive - a lot is a sign of inflammation
-45-70% of WBC, >90% of granulocytes |
|
|
Term
| What are primary and secondary neutrophilic granules made of? What do they fuse with? |
|
Definition
1)hydrolase, lysozyme (break glycosides of cell wall), myeloperoxidase
2)lysozyme, lactoferrin (bind iron), collagenase |
|
|
Term
| How do neutrophils move? WHat is their function? stickiness? |
|
Definition
-they are motile, don't swim - respond to chemotactic factors
-don't stick to plastic or glass
- phagocytize, but don't need an opsin, for immune phagocytosis they have FcR and CR
- have lots of enzymes all ready to go |
|
|
Term
| Eosinophils - how do they phagocytize, what do their granules contain? |
|
Definition
They are FcR+, and CR+, they degranulate - dump their granules onto large targets (i.e. parasites)
- the granules contain enzymes, peroxidase, and histaminase (damage parasite membrane) |
|
|
Term
| Basophils - surface markers. WHat do their granules contain? |
|
Definition
Surfaces have high affinity IgE receptors and CR
- granules have histamin and heparin |
|
|
Term
| Mast cells - relative size, function, nuclear morphology, where are they found, surface receptors? |
|
Definition
- big
-function similar to basophils (allergies)
-mononuclear, not polymorph
-found in tissue
-IgE receptors |
|
|
Term
| Platelets - origin, cell or not a cell, functions |
|
Definition
- come from megakaryocytes
- not nucleated - a cell fragment
- adhere to endothelial surfaces and help form clots, release material important in regulating inflammation |
|
|
Term
| Endothelial cells - origin, location, function |
|
Definition
-not myeloid or derived from HSC
- found in blood vessels (lines)
- during inflammation, they swell, serving as "bus stops" as a place for immune cells to leave circulation |
|
|
Term
| Describe apoptosis and why it doesn't lead to an immune response. How is this different from necrosis? |
|
Definition
the cell sheds apoptotic bodies thatcontain the intact organelles, the cell never spills "guts", so it doesn't provoke an immune response - the bodies get phagocytized
- in necrosis, the cell spills its guts, provoking an immune response |
|
|
Term
| Name the 3 types of lymphocytes and their main functions. |
|
Definition
T cells - cell mediated immunity, make cytokines
B cells - humoral immunity - make ABs
NK cells - innate immunity, don't have ASR |
|
|
Term
| Name the AG and effector functions of the (5)lymphocytes |
|
Definition
|
|
Term
| Describe the morphology of lymphocytes. |
|
Definition
| Can be large or small, T -some are granular, B no granules, NK usually granular |
|
|
Term
| How do you detect surface markers on lymphocytes? |
|
Definition
| Use ABs - they are hard to separate -they both have a common AG,but they also have a specific AG that you can determine using ABs |
|
|
Term
| CD - what are they? Specific or nonspecific? |
|
Definition
a CD is the name of the AG on the T cell - particular CDs tend to associate with particular types of cells, but how specific depends on your method of detection - very sensitive method, you see one overwhelming type of CD, with lots of others, not very sensitive methods - just see the 1 CD - so it's really an amount thing
- CDs can combine like CD 18 and 11a,b,c |
|
|
Term
| Describe the ASRs on T and B cells - what are they composed of, what are the functions of these parts? |
|
Definition
- they are the most important feature for distinguishing lymphocytes
- T cell: antigen specific binding part (hooks AG)- TCR - signal transducing part (signals that they've caught an AG)- CD3 (made of several proteins)
- B cells- ASB-immunoglobulin (AB), transducer - Ig alpha, Ig beta,CD79a,b |
|
|
Term
| What are the 2 types of T cells (based on ASRs)? WHat do these give rise to and where are they found? |
|
Definition
-TCR-1 gamma/delta (protein) - few in circulation, mostly in mucosal surfaces and skin - broadly reactive with common microbial products
-TCR-2 alpha/beta- most common in circulation - gives rise to CD4 (MHC II restricted/Th cells) and CD8 (MHC I restricted/Tc cells)
-CD4 gives rise to TH1 (IL2, IFN gamma)-these are cell mediated- makes a cytokine profile that suppors inflammation and activates mainly certain T cells and macrophages- and TH2 - humoral - activates mainly B cells and immune responses that depend on ABs (IL 4,5,6,10) |
|
|
Term
| With regard to MHC restriction and function, what follows what? |
|
Definition
| Restriction doesn't follow function - the Th are helpers who are class II restricted, not Th b/c they are class II restricted |
|
|
Term
| What are common surface markers on B cells? |
|
Definition
| -ASR - SIg (alpha and beta), MHC II, FcR (receptor for IgG), CR, CD40 - molecule that acts on the CD-40 ligand on the surface of Th cells, B7 |
|
|
Term
| What do NK cells recognize? What types of cells does it kill? What inhibits it? Do they phagocytize? |
|
Definition
-recognize a decrease in MHC I, since all normal cells express it, also recognize antitumor or antiviral ABs on the surface - if the tumor cell has AG's displayed that the body has ABs for, they will coat the tumor cells
- kills tumor cells and virally infected cells
- MHC I inhibits it
-don't phagocytize |
|
|
Term
|
Definition
|
|
Term
| What is the logic behind a virally infected cell not producing MHC I? |
|
Definition
| since the MHC-1 would present the virus and therefore the cell would be killed by Tc cells, the logic is to make less so as to escape the Tc cells, but NK's detect a lack of MHC-I and kill them anyway |
|
|
Term
| What do NK cells produce? |
|
Definition
|
|
Term
| Morphologically, what do NK cells tend to be? What about their surface markers? |
|
Definition
| tend to be large granular lymphocytes, there are few absolutely specific markers - they share many markers with T cells - NKp30, NKp44, NKp46 - these are glycoproteins |
|
|
Term
| Describe Antibody Dependent Cellular Cytotoxicity - what does it, characteristics (6) |
|
Definition
Lymphoid killer cells
- not phagocytic
-the AB (on target)provides specificity
-FcR provides the link (on K cell)
-may be NK not acting like NK
- sometimes they're T cells
-nonlymphoid cells can do it - eosinophils, neutrophils, macrophages |
|
|
Term
| What are lymphoid activated killer cells? |
|
Definition
| Cells that kill in response to in vitro exposures to high concentrations of lymphokines like IL2 or IFN gamma - potential cancer treatment |
|
|
Term
| What does activation mean to lymphocytes and how is this different than macrophage activation? |
|
Definition
| means proliferation and differentiation - different b/c macrophage means it's able to do something better |
|
|
Term
| How are l'cytes activated without AG? |
|
Definition
| mitogens - trick the cell into thinking its caught an AG - has a lectin that binds to a particular carb and an AB against the receptor anti-Ig, anti Cd3 |
|
|
Term
| How does activation lead to proliferation and differentiation in l'cytes |
|
Definition
| the signal transducer turns on certain genes in the nucleus which lead to P&D |
|
|
Term
| How can you tell when l'cytes are proliferating? |
|
Definition
| -get bigger, cytoplasm gets bluer (more RNA) and more of it, nucleus larger and less dense, nucleolus produces RNA, get mitotic figures (measure by radioactive thymidine uptake) |
|
|
Term
| What do B cells differentiate into? |
|
Definition
| memory cells and plasma cells- make lots of soluble AB, not lot of SIg, short life span (days) |
|
|
Term
| What are the generative lymphoid organs? The peripheral organs? |
|
Definition
Generative - where B & T cells grow up - bone marrow and thymus - free of AG interaction
Peripheral - where they're educated (bind to AG, stimulate ASR, P&D) - spleen, lymph nodes, mucosal and cutaneous lymphoid tissues |
|
|
Term
| What are the highways of the lymphatic system? |
|
Definition
| lymph vessels, blood vessels |
|
|
Term
| What is the bursa of Fabricius? How is it organized? |
|
Definition
the place in birds where B cells mature - no Bursa, no mature B cells (form in bone marrow)
- organzied into folds (plicae) and have follicles - medulla in inner part (light, more cytoplasm), outer cortex (darker, more cells) |
|
|
Term
| WHat purpose does bone marrow serve? |
|
Definition
source of stem cells for all blood cells
-AG indepedent differentiation of B cells - destroy those that can't distinguish self |
|
|
Term
| How is bone marrow organized? |
|
Definition
| Bony trabeculae, good vascular supply, reticular and hemopoeitic tissue framework, has adipose tissue |
|
|
Term
| Are there "rooms" in bone marrow for differentiation of B cells? |
|
Definition
| No, but there are clusters of different types |
|
|
Term
| What is the function of the thymus? |
|
Definition
| AG independent differentiation of T cells - kill those that can't recognize self |
|
|
Term
| Where is the thymus? Shape? Organization? |
|
Definition
Over the heart - bilobed
-has lobules, made by trabeculae that project in from the capsule, each has an outer cortex and inner medulla |
|
|
Term
| What are the ramifications of having no thymus? |
|
Definition
| no mature T cells - you'd still have immature ones |
|
|
Term
| Describe the path of thymocytes through the thymus. |
|
Definition
| They enter via blood vessels into the subcapsular space - they percolate down into the medulla, having contact with nurse cells along the way - on the way they proliferate and mature and those that can tell self from non-self leave through post capillary venules |
|
|
Term
| Why is the blood-thymus barrier important? |
|
Definition
| Keeps crap in the blood out of the thymus - important b/c the T cells are learning self from non-self - don't want them thinking that all that crap is self |
|
|
Term
| What is the purpose of HEPCVs in the thymus? |
|
Definition
| Serve as signals for T cells to get out in the absence of inflammation |
|
|
Term
| Education of T and B cells - what is the process? is AG receptor specificity random? |
|
Definition
| it is random - 1)determine which cells have functional receptors - kill those that don't 2) kill ones that react with self |
|
|
Term
| Describe the relative size of the thymus throughout life |
|
Definition
| Biggest relative to body size at birth, size increases until puberty, then it starts to shrink - this reflects a decrease in function, but it still works fine |
|
|
Term
| What is the purpose of the peripheral lymphoid organs in general and specifically? |
|
Definition
general - remove material, concentrate AG, provide an environment for components to come together for a response
spleen - immunologic filter of blood
lymph node - immunologic filter of lymph |
|
|
Term
| Where is the spleen located? What is its specialty? |
|
Definition
left side abdominal cavity under the ribs, cigar shaped
- traps and filters blood-borne AG - can respond to systemic infections |
|
|
Term
| Describe the organization of the spleen. |
|
Definition
| No lobules, just trabeculae projecting in from the capsule - supplied by the splenic artery |
|
|
Term
| What happens if the spleen is damaged (literally)? |
|
Definition
| It's like a big bag of blood - have to cut off the blood supply b/c there's no other way to stop the bleeding - the arterial and venous capillaries aren't anastomosed |
|
|
Term
| What are the areas in the spleen - describe them. |
|
Definition
white pulp - lots of WBCs
red pulp - between white pulp areas - lots of RBCs
marginal zone - between red and white-little of both |
|
|
Term
| Describe white pulp - areas, etc. |
|
Definition
| white pulp - around each splenic artery branch is the PALS - has an inner, T cell rich portion and an outer B cell rich corona (marginal zone) - in the corona you can get follicles - primary (resting) all dark, but if they are activated you get a 2ndary follicle - with a lighter center (proliferating cells) and outer dark part (rest of follicular cells) |
|
|
Term
| What happens to cause B cell proliferation in the spleen? |
|
Definition
| in PALS, dendritic cells capture and present AG to Th, these activate B cells --> B and Th migrate to primary follicles in the marginal zone, and the B cells proliferate, turning it into a secondary follicle |
|
|
Term
| What is the marginal zone - what happens here, what's there? |
|
Definition
transitional zone- lots of macrophages - more than red pulp, but not as many as white
- major area where arterial capillaries empty cells into the spleen |
|
|
Term
| Describe red pulp - location, structure, what's there |
|
Definition
Spaces between white pulp
Higher concentration of rbc
Sponge-like structure
Sinuses
- have some of every kind of cell
Cords
-structures that surround sinuses
-Lined by: Macrophages, Plasma cells, and B-blasts, Ab-producing
-easy drainage to blood |
|
|
Term
| Describe circulation through the spleen. |
|
Definition
Enter through splenic artery-->
Central arteriole
near center of white pulp area
surrounded by PALS-->
Arterial capillaries
empty cells into one of three areas:
-White pulp - a few
-Venous sinuses in red pulp - a few
-In the marginal zone - most
Both white pulp and red pulp sinuses drained by small veins - larger - splenic vein.
--cells cruise around hoping someone gives them an AG |
|
|
Term
| What do lymphatic vessels do? What is their flow pattern? What pumps lymph? |
|
Definition
collects fluid, cells, and AG from tissue
-has 1 way flow - no real pump, pressure from muscles keeps it flowing |
|
|
Term
| What are lymph nodes the site of? |
|
Definition
| the site of immune response in response to AG in the lymph - a swollen LN indicates an infection somewhere in the drainage bed of that LN |
|
|
Term
| Where are LN commonly found? How are they arranged? Where do they meet? |
|
Definition
-Concentrated where limbs attach to trunk, and around intestinal tract, and lungs
-Often arranged in series
- meet in the thoracic duct, drain into the subclavian where everyone is dumped back into the blood |
|
|
Term
| How are lymph nodes arranged (describe)? |
|
Definition
-has a capsule and trabeculae
-cortex - B cell rich area - has follicles (primary and secondary)
-paracortex - rich in T cells
-medulla - has cords
vessels - afferent (how cells come in), efferent (out), blood vessels (in) |
|
|
Term
| What is the pattern of circulation in the lymph node? |
|
Definition
Afferent lymph traverse cortex and medullary cords and collect in medullary sinus - out through efferent lymphatic
Enter through artery -> arteriole -> capillary -> venules
Post capillary venules - located in paracortical
receptors for lymphocytes which adhere and then pass through into paracortical area,
then through medulla to efferent lymph
eventual -> blood through duct to subclavian vein. |
|
|
Term
| Why does lymph leaving the LN have a lot of ABs after an infection? |
|
Definition
1)l'cytes proliferate in the node
2)blood borne l'cytes migrate into the node by passing through the HEPCVs |
|
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Term
| Why is it good that the cells are segregated (T and B) in the LN? |
|
Definition
| -provides maximum exposure to AG - gets the best response |
|
|
Term
| If you have no thymus, what happens to your lymph nodes |
|
Definition
|
|
Term
| What is MALT and where is it found? |
|
Definition
mucous associated lymphoid tissue
-Extra protection where there is a possible threat:
Gut
respiratory tree
oral-nasal cavity
urogenital tract
-Collections of lymphocytes either diffuse or organized into follicles
-mucous tissues are major sites of entry for most pathogens |
|
|
Term
| What does MALT have lots of? |
|
Definition
| plasma cells and therefore ABs |
|
|
Term
| How does the innate system protect us in the gut? (what cells involved, methods) |
|
Definition
Commensal bacteria in the gut lumen are continuously sampled by cells of the innate immune system, such as dendritic cells (DCs) and M cells.
-M cells of the gut epithelium may import bacteria into the dome region of the GALT where DCs engulf the microbes.
-DCs may sample commensals directly by prying open the tight junctions between epithelial cells and projecting their dendrites into the gut lumen. DCs present antigenic peptides from captured microbes to B and T lymphocytes either locally in the GALT, or within the mesenteric lymph nodes that drain the gut submucosa.
-Presentation of microbial antigens to B cells triggers production of a commensal-specific IgA response that prevents the commensals from straying beyond the gut mucosa where they could elicit a systemic inflammatory response. |
|
|
Term
| Describe M cells - shape, function, location |
|
Definition
M cells:
- Special epithelial cells flattened cells with no microvilli
-Found over concentrations of lymphocytes (inductive sites)
-Transports material from lumen to lymphoid tissue underneath - can activate B cells in these follicles, which become plasma cells and make IgA ABs (specialized for gut), which go back into the lumen and fight the AG
- Have pocket:
localize transported antigen
lymphocytes (B&T)
macrophages
dendritic cells - if any of these cells react with the AG, you get the above immune response |
|
|
Term
| How are MALT lymphocytes recirculated? |
|
Definition
-draining LN
-thoracic duct to blood
-HEV in mucosal tissue - activated mucosal l'cytes have a marker for them - once they leave, proliferate and differntiate, they could go to any mucous tissue, not just where they came from and now all systems are up |
|
|
Term
| What 3 main cells are associated with CALT? |
|
Definition
- Langerhans cell-Dendritic,Ag-presenting,Migrates to lymph node and present on MHC II to Th
- Intraepidermal lymphocytes:
Gamma/delta TCR - good for things that come in through the skin - most are CD8+
Keratinocytes-Skin cells
Produce cytokines that alert Langerhans and other macros that it's ok to respond |
|
|
Term
| What are the 3 layers of defense in innate immunity? |
|
Definition
-physical barriers like skin
- killing of microbes by locally produced antibiotics
-killing of microbes and infected cells by intraepithelial lymphocytes |
|
|
Term
| What does innate immunity respond to? |
|
Definition
| microbes or microbial damage only - recognizes structures on classes of microbes that aren't on host cells, like mannose |
|
|
Term
| Describe the 3 main receptors on the cells of the innate sytem, including what they respond to, what the cellular response is, and the functional outcome |
|
Definition
7TM protein-
responds to N-formylmethionyl peptides (start codon for prokaryotes), chemokines, and lipid mediators
response: increased integrin avidity, cytoskeletal changes
outcome: migration into tissues
TLR-mannose, LPS, CD14
- production of cytokines, ROIs
-killing of microbes
Mannose receptor - mannose
-phagocytosis and production of cytokines
-killing of microbe |
|
|
Term
| What are TLRs (function, what do they recognize)? |
|
Definition
| receptors for different things on the surface of professional phagocytes - different ones recognize different things - signal present of a general group of threats (i.e. sense LPS = bacteria, mannose = prokaryote) |
|
|
Term
| Who are the professional phagocytes and what do they have on them? |
|
Definition
| monocytes/macrophages, neutrophils, - have receptors for microbial structures, complement, and antibodies |
|
|
Term
| Describe what happens in phagocytosis |
|
Definition
-microbe binds to phagocyte receptor and gets engulfed into a phagosome
-phagosome fuses with lysosome, broken down into peptides by lysozymes, ROI, NO |
|
|
Term
| Name 4 functions of macrophage activation and give the molecules that are produced that lead to these outcomes. |
|
Definition
\*killing of microbes-phagocyte oxidase (ROI),NO synthase (NO)
*inflammation, enhanced adaptive immunity- cytokines (TNF, IL-12)
*tissue remodeling-fibroblast growth factor, angiogenic factors,metalloproteinkinases
*enhanced AG presentation-increased MHC molecules, costimulators |
|
|
Term
| What are the 2 types of intraepithelial lymphocytes? |
|
Definition
*TCR-1 cells with gamma/delta receptors - react with shared microbial structures
*B-1 B l'cytes - in the peritoneal cavity, make IgM to carb structures common on microbial surfaces |
|
|
Term
| What do NK cells produce and what is the result? |
|
Definition
They produce IFN-gamma - these activate macrophages to make them better killers
*activated macrophages make IL-12, which stimulates greater IFN production from the NK cells |
|
|
Term
| Name the 4 categories of soluble effectors of innate immunity. |
|
Definition
*acute phase reactants
*complement
*interferons
*cytokines |
|
|
Term
| What are the 3 major pathways in the activation of the complement system? What are they based on? |
|
Definition
1) alternative - recognizes structures (microbes), has to do with the innate system
2) classical - has to do with AB recognition - part of humoral immunity
3) lectin-recognizes structure (mannose binding lectin)-part of innate |
|
|
Term
| Go through complement activation, starting with the 3 pathways and describing the early and late stages. |
|
Definition
| [image]
C3-major protein of complement, C3b is the major fragment that activates others
C9 is a membrane attack complex that makes holes in the plasma membrane |
|
|
Term
| What are IFN alpha and beta produced by? What do they do? |
|
Definition
| *made by virally infected cells - they react with a non-infected cell to confer resistance - both made by the same trigger and bind to the same receptor, mammals make a combination of both |
|
|
Term
| What does IFN gamma do and what is it produced by? |
|
Definition
*regulates activity of host defense, like activating macrophages
*made by a T cell that's been stimulated by and AG, or an NK cell stimulated by microbial products |
|
|
Term
| Why are cytokines made? What do they do? What determines their function? |
|
Definition
*chemical signals made b/c a cell recognized a pattern (AG, etc)
*they stimulate cells to do things, like initiate or amplify initiation
*what info they transmit depends on the combination of cytokines released - their ratio and what's there |
|
|
Term
| Describe T cell and B cell P&D in terms of what signals it gets from the innate system. |
|
Definition
| [image]
B7 is a costimulator
CD28 is a receptor for B7 |
|
|
Term
| What are the 3 physiological results of inflammation? |
|
Definition
1.Vasodialation > Increase blood flow
2.Increased vascular permeability
3.Accumulation of cells |
|
|
Term
|
Definition
| Nonspecific response to cell injury |
|
|
Term
| Diagram the overview of all the systems that endothelial damage triggers. |
|
Definition
| [image]
Hageman factor - plasma clotting factor |
|
|
Term
| What are the 4 mediator systems found in plasma? |
|
Definition
| kinin, fibrinolytic (breaks up clots), clotting, complement |
|
|
Term
| Give the overall overview of inflammation, starting with a bacteria entering on a knife. |
|
Definition
|
|
Term
| What are the 4 cardinal signs of inflammation and what are their physiological causes? |
|
Definition
| pain, redness, swelling, heat - heat and redness are the result of vascular dilation, swelling - increased vascular permeability (accumulate cells), and pain is caused by swelling impinging on nerves |
|
|
Term
| What are the 2 clotting systems and how do you activate them? |
|
Definition
Intrinsic clotting system
*Plasma contact with collagen (endothelial cells have been moved = blood vessel damage)
Hagemann factor "XII".
Extrinsic clotting system
*Damaged cells release material "guts" |
|
|
Term
| Describe how the clotting cascade also activates the fibrinolytic,kinin, and complement systems. |
|
Definition
| [image]
*plasmin also causes C1 to split to C1_ and C3 to split to C3_ |
|
|
Term
| Describe how granules are released from platelets and what this leads to. |
|
Definition
| *Physical stimulus to trigger granule release.
**Causes an influx of Ca++ ions-->
*Activates Adenylase cyclase to produce cAMP-->Activate phospholipases -->
generate arachidonic acid and its metabolytes
prostaglandins + thromboxanes-->
Increased microtubules
**Combination leads to release of granules
Granules contain serotonin:
increased blood vessel permeability
leakage back to clotting
[image] |
|
|
Term
| Why are mast cells released? What do the granules contain and what to they do? |
|
Definition
Granule release:
*Physical damage
*Complement
*Allergies
Granules full of mediators:
*histamine-->dialate blood vessels-->
increase vascular permeability |
|
|
Term
| Can mast cells initiate the clotting cascade? |
|
Definition
| yes - even though you don't have blood clots |
|
|
Term
| Diagram the role of membrane phospholipids in inflammation (chemicals released, effects) and what common treatments are available. |
|
Definition
|
|
Term
| What do C3a and C5a do? What are they activated by? |
|
Definition
Plasmin - activates both C1 and C3
Start classic and alternate pathways
C3a, c5a
*Induce degranulation of mast cells
*Dilation and permeability of blood vessels
*C5a chematactic |
|
|
Term
| How do microorganisms activate the complement pathway and what paths do they activate? |
|
Definition
Act as chemotractants.
Support alternative complement pathway
*LPS Gram neg
*Teichoic acids - Gram pos
Classical (lectin) pathway |
|
|
Term
| Where is margination most prominent and why? What marginates the most often? |
|
Definition
*the venules -pressure drops, low shear, easier for WBCs to get caught
* neutrophils and monocytes |
|
|
Term
| Give the steps in margination (don't describe molecules) |
|
Definition
1)inflammatory signals make endothelial cells in BV express P selectin (later E selectin) and PAF
2) P-selectin bind to oligosaccharides on the WBC, causing it to slow down and loosely bind
3)PAF binds to PAF receptors on the WBC, activating intergrins on the WBC
4)Intergrins bind ICAM on the endothelial cells, causing a tight adhesion
5)cell flattens (imp b/c you don't want it blocking traffic) and exits the BV |
|
|
Term
| Describe P&E selections - what are they related to, what do they bind, bond strength. |
|
Definition
Related to CR1
-Bind to carbohydrate
**Sialyted (sialyc acid)
**CD15
---High on neutrophils and macrophages
-Binding not very strong
-Cells roll along wall |
|
|
Term
| Describe the 3 types of CAMs - what they're induced by and when they appear. |
|
Definition
P-selectins
*induced by Thrombin and histamine
*appear in minutes
*short lived
E-selectins
*Induced by Cytokines (TNF, IL-1)
*appear within 3-6 hrs
*Last longer
Immunoglobulin superfamily adhesion molecules
*ICAM or VCAM
*Induced by cytokines (TNF and IL-1)
*Appears >6 hrs |
|
|
Term
| Describe where PAF and chemokines come into play in margination and how they affect leukocytes. |
|
Definition
PAF: Platelet Activating Factor
*Bound to surface of endothelial cells
Chemokines
*IL-8 and others
*Secreted
*Chemotactic for neutrophils
Upregulate expression and activity of leukocytes adhesion molecules
*Intergrins
*L-selectins |
|
|
Term
| Describe intergrins - structure, examples, what they bind to. |
|
Definition
Two part structure
*alpha + beta chains
Most important in leukocyte endothelial adhesion
*LFA-1 (leukocyte functional AG 1)
*CR3
*CR4
Bind to endothelial immunoglobulin cellular adhesion molecules |
|
|
Term
| ICAMs - where, what increases expression, function. |
|
Definition
*Expressed on endothelial cells
*Expression increased by TNF and IL-1
*Interact with Intergrins
*Causes capturing, latching, tight binding |
|
|
Term
| L-selectin - where is it found, what upregulates it, what does it do? |
|
Definition
*Found on leukocytes
*Upregulated by leukocyte activation
*involved with WBC trafficking - the combination determines who gets out |
|
|
Term
| Describe acute inflammation - what happens, major players, failure. |
|
Definition
*Irritants and damage gets cleaned up
--Stimulants of inflammation decrease
--PGE from Macrophages and platlets inhibit inflammation
*Macrophages secrete fibroblast growth factors (attracts fibroblasts to make collagen)
*New cells and blood vessels grow into area
--follow fibrin strands
*Failure to clean up leads to Chronic Inflammation |
|
|
Term
| What are some causes of chronic inflammation? What results from chronic inflammation? |
|
Definition
*Continued damage
Mycobacteria
Grow in macrophages
Waxy cell wall resists degradation
Fungi
Parasites
Physical irritants
--silica
--asbestos
*Granuloma
Attempt to wall off material |
|
|
Term
| What WBC is usually the 1st to arrive at the site of inflammation? What is pus? |
|
Definition
| neutrophils - a bunch of dead neutrophils |
|
|
Term
| What role does prostaglandin E play in acute inflammation? |
|
Definition
| It's a damper - won't prevent inflammation, but it helps shut it down - it's made at the same time as things that drive inflammation, like driving with the gas and brakes at the same time |
|
|
Term
| What is a granuloma - what causes it? |
|
Definition
*Layers of cells around chronic irritant
--Macrophages (produce TNF)
-lymphocytes
-fibroblasts
If antigenic, stimulate T cells
--produce cytokines (Interferon-gamma)
--induce changes in macrophages
***Activate macrophages to be better killers
***Giant cells
***Epithelioid cells |
|
|
Term
| What is a giant cell? Epitheloid cell? |
|
Definition
giant cell - bunch of macrophages fused together
epitheloid - stretched out macrophages that are trying to act like a coating |
|
|
Term
| Why are granulomas considered to be last ditch efforts to wall off inflammation? |
|
Definition
- you have all these layers, and eventually food and O2 can't get to the middle so you get necrosis and accumulate Ca++
-also, the normal cells get pushed to the side, so tissue can get damaged trying to wall it off |
|
|
Term
| Compare acute and chronic inflammation - duration, cells, results |
|
Definition
acute - Short duration,
Predominately neutrophils then macrophages Swelling
chronic - Long duration, predominately lymphocytes and macrophages
*has Giant cells and epithelioid cells
*Space filling |
|
|
Term
| What do NSAIDs do? What are the 2 different kinds and why is the new kind bad? |
|
Definition
| [image]
normal NSAIDs block cox-1 and cox-2, but cox 1 maintains the stomach lining, so new ones only inhibit cox-2, but these have lead to heart attacks and strokes |
|
|
Term
| What do steroids do chemically? |
|
Definition
*Block phospholipase A2
*Induces production of IKB
*Inhibitor of kappa B
Bind to NF KB, blocks its transport to nucleus
NF KB
-Nuclear factor kappa B
-transcription factor
-promotes transcription of many cytokine genes involve in immune response |
|
|
Term
| What do antihistamines and Tylenol do? |
|
Definition
Anti-histamines
*block action but not release of histamine
Histamine
increases vascular dilation and permeability
Tylenol
*works in hypothalamus to reduce feelings of pain and to reduce fever
*Not anti-inflammatory |
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