Quiz 2
Binding of peptide antigens to MHC Molecules
"promiscuous binding specificity" for peptide Ags = can potentially bind many different peptide sequences (* looks like a hot dog)
Isotype switching
- DNA rearrangement between the constant regions resulting in an exchange of the Cmu coding region for one of the constant regions - activation induced cytidine deanimase (AID) - cells can change which isotype of antibody they produce when stimulated by specific cytokines
Alpha-Beta vs. Gamma-Delta T cells
- Expressed by T cells - Gamma are less abundant than Alpha-beta and play a limited functional role, Gamma are not MHC restricted
explain the role of follicular dendritic cells (FDCs) in B cell maturation
- NOT of hematopoeitic origin; thus not considered leukocytes. - do not express MHC class I - do not function as antigen presenting cells for the activation of T cells - function is to provide stimulatory signals that promote B cell survival and maturation - B cells activated by FDCs will live much longer
Explain the function of tTreg cells
- T reg cells that mature in the thymus - The function of T reg cells is to suppress the action of potentially auto reactive T cells in the periphery and, accordingly, T regs constitute an important functional component of peripheral tolerance t
IgE
- associated with allergic inflammation due to its ability to sensitize mast cells and basophils - protects roll in response to helminthic parasites
Understand the role of the surrogate light chain
- block further H- chain rearrangement - signal proliferation - signal light chain rearrangemnt
TCR/co-receptors with Ag/MHC , binding to MHC class II or I
- co-receptors bind outside peptide binding regions - TCR recognizes and binds to both peptide Ag and MHC - CDB binds the a3 domain of MHC class 1 (not involve in antigen binding) - CD4 binds the b2 domain of MHC class II (not involve in antigen binding)
CD8 T cells
- cytotoxic T cells (CTL) - recognize peptide antigens presented by MHC class I molecules - enable recognition of antigens expressed by diseased or infected cells - main function is to induce death of target cells
How do P and N additions contribute to junctional diversity and whats their relationship to hypervariable regions?
- during recombination, random nucleotides can be added to the exposed end, these are called N-additions. - hairpin DNA loops created during recombination can be opened up and refilled by DNA repair enzymes to create P-additions - hyper variable regions are created by the junctional diversity mechanisms
Fluorescence ActivatedCell Sorting (FACS)
- enables the labeled cells to be physically separated and counted from those who are not labeled with antibody. - useful for identification of different types of leukocytes based on differential expression of CD molecules
exogenous antigens
- extracellular proteins - endocytic processesing pathway - presentation on MHC class II to CD4 T cell - originate outside of a self cell
structure and profiles of MHC class II
- heterodimer: beta chain and alpha chain - 2 domains in each with peptide binding groove between b1/a1 - expressed by "professional" APCs - antigen presentation to CD4 T cells
IgA
- humans have 2 subtypes - predominant in the body's secretions including mucous and breast milk (passive immunity for new borns) -secreted form is usually a dimer with 4 antigen binding sites - resistant to proteolytic enzymes
Explain the role of adhesion molecules and co-stimulatory molecules in the APC mediated activation of a T-cell
- initial non-specific binding between T cell and APC mediated by adhesion molecules The physical interface between the APC and the T cell is referred to as the immunological synapse the binding of cell surface adhesion molecules between a T cell and an APC serve to stabilize the cell-cell interaction independently of the possible antigenic specificity. activation of T cell requires co-stimulatory signals from other cell surface protein interactions between the T cell and the APC. Ex: CD28 interacts with B7
endogenous antigens
- intracellular proteins - cytosolic processing pathway - presentation on MHC class I to CD8 T cells - originate inside a cell, a self cell
Describe the cellular organization of the thymus gland
- located above the heart - organized into lobules - cortex densely packed with thymocytes and cortical epithelial cells - medulla is less densely packed and contains thymocytes, medullary epithelial cells macrophages, dendritic cells
Describe the phases of B cell antigenic activation that occur in a lymph node
- mature naive B cells encounters Ag - Activation via partnership with T helper cells - migration to primary follicle - Proliferation and differentiation in germinal centers - plasma cells migrate to medulla (some to bonemarrow)
immunoglobulin structure
- membrane and secreted - bind free antigens - 2 Ag binding sites (bivalent) - bind protein, carbohydrates, lipid and nucleic acid antigens, small molecules
TCR protein structure
- membrane only, short cytoplasmic tails - require antigen presentation via APC - always associated with CD3 complex - 1 Ag binding site (monovalent) - bind peptide antigens i MHC pocket
IgG
- most abundant isotype in the serum - predominates in most secondary responses Four subtypes: IgG1, IgG2, IgG3, IgG4
Describe the process and outcome of negative selection and explain the role of AIRE
- must survive positive selection first - Thymocytes that bind too tightly to thymic APCs die by apoptosis. - negative selection process results in clonal deletion of otter reactive T cells and constitutes the other half of central tolerance. - AIRE protein is a transcription factor expressed in thymic epithelial cells and it plays an important role. AIRE stands for Auto ImmuneRegulator and it functions to induce expression of hundreds of tissue specific proteins that are then presented on MHC molecules to the developing T cells.
Define central tolerance
- negative selection of immature B cells and T cells - it is not perfect some self reactive T and B cells can slip through
Describe the process and outcome of positive selection
- occurs at double positive stage of thymocytes development - alpha-beta TCR is fully formed and displayed on the thymocytes surface and the thymocytes express both CD4 and CD8 co-receptors. - Thymocytes are given an opportunity to test out the functionality of their TCR by interacting withMHC molecules displayed on the surface ofthymic epithelial cells - Thymocytes that are notable to engage with the MHC will die, while those that are capable of moderate binding are positivelyselected for survival. Only functional TCRs capable of interacting with self MHC survive the functional role of aT cell is either a helper T cell or a CTL is largely determined by the process of positive selection in the thymus based on the interaction with MHC.
rearrangement and modifications of TCR genes in T cells
- occurs during T cell development in thymus - mediated by RAG1/RAG2 and RSS recognition - P and N additions add further diversity - no shared or overlapping segments with Ig - no isotype switching - no somatic hypermutation
VDJ recombination
- occurs during early commitment phases of B cell development in the bone marrow - B cell randomly selects a combination of VJ for the light chain and VDJ for the heavy chain which are then recombined at the DNA level - VJ and VDJ regions will encode the variable regions of light and heavy chain proteins - constant region segments will encode the constant region - V and C gene regions joining occurs at level of RNA splicing
IgM
- predominant isotype secreted in a primary response to antigen - secreted form is a pentamer with 10 binding sites
structure and profiles of MHC class I
- single polypeptide (alpha) - associated with beta-2-microglobgulin - 3 domains with peptide binding groove between a2/a1 - expressed by APCs and most other nucleated cells - antigen presentation to CD8 T cells
Western blotting
- useful for for qualitative semi-quantitative identification of a particular protein or set of proteins from within a mixture of proteins. - Technique in which proteins are separated by gel electrophoresis, transferred to paper and analyzed using antibodies
MHC polymorphism to pathogen recognition and transplantation
- variability in Ag binding site: enhances probability of pathogen recognition within the population - major histocompatibility complex: transplantation Ags - MHC is like a genetic finger print - polymorphisms concentrated at regions of peptide binding - bad for transplant patients but good for the population at large by decreasing odds of pathogen survival
immunofluorescence microscopy
-Utilizes fluorescent-tagged antibodies to recognize a specific antigen in a sample -Requires a specialized fluorescent microscope - useful in the field of cellular biologyfor identifying and studying the distribution and functionsof cellular structures.
immunoaffinity chromatography
-used for purification of a particular macromolecule. - commonly used in research for large scale purifications and in the biotechnology industry an antibody is attached to the matrix to purify the protein against which the antibody was raised
Describe how dendritic cells and macrophages become activated APCs
Activation via by pathogen recognition receptors (PRRs) T cell activation is strictly dependent upon direct interaction and stimulation by antigen presenting cells (APCs) APCs must be appropriately activated before they are capable of stimulating T cells. APC activation requires stimulation by PRRs such as TLRs. dendritic cells in tissues pick up antigens and migrate to local lymph nodes where they can potentially activate T cells. The encounter between a naiveT cell and an activated APC, takes place in secondary lymphoid tissues such as a lymph node the APC first picks up the pathogen in inflamed tissue, which leads to activation and migration of the APC to the secondary lymphoid organ. Meanwhile, the naive T cells are in constant circulation through the blood and the lymphatic vessels. The chance meeting of activatedAPCs presenting antigens to pathogen specific Tcells, induces the T cells to proliferate and differentiate in accordance to the clonal selection mechanism previously described
polyclonal antibodies
Antibodies produced by injecting animals with a specific antigen. A series of antibodies are produced responding to a variety of different sites on the antigen.
Describe the process of light chain editing
B cells are retained in the bone marrow due to self-reactivity with the bone marrow stromal cells, they will be given several more chances at rearranging the light chain. If the newly rearranged receptor does not bind to stromal cells, it is deemed non-self reactive and allowed to exit the bone marrow
Complement Activation via Classical Pathway
C1q binds Fc activating complement cascade
MHC class 1 vs MHC class II
Class I: expressed on most nucleated cells (low levels on CNS), Ag presentation to CD8 T cells (CTLs), endogenous Ags, human: HLA-A,B,C Class II: expressed on APCs (macrophages, dendritic cells, B cells), Ag presentation to CD4 T cells (Th), exogenous Ags, human: HLA-DR,DP,DQ
Outline the stages of early thymocyte development with regards to TCR formation, co-receptor expression and check points
Early phases of thymocyte development are characterized by surface marker expression and the status of TCR gene rearrangements. - VDJ recombination to form TCR gamma delta or alpha beata : >double positive= co-expression of CD4 and CD8 co receptors >Positive and negative selection Check points: >survival of thymocytes with productively rearranged TCR > CD4 CD8 thymocytes now ready for further selection
Explain how CTLs kill target cells
First, the cells express the high-affinity IL-2 receptor that will drive their proliferation to the cytokine Interleukin 2 (IL-2). Second, the cells gain the killing functionality through expression and package of cytotoxic compounds into secretory vesicles called lytic granules. The activated CTLs exit the secondary lymphoid tissue and move through the peripheral circulation in search of infected cells or diseased cells. Target cells can be identified by the CTL via recognition of specific antigens displayed on surface MHC class I molecules.
Distinguish between a naive CD8 T cells and an effector CTL
Following activation, naive CD8 T cell proliferate and differentiate into effector CTLs.
5 antibody types
IgG, IgM, IgA, IgE, IgD differences in heavy chain constant regions that are encoded by distinct structural gene segments
Describe the DAG, PKC, NF-kb pathway
In the first DAG signaling pathway, protein kinase C,PKC, becomes activated and subsequently phosphorylatesa protein called IKK. In a non-activated T cell,t he inhibitor of kappa B is bound to NF kappa B, a transcription factor, and this holds NF kappaB in the cytoplasm. Once IKK is phosphorylated, it will in turn phosphorylate the inhibitor kappa B, causing it to release its hold on NF kappa B. So NF kappa B can then enter the nucleus and activate gene expression.
Understand the flow of intracellular signaling events that result from B-cell activation
Initiation of B cell activation requires cross-linking of surface antibody molecules referred to as the B cell receptor(BCR), and phosphorylation of ITAM sequences in the Ig alpha/Ig beta chains' cytoplasmic domains.
RAG1 and RAG2 recombinase enzymes
Mediates VDJ recombination RAG binds to recombination signal sequence (RSS) located adjacent to targets segments. RSS sequences are brought together and cleaved, DNA from the middle is excised
Exlpain what induces naive Th0 cells to differentiate into effector Th cells
Naive T helper cells are sometimes referred to as Th0cells to reflect their uncommitted status. a third type of signal induced by cytokines is required to direct the differentiation of a Th0 cell into an effector T cell. The source of the cytokines might maybe from the APC, or from other cells in the local micro environment where the Th cell is being activated.
Distinguish between the perforin and the FAS killing mechanisms
Perforin mechanism : The lytic granules of activated CTLs are loaded up with two key types of proteins, perforin and granzymes. As indicated in the previous slide, upon binding to a target cell, the CTL releases granule contents in the direction of the target cell. Perforin proteins form pores on the surface of the target cell and the granzymes enter through these pores into the target cell cytoplasm. The granzymes activate the apoptosis pathway signals the target cell to under go programmed cell death. FAS mechanism: Activated CTLs also express a cell surface molecule called Fas ligand, otherwise known as CD178 or CD95L, which binds to a cell surface molecule called Fas, CD95. Fas is present on the surface of most cells of the body, the binding of Fas ligand on theCTL to Fas on the target cell, induces the target cell to undergo apoptosis.
Describe the 6 phases of B cell development.
Phase 1 and 2 occur in bone marrow Phases 3-6 occur in peripheral secondary lymphoid tissues Phase 1: Repertoire assembly. generation of diverse and clonally expressed B-cell receptors in the bonemorrow Phase 2: Negative selection. alteration, elimination or inactivation of B cell receptors that bind to components of the human body Phase 3: positive selection. promotion of a fraction of immature B cells to become mature B cells in the secondary lymphoid tissues Phase 4: searching for infection. Recirculation of mature B cells between lymph, blood, and secondary lymphoid tissues Phase 5: Finding infection. activation and clonal expansion of B cells by pathogen-derived antigens in secondary lymphoid tissues phase 6: Attacking infection. Differentiation to antibody-searching plasma cells and memory B cells in secondary lymphoid tissues
Discuss key distinguishing characteristics of T reg cells and postulated suppressive mechanisms of T reg cell action
Proposed mechanisms include cytokine mediated suppression by Treg secretion of inhibitory cytokines such as IL-10 and TGF beta; indirect inhibition of T cells by out competing for binding to the cytokine IL-2; and inhibition of APC function by killing or by stripping away stimulatoryB7 through the expression of CTLA-4.
Understand the end result of the RAS-MAPK signal pathway
Protein kinase C also activates the ubiquitous Ras/ MAPK signaling cascade that leads to activation of the AP-1 transcription factor.
Outline the Ig gene recombination steps that occurs during each phase of B cell development in the bone marrow
Stem cell: H and L chain germlines Early Pro B cell: H chain D-J rearrangement; L chain remains germline Late pro B cells: H chain V-DJ rearrangement; L chain remains germline Large pre B cell: H chain VDJ rearranged, L chain remains germline; Ig staus = u heavy chain is made Small pre B cell: H chain VDJ rearranged, L chain V-J rearranging, Ig status = U chain n ER Immature B cell: H chain VDJ rearranged, L chain VJ rearranged, Ig status= u heavy chain/ y or k light chain, IgM on surface
Opsonization by antibodies
Target the pathogen and mark for destruction. Neutrophils and macrophages have Fc receptors for IgG1 and IgG. When antibodies have coated the pathogen, uptake of pathogen in enhanced.
Understand the role of Th2 in response to parasites in allergic inflammation
Th2: - extracellular pathogen - helminthic parasites - type I hypersensitivity: IL-4; IgE and allergic inflammation Th2 responses are also significant in the context of Type 1 hypersensitivity responses as Interleukin 4 induces B cells to produce IgE. The Th2 cytokine profile also contributes further to symptoms of allergic inflammation.
Explain the role of PLC-y, DAG and IP3 in signal transduction
The hydrolysis of PIP2 yields two byproducts, diacylglycerol(DAG) which remains in the membrane and inositol triphosphate,(IP3) which defuses into the cytosol.
immunoglobulin genes in germ-line configuration
The unrearranged organization of coding cassettes composed of V and J regions, and D regions in heavy chains.
Distinguish between Th1, Th2, TFH, Th and T reg cells in terms of cytokines that signal their differentiation, characteristic transcription factors they express, cytokines they secrete and their key effectors functions
There are at least five different effector cell subtypes into which a CD4 Tcell can differentiate into Th1, Th2, pTreg, Th17, and Tfh. Tregs are known to develop in two places; during the development of T cells in the thymus and in the periphery under the influence of the cytokine TGF beta. These are designated as pTreg cells to indicate that they differentiate in the periphery as opposed to in the thymus.
Distinguish between tTreg and pTreg cells
Treg cells differentiate by at least two distinct mechanisms: as a distinct lineage of CD4T cells during development in the thymus to yield t Treg cells; or in the periphery where naive CD4 Th0 cells are activated under the influence of TGF beta to yield pTreg cells.
Provide a historical account of Treg cell discovery
Ts cells hypothesized for decades; lack of well defined cellular markers Th cells in that they also express CD4. Additionally, Treg cells characteristically express CD25 which is simply the alpha chain of the high infinity IL-2 receptor. The greatest seriesof breakthroughs, leading to acceptance ofthe existence of these cells came in the years approximately 2000 to 2006 from studies of autoimmunity syndromes described in both mice and humans. Scurfy is a mouse strain that bears an X-linked recessive mutation that causes a multi-organ autoimmunity syndrome where in there is an overproduction of cytokines and hyper activation of CD4 T cells. Significantly, a similar but rare human autoimmune disease called IPEX results from asingle defective X-linked gene. Both the murine scurfy and the human IPEX genes were cloned and both were identified asa transcription factor called FOXP3. We now know that FOXP3 isa master regulator for Treg development and function, and that FOXP3 is a reliable marker for unambiguous identification of Treg cells.
generic antibody molecule
Y shaped with 2 heavy chains and 2 light chains - IgG, IgE & IgD have generic shape - IgA, IgM do not have generic Y shape - disulfide bridges - Variable and constant regions - Fc and Fab regions - Symmetrical
Distinguish between the roles of CD28, CTLA-4, and PD-1 in T-cell activation
a T cell molecule called CD28 interacts with B7, also known as CD80 or CD86, on the surface of an APC to provide required additional stimulation. CD28 is expressed on the surface of all T cells while B7 is expressed only on the surface of previously activated APCs. Activated T cells express a cell surface protein called CTLA-4, also known as CD152, that also binds to B7. In fact, CTLA-4 binds even more tightly to B7 than does CD28. *CTLA-4 as an inhibitor ofT cell activation. Thus, T cells have built-inself inhibiting mechanisms to finely regulate their levels of activation* PD-1 is another inhibitoryT cells surface protein that has been gaining attention due to its potential as a target for immuno-therapies in the treatment of diseases, including cancer.
cytosolic pathway
a process by which any cell can process and present endogenous antigens, induces appropriate effector functions to antigens of different origins - cellular proteins broken down and degraded by a barrel shaped protein complex called proteolytic enzymes called the proteasome. peptide fragments are actively transported by a complex of transport proteins Tap1, Tap 2, into the endoplasmic reticulum. Peptides are then loaded onto MHC class I molecules and released in vesicles transported to the cell surface for presentation. - endogenous Ags presented to CTLS: >elimination of infected cells or diseases self > "red flag" indicates state of inner health or disease
Understand the significance of Co-stimulatory signaling in T cell activation, and what is meant by the term anergy
additional co-stimulatory signaling from CD28, which is signal 2, that is required for a full response. a T cell will become anergic, taking on a state of non-responsiveness, if it receives signal 1 in the absence of co stimulation. Anergy is considered to be an important regulatory mechanism that contributes to peripheral tolerance
Understand what happens to naive B cells after they exit from the bone marrow
after leaving the bone marrow, naive B cells are released into the peripheral circulation and then must enter secondary lymphoid tissue such as a lymph node, the spleen, or MALT. they enter the tissues through high endothelial venule (HEV) that lead to T cell rich paracortex. Then they travel to a primary lymphoid follicle in the outer area called the cortex.If they do not encounter their specific antigen there, they exit back into circulation via an efferent lymphatic vessel - survival signal from secondary lymphoid tissue required for further maturation - entry into lymph node from blood via HEV
endocytic pathway
antigen presenting cell endocytosis of extracellular antigens, induces appropriate effector functions to antigens of different origins - endocytosed material is degraded followig fusion with a lysosome forming a phagolysosome. MHC class II mmolecules are synthesized, passing through the endoplasmic reticulum and golgi apparatus. whiel in the ER, MHC class II proteins are complexed with a protein called the invariant chain which serves to block peptide binding from interacting with other proteins in the ER. Invariant chain gets clipped in the golgi apparatus and leaves behind a fragment called a CLIP that is bound to the peptide binding site. The vesicle will fuse with the phagolysosome, CLIP is exchanged for a peptide derived fro exogenous antigen and the whole complex moves to the surface. - Exogenous Ags presented to the Th cells: > infectious agents in body's tissues > stimulate B cells to make Abs > Activate phagocytes
monoclonal antibodies
any of a class of antibodies produced in the laboratory by identical offspring of a clone of specific cells
CD3 complex
complex of signaling proteins that associates with T-cell receptors. It consists of CD3γ, δ, and ε chains, and ζ chains.
Understand the concept of cross-presentation of Ags and why this is significant for CD8 T cell activation
dendritic cells have been shown to be capable of presenting such antigens on MHC class I molecules even if they gather these antigens from outside sources. This phenomenon is called cross presentation.
affinity maturation
during a secondary response and later responses the antibodies produced are of progressively higher affinities
Explain the role of the bone marrow stromal cells during early B cell development
early phases of B cell development are highly dependent on signals provided by the bone marrow stromal cells. Signals are provided by direct cell-cell contacts as well as through cytokines secreted by the stromal cells.
Summarize all phases of B cell development including events that occur in the bone marrow and the periphery
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Summarize the phases of thymocyte development
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Compare and contrast the effects of Th1 vs Th2 response to M. leprae
in patients with the milder form of the disease, tuberculoid leprosy, Th cells secrete high levels of IL-2 and interferon gamma characteristic of a Th1 response. By contrast patients with the more severe form of the disease, lepromatous leprosy, Th cells secrete high levels of IL-4 and IL-5 characteristic of a Th2 response. Thus a Th1 response is more effective at managing this intracellular pathogen. The Th1 responses are generally most effective for clearance of intracellular pathogens whereas Th2 responses are more effective for extracellular parasites and pathogens. Th1 cells can induce the formation of structures called granulomas that function to limit the spread of these types of pathogens. Note also that Th1 cells characteristically secrete elevated levels of IL-2, aT cell growth factor that is necessary for CTL activation. Thus this type of response is generally relevant through intracellular infections, such as those involved in viruses.
Plasma
liquid portion of blood contains variety of proteins including clotting factors
Understand the role of IP3, CA2+ and calcineurin in T cell activation
n parallel to the DAG activation pathways, the inositol triphosphate derived from the membrane PIP2 diffuses into the cytoplasm and stimulates the endoplasmic reticulum to release calcium ions into the cytoplasm. Most significantly, this activates a calcium sensitive protein called calmodulin. Activated calmodulin in turn binds to and activates a phosphatase enzyme called calcineurin, that is then able to remove an inhibitory phosphate group from the NFAT transcription factor. NFAT can now move into the nucleus.
Effector functions of antibodies
neutralization, opsonization, ADCC, complement activation
What is anergy?
non functional cell immature B cells that react with soluble antigens in the bone marrow can enter the circulation but they are non functional. These non responsive cells will begin to express IgD but will be short lived and eventually die by apoptosis after a few days in circulation
IgD
not associated with any particular function or effect but is expressed along with IgM on the surface of naive B cells. May serve a function in regulating B cell physiology
what is allelic exclusion?
one specificity per B cell only one allele of the immunoglobulin gene is expressed
Serum
plasma without clotting factors
neutralization by antibodies
protective function - antibody binds to its target antigen - block viruses and toxins - Fab binds to virus and toxins preventing attachment
ELISA (enzyme-linked immunosorbent assay)
sensitive quantitative technique, A quantitative in vitro test for an antibody or antigen in which the test material is absorbed on a surface and exposed either to a complex of an enzyme linked to an antibody specific for the antigen or an enzyme linked to an anti-immunoglobulin specific for the antibody followed by reaction of the enzyme with a substrate to yield a colored product corresponding to the concentration of the test material
Describe the role of CD4, CD3, ITAMs, and ZAP70 in early signaling events following antigenic stimulation of a T cell
specific binding of TCR to MHC class II plus peptide signals the activation of a kinase, Lck, that is associated with CD4. Phosphorylation of ITAMs, immunotyrosine activation motifs, in thecytoplasmic tails of CD3 allow for the docking and activation of another kinase called ZAP-70. The activated ZAP-70kinase phosphorylates a membrane associated enzyme called phospholipase C, whose function is to cut off the hydrophilic head of a specialized phospholipid called phosphatidylinositol bisphosphate, or PIP2 for short.
humoral immunity
specific immunity produced by B cells that produce antibodies that circulate in body fluids
Explain the end results of T cell activation signaling
the end results of these activation cascades will initially cause the T helper cell to do three things. First, induce expression of a high affinity interleukin 2 receptor. Second, up-regulate expression and secretion of the cytokine IL-2, which is an important T cell growth factor, and three, it will induce proliferation. This is one of the distinguishing aspects of clonal selection that is essential to adaptive immunity. Later events in the activation process will cause the T cell to fully differentiate into a functional effector cell
Explain what happens when Ig receptors on the surface of immature B cells recognize antigens within the bone marrow or on the surface of bone marrow stromal cells?
they will be retained in the bone marrow and allowed to leave
Explain what happens to the thymus during the aging process and the effects this has on T cell immunity
thymus gland shrinks significantly as we age. We become more dependent on our pre0existing pool of mature T cells. Mature naive peripheral T cells are long lived and self renewing
Antibody-dependent cell-mediated cytotoxicity (ADCC)
trigger Natural Killer cells to kill. involves interaction of Fc receptors with antibody Fc domains ex: IgE antibodies coat the surface of a helminthic parasite and activate eosinophils to secrete toxins that damage the worms surface
Germ-line organization of TCR alpha and beta genes
unrearanged organization of TCR genes - include multiple V and J regions for alpha chain - multiple V,D,J regions for beta chain
somatic hypermutation
variable region of the rearranged immunoglobulin DNA is targeted for excessive point mutations that can alter the affinity of the antibody for its antigen
CD4 T cells
•Helper T cells (Th) - Produce cytokines - modulate immune response of both innate and adaptive • Activate other cells ( most B cells depend on direct cell-cel contact signals fro Th cells • Direct immune response
