Term
| What are the three main routes of entry of microbes into the body? |
|
Definition
| Skin, airway, GI tract (also reproductive tract and insect bites) |
|
|
Term
| Where do T-cells finish their maturation? |
|
Definition
|
|
Term
| Where do B-cells finish their maturation? |
|
Definition
|
|
Term
| True or False: The immune system generates cells continuously, even in the absence of antigen. |
|
Definition
| True. Output can increase dramatically in the presence of infection, but there is a significant basal level of production even in the absence of challenge. |
|
|
Term
| Which cell type is more efficient at phagocytosis and killing: macrophages or dendritic cells? |
|
Definition
| Macrophages are more efficient at phagocytosis and killing. |
|
|
Term
| Are macrophages active after exiting the bone marrow while circulating? |
|
Definition
| No. Macrophages can only differentiate and activate into active effector cells when it has entered peripheral tissues. |
|
|
Term
| What are two cytokines that activated tissue macrophages release to activate the lining of the endothelium? |
|
Definition
| TNF and IL-1 cause upregulation of E- and P- selectins on the lining of the endothelium. E- and P- selectin ligands are expressed on leukocytes (and mature lymphocytes). |
|
|
Term
| What is the time span for activation of lymphocytes? (primary response) |
|
Definition
| APCs may begin to interact with cognate lymphocytes ~1 day after infection. Large populations of clonally expanded lymphocytes will begin effector function proper ~3-5 days after infection. |
|
|
Term
| How do dendritic cells migrate to the lymph node? |
|
Definition
| Pro-inflammatory cytokines (produced by macrophages) cause dendritic cells to lose their peripheral tissue adhesiveness. They are then attracted to lymph nodes by chemokines that are continually expressed their. |
|
|
Term
| In a lymph node, where are the majority of B-cells? |
|
Definition
| In the follicles (cortex). |
|
|
Term
| In a lymph node, where are the majority of T-cells? |
|
Definition
|
|
Term
| How do B-cells and T-cells know to migrate toward each other in the lymph organs? |
|
Definition
| Chemokines are always being produced by the B- and T-cell zones. Once a B- or T-cell has seen antigen through its BCR or TCR respectively, it is able to respond to the chemokine and will migrate toward its lymphokine partner in search of second signal. |
|
|
Term
| Where are blood-borne pathogens detected? |
|
Definition
|
|
Term
| What is special about the B-cells in the marginal zone in the spleen? |
|
Definition
| They mostly express evolutionarily-conserved Igs (germline-encoded). They are very easily triggered and require much less T-cell help. |
|
|
Term
| What does the “M” in M cell stand for? |
|
Definition
| Multi-fenestrated (many cortical processes). They transcytose antigen (from apical-gut to basal-Peyer’s Patch). |
|
|
Term
| What is the Ig that is predominantly expressed by B-cells in the gut? |
|
Definition
| IgA. It is particularly good at crossing mucosal membranes. There is also a [large] of memory B-cells in this area. |
|
|
Term
| What are the three main roles of B-cells in the immune system? |
|
Definition
| Differentiate into effector cells (secrete large amounts of Abs), differentiate into memory cells, and as APCs for activation of T-cells. |
|
|
Term
| Is the variable end of an Ig the N- or C-terminal end? |
|
Definition
| The N-terminal end is variable. The C-terminal end is constant and identical for all Igs within a single isotype. |
|
|
Term
| What are the primary BCR components responsible for activating intracellular signaling cascade? |
|
Definition
| The Ig-alpha and Ig-beta peptides associated with the Ig heavy and light chains. (Ig-alpha and Ig-beta have extensive intracellular domains while the Igs, even those embedded in the membrane, are almost wholly extracellular). |
|
|
Term
| What were the two initial dogmatic theories for B-cell diversity generation? |
|
Definition
| 1. Germline-coding OR 2. Somatic mutation (in truth, both were correct, at least in part). |
|
|
Term
| Who is the scientist whose lab explained V(D)J recombination? |
|
Definition
| Susumu Tonegawa (but really, probably mostly his post-docs!!) |
|
|
Term
| What is the active complex of somatic V(D)J processing? |
|
Definition
| The RAG1 and RAG2 complex (Recombinase-activating gene). |
|
|
Term
| What are the two sub-types of Ig light-chain called? |
|
Definition
|
|
Term
| Do kappa and lambda light-chains contain a D-region? |
|
Definition
| No. Their variable regions are just made up of a V- and J-region. |
|
|
Term
| What is the process called that results in a B-cell only making one mature Ig? |
|
Definition
| Allelic exclusion. This process suppresses V(D)J recombination at the homologous locus. |
|
|
Term
| Are the RAG enzymes precise cutters during V(D)J recombination? |
|
Definition
| No. This imprecise cutting will affect the final sequence. This adds to junctional diversity. |
|
|
Term
|
Definition
| Terminal deoxyribonucleotide transferase (TdT) adds random nucleotides to the ends of the imprecisely RAG-cut regions until there is sufficient base-pairing. |
|
|
Term
| How does the action of TdT affect reading frame? |
|
Definition
| If TdT adds nucleotides that are not multiples of three, the D-region can be out of frame. This makes the D-region the area of maximum diversity. However, TdT must add enough nucleotides to ensure that the J-region is back in frame. Cells who produce Igs that do not get back into frame for the J-region are selected against. |
|
|
Term
| What is the enzyme central to somatic hypermutation in a germinal center in a (usually) secondary immune response? |
|
Definition
| AID (activation-induced cytidine deaminase). It induces error-prone repair in the IgV region, randomly mutating the BCR to select for increased antigen-Ig fit. |
|
|
Term
| Besides somatic hypermutation, what other process is AID central to? |
|
Definition
|
|
Term
| What is necessary for light-chain recombination? |
|
Definition
| Successful heavy-chain recombination. |
|
|
Term
| What is the first Ig produced for surface expression? |
|
Definition
| IgM on immature B-cells. IgD is expressed on mature B-cells. |
|
|
Term
| When immature or transitional B-cells recognize antigen, what program do they undertake? |
|
Definition
|
|
Term
| When mature B-cells recognize antigen, what program do they undertake? |
|
Definition
|
|
Term
| How does the CR2/CD19/CD81 complex lead to more efficient activation of the BCR? |
|
Definition
| When complement becomes bound to antigen, CR2 is able to recognize this. CD19 has a large intracellular domain which acts with Ig-alpha and Ig-beta to generate a very active B-cell response (even without T-cell help.) |
|
|
Term
| Weak signals trigger what processes on B-cells? |
|
Definition
| Weak signals prompt B-cells to seek further reassurance that they need to be activated to high-levels. To do this they upregulate B7 (to interact with T-cells) and also migrate out of lymphoid follicles to interact with CD4s. |
|
|
Term
| Why is the B-cell a particularly good APC? |
|
Definition
| It is extremely selective for presenting the antigen that its BCR is designed to recognize. The antigen is presented on Class II MHC, which can activate a CD4+ T-cell. |
|
|
Term
| When a T-cell becomes activated, what ligand becomes quickly upregulated? |
|
Definition
| CD28. This can interact with B7 on APCs to upregulate their activity. |
|
|
Term
| Where is potentially dangerous auto-reactivity generated? |
|
Definition
| During class-switching and hypermutation in B-cells. |
|
|
Term
| What alternative exon can all Igs (except D) possess at their C-terminal end? |
|
Definition
|
|
Term
| What are the two isotype classes that can be co-expressed on a B-cell? |
|
Definition
| IgM and IgD. Class-switching to (only one) of IgG, IgE, and IgA) can only occur after class-switching and somatic hypermutation. These are also the isotypes expressed on memory cells. |
|
|
Term
| What is AID’s role in class switching? |
|
Definition
| After cytokines have signaled to open up chromatin, AID will hypermutate the switch regions upstream of the “old” isotype and the “new” isotype. The region between the hypermutated nucleotides is processed out. |
|
|
Term
| Can an IgE class-switched B-cell express IgG? |
|
Definition
| No. The upstream gamma exon has been irrevocably excised. It may, however, through the action of AID, class-switch to IgA. |
|
|
Term
| What Ig isotype is best for complement activation? |
|
Definition
|
|
Term
| What Ig istoype is best for opsonizing microbes for phagocytes? |
|
Definition
| IgG. Phagocytes bind through their Fc receptors and phagocytose the IgG-bound microbe. |
|
|
Term
| What Ig isotype is best for combating extracellular parasites? |
|
Definition
| IgE. It cooperates with mast cells and eosinophils. |
|
|
Term
| How can NK cells destroy an infected host cell? |
|
Definition
| Some viruses put viral particles on the plasma membrane of the infected cells. If Ab binds to the surface of the infected cell, the NK cell will recognize this through its Fc receptor. |
|
|
Term
| What are the three main components of the innate epithelial barrier’s resistance to infection? |
|
Definition
| Physical barriers, locally-produced antibiotics (defensins), and intraepithelial lymphocytes (recognize bacterial lipids) all help prevent infection through the epithelia. |
|
|
Term
| How are mast cells important to the initial stages of the immune response? |
|
Definition
| They sense damage to tissues and activate by releasing histamine and leukotrienes, which causes vasodilation, causing influx of complement and blood cells. |
|
|
Term
| How is complement important to the very initial stages of the immune response? |
|
Definition
| C5a is a powerful chemoattractant which acts on cells in the tissue and in the blood vessels. C3b marks antigens for phagocytosis by macrophages (it is an opsonin). |
|
|
Term
| How is the short half-life of neutrophils relevant to clinical therapy? |
|
Definition
| When you put patients on immunosuppressant therapy, it knocks out the stem cells which quickly leads to severe neutropenia. |
|
|
Term
| Macrophages that are attracted to initial infection by complement cause recruitment of leukocytes how? |
|
Definition
| They secrete IL-1 and TNF. |
|
|
Term
| How are NK cells an important part of the very initial stages of the immune response? |
|
Definition
| NK cells reside in the tissue and sense initial injury. They secrete IFN-gamma, which serves to activate macrophages further. There can be a positive feedback loop onto NK cells by macrophages involving IL-12 secretion by macrophages. |
|
|
Term
| What are the actual killing agents in the phagolysosomes? |
|
Definition
| Reactive oxygen intermediates (ROIs) like hydrogen peroxide and superoxide. |
|
|
Term
| What is the NK cell effector function in the innate immune response? |
|
Definition
| They can bind to Ab-bound cells (virally-infected cells) or tumor cells and kill them without previous priming (they are natural killers). Their main killing is by perforin but they can also interact with macrophages via IFN-gamma to tell the macrophages to kill ingested microbes. |
|
|
Term
| How do natural killer cells decide whether to kill a cell? |
|
Definition
| There is a balance of inhibitory and stimulatory receptors on cells. One example is MHC, which is an inhibitory marker. However, when certain viruses or tumors cause downregulation of MHC, NKs have the ability to kill. |
|
|
Term
| How do Toll-like Receptors (TLRs) allow macrophages to differentiate between self- and non-self? |
|
Definition
| When macrophages bind and endocytose self- (as in tissue cleanup of dead cells), they do not cause activation of inflammation and an immune response (just proliferation of macrophages). When they engage TLRs and endocytose there, they cause it to differentiate into a type of macrophage that can stimulate the adaptive immune response. |
|
|
Term
| What is one extremely important molecule that becomes upregulated on macrophages after engaging a microbe through a TLR? |
|
Definition
| B7. This can activate T-cells. |
|
|
Term
| What are the 5 classical signs of innate immune response? |
|
Definition
| Redness (rubor), heat (calor), swelling (tumor), pain (dolor), loss of function (funcio laesa). |
|
|
Term
| Do complement proteins circulate in an active or inactive configuration? |
|
Definition
|
|
Term
| What is the critical early enzyme shared by all three pathways? |
|
Definition
| The C3 convertase. It leads to generation of C3b and C3a which ultimately leads to the membrane attack complex (MAC). C3b decorates microbes so that APCs can bind to them and activate the complement receptor. |
|
|
Term
| What two complement proteins can act as chemoattractants (for neutrophils) and as anaphalotoxins? |
|
Definition
| C3a and C5a can act as chemoattractants and anaphylotoxins (cause mast cells and other granulocytes to enhance blood vessel permeability). |
|
|
Term
| How are immune complexes cleared? |
|
Definition
| CRs on erythrocytes bind opsonized antigen-antibody complexes, which are removed from them in the spleen or liver by resident macrophages. |
|
|
Term
| What is the best Ig for activating complement via the classical pathway? |
|
Definition
| IgM. IgG is also proficient at activating the classical pathway. Two IgG molecules are necessary to bind complement. IgM can bind two molecules of C1. |
|
|
Term
| How does self avoid the alternative complement pathway? |
|
Definition
| Host cells have inhibiters of functional C3 convertase. |
|
|
Term
| What is the actual complement component that forms the MAC? |
|
Definition
|
|
Term
| How does the C1 inhibitor work? |
|
Definition
| It is a soluble inhibitor that prevents the C1 complex from becoming proteolytically active, terminating classical pathway activation. |
|
|
Term
| What disease results from failure of DAF (the C3 convertase inhibitor)? |
|
Definition
| Paroxysymal nocturnal hemoglobinuria. |
|
|
Term
| What Ig has higher affinity (IgG or IgM)? |
|
Definition
|
|
Term
| Can complement bind antibody in solution? |
|
Definition
| No. Antibody must be bound so that its Fc can change structure so that C1 can bind. |
|
|
Term
| What are the three ways we protect ourselves from complement? |
|
Definition
| Block C1 binding, C3 convertase function, MAC function. |
|
|
Term
| What is the major difference between the kind of antigens that B- and T-cells can see? |
|
Definition
| B-cells will see a soluble antigen, but T-cells will only see the antigen that is on the surface of other cells. |
|
|
Term
| What are the two parts of the antigen-MHC complex that the T-cell binds? |
|
Definition
| The T-cell binds the polymorphic region of the MHC and the “contact residue” of the peptide. |
|
|
Term
| Where is MHC class II expressed? |
|
Definition
| On the surface of APCs. CD4+ cells can then recognize this and tell them to kill ingested microbes (in the example of macrophages) or begin to produce high levels of antibodies (in the example of B-cells). |
|
|
Term
| Do professional APCs present MHC Class I or Class II? |
|
Definition
| They present both Class I and Class II. Under extreme circumstances non-professional APCs can present Class II. |
|
|
Term
| What is cross-presentation? |
|
Definition
| Antigen-presenting cells take up, process and present extracellular antigens with MHC class I molecules to CD8+s. This process is necessary for immunity against most tumors and against viruses that do not infect antigen-presenting cells. It is also required for induction of cytotoxic immunity by vaccination with protein antigens, for example in tumor vaccination. |
|
|
Term
| A single MHC molecule can bind only to a specific peptide sequence: true or false? |
|
Definition
| False. MHC molecules have a great deal of flexibility in binding to processed peptides. In addition, there are multiple HLA loci and there are codominantly expressed. The loci are HLA-A, -B, and –C and you receive one each from your mother and father. Since they are codominantly expressed a mature cell will usually express 6 different MHCs. |
|
|
Term
| Where are the polymorphisms in the MHC molecules? |
|
Definition
| In both Class I and in Class II, there are polymorphisms in both the residues that bind peptide and those that bind T-cells. However, the parts of MHC that bind CD4 or CD8 are constant? |
|
|
Term
| Why does Class I only stimulate CD8 and Class II only stimulate CD4? |
|
Definition
| Because Class I only binds CD8 and Class II only binds CD4. |
|
|
Term
| Is the affinity of the TCR-antigen higher or lower than the affinity of the antibody-antigen interaction? |
|
Definition
| The antibody-antigen interaction has a higher affinity. However, the T-cell makes up for this lower affinity by necessarily binding coreceptors such as CD4 and CD8 to increase total avidity. |
|
|
Term
| Where is Class I loaded with antigen? Class II? |
|
Definition
| Class I is loaded with antigen in the ER. Class II is loaded with antigen in the endocytic vesicle. |
|
|
Term
| Can bare MHC molecules be expressed on the cell surface? |
|
Definition
| No. Only MHC molecules loaded with antigen can be expressed on the surface of the cell. |
|
|
Term
| How does the proteosome know to only cut up microbial particles for loading into the ER? |
|
Definition
| It doesn’t. Self and microbial particles become imported into the ER. |
|
|
Term
| How do the peptides digested by the proteosome get loaded into the ER? |
|
Definition
| TAPs are the specific transporters that load the digested proteins into the ER. |
|
|
Term
| How does invariant chain becomes dissociated from MHC Class II? |
|
Definition
| The pH is lower in the endocytic vesicle which encourages dissociation of invariant chain. Also, there is a protein called DM in the endosome with a high affinity for invariant chain. Once invariant chain is removed, peptide can bind to Class II. |
|
|
Term
| What is the primary method that dendritic cells take up microbial particles? |
|
Definition
| Non-specific macropinocytosis. |
|
|
Term
| TAP deficiency results in a form of what immunodeficiency? |
|
Definition
|
|
Term
| What is bare lymphocyte syndrome? |
|
Definition
| Bare lymphocyte syndrome is a transcription factor mutation which results in failed expression of MHC Class II. |
|
|
Term
| How do some bacteria keep their molecules away from Class II? |
|
Definition
| Some bacteria can interfere with the endosome/lysosome transport. |
|
|
Term
|
Definition
| Simply put, allogenicity is responding against foreign antigens (particularly foreign MHC). |
|
|
Term
| Why does such a high percentage of T-cells respond to alloantigen? |
|
Definition
| It is thought that foreign cells appear similar to MHC bound to antigen. |
|
|
Term
| Why does the thymus become smaller in the adult? |
|
Definition
| T-cells have a relatively long half-life and the rate of production goes down in an adult, so the thymus gets smaller. It of course does not go completely away. |
|
|
Term
| How can a T cell be differentiated from a B cell or an NK cell under the microscope? |
|
Definition
| They can’t. They must be identified using a technique which differentiates them due to surface antigens (IF microscopy, FACS, etc.) |
|
|
Term
| What are the two parts of the T cell (homologous to the Heavy and Light chain of Ig)? |
|
Definition
| Alpha and beta (small, poorly understood population of T-cells that instead have gamma and delta chains instead). |
|
|
Term
| Which chain of the TCR has V, J, and D regions? Which has only V and J regions? |
|
Definition
| Only beta chains of the TCR have V, J, and D regions. Alpha chains have only V and J regions. |
|
|
Term
| Do T-cells somatically hypermutate? |
|
Definition
| There is no evidence that T-cells somatically hypermutate. |
|
|
Term
| Does the TCR do signal transduction directly? If not, what non-covalently associated molecule at the TCR complex does? |
|
Definition
| The CD3 complex is critically involved in signal transduction at the TCR. CD4 and CD8 also contribute. |
|
|
Term
| Why is calcineurin important in the clinics? |
|
Definition
| It’s the target of a major immunosuppressant drug, cyclosporine. Calcineurin normally allows NFAT, a transcription factor, to shuttle into the nucleus. |
|
|
Term
| Can you express the TCR without CD3? |
|
Definition
| You cannot express TCR without CD3 or vice-versa. They both must be properly expressed for maturation. |
|
|
Term
| If a T-cell interacts with an antigen through its TCR, but does not encounter co-stimulation (for example B7), what two processes can happen? |
|
Definition
| It can undergo either anergy (tolerance) or ignorance (no response). |
|
|
Term
| What is signal 1 for a T-cell? |
|
Definition
|
|
Term
| What is signal 2 for a T-cell? |
|
Definition
| Activation of a costimulator. |
|
|
Term
| An activated APC expresses B7. It costimulates a T-cell by interacting with what cognate molecule? |
|
Definition
|
|
Term
| When CD4+ cells first engage APCs, what autocrine receptor and cognate ligand are transcriptionally upregulated? |
|
Definition
| IL-2R and IL-2 are upregulated when the CD4+ cell first contacts APC. |
|
|
Term
| After the IL-2 binds to the upregulated IL-2R, what is the signal cascade? |
|
Definition
| After IL-2 binds to IL-2R, JAKs (kinase) are activated. STATs (transcription factors) then are phosphorylated, dimerize, and translocate into the nucleus. |
|
|
Term
| How do activated T-cells activate APCs? |
|
Definition
| Activated T-cells can express CD40 ligand, which interacts with CD40 on APCs. They may then upregulate B7, which can concomitantly upregulate CD28 on T-cells. |
|
|
Term
| CD28 is a major positive regulator of T-cell activation. What is a major negative regulator? |
|
Definition
| CTLA4 is a receptor that gradually becomes upregulated on a T-cell and both deprives the T-cell of CD28 signals (by outcompeting it), but also by negative signaling (when CTLA4 binds to B7 on the surface of APCs). |
|
|
Term
| T cells need to be bound to APCs for a sufficient length of time to cause sufficient activation. How is this accomplished? |
|
Definition
| When T-cells interact with APCs, this causes a low-affinity integrin on their cell surface to adopt a more high-affinity confirmation. This enables better adhesion to ligands on APCs. |
|
|
Term
| When cells of the T lymphocyte lineage enter the thymus, do they have CD4 receptors? CD8? The TCR (and CD3)? |
|
Definition
| No. The first cells in the T-cell lineage are double negative for CD4 and CD8 (and also do not express TCR). |
|
|
Term
| If a developing T cell fails twice in creating a TCR, what is its fate? |
|
Definition
| If a double-negative (CD4-CD8-) fails twice (from both alleles) to make a TCR, it undergoes apoptosis. |
|
|
Term
| If a T-cell creates a functional TCR, what is its next step? |
|
Definition
| If a developing T-cell expresses a functional TCR, it becomes double positive (CD4+CD8+). |
|
|
Term
| Gamma/delta T-cells are not restricted by classical MHC. They bind lipids and are restricted by what cluster of differentiation? |
|
Definition
| Gamma/delta T-cells are restricted by CD1. |
|
|
Term
| Do most T-cells that become double-positive, successfully transition to single-positive cells? What is the relative ratio? |
|
Definition
| No, the vast majority of double-positive cells do not survive. Those that successfully transition to single-positive express CD4:CD8 in a 2:1 ratio. |
|
|
Term
| At what transition is auto-reactive (high affinity) or non-reactive (no affinity) receptors selected against? |
|
Definition
| The transition from double- to single-positive T-cells is when the thymus tests for irresponsibly high (die by negative selection) or low receptor binding (fail positive selection – die by neglect). |
|
|
Term
| What MHC Class do thymic epithelial cells expression? |
|
Definition
| Thymic epithelial cells express both Class I and Class II. They can thus interact with both CD4 and CD8 on double-positive T-cells. |
|
|
Term
| What are opportunistic infections? |
|
Definition
| They are microbes that cause pathology only if you are immunosuppressed. |
|
|
Term
| What infamous disease particularly targets CD4+ cells for death? |
|
Definition
| CD4+ cells are targeted for death by HIV. This causes immunosuppression from the virus. |
|
|
Term
| Will most of the MHC Class I on a cell’s surface be self- or non-self peptide? |
|
Definition
| The vast majority of antigen presented on a nucleated cell’s surface in Class I will be self peptide. It is up to the T-cell to differentiate that as self. |
|
|
Term
| What important interleukin is expressed by macrophages in the tissues that activates TH1 cells? |
|
Definition
| IL-12 is expressed by macrophages that have ingested harmful antigen in the tissues. It activates TH1 cells. These activated TH1 cells in turn secrete IFN-gamma, which makes macrophages more active. |
|
|
Term
| How do cytolytic T-cells kill infected cells when they recognize their cognate antigen on Class I MHC? |
|
Definition
| CD8+ cells secrete perforins which polymerize on the membrane, creating a pore. They then secrete granzymes through the pore which ultimately activates caspases, killing the infected cell. |
|
|
Term
| Can CD8+ cells secrete cytokines? |
|
Definition
| Yes. All T-cells are capable of secreting cytokines and interacting with other cells of the adaptive and also those of the innate immune system. |
|
|
Term
| If activated T-cells are exposed to IL-4, what type of TH cell might it become? |
|
Definition
| If an activated CD4+ cell is exposed to IL-4, it might become a TH2 cell. IL-4 is also important for telling plasma cells to class-switch to IgE, which acts in mast cell degranulation. |
|
|
Term
| What interleukin do TH2 cells secrete to activate eosinophils? |
|
Definition
| TH2 cells secrete IL-5, which allows eosinophils to effectively combat helminths. |
|
|
Term
|
Definition
| Following eradication of a pathogenic challenge, most effector T cells are eliminated by apoptosis. A small number of activated T cells enter a long-lived pool known as memory T cells. These cells are found in the circulation and in secondary lymphoid organs. Memory T cells do not actively produce cytokines or exert effector function, but they do so rapidly if antigen is encountered again. |
|
|
Term
| How do regulatory T-cells suppress other T-cells? |
|
Definition
| Regulatory T-cells secrete IL-2 and TGF-beta, which turns off effector T-cell responses. |
|
|
Term
| How are Fas and Fas-ligand able to promote cell death? |
|
Definition
| When T-cells are actively proliferating and working, they express anti-apoptotic molecules which oppose FAS activation. As the T-cells get older or stay un-co-stimulated, Fas and FasL interact with sufficient strength to activate caspases. |
|
|
Term
| What is molecular mimicry? |
|
Definition
| Molecular mimicry seeks to explain why autoimmunity might arise. It is possible that some pathogenic microbes can activate an immune response. However, these lymphocytes might also recognize host antigens that are similar. This would not happen in everyone in the population because of the different binding specificities of MHC. Some MHC genotypes are at much higher relative risks for different autoimmune diseases. |
|
|
Term
| In the case of ILI-2R mutation, what is the human phenotype? |
|
Definition
| Severe Combined Immunodeficiency (SCID) results from mutations in human IL-2R. |
|
|
Term
| What are the 4 cardinal features of adaptive immunity? |
|
Definition
| Specificity, inducibility, memory, and tolerance to self are cardinal features of adaptive immunity. |
|
|
Term
| T cells can undergo V(D)J recombination, H+L chain pairing, and junctional diversity to generate a multitude of specificities. What can B cells do that T cells cannot? |
|
Definition
| B cells can undergo somatic hypermutation after the primary response to increase affinity to antigen. T cells do not undergo somatic hypermutation and instead must rely on other proteins at the TCR complex to increase avidity. |
|
|
Term
| How many binding sites does each antibody unit have for recognizing antigen? |
|
Definition
| Each antibody unit is bivalent for a specific antigen. |
|
|
Term
| When you undergo isotype switching, what region of the antibody actually switches? |
|
Definition
| The constant region of the heavy chain is switched in isotype switching. The constant region of the light chain does not change, neither does either of the variable regions. |
|
|
Term
| If a T cell receives costimulation alone, what is the result? |
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Definition
| There is no effect on the T cell if it receives costimulation without recognition of an antigen-MHC complex. |
|
|
Term
| IgM is very good at fixing complement. Can it do this in solution? |
|
Definition
| No. IgM must change its conformation by binding before it can fix complement. |
|
|
Term
| What is the order of Ig heavy chain constant regions from 5’ to 3’ on the chromosome? |
|
Definition
| C-mu (IgM), C-delta (IgD), C-gamma (IgG), C-epsilon (IgE), C-alpha (IgA). |
|
|
Term
| What is the most common isotype for a memory cell to display? |
|
Definition
| IgG is the most common antibody isotype a memory cell displays. |
|
|
Term
| How many binding sites does IgM have for antigen? |
|
Definition
| IgG is pentameric. Therefore since each antibody unit is bivalent, the entire complex is decavalent. |
|
|
Term
| What is the only antibody isotype that is not secreted? |
|
Definition
| IgD is membrane-bound on mature, resting B lymphocytes before they’ve become activated. Its primary function is unknown. |
|
|
Term
| What is the most abundant gamma globulin (antibody) in serum? |
|
Definition
| IgG is the most abundant gamma globulin in serum. IgM, IgA, and IgE (very small amounts) are also present. |
|
|
Term
| What antibody isotype can cross the placenta? |
|
Definition
| IgG can cross the placenta. |
|
|
Term
| What antibody isotype can cross mucosa? |
|
Definition
| IgA can cross the mucosa. It is actually the most abundant isotype in your body, since the mucosa have so much surface area (though IgG is most abundant in serum). |
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Term
| What is one way cytolytic T cells use besides perforin and granzymes to kill an infected host cell? |
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Definition
| Cytolytic T cells can express FasL, activating the Fas death receptors on the surface of infected host cells. |
|
|
Term
| What facet of the immune system are most primary immunodeficiencies in? |
|
Definition
| Most primary immunodeficiencies are in antibody function. |
|
|
Term
| What is the effect of IL-7 on T cells? |
|
Definition
| IL-7 acts on T cells developing from a common lymphoid progenitor, allowing them to survive until they reach the thymus. |
|
|
Term
| What is the effect of IL-15 on NK cells? |
|
Definition
| IL-15 acts on NK cells developing from a common lymphoid progenitor, allowing them to survive until they become mature NK cells. |
|
|
Term
| What is a good marker for FACS detection of B cells? |
|
Definition
| CD19 is a good marker for detection of B cells. It associates with complement receptor. |
|
|
Term
| What is a good marker for FACS detection of T cells? |
|
Definition
| CD3 is a good marker for detection of T cells. It associates with the TCR to enable intracellular signaling. |
|
|
Term
| What is Bruton tyrosine kinase? |
|
Definition
| Bruton tyrosine kinase allows phosphorylation of PLC-gamma2 and NF-kappa-B through the action of phospholipase C. If this kinase is mutated, pre-B cell maturation is blocked, resulting in agammaglobulinemia. |
|
|
Term
| What is the molecular defect in X-linked Hyper-IgM syndrome? |
|
Definition
| The molecular defect in X-linked Hyper-IgM syndrome is in CD40L. Because CD40L is not expressed on T cells, they cannot be costimulated by B cells, resulting in depressed T cell function. Additionally, CD40 activation on B cells results in isotype switching, resulting in elevated IgM levels. Additionally, there is also lack of activation of macrophages. |
|
|
Term
| What is ADA? What cells does it affect? |
|
Definition
| ADA is an autosomal recessive conbined immunodeficiency that results in defect T, B, and NK cells. |
|
|
Term
| What is gamma-chain IL-2R deficiency? |
|
Definition
| Gamma-chain IL-2R deficiency is a relatively common x-linked recessive disorder that affects the development of T, and NK cells. T cells die because of loss of IL-2 signalling, and NK cells die because of lack of IL-15 signaling (IL-15 signals through IL-2R). This is a form of SCID. |
|
|
Term
| What are a few reasons patients acquire secondary immmunodeficiencies? |
|
Definition
| Some causes of secondary immunodeficiencies are: HIV infection, protein-calorie malnutrition, irradiation and chemotherapy for cancer, cancer metastases to bone marrow, removal of spleen. |
|
|
Term
| Does HIV have a proviral state? |
|
Definition
| Yes, HIV has a proviral stage where it resides until an infected CD4+ cell becomes activated (when it kills it and reproduces). |
|
|
Term
| What hypersensitivity type does allergies fall into? |
|
Definition
| Allergies are a Type I – immediate hypersensitivity response. |
|
|
Term
| What Ig isotype is bound to mast cells, ready to trigger granule release when antigen is encountered? |
|
Definition
| IgE is bound to mast cells in immediate hypersensitivity, ready to trigger granule release when antigen is encountered. |
|
|
Term
| Besides mast cells, what other lymphocytes bind IgE? |
|
Definition
| Mast cells are most important in immediate hypersensitivity because of their relative densities in the tissue, but eosinophils and basophils also bind IgE. |
|
|
Term
| What is the half-life of IgE? |
|
Definition
| When bound to receptor, IgE can last in the blood for months. When in serum, its half-life is only two days. |
|
|
Term
| What molecules are responsible for the late-phase of the response? |
|
Definition
| Prostaglandins, leukotrines, and cytokines like TNF, are responsible for the late-phase of the response, which causes most of the long-term pathology. |
|
|
Term
| What cells accumulate during the late phase of immediate hypersensitivity? |
|
Definition
| In the late phase, neutrophils, eosinophils, and basophils and lymphocytes (Th2) cells accumulate at the site of reaction. These cells change the composition of the tissue itself. |
|
|
Term
| What drug is given to stabilize acute immediate hypersensitivity? |
|
Definition
| Epinephrine is given, which causes immediate smooth muscle contraction, increased cardiac output, and inhibition of further mast cell degranulation. |
|
|
Term
| What are immune complexes? Where are they deposited? |
|
Definition
| Immune complexes are small complexes of antibodies and antigens that are deposited in blood vessels or sites of high tissue filtration like the kidneys or joints, recruiting monocytes and neutrophils, creating inflammation and causing pathology there. |
|
|
Term
| How do you distinguish between Type II and Type III glomerular disease? |
|
Definition
| Type II (antibody-mediatd) results in smooth linear lesions. Type III (immune complex-mediated) results in lumpy bumpy deposits on histopathology. |
|
|
Term
|
Definition
| Serum sickness resulted when horse serum was given to patients. They produced antibodies to horse antigens, causing immune complexes that produced joint pain, kidney pain, and vasculitis. |
|
|
Term
| What is a Type IV hypersensitivity response? |
|
Definition
| There are two types of Type IV diseases. The first, mediated Th1 cells is called delayed type hypersensitivity, results from CD4+ and CD8+ cells, in which tissue injury is caused by activated macrophages and inflammatory cells, and direct killing of target cells. The second, T-cell mediated cytolysis, is mediated mostly by CD8+ cells. |
|
|
Term
| An initial immune response is dominated mostly by B cells. What is the primary Ig isotype they secrete? |
|
Definition
|
|
Term
| In a secondary immune response, large amounts of T cells are activated, and plasma cells primarily secrete Igs of what isotype? |
|
Definition
|
|
Term
| Where do memory cells reside, granting them their long life span? |
|
Definition
| Memory cells reside primarily in memory cell niches, but will percolate through tissues periodically, providing surveillance against their cognate antigen. |
|
|
Term
| Does the follicular dendritic cell develop in the hematopoietic niche? |
|
Definition
| No, the follicular dendritic cell develops in the follicle itself. |
|
|
Term
| Why must booster shots be given for peptide and protein vaccines? |
|
Definition
| Booster doses must be given to generate a potent IgG response and generate good memory. |
|
|
Term
| What type of virus is more immunogenic, attenuated or killed virus? |
|
Definition
| Attenutated live virus is a better vaccine, as it can generate a T cell mediated response. |
|
|
Term
| What is a large disadvantage of live attenuated viral vaccines? |
|
Definition
| There can be rare revertants in live attenuated vaccines which can result in the disease. |
|
|
Term
| What are some advantages of vaccinations with inactivated vaccines? |
|
Definition
| Inactivated vaccines are more effective than subunit vaccines and there is little or no risk of infection if the pathogen is properly attenuated. However, this is not possible for all viruses, there is a lack of mucosal immunity (IgA), poor or no cellular immunity, and booster shots are necessary. |
|
|
Term
| What are some advantages for vaccination with sub-unit vaccines? |
|
Definition
| Sub-unit vaccines are almost completely safe, but produce relatively poor antigenicity and adjuvants are always needed. |
|
|
Term
| What are some examples of attenuated viral vaccines? |
|
Definition
| Yellow fever, measles, mumps, rubella, the Sabin polio vaccine, varicella, rotaviral diarrhea, influenza, and rabies. |
|
|
Term
| What are some examples of killed viral vaccines? |
|
Definition
| The Salk polio vaccine and rabies are examples of killed viral vaccines. |
|
|
Term
| What are some examples of currently used sub-unit vaccines? |
|
Definition
| Hepatitis A and B vaccines are examples of sub-unit vaccines. |
|
|
Term
| Very early tumor responses are eradicated by what cells? |
|
Definition
| T cell responses don’t develop very effectively unless the entire tumor is removed. Therefore, most tumor immune cell responses are by NK cells and activate macrophages. |
|
|
Term
| What are the four examples of tumor antigens? |
|
Definition
| Tumor antigens may be derived from mutated self proteins, oncogene or tumor suppressor products, overexpressed or aberrantly express protein, or oncogenic virus proteins. |
|
|
Term
| What are three parts of the body where there can only be weak (if at all) responses to tumors? |
|
Definition
| The brain, the eye, and the testis cannot be accessed by lymphocytes either because they lack lymphatics or (in the case of the eye), FasL is highly expressed, triggering apoptosis of lymphocytes. |
|
|
Term
| What are some strategies that tumors use to reduce immunogenicity? |
|
Definition
| Tumors decrease expression of peptide:MHC complex, induce suppressor T-cells to secrete IL-10 and TGF-beta, and can mutate their antigens to avoid surveillance. |
|
|
Term
| What cells are activated in graft rejections? |
|
Definition
| T cells are responsible for rejecting the graft, primarily by recognizing the donor MHC molecules. |
|
|
Term
| Why is there such a large pool of alloreactive T cells? |
|
Definition
| It is thought that there is such a large pool of alloreactive T cells because alloantigenic MHC is structurally very similar to self MHC with an antigen in it. It is estimated that 2-5% of total T cells will respond to a graft. |
|
|
Term
| What are the two ways that the host can recognize the allograft? |
|
Definition
| In direct recognition, T cells see donor MHC as MHC bound to antigen and become activated. In indirect presentation, host APCs process and present a graft allopeptide. In both cases the development of immunity occurs in the lymph nodes. |
|
|
Term
| Why do you need some sort of biological disturbance to generate graft rejection? |
|
Definition
| T cells need to be activated by costimulation, either through PAMPs or through some other mechanism. |
|
|
Term
| Why can cornea be transplanted so well? |
|
Definition
| The cornea is isolated from the immune system, so there cannot be rejection. |
|
|
Term
| What causes hyperacute rejection? |
|
Definition
| Preformed antibodies react with graft, activating complement, rejecting the graft within minutes. |
|
|
Term
| What causes acute rejection? |
|
Definition
| In acute rejection, CD8+ cells react with alloantigens on graft endothelial cells and parenchymal cells, causing damage. |
|
|
Term
| What causes chronic rejection? |
|
Definition
| In chronic rejection, T cells may produce cytokines that induce proliferation of endothelial and smooth muscle cells in the walls of blood vessels, leading to luminal occlusion over the long term. |
|
|
Term
| Compare the decay rate in secondary immune responses versus primary immune responses. |
|
Definition
| Secondary immune responses show a more protracted decay rate than primary immune responses. |
|
|
Term
| What antibody isotypes generate complement via the classical pathway? |
|
Definition
| IgG and IgM are capable of generating complement responses via the classical pathway. |
|
|
Term
| What genes are Class I MHC products encoded by? |
|
Definition
| Class I MHC products are encoded by the HLA A, B, and C gene clusters. |
|
|
Term
| What type of signaling is required for activation of naïve T cells? |
|
Definition
| Costimulation is required for activation of naïve T cells. |
|
|
Term
| True or false: Interleukins display exquisite antigen specificity. |
|
Definition
|
|
Term
| What are two types of receptors on phagocytic cells that help mediate opsonization? |
|
Definition
| The Fc and complement receptors aid greatly in opsonization of foreign microbes by phagocytes. |
|
|
Term
| The gamma chain of the T cell receptor is mutated in most cases of SCID, shared by other receptors (IL-4 and IL-7), and needed to create a fully functional IL-2 receptor: True or False? |
|
Definition
|
|
Term
| Must both T and B cells be costimulated by other cells to be fully activated? |
|
Definition
| T cells have an absolute requirement for costimulation, however if a strong enough signal is presented to B cells (i.e. antigen bound to complement), they may activated without stimulation by other cells. |
|
|
Term
| What are the two subunits of MHC Class I that bind the peptide? The two that form the binding platform? |
|
Definition
| In MHC Class I, alpha-1 and alpha-2 bind peptide while alpha-3 and beta-2 form the binding platform. |
|
|
Term
| What are the two subunits of MHC Class II that bind the peptide? The two that form the binding platform? |
|
Definition
| In MHC Class II, alpha-1 and beta-1 bind peptide while alpha-2 and beta-2 bind platform. |
|
|
Term
| Is the MHC Class II presentation pathway constitutively active? |
|
Definition
| The MHC Class II presentation pathway is not constitutively active. For example, dendritic cells are only highly active during inflammation, while B cells are only highly active after antigen binding to BCR. |
|
|
Term
| A genetic defect in IL-2R common gamma chain can cause what disease? |
|
Definition
|
|
Term
| At what level in complement activation do the three pathways meet? |
|
Definition
| The three pathways of complement activation meet at C3 (they all lead to activation of a C3 convertase). |
|
|
Term
| What class if antibodies act as natural isohemaglugglutinin (clumps unmatched blood)? |
|
Definition
|
|
Term
| What is the mast cell mediator must responsible for the wheal and flare reaction? |
|
Definition
|
|
Term
| At the site of an infection of an organism that triggers a cell-mediated immune response, yet cannot be easily digested by macrophages, you might see an abundance of what types of cells? |
|
Definition
| CD4+ cells, activated macrophages, and giant cells might be present. A granuloma may form. |
|
|
Term
| Besides opsonization and direct killing, what is another feature of a healthy immune system that complement participates in? |
|
Definition
| Complement also participates in the clearing of immune complexes. |
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