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113 Cards in this Set
- Front
- Back
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What is the main goal of the immune system? Why is the blood important component of the immune system? The immune system consist of two related activities first is the __ that a pathogen is present (involves surface receptors and serum proteins), second is the recruitment of __ to kill and eliminate the pathogen (involves effector cells and complement) |
-the ability to discriminate between self and non self (if this fails then disease will result) -b/c it contains leukocytes, lymphocytes, clotting factors, complement, antibodies -recognition -effector mechanisms |
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The function of the immune system is to _ and __ infections by pathogenic microbes and __ the pathogens and their harmful products .
The Immune system has two characteristics. __ is the multiple of levels of protection. What are the types of levels of protection? The second characteristic of the immune system is __ meaning a single pathogen can be fought by the immune system in multi ways (ex: diff antibodies and different cells that can be phagocytic) |
-prevent
-control -eliminate -layering -innate and adaptive -redundancy |
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The __ is the other circulatory component of the immune system. Lymph nodes filter interstitial fluids which means they remove anitgens and makes them available to what? What are the 3 things lymph nodes perform? |
-lymphatic system -B and T cells -allows B and T cells to interact, provides a location where antigens can initiate an immune response, and B cells make antibodies
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Branches of the Immune system: __ immunity is non specific, and responds non self and and to conserved structures. You are born with this system. It is always present at basal levels __ immunity is acquired by antigen exposure and specific to a given antigen. during this immunity only those lymphocytes with __ that recognize the pathogen are selected to participate in this response |
-innate -adaptive -receptors |
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___ immunity will have specialized defense against one pathogen but little defense against others. Why is the adaptive immunity response slow? The adaptive immunity will provide __ What is the subdivisions of the adaptive immunity response? |
-adaptive -b/c it must be up regulated upon antigen encounter meaning that it takes time for the activated B and T cells will increase in number (clonal expansion) -memory -humoral and cell-mediated |
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__ immunity is the first line of defense (PAMPs), it will prevent establishment of a pathogen in the host and it is activated quickly (fast response) Leukocytes, enzymes, chemical and physical barriers, protiens and inflammation are examples of _ and __ components of the innate immune system. Why is inflammation/temperature a good mechanism for defense against pathogen? |
-innate -cellular and non cellular -b/c it slows down the growth of pathogen and allows the immune system to catch up |
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What is the key to the adaptive immune system? The adaptive immunity is effective and protective because of __ (different type of cells and soluble molecules), __ (cells and soluble molecules are specific for a particular antigen/pathogen), __ (memory cells ensure a better, faster response upon the next encounter) |
-discrimination of self/non-self -diversity -specificity -memory
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T or F: In adaptive immunity B and T cells circulate through out the body and is genetically programmed to respond to a single foreign antigen and become activated only when that antigen is encountered. When __ cells encounters an antigen (with a antigen recognizing receptor) it will poliferate aka__ and some will become __ cells (carry out immune function) and some into _ cells (circulate and await next encounter with the antigen) |
-True -naive (unprimed) -clonal expansion -effector -memory |
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Antigen presenting cells (APC) like __ (3) will engulf pathogens, break them down into smaller pieces and present them to T cells Humoral immunity is part of the adaptive immunity and involves the production of antibodies. It protects against ___ pathogens. Invloves B and T cells (CD4 TH2). cell mediated immunity protects against __ pathogens and involves T cells like CD8 and CD4 Th1 |
-dendritic cells, macrophages, and B cells -extracellular -intracellular
**read examples of regulation of innate and adaptive immunity have on each other on page 7 also look at chart of immunity as well** |
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The single effector function of B cells is to produce __. The B cell receptor (BCR) is a membrane bound form of antibody with the same __ and same __ specificity, but with some minor differences at the C-terminal end of the protein that cause it to be anchored in the membrane of the B cell. The BCR plays an important role in __ activation. |
-antibodies (immunoglobins/ Ig) -structural features -antigen -B cell |
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Soluble (secreted) antibodies serve to *recognize and bind __ pathogens and their products* and deliver them to phagocytes for destruction. T or F: antibodies have any toxic effect on the antigen. |
-extracellular -false, they do not have a toxic effect
*antibodies are both highly specific (for antigen) while at same time highly diverse (in their sequence and specific functions), yet they carry out common effector functions* |
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**the specificity of an antibody is attributed to a defined region called the __ of the molecule that differs greatly from antibody to antibody. The biological activity is determined by a separate region of the molecule that is less varied called the _ differs between different iso-types of antibodies (ex: IgA and IgG)** |
-variable region -constant region
*every antibody has 4 polypeptide chains (2 heavy and 2 light)* |
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Each L chain is attached to a H chain by __ bonds and the 2 H chains are attached to each other by _ bonds. Does the 2 L chains interact with each other?
*heavy chains are about 50,000 da each, and light chains are about 25,000 da each* |
-interchain S-S -interchains S-S -no they do not |
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The _ region is the N terminal region of both H and L chains; they vary greatly in their amino acids sequence from one antibody to another. This variability in sequence determines the __. The remaining sequence of the L and H chain remain relatively unchanged differing only by iso-type (IgG vs IgA), this region is termed __ and determines the _ of the antibody and is why different antibody iso-types have different functions |
-Variable (termed Vl or Vh) -antigen specificity -constant region -function *the constant region is divided into domains. 3 heavy constant regions domains and 1 light constant region. IgE and IgM have 4 heavy constant region domains so no hinge* |
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Hinges are present in which anitbodies? __ is the portion of the antibody molecule that retains the ability to bind to antigens. its variable regions is consisted of what? and its constant region only consist of what? How many fab per anitbody? |
-IgA, IgD, and IgG (b/c they have 3 Constant heavy domains and not four) -fab (fraction antigen binding) -Varible Heavy and Variable light -constant light and constant heavy domain 1 -2 |
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__ is includes most of the hinge and the CH2, CH3 (CH4 in case of IgE and IgM). How many fc fragments per antibody? The fc region is held together by what? The Fc region is responsible for __ which occurs when the fab portion binds to the antigen while the fc portion is bound to fc receptors on immune cells that phagocytose the attached antigen. *The fc region is also responsible for what?* |
-Fc region (fraction crystallizable) -1 per anitbody - S-S bonds below the hinge region -Opsonization -Delivers the antibody to specific anatomical sights |
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__ is a single piece consisting of *2 Fab regions and the hinge* held together by the S-S bond. No Fc is generated as this portion is digested into multiple fragments. How is Fab2 created? What enzymes will make 3 pieces which includes 2 fab and 1 fc? The Hinge region is composed of a short segment of amino acids and is found between the _ and _ domains of the H chain and is made of predominately of which amino acid residues?. The __ region allows for the 2 fab arms to open and close to accommodate binding to 2 epitopes. |
-Fab 2 -the enzyme pepsin -the enzyme papain -CH1 and CH2 domians -Pro ,Ser, and theorine -Hinge |
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__ chain is a small glycoprotein that is associated with IgA and IgM (BUT NOT HEXAMERIC IgM) that is important for secretion process of the anitbody. How many J chains per antibody polymer? J chain is required for _ and interacts the the _ receptor that transports these antibodies from the basal side of epithelium onto the luminal side of the mucosal surface this process is called __ (transporting through the cell). |
-J -1 -polymerization -poly-Ig or pIg -transcytosis *leaves a secretory component to get the antibodies into the organs* |
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__ bonds will form loops within each chain and help give the molecule its **globular shape and separate the domains within each chain**. In the Fab portion which segments of the heavy and light chain interact? In the Fc region which part of the heavy chain interacts with each other through the disulfide bond? *Why not CH2?* |
-intrachainS-S -Variable light w/ variable heavy and Constant light with Constant heavy domain 1 -The constant heavy domain 3 -b/c of steric hindrance and attached carbohydrates |
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The variable region is further divided into the the hypervariable regions and the framework regions. It is the _ region that that actually makes contact with the epitope/antigen. In the Variable light and variable heavy chains of the Fab region there are _ regions of 8-11 amino acids that are extremely varied termed the hypervariable region. these three regions are also called what? How many CDR per antibody? |
-hypervariable -3 **(these are the amino acids that actually make complementary bonds with the antigen; they are the exact portions of the antibody that determine antigen specificity) ** -Complementarity- determining regions (CDR1, CDR2, and CDR 3) -12 |
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The remaining 80 or so amino acids of the variable region between the CDRs, show less variability and are called the _ regions. How many framework regions in each variable region? |
-framework -4 (16 per antibody) |
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What are the two types of light chains? Are both the Light chains in a given antibody identical? Is there any known effector function associated with the light chain? It is the _ chain that determines that class or iso-type of the antibody and also determines the effector function of the antibodies. What are the five major H chain classes or iso-types? How many classes of IgG? IgA |
-kappa and lamda -Yes *so there is never both lamda and kappa on one light chain* -heavy -IgA, IgG, IgE, IgM, IgD -4 -2 *every other iso-type of antibody only has one class im assuming* |
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__ determines the class of the antibody (IgM vs IgG1 vs IgG2) and also *distinguishes the type of L chain present in the antibody (Kappa or Lamda)
__ region determines the function and anatomical location; will determine where the antibody will go
**different classes of antibodies are found in different parts of the body and not all antibodies perform all functions equally (or at all)** |
-iso-type -constant heavy chain
**Iso-type has nothing to do with the variable region or has nothing to do with the antigen binding specificity; only the constant heavy chain will be changed if the iso-type is changed** |
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__ antibody will present has a monomeric membrane bound BCR on mature B cells. T or F: It is the first iso-type secreted when B cells are activated by T cells. **It is the predominant antibody made in response to T-independent antigens (or antigens that have not been presented to T cells)** What is the predominate form of IgM? Does it have a CH4 domain? IgM is the most efficient type of antibody to activate what? Where is IgM mostly found? What is major source of IgM in Saliva? IgM is the only antibody to be made by the what? |
-IgM -True -pentamer -yes -complement pathway -serum -Gengival cervicular -fetus (20 weeks of gestation) and infants(4-6 months which when infant can start to make other iso-types)
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What antibody is most common in the blood, tissue and serum? What are the subclasses of IgG? What is used to distinguish the subclasses? Why does IgG have a long half life (about 23 days except IgG3 which is 7 days). Is IgG the most abundant antibody overall? **but it is the most of ALL iso-types in the tissues and serum** What is the only antibody to cross the placenta? *remains at titers until after 6 months* |
-IgG -IgG 1,2,3 and 4 (made from different genes) -hinge -because it is recycled -no -IgG |
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Which sub-classes of IgG activate the complement pathway? IgG can be found on Fc receptors on various cells types to increase __. IgG can participate in __ when bound by Fc receptors on NK cells. When does production of IgG begin? What makes the sub classes different from each other? __ **will neutralize bacteria, toxins by preventing pathogen/bacteria into host cell and stops bacteria mobility** |
-IgG 1, 2, and 3 -opsonization **(IgG 1 is the best opsonin)** -antibody-dependent cell mediated toxicity (ADCC) -4-6 months -glycoslation, hinges, and S-S bonds -IgG *(they will also flag pathogen for recognition)* |
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the human body makes __ the most out of all antibodies, it is the most antibody overall! IgA main function is for ___, **this secretion portion protects IgA from being degraded**. which subclass of IgA is most abundant in the serum (about the same in mucosal surface). *Which subclass is directed against protein epitopes?* which is used against polysaccharied epitopes?* |
-IgA -secretion (mostly found in secretion) -IgA 1 -IgA 1 -IgA 2 |
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Which antibody is the second most in the serum? Which antibody is the predominant or most abundant in secretion? Most of monomeric IgA is found where? Can IgA be used degrade pathogens (even though antibodies are non harmful)? Most of polymeric IgA (SIgA) is found where? |
-IgA -IgA -serum -yes by bacteria -secretions (SIgA is from saliva, also remenants of PIg R) |
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Most of IgE is bound to Fc epsilon receptors of mast cells, basophils and eosinphils by what? Does IgE have a CH 4 domain? **When IgE's Fab regions are cross linked by binding antigens, the cell is activated and releases ___. IgE will mediate __ activity. IgE also plays a role in the protection from __ when repeating eptitopes on the parasite cause cross linking and granule contents from the attached cell are released directly on the parasite to kill it. Most IgE secreting cells are thought to be located primarily in the __ tonsils |
-their Fc region -yes -granules -hypersensitivity -parasites -pharyngeal |
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__ is found on naive B cells, meaning they have not interacted with an antigen. *very little is secreted and is present at low levels in the plasma. IgD as a BCR functions to activate __ cells. IgD also plays a role in the regulation of __ cells |
-IgD -B -B *if IgD is missing from the B cell surface, self reactive B cell can enter lymphoid organs and proliferate* *most abundant in serum goes IgG > IgA > IgM > IgD > IgE* |
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Monocytes circulate in the blood when the move into the tissue (fixed there) they are called __. This cell will aid in __ because it has a CR3 receptor (complement receptor) for complement protein C3b. The cell also as a Fc receptor for the Fc region of antibodies __ and __ which will also aid in opsonization and antibody dependent cell mediated cytoxicity (ADCC). How can macrophages become actvated? (3) |
-macrophages (tisse fixed macrophages) -opsonization -IgE -IgG -by interferon gamma (produced by TH1, CD8 or Nk cells), Pathogen-associated molecular patterns (PAMPs) and opsonization |
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When macrophages are activated by opsonization what affect does that have on the macrophage? Functions of Macrophages: In the __ state macrophages will act as garbage collectors, taking up debris and dead cells. In its _ state it takese up foreign invaders either by recognition of a PAMP or opsonization. *(this is where it is a antigen presenting cell)*. In the __ state it kills pathogens by cytotoxic enzymes and oxidative burst |
-enhances phagocytosis -resting -activated -hyperactive
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What are some of things macrophages uses to kill pathogens? What is the mechanism of an macrophage to kill the phagocytosed pathogen? What happens to the pathogen particles that are not released? |
-release toxic O2 (oxidative burst) and nitogen radicals (NO, NO2, HNO2, HCLlO, OH, and O2) -increases the acidity by pumping H ions and there is a fusion with an lysosome, lysosomes enzymes are now released and digested prodcuts are released. -used for antigen presentation (presents Antigens to T cells w/ MHC class 1 or 2 thats why they are antigen presenting molecules) |
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What is the first phagocytic cell to sense an invading microbe? What soluble medaitors does it release after phagocytosing a pathogen? Antigen dependent cell mediated cytoxicity with macrophages occurs when the target is coated with __antibodies. Now activated macrophages directly kill the target cell **WITHOUT** phagocytosis |
-macrophages -Cytokines (IL 1 and 6, TNF- alpha *recruit neutrophils and other leukocytes to infected areas*) and complement proteins -IgG
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__ are short lived dedicated killer s that circulate in the blood until *recruited* these cells are replaced rapidly; makes RNA more. What cell is the most predominant granulocyte making up more than 90% of circulating granulocytes and 50-70% of all circulating of all WBC. What is another name for this cell? How many types of granules (that contain various types of enzymes for killing pathogens) does this cell have? *Release of these enzymes (from the granules) cause collateral damage to "innocent bystander cells during infection this is called__.* |
-Neutrophils -Neutrophils -Polymorphonuclear cells (PMNs) -3 -immunopathology
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What are the functions of the neutrophils? (2) Neutrophils (when phagocytic) will release lytic enzymes and __ (small peptides that pole holes in membranes) to kill phagocytosed pathogens. What cytokines does neutrophils produce? (4) |
-phagocytes and cytokine production -neutrophils -defensins -IL- 1, 6, 8, an TNF alpha
*neutrophils also have an oxidative burst*
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__ is a granulocyte that has a bilobed nucleus and has an high affinity surface receptors for Ig_ antibodies and low affinity receptors for Ig_. *What is this cells key role?* is the cell phagocytic? The cell will attach to targets with __ receptors or __ receptors then release the toxic contents of their granules to destroy the target. *Do they play a role in allergic reactions?* |
-Eosinphils -E -G -yes -Fc -complement -yes *Eosinphils are important in the pathogenesis of asthma and other chronic inflammatory disease* |
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__ have a surface receptor for Ig_. Does this cell play a role in allergic reactions. Cross linking of the Fc epsilon receptors with IgE and its antigen leads to the release of contents from granules this called __. *What does the granules contain of basophils?* |
-Basophils -E (Fc epsilon receptors) -degranulation -histamine and vasodilators
*Basophils circulate until needed*
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__ cells are mostly found along connective tissue and skin. They have a high affinity for Ig_. *what do they play a major role in?* Cross linking of Fc epsilon receptors with IgE and its antigen leads to degranulation. Granules will contains __ and __ |
-Mast -E (Fc Epsilon receptors) -allergic reactions -histamine -vasodilators |
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__ is involved in blood clotting and inflammation . They are derived from megakaryocytes. What surface receptors do they have? (3) |
-Platelets -Fibrinogen (clotting), complement protein C3b (inflammation), and cytokines (CXCR4)
*2/3 are in circulation and 1/3 are in spleen* |
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___ are identification cells, they have cytoplasmic extensions called __. Where are they mostly found? This cell will phagocytose the microbe *and then migrate to nearest lymphoid organ to present antigen to T cells at which point they are often referred to as __ cells* What is the differnce between interdigitating DC's and macrophages? What are the functions of dendritic cells? (4) |
-Dendritc cells -dendrites -in the skin (langerhans cells) -interdigitaing DC's -Differnce is that IDC migrate and macrophages do not (tissue fixed) -phagocytose, antigen presentation, negative selection, and cytokine production |
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What kind of dendritic cells will phagocytose? What cell is the most effective Antigen presenting cell? __ cells phagocytose antigen then migrates ti a secondary lymphoid organ where they mature to __ cells to present processed antigens to T cells. W/ __ molecules they present to CD4 cells (TH1 intra and TH2 extracellular). W/ __ molecules they present to CD* cells (viral antigens; intra). W/ __ (a type of MHC molecule) to CD8 cells |
-immature (langerhans cells) -dendritic cells -immature dendritic -interdigitating dendritic -MHC class 2 -MHC class 1 -CD1
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__ selection occurs in the thymus, and DCs present self antigen to developing T cells (thymocytes) to determine if the thymocyte is self reactive and needs to be destroyed. What cytokines does it produce? |
-negative selection -IL 1B, TNF alpha, and IL 12 |
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_ cells are not related to DCs but present the whole antigen (not processed) to B cells in the lymphoid germinal center. Are these cells phagocytic? *Where are these cells found?* Do they express MHC class molecules? Why? These cells have extensive surface processes that bind __ complexes w/ Fc portion of antibodies. *They present antigens to B cells to play a role in what? (2)* |
-Follicular Dendritic Cells -no -germinal centers and follicles of lymphoid tissues -No, b/c they do not present antigens to T cells -antigen/antibody -Affinity maturation of B cells, and maintenance of immunologic memory of B cells |
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All _ cells have a surface receptor called a __, which is specific for a particular antigen (much like antibodies exhibits specificity). T cells are categorized into sub populations based on what? (2). __ cells become terminally differentiated into Th cells whose effector function is the production of cytokines. __ cells become terminally differentiated into CTLs whose effector functions is to kill infected cells or tumor cells |
-T -TCR -function and surface protein -CD4 -CD8 |
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CD4 and CD8 are more that just surface markers for T cells but they also act as* __ co-receptors* *they are both usually expressed in mutually exclusive fashion* CD4 recognizes MHC class _ and CD8 recognizes MHC class _ |
-antigen -2 -1 |
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CD4 is further divided into groups based on __ production. Cytokines plays an important role in the development of __ cells into TH1 or TH2 cells. Cytokines __ and __ will promote TH1 differentiation and cytokine __ will promote TH2 differentiation. What cytokines does TH1 cells produce? TH1 stimulate __ cells (cell mediated response). TH1 stimulate __ in B cells to produce what? |
-cytokine production -TH0 -IFN gamma *(inhibits TH2 differentiation and is produced by TH1)* -IL-12 *(produce by macrophages, DCs, and neutrophils)* -IL 2, IFN gamma, and TNF beta *(these cytokines tell b cells to stop making IgM's and make something else)* -CD8 -iso-type switching -IgG 2, 3 and IgA
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What cytokines does TH2 cells produce? TH2 cells stimulate __ cells to produce __ (humoral response). TH2 cells stimulate iso-type switching in B cells to make what antibodies?**Although most adaptive immune responses involve both TH1 and TH2 cells, in many cases the response will become biased toward one or the other type of CD4 cell** |
-IL 4, 5, 6, and 10 -B -antibodies -IgG1, IgE, and IgA
*TH1 vs TH2 phenotypes has clinical implications- the predominance of one phenotype over another determines the presentation and severity of the disease*
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CD8 cells will *kill its target through release of __ enzymes (cell mediated response).* *it only attacks pathogen infected cells not the pathogen itself* |
-cytotoxic
*kills host cells with intracellular pathogen, tumor cells, and incompatible grafted transplanted tissues* |
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Identification of B lymphocytes: Naive B cells will have what antibodies on their surface? T or F: activated B cell have 2 types of BCR on their surface. __ (of B cells) interacts with __ on T cells to provide the second activation signal for B cells and signals B cell to undergo __. __ of the B cell interacts with __ on T cell to provide the second activation signal of __ cell |
-both IgM and IgD -false' only one type -CD40 -CD40L -iso-type switching -CD80/CD86 (B7) -CD28 -T
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What are the functions of B lymphocytes? (3) __ cells are terminally differentiated B cells that become antibody factories. __ cells develop from naive B cells activated by antigen and return to a resting state waiting tor respond when the cognate antigen is encountered |
-Production of antibodies, immunologic memory, and antigen presentation -Plasma -memory |
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_ ells neither have TCR or BCR (no t cell or B cell receptors). these cells have a __ receptor, also a __ receptor which allows them to proliferate in response to very low levels of IL 2. Is the cell part of the innate or adaptive immune systems? What are the functions of NK cells include?(2) How do they kill the target cells mainly? How do they recognize tumor cells? If NK cells kill w/ the ADCC system what receptor and antibody do they use? How is NK told not to kill? What are the three functions of INF gamma? |
-NK -FC gamma -IL-2 -both -killing target cells (tumor and infected cells) and producing IFN gamma -by releasing cytotoxic enzymes from granules -recognize a protein MICA on cancer cells -its own Fc gamma receptor and IgG -by a signal sent from killer inhibitory receptors (MHC class one receptor) -protect non infected cells from viral infection and they stimulate cytotoxic activity of Tc cells and activates marcophages |
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What are the two primary lymphoid organs? *(meaning where lymphocytes are born and mature)*. __ contains the pluripotent stem cells that become immune cells and the progenitor cells that eventually become B cells remain in the bone marrow. __ where progenitor cells that are to become mature T cells. Developing T cells undergo __, a process called education in which self reactive T cells are eliminated while T cells that do not recognize self antigens enter the blood stream. |
-bone marrow and thymus -bone marrow -thymus -thymic selection |
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__ organs are where mature B and T cells interact with the antigen and undergo further differentiation and proliferation. What are the 3 secondary lymphoid organs? what are the 3 functions of secondary lymphoid organs? The __ has red pulp which act as a filter to remove old/damaged blood cells. In the spleen where does the immune response happen? Where are blood borne antigens processed and presented? |
-Secondary lymphoid organs -spleen, lymph nodes, and MALT (mucosa-associated lymphoid tissue) -allow lymphocytes to interact with the antigen, to interact with each other, and allows these interactions to occur in the presence of cytokines that promote proliferation and differentiation -spleen -white pulp (25% of bodys mature lymphocytes are here) -the spleen |
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Which lymphoid organ will antigens from the tissue be processed and presented? The __ will trap the antigen and activating lymphocytes. pathogens arrive in the MALT by *direct delivery across the mucosa by specialized mucosal cells called __ cells. These cells "sample" their surroundings, antigen is transcytosed through the cell into a pocket on the basoateral side of the cell which contains __. Lymphocytes enter MALT through the __ and if not activated exit with the __ |
-lymph node *(germinal center has activated B cells no where else in the lymph node)* -MALT -lymphocytes, macrophages, and DCs
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For antibody to be made, both _ and _ cells, each specific for that antigen must interact. Lymphocytes circulate in a manner that maximizes opportunities to encounter the __ and other lymphocytes specific for that antigen. What is the circulation of lymphocytes? Where are lymphocytes most of the time? |
-B -T -antigen -from blood to lymphoid tissue to non lymphoid tissue -lymphoid tissue (not blood)
*there is traffic between lymphoid and non lymphoid tissue to ensure that the antigen and lymphocyte will interact in the lymphoid tissue so the lymphocyte can proliferate and differentiate* |
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Naive T cells have __surface proteins that allow them to enter lymph nodes. The naive T cells will migrate into the __ cell zone in lymphoid organ where antigens are displayed by APCs. What happens to these cells are activated? not activated? |
-L selectin -T -becomes an effector T cells or memory T cell -reenters the lymphatics or the blood stream to continue to next lymph node |
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Effector T cells once activated will loose their __ receptor *so they wikk not reenter the lymph nodes to search for antigens* the vast majority of these cells leave the lymph node and reenter __. They preferentially migrate into tissue that are colonized by __. Some __ T cells will act like naive T cells and reenter lymph nodes where they can mount a secondary immune response to captured antigens or some will migrate to sites of infections in the tissue where they can carry out their effector functions to eliminate the pathogen. |
-L selectin -circulation -infections -memory |
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Lymphocytes circulate through the body in both the blood and the lymph where they can enter and exit the secondary lymphoid tissue.. What is the exception? |
-the spleen b/c all pathogens and lymphocytes enter/exit w/ the blood, the spleen is not physically connected to the lymphatic system
*Only a very small amount of the circulating lymphocytes will become activated and remain in the lymphoid tissue, all others will reenter circulation to repeat the process at the the next secondary lymphoid tissue* |
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Is there any need for exposure for your innate immunity to be initiated? *innate immunity is non specific, non adaptive (doesnt get stronger/faster) and does not expand upon activation (does not result in memory)* |
-no |
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Skin (a physical barrier, part of the innate immune system) consist of _ which is a small fatty acid that has antibacterial and chemotactic properties. What are the functions of normal flora? What are so special about tears? What is so special about fevers? |
-Psorarian -prevent binding by occupying binding sites, utilize available nutrients, secrete bacteriocins (toxins that are harmful to other bacteria) -contains lysozome (they break down the cell wall in pathogens) -prevents growth of pathogens and speeds up hematopesis (neutrophils) |
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Antimicrobial peptides (defensins) are most effective against which bacteria? Iron sequestering proteins: Chelate free iron and remove it from the blood which are ___ or mucosal surfaces which are __, make it unavailable for bacteria (induced hyperuremia) |
-gram negative -transferrin -lactoferrin
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When neutrophils pass from capillaries to tissues (being recruited) this called ___. What are the four steps of extravastion? ___ is formation and breaking of low affinity interactions with glycoproteins on endothelial cells. __ when chemokines cause PMS to activate their integrins and endothelial cells express ICAMs. __ is when PMN adheres to endothelial cells. ___ is when PMN squeezes into tissue. |
-extravastion -rolling, activation, adhesion, and entry -rolling -activation -adhesion -entry |
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-Receptors that recognize PAMPs are called __ . __ recognize and bind PAMPs such as LPS for gram negative bacteria. (different TLR recognize different PAMPs). __ recognize and binds carbohydrates with a high mannose content, and is used to activate the compliment pathway. __ are intracellular PAMP receptor and will detect microbial motifs that again entry into cell. |
-pattern recognition receptors (PRR) -Toll like receptor -Mannose binding lectin -Nod proteins |
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__ expression is ubiquitous in adult tissues, recognize a gram negative derived peptidoglcycan motif. __ is mainly expressed in cells of the myeloid lineage, it recognizes a different peptidoglycan peptide motif *(mutation of this receptor is correlated with crohns disease)* |
-Nod 1 -Nod 2 |
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What are the four things inflammation is defined by? What are the functions of inflammation? What will cause the vessels to be leaky (more permeable) during inflammation? -Which lymohcyte is first to the site of infection? __ will cause upregulation of adhesion molecules on the local vascular endothelial cells to help neutrophils and monocytes know where to extravasate into the tissue. |
-rubor (redness), calor (heat), dolor (pain), tumor (swelling) -remove and limit the spread of infections, clean up damage, repair tissue -cytokines, kinins, and histamine -neutrophils (30-60 minutes) then macrophages (4-6 hrs) which follow a gradient of complement proteins to infected tissues -cytokines |
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__ is considered the systemic arm of the inflammatory response. _ binds to LPS of bacterial and fungal cell walls and acts to opsonin which can initiate the classical complement pathway (binds C1q). __ binds to mannose sugars on bacterial and yeast surfaces, activating the lectin pathway of the complement system |
-acute phase response -C reactive protein -mannose binding lectin
**this acute phase response induce fever, hematopoesis, replacement of complement protein in liver, and induced hypoferremia (sequestration of iron by transferrin and lactoferrin) ** |
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__ is the total variety of antigenic receptors. There are two theories that explain this concept which is __ theory which is the theory that the genome contains a gene fore every antigen receptor we make but this theory did not offer any special genetic mechanisms to account for the huge variety of antigen receptors we can produce . the __ theory suggested the idea of multiple genes coming together to form unique combinations as a way to increase the variety; theory offered an unheard of idea of gene recombination in humans and animals. |
-antigenic repertoire -germline |
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The somatic mutation/diversification theory said "we have a limited number of genes for the variable regions of each L and H chain and the diversity is generated through __ or __ of this limited gene set" The recombing of these genes (H and L) only happens in what kind of cells? (2) Prior to rearrangement they are said to be in the __ because this how they are present in the germ cells The process of Ig and TCR rearrangement is called __ because this process occurs in the somatic cells (not germ cells) |
-point mutations -recombination -T (TCR) and B (Ig) cells -germline configuration -somatic recombination |
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The light chain region codes for how many genes? The variable light chain region has how many genes? How many genes encodes for the variable heavy gene? the variable heavy gene encodes which CDRs? THe Diversity gene encodes which CDR? The joining gene encodes which CDR? *the constant region is always one gene*
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-3 ( variable genes that encodes cdr1,2, and 3; joining gene and the constant light gene) -2 genes (variable and joining gene) -3 (variable, diversity and joining genes) (with the constant heavy gene it is four) -CDR 1 and 2 -part of CDR 3 -part of CDR 3 |
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Rearrangement of the variable regions (for both L and H chains) is referred to as __ recombination The recombination of V to J genes in the L chains and the V to D genes and D to J genes in the H chain is regulated by conserved DNA sequences called ___ that flank each V,D, and J gene |
-V(D)J -recombination signal sequences |
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Why is there 4 different types of lamda chains inside of the human? How many constant Heavy gens ( in the constant heavy chains) are downstream from the J heavy genes? Name the order |
-B/c there are four different types of constant lambda genes in the human (unlike constant kappa genes, there is only one type of kappa class) -11 -gene for Igm, IgD, IgG3, IgG1, IgE2, IgA1, IgG*, IgG2, IgG4, IgE1, and IgA2
*=non functional pseudogenes |
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Which chain rearranges first? Why? Each cell has how many alleles of each gene? __ ensures that only one of the alleles will be produced and applies to both H and L chains. If one allele is successful before the other allele what happens to that allele? __ ensures that there will be only one type of L chain |
-H chains -The H chain has the best chance of messing up the reading frame which will result in a non functional antibody - 2 (one maternal and paternal) -Alleleic exclusion -The allele that looses the race will stop being expressed -Isotypic exclusion
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What happens of both alleles of the H chain fail to rearrange? If the H chain is succesful in rearrangement what will rearrange next? Which L chain isotype do humans have a preference for?
*there is a competition between K and L chain alleles (to see which one is expressed first)* |
-results in apoptosis (H chain has two chances to rearrange since there are two alleles) -the L chain -kappa chain (success of rearrange of first allele vs second allele applies to L chain too; first one to rearrange is expressed; if it fails then second allele is given a chance to rearrange; if none of them rearrange it will result in cell death) |
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For a complete Ig gene to be expressed individuals must arrange what expression for the H and L to assemble a single functional whole protein? How do we generate two different mature mRNA transcripts to be translated into proteins (antibodies)? |
-For H chain it is VDJC and for L chain it is VJC -alternative splicing to generate constant Mu gene for IgM or constant delta gene for IgD |
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Ig_ and Ig_ are made in the membrane-bound form and both are found on the surface of the mature, naive _ cell T or F: All the secreted forms are made in the same manner after the B cell has received a signal from an activated T helper cell to switch the iso-type (iso-type switching) *When this happens the H chain genes rearrange once again linking the already arranged VDJ variable genes next to the appropriate Constant heavy genes* |
-M -G -True |
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When the heavy chain rearranges, which genes rearrange first? second? When the light chain rearranges, which genes rearrange first? second? At this point is the primary transcript made? What occurs to produce the mature mRNA transcripts of this light chain? What happens after splicing? |
-D and J first -then V,D and J arrangement (Then the VDJ rearranged DNA is transcribed along w/ the Mu and Delta gene (IgM and IgD) -V (kappa) and J (kappa) genes rearrange first -Then the V and J rearranged genes will rearrange with the constant kappa -yes -splicing -The translated kappa light chain moves to the lumen of the ER where it is joined to the H chains to make the complete Ig molecule |
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What happens if kappa light chains were unsuccessful? (which has two chance; 2 alleles) Which genes rearrange first? Which gene arrangement generates the primary scripts with introns? we get rid of the introns through __. Then the lambda mRNA is translated into protein that is moved to the lumen of the ER to be joined with H chains to make the complete Ig molecule |
- the light chain start to rearrange -The V and J chain will rearrange with the constant lambda light gene (remember only one J gene in lambda) -VJC lambda -splicing
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__ with in the introns dictate the distance and rotation of the DNA when bringing antibody genes together and prevent V genes from combining with J genes (in H chains) The RSSs are _ DNA sequences that flank each V, D, and J gene. RSSs are recognized by the __ which bind to the RSSs, creating nicks in the DNA, removing the intervening DNA allowing two genes to become juxtaposed |
-recombination signal sequence (RSS) -conserved -recombination activating genes (RAG1 and RAG2) |
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What are the two types of recombination signal sequence (RSSs)? A 12 bp spacer can only combine with a 23 bp spacer this is called what? For H genes there is a __ spacer behind each V heavy gene. a _ spacer in front and behind each D heavy gene, and a _ spacer in front of each J heavy gene What does the 12/23 rule ensure? |
-one turn RSS with a 12 bp spacer and a two turn RSS with a 23 bp spacer 12/23 rule or one turn/two turn rule (NO 12-12 or 23-23) -23 -12 -23 -That the V heavy genes cannot recombine with J heavy genes skipping the D heavy gens |
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*Special Note: The 12/23 rule applies to the light chains but the 12 bp and 23 bp spacers are opposite* what does this mean? |
-means that the V kappa gene is followed by the 12 spacer and the 23 spacer is in front of the J kappa gene, and the 23 spacer is in behind the V lambda gene and the 12 spacer is front of the j lambda gene |
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__ diversity is the random rearrangement of the VDJ genes of the H chains and the random rearrangement of the VJ genes of the light chain __ association of the rearranged H and L protein chains (any L chain can combine with any H chain) |
-Combinatorial diversity -Combinatorial association |
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What are the 3 types of junctional diversity? |
P nucleotide addition, junctional flexibility, N-nucleotide addtion |
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__ is when there is cleavage of the DNA within the palindromic heptamer by the RAG enzymes which will cause the formation of harpin loops in the DNA which then must be cleaved/opened by an endonuclease. What is the end result of the nuclease? What happens after the endonuclease does its job? What region is only affected by this action? |
-P nucleotide addition -(a symmetrical cut) overhang of nucleotides on one of the DNA stands leaving the different strands different lengths -DNA polymerase adds nucleotides to the shorter strand to make them the same length -CDR3 |
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__ is when one of the hair pin loops is opened by the endonuclease and the ends of the DNA are exposed. Now the exposed ends are subject to __ enzymes that will remove the nucleotides. How many nucleotides are removed by the exonuclease? Which chain is it most common in? What region is affected by this mechanism? |
-junctional flexibility -exonuclease -1-10 including the P nucleotides just added and the nucleotides from the original gene sequence -H chain -CDR3
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__ is when after the hairpin loop is opened, P nucleotides have been added and the exonuclease has trimmed nucleotides now more nucleotides can be added. The N nucleotides are added by what enzymes? Does the enzyme require a template? What region is affected by this action? Once this step has occured which genes can be brought together? Which chain does this occur in? why? |
-N nucleotide addition -TdT (terminal deoxynucleotidyl transferase) (adds about 1-10 nucleotides after the DNA polymerase uses the new over hang as a template to fill in the gap) -No (it creates a template) -CDR3 -D and J genes -H chains -TdT enzyme is not present in pre B cells when L chain rearrangement occurs
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What is the only mechanism that will generate genetic diversity after gene arrangement and after exposure to antigen? (in the periphery left the bone marrow) ___ introduces point mutations into the variable regions of the H and L chains, altering individual nucleotides but without altering the __ of nucleotides. This mechanism affects all of CDRs... why? |
-somatic hypermutation (SHM) -SHM -cause it occurs everywhere within the variable region (hypervariable and framework region) |
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What is the main role of SHM? what is that process called?
When does SHM and affinity maturation take place? What happens to the cells that gained affinity? no affect or decreased affinity? |
-is production of antibodies with a higher affinity for the antigen -affinity maturation -takes place during the process of antibody for the antigen which is present on the surface of follicular dendritic cells -receive survival signals from the FDC -they will undergo apoptosis *(this is why second and third exposure to an antigen produce antibodies with greater antigen affinity than those from a first exposure)*
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B cell development occurs in the __ and is dependent on bone marrow stromal cells and soluble factors (such as cytokines and growth factors) produced by these stromal cells. *development within the bone marrow occurs INDEPENDENT of antigen* What must the B cell have in order to survive the early stages of development? |
-bone marrow -productive rearrangement of the Ig H chain genes and L chain genes (either kappa or lambda) or cell dies by apoptosis |
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The Pro B cell stage is the rearrangement of the _ chain. __ are up regulated to initiate the VDJ rearrangement . In the early pro B cell __ is rearranged and in the late pro B cell _ is rearranging. There will be expression of __ at the end of this stage that are linked together by S-S bonds but are not linked to the M chain (codes for IgM) or surrogate light chain (light chain has not been rearranged yet |
-heavy -RAG (recombinase activating genes -D and J genes -V with DJ genes -Ig alpha and Ig beta |
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__ stage is when the Mu chains is synthesized and expression of the Mu chain is on the surface of the B cell along with the surrogate light chain (linked by a S-S bond). What forms the Pre B cell complex? __ and _ will remain associated with memebrane Ig molecules on all cells in the B cell lineage, in mature B cells these two molecules are part of the BCR along with membrane Ig (mIg). What signals the successful rearrangement of Heavy chains genes in the pre B cell? What stops the rearrangement of other allele? |
-Pre B cell (large) -the Mu chain, (14.1 and V pre B: which are the light chains), Ig alpha and Ig beta -Ig Alpha and Ig beta -Ig Alpha and Ig beta -cross linking by ligand on stomal cells |
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In mature B cells, _ and _ transmit a signal to the nucleus when the BCR binds to the antigen. Does Ig alpha or beta bind to the antigen? What happens to the cells that have succesful H chains? why do the do this? __ is when RAG genes are upregulated to initiate recombination of antibody L chain genes. Also L chain genes rearrangement occurs at this stage, cell now cease to express surrogate L chain genes 14.1 and V preB |
-Ig alpha and Ig beta -No -undergo several rounds of cell division to increase their number before L chain rearrangement begins -just in case L chain rearrangement is not successful they have many backups -small (resting) B cell |
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Immature B cell: Now L chains will pair with __ chain forming a complete BCR (IgM + Ig alpha and beta) on the surface. Interaction of the immature B cell with antigen within the bone marrow leads to ___ where cells may go under apoptosis or become anergic (non responsive to their antigen) but still circulate or the may undergo __ if they recognize self and now they are given a second chance which there is additional rearrangement of ONLY the L chain alleles and try to develop a BCR that does not recognize self antigen |
-Mu chain -self tolerance -receptor editing (only given once chance; for example if kappa recognized self now lambda will have shot to rearrange) |
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Immature B cells leave the Bone marrow with what Ig on their surface? Naive/mature B cells: the immature B cell will acquire what molecules that will distinguish them as a mature lymphocytes? What is done to the primary transcript in order to produce IgD on the cell surface? (this happens in the spleen) A mature/naive B cell will express what Igs on their surface? Further development of the mature B cell after this point occurs upon exposure to __ and is said to be antigen dependent |
-IgM -IgD, CR1, CR2, CD40 and L selectin -alternative splicing -IgM and IgD -antigen |
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When does antigen dependent development occur? Cells will undergo ___ and some become _ cells to secrete antibodies. In antigen dependent development, activated B cells undergo __ of their H and L chain CDRs, and activated B cells undergo isotype switching to produce what antibodies? |
-upon recognition of cognate antigen -clonal expansion -plasma cells -affinity maturation -IgA, IgG and IgE
*some cells also become memory cells when they undergo antigen dependent development* |
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B cells activation by T independent antigens: B cells can be activated by antigens with the help of __ cells (T dependent antigens) or by the antigen directly in the absence of CD4 T helper cells (T-independent antigens) T independent antigens will stimulate _ production in the absence of T cell help (CD4). B cell activation by TI antigens does not result in ___ (no isotype switching, this is like a primary response) |
-CD4 -antibody -memory |
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TI antigens results in what antibodies mostly? Are antibodies produced by TI activation less specific (no affinity maturation) and less numerous than TD (t cell dependent) activation? What is the required signal for full activation of B cells to differentiate into plasma cells? What are the two types of TI antigens? |
-IgM exclusively -yes -IFN gamma (produced by innate immune cells responding to infection) -TI-1 and TI-2 |
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__ are also called mitogens and result in the non specific activation of B cells and can activate both naive and memory B cells of ANY SPECIFICITY. __ antigens can only activate antigen specific mature B cells |
-TI-1 -TI-2 |
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__ antigens tend to be components of a bacterial cell wall. They are mitogens that can activate B cells through their __ receptors (much like PRR on macrophages (nonspecific)); they do not require __ cross linking. Activation of TI-1 antigen is called what type of activation? Are mitogens identical and present on all B cells? *LPS induced stimulation of B cells also require _ as a cofactor for IgM production* |
-TI-2 -mitogen -BCR -polyclonal activation -yes -IL-1 |
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__ are large repetitive epitopes (eg: capsular polysaccharides, flagella). The binding of these large repetitive epitopes by many BCR's causes __ and generates a very strong intracellular activation signal (eg: eliminates the need for CD40 interation with CD40L on the CD4 T cell). *what else do they recognize or bind to?* What does TI-1 and TI- have in common? |
-TI-2 -cross linking -also recognize CD21 that binds to C3d w/antigen to bind to BCR -both going to create plasma cells to create antibodies |
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People who cannot respond to TI-2 antigens are highly susceptible to infection by encapsulated bacteria and suffer from an immunodeficiency called what? The bulk of the pathogen specific antibody responses are produced through T cell ____ antigen activation |
-wiskott-Aldrich -dependent |
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Typical B cell activation by TD antigens: Antigen is encountered in the periphery by __ cells. The DC can present both processed antigen (to T cells) and intact (whole antigens) to __ cells. The DCs are retained in the paracortical region where their processed antigens (complexed to MHC class 2) are sampled by the __ T cells passing through. What are the two ways of B cells encountering antigen w/this classical pathway activation? |
-Dendritic Cells -B cells -CD4 -B cells can circulate normally into the lymph node/spleen where they encounter INTACT antigen on the surface of the DCs or FDC, or B cells encounter and bind antigen in the periphery and migrate to the lymph node/spleen where the B cell becomes the APC for the CD4 T cells |
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Upon BCR binding to its cognate antigen, __ and __ send the first signal for activation (What is the B cell called at this point?) Once the mIg on the B cell encounters its antigen, the antigen specific B cell and antigen specific T cell interact through surface proteins _ (on the B cell) and __ (on the T cell) . *This provides the second signal required to activate the B cell* |
-Ig alpha -Ig beta -Prime B cell -CD40 -CD40L |
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The activated B cell moves from the _ (where the B cells interact with T cells) to the __ (where the germinal center develops and several actions associated with the activated B cell occurs). What are the four actions that could occur when the B cell goes into the follicle? |
-paracortical region -follicle -Clonal expansion, somatic hypermutation and affinity maturation, iso-type switching, and differentiation into plasma and memory cells |
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During the process of affinity maturation, the B cells mutate their BCRs (this is called __) then leave the germinal center and interact with FDCs. Those with higher affinity BCRs will again receive the __ signal from the FDC and return to the germinal center to repeat the process of clonal expansion and somatic hypermutation. What will happen to the cells with decreased or no change in affinity? |
-somatic hypermutation -CD40/CD40L survival -they will die by apoptosis |
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Iso-type switching from IgM to the other antibodies also occurs in the germinal centers but the class produced depends on what? What happens to plasma cells after 2-4 weeks of secreting antibodies? Antigen -specific __ B cells (with higher affinity BCRs and an iso-type possibly other than IgM) may circulate or remain in the lymph node/spleen for its next encounter with antigen |
-the cytokines present -they will die (apoptosis) -memory |
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Full activation of Both B and T cells require how many signals? What is the first signal? And the second? What signal only occurs between the B and T cell that are specific for the same antigen? What is this phenom called? Now, activation of the CD4 T cell releases _ that in turn help activate the B cell and lead to further differentiation of the activated T cell (now a Th0 to a Th1 ot Th2) |
-2 -first signal is for B cell: BCR antigen interation cross-links the BCRs then Ig alpha and beta initiate the signal cascade to the nucleus -The second signal is co-stimulatory signal for B cells (CD40 on the B cell with CD40L on the T cell) -CD40 B cell with CD40L on T cell (the second signal) -linked recognition -cytokines |
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The CD40-CD40L interaction increases the expression of what molecules? What is the CD40-CD40L interaction required for? What cells express CD40? CD40's interaction with CD40L initially causes the upregulation of ___, followed by upregulation of ___, on B cells |
-MHC class 2, CD80, CD86 on the B cell -it is the required signal for B cell activation, iso-type switching (but specific iso-type is dependent on cytokines), production of memory B cells, required for affinity maturation -B cells, DCs, and FDCs -CD86 -CD80 |
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What cell is CD40L found on? What is the effect of lacking the CD40L receptor? What cell is CD80 (B7-1) present on? What is CD80 (B7-1) upregulated by? What receptors can CD80 (B7-1) bind to? What receptor does CD80( B7-1) has the greatest affinity for? What happens when CD80 (B7-1) binds to CD28? -CD80 (B7-1) preferentially stimulates __ response |
-Mostly on CD4 cells but a few on CD80 cells -undergo very little iso-type switching and suffer from hyper-IgM syndrome (pt more susceptible to infections) -APCs -CD40-CD40L interaction (after CD86 has been upregulated) -CD28 and CTLA-4 -CTLA-4 -provides second signal required for activation of T cell -Th1 response |
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CD86 receptors are present on what cells? They are upregulated by what interaction? What receptors do they bind too? They have the greatest affinity for which receptor? What does the interaction between CD86 and CD28 provide? CD86 preferentially stimulates a __ response |
-APCs -CD40-CD40L -CD28 and CTLA-4 -CD28 -provides a second required signal for activation of T cells -Th2 |
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__ receptor is present on T cells. CD28 interacts with which receptors that will provide the required co-stimulatory signal for full activation of the T cell? CTLA-4 is also present on T cells, How are they upregulated? What receptors do they interact with? The interaction of CTLA-4 with either CD80 or CD86 will do what to the T cell? |
-CD28 -CD80 or CD86 -upon T cell activation -CD80 or CD86 -terminates activation of T cells |
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Iso-type switching: The iso-type of the mIg depends mostly on what? Iso-type switching involves changes of Ig genes in __ B cells These changes result in the movement of __ next to a new __ gene; thereby changing the antibody lass (iso-type) and the effector function of the antibodies secreted (BUT NOT THE ANTIGEN SPECIFICITY) |
-the maturation state of the B cell (naive have both IgM and IgD, experienced cells have only one iso-type) -activated (these changes occur in the DNA) -V heavy gemes (VDJ) -Constant heavy genes |
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The molecular mechanisms of iso-type switching involve specialized sequences upstream (5') of each Constant heavy gene (except which gene?), called ___ (the small boxes in front of constant heavy genes) When the VDJ gene is moved next to the constant heavy gene what happens to the genes between? What determines the class of Ig to be mad |
-switch region -they are spliced out (meaning the cell will never be able to make those iso-types in the future because the DNA has been removed |
