Term
| Where does the processing of endogenous antigens take place? exogenous antigens? |
|
Definition
the cytoplasm.
within the endocytic or phagocytic vesicle. |
|
|
Term
| What is a immunoproteasome and how is it formed? |
|
Definition
| it is an altered proteasome and is formed when gene products that were transcribed on the MHC locus (due to IFN-γ) replace part of the regular proteasome |
|
|
Term
| Where does the immunoproteasome cleave? |
|
Definition
| after hydrophobic or basic amino acid residues...making peptides more likely to bind to MHC Class I |
|
|
Term
| How do the peptides that were broken down in the cytoplasm (endogenous antigens) reach the ER to be loaded onto the MHC molecules? |
|
Definition
| TAP genes are upregulated upon IFN-γ and TAP-1 and TAP-2 translocate the peptides. Calnexin is a chaperone protein that makes sure the MHC Class I does not leave the ER prematurely by stabilizing it's α chain-β2m heterodimer until the peptide is loaded. Tapasin is a chaperone protein that increases the efficiency of peptide loading. TAP and tapasin dissociate after the peptide is loaded and the complex is transported to the surface via the golgi |
|
|
Term
| How are exogenous antigens processed? |
|
Definition
| After they are internalized by the phagosome, it fuses with a lysosome and becomes a phagolysosome. The decrease in pH allows the enzymes of the lysosome (cathepsins and hydrolytic) to function properly and form peptides to be loaded onto the Class II molecules |
|
|
Term
| How are exogenous peptides trafficked? Where are MHC Class II molecules assembled? |
|
Definition
| MHC Class II are translated/assembled in the rough ER. They associate with the invariant chain which binds to the peptide cleft. This enters the golgi and exits as a membrane-bound vesicle whose proteases cleave the invariant chain to form a CLIP in the binding cleft. This vesicle then fuses with the phagosome and HLA-DM removes the CLIP and loads peptides onto the class II which is then transported to the cell surface |
|
|
Term
| What are the three functions of the invariant chain? |
|
Definition
1.) chaperone for proper folding of MHC Class II
2.) prevents association of endogenous peptides with MHC Class II
3.) traffics class II mole to the endosomal/lysosomal pathway |
|
|
Term
| What molecules present lipid, glycolipids and phopholipid antigens to T cells? |
|
Definition
|
|
Term
| What are CD1 molecules similar in structure to? What are is characteristic of their binding cleft? And what processing pathway is it most similar to? |
|
Definition
MHC Class I
very hydrophobic
class II, exogenous antigen pathway |
|
|
Term
| During and immediately after an infection, higher levels of complement are produced by what? |
|
Definition
| the liver, monocytes and macrophages |
|
|
Term
| What three categories do complement proteins fall into? and which are serum/membrane proteins? |
|
Definition
1.) proteins that react with foreign antigens (these are all serum)
2.) regulatory proteins that protect the host from complement or inhibit/regulate complement activation (serum and membrane)
3.) complement receptors that bind split products to signal for participation in inflammatory/immune reactions (these are membrane proteins) |
|
|
Term
| What are the functions of complement? |
|
Definition
1. opsonization/production of opsonins
2. virus neutralization
3. clearance of immune complexes
4. lysis of cells
5. enhancing B cell responses
6. chemotaxis and cellular activation
7. production of anaphylatoxins |
|
|
Term
| What complement coats pathogens and what receptor binds it on RBCs to clear the immune complexes from the blood? |
|
Definition
| C3b coats the pathogens and it binds to CR1 on RBCs which takes it to the spleen/liver which strips it from the RBC and phagocytoses it. |
|
|
Term
| What does the MAC form holes in? |
|
Definition
| gram negative bacteria, parasites, nucleated cells, RBCs and enveloped viruses |
|
|
Term
| What do C3a, C4a and C5 act as? WHat does C5a cause production of? |
|
Definition
| they act as chemoattractants for monocytes and neutrophils and act as anaphylatoxins. C5a causes production of proinflammatory cytokines (IL-1, IL-6 and TNF-α) by macrophages. They all degranulate mast cells and 3 and 5 degranulate basophils. |
|
|
Term
| What activates the classical complement pathway and describe the process? |
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Definition
| activated when 2 or more globular heads of the C1 complex engages an antigen. C1r cleaves C1s which cleaves C4 (C4b binds target) and C2 (binds to C4b making C4b2a - aka C3 convertase) which then cleaves C3 making C4b2a3b (C5 convertase) which then cleaves C5 into C5b which binds to target and has C6, C7, C8 bind to it, and then multiple C9s bind to for C5b678(9)n which is the MAC complex |
|
|
Term
| What activates the lectin complement pathway and what is its sequence? |
|
Definition
| When mannose binding lectin complexed with serine proteases (MASP-1 and MASP-2) bind carbohydrates (mannose or N-acetylglucosamine) on the microbial surface. It is the exact same as the classical complement pathway except the initiating complexes are different. |
|
|
Term
| What activates the alternative complement pathway and describe its process |
|
Definition
| activated by foreign antigens. C3 undergoes spontaneous cleavage and activates complement only if it binds quickly to a foreign surface. if it binds to host cell, regulatory/protective proteins dissociate it. Factor B then binds to the C3b on the microbial surface forming C3bB. Factor D cleaves Factor B making C3bBb, and properdin binds to stablize this molecule. C3bBb (C3 convertase) cleaves C3 to make C5 convertase, C3bBb3b which cleaves C5 into C5a which binds the target. The cascade of C6, 7, 8 and multiple 9's bind to form the MAC. |
|
|
Term
| C1 inhibitor - serum or membrane? what does it do? |
|
Definition
serum
irreversibly binds C1r and C1s to dissociate them from the C1 complex so they cannot convert C4 |
|
|
Term
| C4-Binding protein : serum or membrane? what is its function? |
|
Definition
serum
binds C4b portion of C3 convertase to displace C2a |
|
|
Term
| Factor H and Factor I - serum or membrane? what are their functions? |
|
Definition
serum
Factor H binds to C3b to allow Factor I to cleave it into its inactive form iC3b |
|
|
Term
| Decay Accelerating Factor (DAF) - serum or membrane? what is its function? |
|
Definition
membrane.
binds C4b and C3b in the C3 convertases for each pathway and inactivates them via dissociation |
|
|
Term
| CD59 - serum or membrane? what is its function? |
|
Definition
membrane
binds the C5b678 complex to prevent recruitment of C9 and completion of the MAC |
|
|
Term
| What is the immune synapse? |
|
Definition
| Where the cell surface proteins of B and T cells interact |
|
|
Term
| What is the first signal/recognition interaction of the immune synapse? |
|
Definition
|
|
Term
| What role does CD4-MHC Class I or CD8-MHC Class II play in the immune synapse? |
|
Definition
|
|
Term
| What interaction takes place at the immune synapse for isotype switching, memory, and 2nd signal for B cel activation? |
|
Definition
|
|
Term
| What interaction takes places for the 2nd T cell activation signal? |
|
Definition
|
|
Term
| What interaction takes places for the deactivation of T cells? |
|
Definition
|
|
Term
| Where are E-selectins found and what upregulates them? what do they bind and what is it critical for? |
|
Definition
| Found on endothelial cells. Upregulated by IL-1 and TNF. Binds neutrophils, monocytes and T cells to help extravasate them. It is critical for initial stages of inflammation |
|
|
Term
| Where is P-selectin found? what is it upregulated by? and what does it do? |
|
Definition
found on platelets.
upregulated in response to soluble mediators of the clotting cascade.
regulates adhesion of neutrophils and monocytes |
|
|
Term
| where is L-selectin found? where is it expressed? and what does it do? |
|
Definition
found on leukocytes
expressed in ciculating neutrophils, monocytes, B and T lymphocytes.
Binds ligand on vascular endothelial cells to aid in extravasation |
|
|
Term
| What are the two categories of cytokines? |
|
Definition
| interleukins which mediate interactions among leukocytes...and chemokines which provide signals for cell migration and chemotaxis |
|
|
Term
| Upon activation of cytokines, what happens? |
|
Definition
| they are synthesized and secreted, they are not stored in a preformed state |
|
|
Term
| T/F: cytokines are antigen specific |
|
Definition
| False, they are NOT antigen specific |
|
|
Term
| What is pleiotropism and what molecule exerts this? |
|
Definition
| Having a different biological activity when bound to different cell types...cytokines exert this |
|
|
Term
| What cytokines induce an inflammatory response what what is their function? |
|
Definition
| IL-1, IL-6, TNF-α and INF-γ. They initiate the inflammatory cascase/acute phase response after interacting with microbial pathogens or suffering trama/damage to host cells. They serve to increase vascular permeability and induce fever |
|
|
Term
| what does pyrogenic mean? |
|
Definition
|
|
Term
| B and T cell activation in response to antigens is regulated by what? |
|
Definition
|
|
Term
| what is the main source of immunoregulatory cytokines? |
|
Definition
|
|
Term
| TH1 cytokines do what? What are they? |
|
Definition
| facilitate the induction of cell mediated immunity by activating macrophages, NKs and CTLs. IL-2, IL-12, IFN-γ, and TNF-β |
|
|
Term
| TH2 cytokines do what? What are they? |
|
Definition
| mediate humoral responses. IL-4, IL05, IL-10, IL-12 |
|
|
Term
| which cytokines prevent differentiation of TH0 to TH2 cells? |
|
Definition
|
|
Term
| which cytokines prevent TH0 to TH1 cells? |
|
Definition
|
|
Term
| What are the colony stimulating factors? What is their function? |
|
Definition
| IL-3, LT, GM-CSF, G-CSF, M-CSF and TGF-β. They are responsible for the development and maintenance of lymphoid tissue, maturation of new cells and replenishing leukocyte populations depleted during immune or inflammatory responses. |
|
|
Term
| What chemokines affect leukocyte traffiking? how do they affect it? and what groups are they subdivided into? |
|
Definition
| IL-8, MCP-1, MIP-1α, MIP-1β and MIP-2. Affect it by recruiting cells to specific sites. Subdivided based on cysteine residues into CC or CXC families |
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|
Term
| What happens in Bacterial Septic Shock in regards to cytokines? |
|
Definition
| bacterial cell walls (LPS, etc) stimulate macrophages to produce mass amounts of IL-1 and TNF-α which leads to disseminated intravascular coagulation, hemorrhage, drop in BP and shock. |
|
|
Term
| What happens in bacterial toxic shock and what microorganism acts as a superantigen to cause it? |
|
Definition
| extremely high levels of IL-1 and TNF-α from the superantigen Staph aureus toxin which causes fever, blood clotting, diarrhea, drop in BP and shock |
|
|
Term
| What two receptors provide sites of attachment/entry for HIV? |
|
Definition
| CCR5 on macrophages and CXCR4 on CD4+ T cells |
|
|
Term
| What happens with HTLV-1 in regards to cytokines? |
|
Definition
| T cells with HTLV-1 produce IL-2 and express IL-2R without stimulation by an antigen, which causes the T cells to be constantly stimulated via an autocrine fashion and leads to uncontrolled growth and T cell related leukemia or lymphoma. |
|
|
Term
| What happens in Chagas disease in regards to cytokines? |
|
Definition
| The parasite Trypanosoma cruzi inhibits expression of IL-2R on T cells so they cannot respond to IL-2 |
|
|
Term
| What is being used to treat patients with rheumatoid arthritis, chron's disease and ankylosing spondylitis? and how does it work? |
|
Definition
| TNF inhibitors by competing with endogenous TNF for binding to the TNF receptors, preventing the pain, swelling and stiffness associated with the disease. Enbrel is a soluble TNF-α receptor that binds TNF-α to prevent it from binding to its receptor on host cells. Humira and Remicade are IgG1 anti-TNF-α antibodies that bind TNF-α to prevent it from binding to its receptor |
|
|
Term
|
Definition
| patients undergoing chemotherapy to reverse neutropenia |
|
|
Term
|
Definition
| patients undergoing bone marrow transplantation to boost clonal expansion of the granulocyte and monocyte population |
|
|
Term
| What is used in Chronic Granulomatous Disease and for what reason? |
|
Definition
| IFN-γ to help macrophages kill ingested pathogens |
|
|
Term
| What is used in Chronic Granulomatous Disease and for what reason? |
|
Definition
| IFN-γ to help macrophages kill ingested pathogens |
|
|
Term
| What is used in Chronic Granulomatous Disease and for what reason? |
|
Definition
| IFN-γ to help macrophages kill ingested pathogens |
|
|
Term
| What is used in Chronic Granulomatous Disease and for what reason? |
|
Definition
| IFN-γ to help macrophages kill ingested pathogens |
|
|
Term
| Which cytokine is mainly responsible for promoting B cell isotype switching the IgE which can cause allergic reactions? |
|
Definition
|
|
Term
| Which cytokine is mainly responsible for promoting B cell isotype switching the IgE which can cause allergic reactions? |
|
Definition
|
|
Term
| What cytokines act as soluble mediators, such as chemoattractants and which is most effective? |
|
Definition
|
|
Term
| Humoral immunity is primarily mediated by which cells? |
|
Definition
| B lymphocytes and TH2 cells |
|
|
Term
| What are the 4 ways antibodies protect the body from infection? |
|
Definition
| neutralization, opsonization, complement activation (classical pathway) and ADCC |
|
|
Term
| T/F: Neutralizing antibodies DO NOT always stop bacteria from dividing or secreting toxins |
|
Definition
|
|
Term
| What are the best neutralizing antibodies? |
|
Definition
| IgG and IgA, although IgM (along with IgA) can cross link pathogens and form large aggregates to prevent them from moving into host cells and making them large targets for phagocytes |
|
|
Term
| What is the most effective way to fight viral infections in regards to humoral immunity? |
|
Definition
|
|
Term
| What molecules bind antigens for opsonization? |
|
Definition
IgG and IgA - Fc portion is bound by neutrophils, macrophages, eosinophils and DCs
C3b and C4b - important in early stages, before isotype switching occurs. Uptake is by macrophages, neutrophils, B cells and DC's that have the required CR1 receptor |
|
|
Term
| Once a single IgM pentamer or two IgG bind an antigen and complement is activated, the pathogen can be removed via which 2 ways? |
|
Definition
| lysis through MAC or opsonization by attachment of C3b and C4b |
|
|
Term
| In regards to ADCC, which antibodies and receptors interact? Hint, there are 2 different pathways |
|
Definition
IgG1 or IgG3 bind target and IgG receptor on NK cell binds which triggers release of cytotoxic enzymes on surface of pathogen.
Eosinophils bind IgE in which the contents are emptied on surface as well. |
|
|
Term
| What 3 things does the antibody response depend on? And what are the 4 stages? |
|
Definition
nature of antigen (protein, polysaccharide, etc.), amount of antigen and route of administration.
1. lag phase - antigen is processed/presented, no detectable level of antibody in serum. B and T cell clonal expansion and differentiation
2. Log phase - exponential increase in serum antibody levels
3. plateau phase - serum antibody levels reach peak
4. decline phase - serum antibody levels decrease |
|
|
Term
| Describe the differences between primary and secondary humoral responses in regards to IgM predominance |
|
Definition
| IgM is higher in primary response whereas other isotypes dominate in the 2ndary response |
|
|
Term
| What is the secondary humoral response also called? |
|
Definition
|
|
Term
| What are the antigen specific cells of CMI? the nonspecific cells? |
|
Definition
| antigen specific are CTLs and TH1. Nonspecific are macrophages, neutrophils, eosinophils and NK |
|
|
Term
|
Definition
| when CD8+ cells recognize antigen attached to Class I |
|
|
Term
| Which cells of the CMI reject incompatible grafted/transplanted tissue? |
|
Definition
|
|
Term
| what cytokines do CTLs secrete and what do they do? |
|
Definition
IFN-γ activates macrophages to kill intracellular pathogens they have ingested
TNF-β that helps activate macrophages and enhance their phagocytic activity |
|
|
Term
| Intravesicular pathogens cause APCs to secrete what? What does this do in terms of TH0 cells? |
|
Definition
| Secrete IL-12 and IFN-γ which stimulates naive TH0 cells into TH1 cells |
|
|
Term
| What do TH1 cells secrete to help activate macrophages and neutrophils? |
|
Definition
|
|
Term
| What do TH1 cells secrete to enhance TH1 proliferation and inhibit TH2 production? What do they secrete to stimulate proliferation of T cells and NK cells? |
|
Definition
|
|
Term
| What do TH1 cells do to B cells? |
|
Definition
| induce them to isotype switch (TNF-β does IgA and INF-γ does IgG1 and IgG3) |
|
|
Term
| What receptors do the NK cells have and not have? |
|
Definition
| they have Fcγ receptors but do not have TCR or antigen-recognizing receptors |
|
|
Term
| What are macrophages activated by and what do they do? |
|
Definition
| activated by IFN-γ and TNF-β and remain at the site of infection to help keep T cells activated, increase phagocytic activity and produce the oxidative burst |
|
|
Term
| CTLs recocognize antigens complexed to what? because of this, virtually all cells in the body are potential targets |
|
Definition
|
|
Term
| in addition to the normal 2 signals required for T cell activation, differentiation of CD8+ cells to CTLs requires what else? |
|
Definition
|
|
Term
| What ways do CD8+ T cells become activated? |
|
Definition
1.) Directly by DCs - DCs become infected and present via Class I...or...DCs ingest infected particles and present via both Class I and II. The activated CD8 then releases IL-2 which acts in an autocrine fashion on itself.
2.) The 3 cell model where both CD4 and CD8+ cells recognize different peptides on the same APC and become activated. The CD4+ cell then secretes IL-2 which results in proliferation of CD4 and CD8 cells into their effector cells
3.) Two cell model where CD4+ cell is activated when it binds to Class II and secretes IL-2. CD8 then binds APC and upregulates the IL-2R and proliferates/differentiates in response to IL-2 |
|
|
Term
| Describe perforin-mediated cell death and what happens during its role in CMI |
|
Definition
| it is a Ca2+ dependent process that involves the release of cytotoxin substances contained in granules inside the CTL. the granules contain perforin and granzymes that get secreted onto the surface of the taret. perforin polymerizes to make a ring like channel in the membrane of the target. the serine granzymes then enter the host and interact with caspases to induce apoptosis. |
|
|
Term
| Fas-Fas ligand mediated cell death - what cells/environments can it be activated in? what does it do (which pathway does it activate?) and what is it used to primarily eliminate? |
|
Definition
| It can happen in Ca+ deleted environments and be initiated by Th1 cells which have a FasL on their surface. Fas is on the target cell and Fas ligand (FasL) on CTL. Used to eliminate excess of terminally differentiated antigen-specifc T cells once the antigen is eliminated or diminished (this is called activation induced cell death) |
|
|
Term
| Where are 75% of the body's lymphocytes found? |
|
Definition
|
|
Term
| T/F: Peyers Patches do not secrete antibodies |
|
Definition
| False, they secrete very little antibody |
|
|
Term
| What is found in the dome area of peyers patches? |
|
Definition
|
|
Term
| Where is most of the SIgA for the gut produced? |
|
Definition
|
|
Term
| What is found within the lamina propria layer? |
|
Definition
| mIgA+ memory B cells, plasma cells producing IgA, CD4+ T cells, DCs, macrophages, and mast cells (produce less histamine than connective tissue mast cells) |
|
|
Term
| What are found within the epithelium of the crypts of tonsils? |
|
Definition
| M cells, langerhans, and macrophages |
|
|
Term
| What are the two zones of the tonsils and what happens in each zone? |
|
Definition
mantle zone just beneath the epithelium which contains high amount of memory cells.
the extrafollicular zone where antigens are presented to T cells. |
|
|
Term
| What antibodies do tonsils mainly secrete? |
|
Definition
| IgG, and some pIgA that becomes SIgA |
|
|
Term
| Most SIgA is secreted by what in saliva? |
|
Definition
| Major and minor salivary glands |
|
|
Term
| What does mucosal epithelium have? (receptors, molecules, cells, etc) |
|
Definition
| pIg receptor to transcytose pIgA to lumen. Expresses HLA-D and has lymphocytes, DCs, and macrophages |
|
|
Term
| Intraepithelial lymphocytes are made 90% of what cells? What about the other 10%? What do these cells do when cells become infected, injured, or stressed? |
|
Definition
| 90% equals T cells that express surface markers that indicate they have been activated. the 10% is the gamma delta TCR that bind to MIC-A or MIC-B that is expressed when cells become infected, injured or stressed, and kills the cells. |
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