Exam 2 Immunology

intraepithelial lymphocyte

(a type of CD8 T cell) it is activated - can be αβ or Υδ and express TCR with limited specificity

As we age our thymus shrinks, by a process called onvolution, yet T cell immunity is still functional in old age. 1) Explain how T cell numbers in the periphery remain constant in the abscence of continual replenishment from the thymus. 2) How does this differ from the maintenance of the B cell repertoire?

1) After thymic atrophy, T cells in the periphery self renew by cell division and are long lived. 2) B cells are short lived and replenish from immature precursors derived from the bone marrow.

B cells are activated by Th2 cells only if both cell types recognize the same antigen, though not necessarily the same epitope (cognate interaction). discuss why this characteristic is important in vaccine design.

1) If a polysaccharide is conjugated to a protein, peptides from the protein part of the molecule can activate specific Th2 cells. B cells specific for polysaccharide will bind and internalize the whole antigen via their antigen receptors, process it, and then present peptides on their surface. T cells specific for theirs peptides will interact with the B cell, delivering he necessary cytokines and the CD40-CD40 ligand signal required for isotype switching. The B cell will then produce IgG antipolysaccharide antibodies. 2)

MHCII deficiency is inherited as an autosomal recessive trait and involves a defect in the coordination of transcription factors involved in regulating the expressions of all MHCII genes (HLA-DP, HLA-DQ, HLA-DR) 1) What is the effect of MHCII deficiency? 2) Explain why hypogammaglobulin is associated with this deficiency

1) MHCII deficiency affects the development of CD$ T cells in the thynmus. If the thymic epithelium lacks MHCII, positive selection of CD4 cells will not occur. CD8 cells remain unaffected. 2) To produce antibody, B cells require T cell help in the form of cytokines produced by Th2 cells. Low immunoglobulin levels (hypogammaglobulin) in MHCII deficiency is attributed to the inability of B cells to proliferate and differentiate into plasma cells in the absence of Th2 cytokines.

1) At what anatomical sites do naive T cells encounter antigen? 2) In which sites specifically would a pathogen or its antigens end up, and how, if they entered the skin, entered the body from the gut, or into the bloodstream? 3) How do naive T cells arrive at these sites? 4) Do all T cells leave these locations after priming, and if so, how?

1) Naive T cells encounter antigen and start the primary immune response in a secondary lymphoid tissue. 2)Lymph nodes: The pathogen and dendritic cells that have ingested the pathogen are carried to the nearest lymph node in afferent lymph. Gut: Pathogens enter GALT via specialized M cells in the gut epithelium. Spleen: pathogens circulating in the blood enter the spleen directly from the blood vessels that feed it. 3) Naive T cells are delivered to all secondary lymhoid organs from the blood. The y can also pass from one lypmh node to another via a lymphatic. 4)After activation by antigen only CD8 T cells and Th1 cells exit the lymphoid tissue via efferent lymph, which delivers them eventually into the blood in search of infected tissues. Antigen activated Th2 cells remain in the lymphoid tissue to help provide antigen specific B cells.

Place the following phases of a B cell's life history in the correct chronological order

1) Repertoire assembly 2) Negative Selection 3) Positive selection 4) Searching for infection 5) Attacking infection

Place the following stages of B cell development in the correct chronological order

1) Stem cell 2) Early pro B cell 3) Late pro B cell 4) Large pre B cell 5) Small pre B cell 6) Immature B cell

1) Which selectins, mucin-like vascular addressins and integrins have a role in the circulation of T cells between the blood and lymphoid tissues? 2) Describe in chronological order how T cells migrate across lymph node high endothelial venules (HEVs) from blood by using these molecules.

1) T and B cells express L selectin, which binds to sulfated carbohydrates of mucin-like vascular addressins in HEVs. Three types of mucin-like vascular addressin are involved: Gly-Cam1 and CD34 expressed on lymph node HEVs, and MadCAM1, expressed on mucosal endothelium. 2) Chemokines my by the endothelium and bound to its extra cellular matrix induce the T cellst express LFA1, an integrin. LFA1 binds with high affinity to an intracellular adhesion molecule, ICAM1, expressed on the epithelium. Finally, the T cell squeezes between the endothelium junctions, a process called diapedesis, and gains entry into the lymph node.

Three main classes of effector T cells are specialized to deal with different class of pathogens and produce different kinds of cytokines. 1) Name these three classes 2) For each class, describe how antigen is recognized and the corresponding effector function 3) Give a general example of an antigen for each class

1) Tc cells, Th1 cells, Th2 cells 2) Tc cells recognize antigen on the surface of a cell that is presenting antigen bound by MHCI molecules The Tc cell responds by inducing the apoptotic pathway. Th1 cells recognize antigen bound to MHCII molecules. The TH1 cell responds by activating the macrophage to destroy intravesicular bacteria and increase the phagocytosis of extracellular bacteria is has taken up. Th2 cells recognize antigen bound to MHCII molecules. Th2 responds by secreting cytokines that will activate B cells into differentiating into antibody producing cells. 3) T ce cell antigens are derived from proteins from pathogens replicating in the cytosol of the target cell. Typical Th1 cell antigens are proteins from bacteria that live in vesicles inside of macrophages. Typical Th2 antigens are derived from protein components of pathogens circulating in the blood or tissue fluids.

What is the role of Treg? How can Treg cells be distinguished from other CD4 cells?

1) Treg suppress the proliferation of naive autoreactive CD4 T cells by secreting inhibitory cytokines. 2) Treg expresses CD25 on their surface and the Foxp3 transcriptional repressor protein

1) Describe the morphology of a granuloma. 2) Which types of infection would lead to the formation of a granuloma? 3) Why is this type of pathology actually beneficial to the host?

1) a granuloma consits of macrophages and giant multinucleated cells created by macrophage fusion, infected with bacteria that are replicating intracellularly. Epitheliiod cells surround the core, which consits of nonfused macrophages.. Epithelioid cells are surrounded by activated CD4 cells. 2) Chronic infections resistant to the killing mechanisms of macrophages can lead to the formation of granulomas. 3) Granulomas surrounded by CD4 T cells cut off the infection from the blood supply, and the cells in the core of the granuloma will die from oxygen deprivation and toxic products of the macrophages. If the infection were not localized in this fashion, it could disseminate systematically to other anatomical locations.

The expression of MHCII molecules is restricted to a small number of cell types. 1)What are these cell types? 2) Which of these cells populate the thymus or circulate through it, and what role do they play in mediating positive/negative selection?

1) cells that express MHCII are professional antigen presenting cells, thymic epithelial cells, neural microglia, and activated T cells. 2) MAcrophages, dendritic cells and thymic epithelial cells either populate the thymus or circulate through it. Cortical epithelial cells participate in positive selection by presenting MHC I an II molecules to double positive thymocytes. Only T cells that can interact with self MHC are positively selected. Thymic epithelial cells, circulating macrophages, and dendritic cells participate in negative selection and aid in the elimination off potentially self reactive T cells bearing high affinity receptors for self-peptides:self-MHC.

sIgA can bind pathogens in several different locations:

1) lamina propria 2) epithelial cell endosomes 3) gut lumen 4) M cell surface 5) M cell endosomes

1) Which cell surface glycoprotein distinguishes professional antigen presenting cells from other cells and is involved in the co-stimulation of T cells? 2)What receptors can it bind on the T cell and what signal does it deliver in each case? 3) Explain why the consequence of antigen recognition by T cells in the absence of this glycoprotein on the antigen presenting cell.

1) of B7, a co-stimulator molecule, distinguishes professional antigen presenting cells from other cells. 2) When B7 binds to CD28, an activation signal is delivered and T cells undergo clonal expansion and differentiation. This interaction requires that the T cell receptor and CD4 co receptor are engaged specifically with the peptide:MHC II complex. VTLA4 then binds B7 with higher affinity than CD28. An inhibitory signal is is delivered to the T cell when B7 on the professional antigen presenting cell binds to the CTLA4. This mechanism serves to regulate T cell proliferation and to suppress T cell activation after an immune response. 3) If they engage antigen in the absence of B7 ecpression and hence, co-stimulation, T cells will become irreversibly non-responsive (anergic) instead of activated. This is one mechanism by which T cell tolerance may be achieved.

In T cells, allelic exclusion of the a chain locus is relatively ineffective, resulting in the production of some T cells with two T cell receptors of different antigen specificity on their cell surface. 1) Will both these receptors have to pass positive selection for the cell to survive? 2) Will both receptors have to pass negative selection to survive? 3) Is there a potential problem for having T cells with dual specificity surviving these selection processes and being exported to the periphery?

1)Only one of the receptors will have to be postively selected to survive. 2) In contrast, both receptors will have to pass negative selection to survive. 3) Yes. If the T cell is activated by an antigen, but survived with a receptor with high affinity for a self peptide, it can then respond to that self peptide without any co-stimulatory signals to activate it.

Which if the following would occur after the production of a functional u chain as a pre b cell receptor? A) RAG proteins are degraded b) the chromatin structure of the heavy chain locus is recognized to prevent gene rearrangement C) Transcription of the RAG1 and RAG 2 genes ceases 4) There is allelic exclusion of a second u chain. 5) all of the above

5

*****Describe the course of events that results in the swollen lymph nodes characteristic of many infections.***** essay question

B lymphoblasts that have bound specific antigen and encountered their cognate T cells in the T cell areas of a lymph node are activated and start to proliferate, forming a primary focus. THje B cells move from the primary foci into primary follicles, which are primarily B cell areas, where they become centroblasts (large diving cells). As centrobloasts accumulate and proliferate, the primmary follicles enlagrs and forms a germinal center. Centroblasts undergo somatic hypermutaton producing centrocytes with mutated surface immunoglobulin. Only cells with mutated surface immunoglobulinn that can take up antigen efficiently through receptor mediated endocytosis and present it to Th2 cells will be selected to differentiate into plasma cells. Antigen will be encountered at the surface of collicular dendritic cells as an immune complex. I B cells do not encounter their specific antigen, they will undergo apoptosis. This process takes about 7 days after an infection begins, and the increase in cell number accounts for swollenn lymph nodes.

Do you think B1 cells should ne categorized as participants in the innate or adaptive immunity response.

B1 cells are probably best associated with innate immunity because of their rapid response to antigen, their limited diversity, and their polyspecificity

Give the three properties that distinguish B1 cells from B2 cells

B1cells express the cell surface protein CD5, possess few N nucelotides at VDJ junctions, and have a restricted range of antigen specificities. They produce IgM antibodies of low affinity and respond mainly to carbohydrates rather than proteins, epitope. B1 are polyspecific for antigen: their immunoglobulins bind several different antigens.

Mature B cells undergo somatic hypermutation after activation, which, after affinity maturation, results in the productions of antibody with a higher affinity for antigen than in the primary antigen response. Suggest some reasons why T cells have not revolved the same capacity.

Because T cells dive almost all immune response, once they have been activated their receptors must continue to recognize the exact complex of foreign antigen and MHC molecule that activated them to be effective, Somatic hypermutation might make it unable to respond the the antigen, making it unable to activate the necessary B cells or attack infected cells, in the case of a Tc.

What is the importance of the bone marrow stroma for B cell development?

Bone marrow stromal cells provide the necessary environment for B cell development by expressing secreted products and membrane bound adhesion molecules. For example, V cam-1 adhesion molecule binds ti the integrin VLA-4 on early B cell progenitors. Cytokines such as IL-7 have ab important role in later stages of B cell development, serving to stimulate the growth and cell division of late pro B and pre B cells.

CCL25 binds T cell receptor

CCR9

Explain why Cd40 ligand expression on T cells is important in the T cell zone of secondary lymphoid tissue and how this contributes to the formation of the primary focus

Cd40 ligand on T cell bidns to CD40 on B cells, signalling B cells to activate NFkB, which is a transcription factor that upregulates the expression of ICAM-1 on the surface of B cells. ICAM1 prolongs the interaction between B and T cells in the T cell zone, trapping the B cell in the T cell zone and causing a primary focus of proliferating B cells to form

What are the two main check points of B cell development in the bone marrow?

Check point 1 is the formation of a complex of a u heavy chain with the surrogate light chain VpreBγ5, Iga and IgB. Checkpoint 2 is when a complete B cell receptor (u heavy and either K or γ chains) Iga and IgB chains are expressed on the B cell surface

Explain how these two checkpoints correlate with the process of allelic exclusion that ensures that only one heavy chain locus and one light chain locus produce functional gene products

Checkpoint 1 delivers an important signal to the cell, verifying that a functional heavy chain has been made. This triggers the cessation of heavy chain rearrangement followed by the inactivation of surrogate light chain synthesis. Thus only one heavy chain locus ends up producing a product. As surrogate light chain becomes unavailable, u accumulates in the endoplasmic reticulum , ready to bind to functional light chain when that is synthesized after successful light chain rearrangement. Check point 2 signals the cessation of light chain rearrangement. This ensures that only one light chain of the possible four produces a functional product.

_______guides lymphocytes into gut tissue

Chemokine CCL25

Why are dendritic cells more efficient than macrophages at stimulating naive T cells?

Dendritic cells are migratory and transport antigen to neighboring secondary lymphoid tissue.

Explain how poly Ig receptor transports dimeric IgA antibodies across the cellular barriers and specify which type of cell barrier(s) are involved. What are the final locations of the transported material?

Dimeric IgA is made in mucosa associated lymphoid tissue (MALT) and is transported across the barrier of the mucosal epithelium. First, dimeric IgA binds to the poly-Ig receptor on the basolateral surface of an epithelial cell, followed by uptake through receptor mediated endocytosis in a vesicle. Upon reaching the opposite face of the cell, the vesicle fuses with the membrane. Here the polyIG receptor is cleaved, thus releasing the IgA into the mucous layer on the surface of the epithelium. Dimeric Iga remains attached to a small piece of the pol-yIg receptor, called the secretory component, which holds IgA at the epithelial surface through interactions with molecules in the mucus.

Explain the origin of the secretory component and the significance after the release of dimeric IgA from the apical face of the gut epithelium.

During transcytosis the poly Ig receptor is cleaved leaving a small piece of the original receptor called the secretory compomnent still bound the the J chain via disulfide bonds. Once dimeric IgA is released at the apical face, the carb molecules of the secretory component anchor the antibody to mucins of the mucus, enabling the antibodies to bind subsequently to microbes in the mucus and inhibit the ability of microbes to bind and invade to mucosal epithelium of the gut.

Which of the following statements regarding negative selection of B cells is correct? A) negative selection is a process that occurs in the bone marrow but not in secondary lymphoid tissues.b) Negative selection is a process that occurs in the bone marrow but not in secondary lymhoid organs. c) negative selectiopn ensures that B cells bearing recptors for pathogens that will not be encoutered in a person's lifetime are eliminated to make room for B cells bearing useful receptors. d) negative selection eliminates Bcells at the end of an infection as a means of terminating an immune responses

E

T/F Plasma cells produce secreted antibody, proliferate and undergo somatic hypermutation to produce antibodies with a higher affinity for antibody.

F. Plasma cell is terminally differentiated B cell that is not dividing and cannot change its antibody specificity.

Unlike innate immune responses, which can begin within hours of the onset of an infection, adaptive immune responses involving T cells usually take several days. What accounts for this delay between the initiation of an infection and the engagement of an adaptive immune response?

First antigen needs to be transported to a nearby secondary lymphoid tissue, processed, and presented by antigen presenting cells to naive Tc cells of Th cells to activate the,. Second, the number of T cells specific for a fiven pathogen will be only around 1 in 10,000 to 1 in 100,00 of the circulating T cell repertoire; thus it can take some time before the relevant T cells circulating through the secondary lymphoid tissues reach the tissue containing the antigen that will activate them. Finally it takes several days for an activated T cell to proliferate and differentiate into a large clone of fully functional effector T cells.

In what ways is the thymic situation of expression and processing of self antigens advantageous fore the purposes of negative selection?

Generating a more comprehensive repertoire of self peptides in the thymus increases the types of potentially autoreactive T cells that are removed from he peripheral T cell repertoire during negative selection.

What would be the effect of the anti-IL-7 antibodies on the development of B cells in the bone marrow, and at which stage would development be impaired?

If anti-IL-7 antibodies were introduced into this environment, developing B cells would be stopped at the late pro-B or pre B cell stage of development.

naive B cells activated in Peyer's patches and mesenteric nodes isotypic switch to

IgA (directed by cytokine TGF-β) -synthesize intact J-chain-linked dimers -transcytose by poly-Ig receptor

Where does transported IgG end up?

IgG antibodt binds to FcRn in the membranes of endothelial cells in blood cappilary walls and is transported by receptor mediated transcytosis from the blood into extracellular spacdes in tissues. IgG is transported into infected tissues and is also transported across the placenta.

What isotype of antibodies are passed through placental transfer and in breast milk?

IgG is transferred placentally, while IgA is found in breast milk.

Why is IgM efficient at preventing blood borne illnesses and fixing complement, but less efficient than other antibody classes in inducing phagocytosis

IgM is the first antibody to be produced, and is secreted in pentameric form that circulates in the blood. Because of its large size, it does not penetrate into infected tissues.

GI Tract

Immune cells within epithelium and in lamina propria (underlying connective tissue);

Describe how immunoglobulin expressed during a primary immune response differs qualitatively and quantitatively to immunoglobulin from a secondary response

Immunoglobulin expressed during a primary immune response is mostly IgM in low concentration and of low antigen affinity. Immunoglobulin in a secondary response has undergone isotypic switching and is often IgG. It has a higher titer and higher antigen affinity because it has undergone somatic hypermutation.

Cyclosporin A is an immunosuppressive drug commonly used in transplant patients to prevent graft rejection by alloreactive T cells. ITs acts by interfering with the signaling pathway that leads from T cell receptor to transcription in the nucleus of the genes for the cytokine IL-2 and the a chain of the IL2 receptor. Why does preventing the transcription of these genes lead to immunosuppression?

In an immune response, the binding of IL2 to a high affinity IL2 receptor composed of a, B or gamma chains drives the proliferation of T cells that occurs after they have encountered their specific antigen. The activated T cell will divide two or three times daily for about a week, producing a clone of thousands of identical antigen specific effector T cells. In the absence of IL2 and its high affinity receptor, T cells will not become fully activated, will not differentiate, and will not undergo clonal expansion. Cyclosporin prevents the clonal expansion of T cells specific for the foreign antigens on the graft and their differentiation into effector T cells, and thus suppresses the immune response against the graft.

lymphocytes express _____ and ______ which bind specifically to mucosal ______

L-selectin and integrin α4:β7;vascular addressin MAdCAM-1

Explain why immunological memory is important in acquired immunity

Memory enables faster, more efficient recall responses when antigen is encountered subsequently. This enables the body to get rid of a pathogen be fore it has time to cause disease.

specialized defense:

Mucosa secretions have approximately 75% of the lymphocytes in the body. 75% of all antibodies is sIgA.

What would be the results if terminal deoxynucleotidyl transferase (TdT) were expressed throughout the whole of small pre-B cell development?

N nucleotides would ne added at the VJ joints of all rearranged light chain genes during gene rearragnement (instead of half), resulting in an increase in immunoglobulin diversity.

What is meant by passive immunity?

Protective immunity acquired by the transfer from another's antibody-containing serum.

Waldeyer's Ring

Ring of Lymphoid Organs Guard entrance to GI and RT. Consists of: adenoid, palatine tonsil, lingual tonsil, tongue.

An antibody dependent cell mediated cytotoxicity is mediated by NK cells, which use their Fc receptors to bind antibody coated target cells which they kill through inducing apoptosis

T

T/F An immunodeficiency called hyper IgM syndrome is characterized by the lack of CD40 ligand expression on T cells.

T

T/F In adults the mature T cell repertoire is self renewing and does not need a thymus for provision of new T cells.

T

T/F Physical association between Treg and its target cell is mandatory for Treg function.

T

T/F T reg secrete TGF-B and suppress effector T cell function

T

Antigen reconition by T cells in the absence of co-stimulation results in

T cell anergy

During the early developmental stages of a:B T cells in the thymus, there are two key checkpoints that must be satisfied to permit the progression of T cell development. Describe these two checkpoints.

THe first checkpoint occurs after the rearrangement of the B chain locus, which tests for the ability of the B chain to associate with pTa, the surrogate light chain, and form the pre T cell receptor on the cell surface. The second checkpoint occurs after the rearrangement of the a locus, which tests for the ability of the a chain to associate with the B chain and from the T cell receptor on the cell surface.

Give an example of both a TI-1 and TI-2 antigen and describe how antigens bypass the need for T cell help.

TI-1: LPS. LPS engages the BCR and coreceptor as well as TLR that drives the B cell into activation, differentiation, and proliferation. TI-2: highly repeptitive protein or carb epitopes on the surface (capsules). The B cells that respond to TI-2 antigens are often B-1 cells and both IgM and IgG can be produced, though IgM is predominant. TI-2 bypass T cell help because crosslinking is efficient, generating strong signals from the BCR.

TI-2 polysaccharide antigens are commonly used in vaccines administered to infants because they stimulate strong antibody responses.

TI-2 polysaccharide antigens only activate only mature B -1 cells, which do not acquire full function until a child is about 5yrs of age.

Virus infected cells attacked and killed by effector Tc cells are often surrounded by healthy tissue, which is spared from destruction. 1) Explain the mechanism that ensures that Tc cells kill only the virus infected cell 2) what cytotoxins do Tc cells produce?

Tc cells focus their killing machinery on target cells through a process called polarization. The cytoskeleton and the cytoplasmic vesicles containing lytic granules are oriented toward the are on the target cell where MHCI molecules are engaging the T cell receptors. In the T cell, the microtubule organizing center, golgi apparatusm and lytic granules, which contain cytotoxins, align towards the target cell. The lytic granules fuze with the cell membranem releasing their contents into the small gap between the T cell and the target cell, resulting the the deposition of cytotoxins on the sruface of the target cell. The Tc cell is not killed in the process and continues to target other cells. 2) The cytotoxins produced include perforin, granzymes, and granulysin, all which induce apoptosis of the target cell.

Cross-linking of immunoglobulin by antigen is essential but not always sufficient to initiate the signal cascade for B cell activation. Stimulation of additional receptors is also necessary for the full activation and differentiation of naive B cells. Describe these receptors and their ligands, and outline how they help activate the B cell.

The B cell coreceptor, made of CD21 CD19 and CD81, cooperates with the BCR in the B cell activation and increases the sensitivity of the B cell to antigen. CD21 binds to complement components that have been deposited on the surface of pathogens like C3d. CD19 provides the long cytoplasmic tail involved in signaling. When the coreceptor and BCR are both ligated by antigen and C3d, Lyn and he cytoplasmic tail of CD19 come close together. Lyn is bound to the ITAMs of Iga which phosphorylates CD19 when its nearby. The phosphorylated CD19 tail will initiate activation signals that complement those generated by the BCR complex. An dditional signal from Th2 may be needed. Th2 express CD40 ligan, which binds to CD40 on the B cell surface. They also secrete IL-4 5 and 6. This helps the B cells differentiate into plasma cells.

What are the roles of the following molecules in the signal transduction pathway leading from the T cell receptor: CD3 complex; protein tyrosine kinase Lck; CD45; Zap-70; the ζ chain; IP3; calcineurin?

The CD3 subunits gamma, delta, and epsilon associated iwth the antigen binding T cell receptor help trasnmit the signal from th T cdell receptor-peptide-MHC interaction at the surface of the cell into the interior of the cell through immunoreceptor tyrosine activation motifs (ITAMS) present on their cytoplasmic tails.; Lck associates with the tails of the CD4 and CD8 co receptors. When these participate in binding to peptide:MHC complexes, Lck is activated and phosphorylates Zap 70; CD45 is a cell surface protein phosphatase that helps activate Lck and other kinases by removing inhiibitory phosphate groups from their tails.; When Zap70 is phosphorylated it binds to the phosphorylated ITAMS of the zeta chain, which initiates the signal transduction cascade by activating PLC gamma; IP3 causes an increase in intracellular calcium levels.; Calcineurin activates the transcription fact NFAT by removing an inhibitory phosphate group. Activated NFAT enters the nucleus, and together with NFkB and AP-1, initiate the transcription of genes that lead to T cell proliferation and differentiation.

The surrogate light chain operating during pre B cell development is made up of VpreBλ5. Its expression with u on the pre B cell surface is an important checkpoint in B cell maturation. Name the T cell analog of VpreBλ5 and discuss how it is functionally similar.

The analog of VpreBλ5 in developing T cells is pTa which combines with the T cell receptor B chain, the first of the two T cell receptor chains to be expressed, to form the preTcell receptor. The B chain, like the immunoglobulin heavy chain, contains VDJ segments. pTa also binds CD3 and zeta components to this complex, and the assembly of the complete complex induces T cell proliferation and the cessation of rearrangement at the TCRB locus.

What is the main effector function of IgM?

The main effector function of IgM is complement activation. in the classic pathway, a single penntameric IgM can initiate complement activation because two Fc regions are needed to bind C1. It can also neutralize pathogens and toxins.

What are the characteristics of follicular dendritic cells in the primary follicles of secondary lymphoid tissues?

They provide a stable depository if intact antigens able to bind to B cell receptors. They also have a large surface area as a result of forming dendrites.

Explain the difference between thymus dependent antigens and thymus independent antigens.

Thymus dependent antigens can only induce the generation of antibodies with the help of T cells. They induce immunological memory as well as affinity maturation after somatic hypermutation. Thymus independent are able to activate B cells without the presence of a T cell. These antigens do not induce isotype switching or somatic hypermutation or affinity maturation.

What is the role of primary lymhoid follicels in eliminating B cells that have antigen receptors specific for soluble self antigen?

To survive, circulating B cells must enter primary follicles where survival signals are delivered by cells in the follicles, including FDCs. Circulating B cells that fail to enter follicles in secondary tissue will die in the peripheral circulation. B cells with antigen receptors specific for soluble self antigen are rendered anergic in the bone marrow or the circulation. Anergic B cells that enter the secondary lymphoid organs area held in the T cell areas adjacent to the primary follicles and are not permitted to penetrate the follicle. As a result, they undergo apoptosis.

How does IgE induce the forcible injection of parasites?

When IgE binds to an antigen, leading to cross linkage of FCε RI on mast cells in connective and mucosal tissues, the mast cells rapidly release chemicals that activate smooth muscle to contract. Muscle activity leads to vomiting and diarrhea, or sneezing and coughing, in an effort to expel the toxic material or pathogen.

In other parts of the body vs infection in a peyer's patch:

activated B and T cells will enter circulation and focus on inflamed tissues, and there is a localized response; they attract to ALL lamina to prevent further spread of disease.

Skin impermeable to microbes but gut _____ so immune response is initiated ____pathogen can breach epithelial barrier and colonize lamina propria

actively moniters contents; before

The activated lymphocytes enter _____

all the submucosal lymphoid not just the ones in which the immune response originated This defends against the spread of infection

Individuals with a defective AIRE gene exhibit

autoimmune polyendicrinopathy candidiasis ectodermal dystrophy (APECED)

The function of negative selection of thymocytes in the thymus is to eliminate

autoreactive thymocytes

gut homing efector T cells bind

bind intestinal vascular epithelium

Immunological tolerance in the B cell repertoire is called _____ tolerance when it develops in the primary lymphoid organs and ______ when it develops outside the the bone marrow

central; peripheral

mucosa sustains a ______immune response due to constant sampling

chronic adaptive

Effector T cells activated in Peyer's patches

circulate in blood and re-enter mucosal tissue by recognizing mucosal addressin MadCAM-1 present on endothelial cells of small blood vessels lining the walls of the gut

An adjuvant enhaces the effectiveness of vaccines by inducing the expression of _____ on _____

co-stimulatory molecules; dendritic cells.

By interacting with _____ cells in secondary lymphoid tissue, reg prevent the interaction and activation of naive T cells.

dendritic cells

transcytosis

dendritic cells process and present antigen and migrate from dome to Peyer's Patch or mestenteric lymph node to stimulate antigen specific naive T cell

major challenges:

eliminate pathogens limit commensals do not attack food

naive B and T cells from the bone marrow and thymus can re-circulate through both mucosal and spleen/lymph node (systemic)

enter HEV (Peyer's patch or mesenteric node) no activation then leave by efferent lymph naive lymphocytes activated in Peyer's patch —> differentiate into effectors and memory cells —> lose CCR7 and L-selectin —> lymph and blood —> home in on ALL lamina propria of mucosal tissue (not just infected area)

Dendritic cells can ______across epithelium and capture antigen from gut lumen

extend processes

only lymphocytes that encounter antigen in GALT will express

gut-homing receptors and integrins;this tissue specificity demands that vaccination vs intestinal infections (polio) be delivered to site where natural responses to infection are made.

most antigens are innocuous and do not cause inflammation because _______

he macrophages lack TLRs and other signaling devices

Peyer's patches

in intestinal wall (overlaid with follicle-associated epithelium). between 5-200 B cell follicles. germinal centers and T cell areas with dendritic cells

T cells destined to become ________ expressαE:β7 (binds E-cadherin)

intraepithelial lymphocytes

GALT ____ initiated response as well as _________ defend the gut

locally; draining mesenteric lymph nodes (if the infection is in other parts of the body, immune response is usually distant from site of infection)

naive lymphocyte enters peyer's patch activated lymphocytes return to blood via

mesenteric lymph nodes and recirculate to ALL mesenteric tissue

effector T cells activate intestinal macrophages to phagocytose and with

minimal inflammation

small intestine:

most heavily invested with lymphoid tissue

isolated lymphoid follicles

mostly B cells

Most pathogens pass through ____verses skin

mucosal surfaces

If a T cell receptor on a double positive thymocyte binds to a self-peptide:MHCI complex with low affinity the result is ____. If a T cell receptor on a double positive thymocyte binds to a self-peptide MHCII complex with low affinity the result is _____

positive selection of a CD8 T cell; positive selection of a CD4 T cell.

purpose of mucosal IR is to

restrain microbes and not remove them this applies to both commensals and pathogens

B cells develop into plasma cells and make

sIgA

M (microfold) cells

take up microbes and transfer to Peyers patch direct drainage to mesenteric lymph nodes. they are specialized for pathogen uptake and continually sample gut flora.

What are the properties of the mucosal tissues

thin, dynamic, permeable barriers and vulnerable to infection. Why?gas exchange, food adsorption, sensory (eye, nose, mouth, throat), reproduction

Double negative thymocytes initiate rearrangement at the ____ locus befor all other T cell receptor genes

β, γ, δ

Which if the following is true of centrocysts? a) somatic hypermutation has occurred. b) they are large proliferating cells c) isotype switching is complete. d) they produce secreted forms of immunoglobulins e) they lack MHCII molecules on their surface

A,C

A plasma cell is characterized by?

ABE It differentiates in the medulla of lymph nodes and in the bone marrow. It dedicates 10-20% of total protein synthesis to antibody production. It produces secreted immunoglobulin instead of the membrane bound form.

What are the similarites between the activation of mast cells and NK cells via FCγRIII? What are their differences?

Activation of both mast cells and NK cells occurs only when their Fc receptors are bound to antigen:antibody complexes. Wehn crosslinking occurs, both mast and NK cells release granules. Mast cells bind IgE- NK binds IgG; Mast cell exocytosisis random- NK cell exocytosis is polarized

Explain 2 ways in which expression and processing of self antigens in thymic epithelium differs from the expression and processing of self antigens outside the thymus.

As well as expressing their own thymus specific self antigens, medullry epithelial cells in the thymus produce a transcirption factor call AIRE, which causes several hundred genes normally expressed in other tissues to be expressed in these cells. The proteins can then be processed to for self-peptides that will be presented by MHCI molecules. The thymic epithelium uses different proteases for self-protein degradation; cathepsin L is used instead of cathepsin S, which is used by other cell types.