MIM Flashcards

Question

What cytokines are required for B and T cell growth? What cell provides this?

Answer 1

Stromal cells (nonlymphoid cells in the bone marrow) secrete SCF, a membrane bound cytokine and IL-7

Answer 2

Effector T cells make IL-3 and GM-CSF which act in an endocrine fashion to stimulate production of monocytes and granulocytes.

Answer 3

CCL21: Chemokine made by vascular endothelial cells, attracts dendritic cells to 2ndary lymphoid organs. CCL21 also binds CCR7 receptors on naive T cells, activating an adhesion molecule on their surface. This stop T cells at the node so that reactive T cells can be activated. CCL19: made by stromal and dendritic cells in the node, entice the naive T cells into the cortex of lymph node CXCL13: made by follicular dendritic cells, bring B cells into the follicles to become plasma cells In sum: produced by dendritic cells, stromal cells and HEV, as well as others. Functions to bring home in lymph node B, T, and dendritic cells

Answer 4

Secreted at the site of infection by T cells, it recruits macrophages

Answer 5

Produced by macrophages and induces chemotaxis of PMNs to site of infection

Answer 6

IL-1, IL-6, and TNF-alpha Liver - acute phase proteins to activate complement Bone Marrow Endothelium - neutrophil mobilization Hypothalmus - increased body temp (endogenous pyrogens) Fat, Muscle - protein and energy metabolism to allow increased body temp.

Answer 7

Triggered by systemic infection, TNF released by macrophages in the spleen, liver and other sites can cause shock.

Answer 8

Hematopoietic Stem Cell Transplantation - b/c regimen involves eliminating a patient's malignant hsc system and making room for grafted cell. This damages tissues containing proliferative cells targeted by the therapy and can create the storm leading graft vs host disease when the adaptive immune system is activated. Exposure to super antigens like toxic shock syndrome and staph enterotoxin can activate large #s of T lymphocytes independent of antigen presentation.

Answer 9

Macrophage | Inflammation, activate lymphocytes; fever

Answer 10

T cells | T cell proliferation, Ig synthesis by B cells, increase NK activity

Answer 11

Th1 | Growth and differentiation of hematopoietic cells

Answer 12

``` Th2, mast cells, basophils Differentiation of Th2 cells; activation of B cell; influences class switch; T cell growth factor ```

Answer 13

``` Th2 B cell differentiation, influences class switch ```

Answer 14

Activate T & B lymphocyte differentiation; fever; acute phase proteins from liver

Answer 15

Stromal cells | B & T cell development in marrow; T cell growth factor; survival signal for memory T

Answer 16

Regulatory T cells, Th2, macrophages | Suppression; interfere with Th1 differentiation

Answer 17

Macrophages, dendritic cells | Activate NK cells; differentiation of Th1 cells

Answer 18

Many non-T cells | T cell growth factor; survival signal for memory T cells

Answer 19

Th17 | Binds to many cell types to induce inflammation

Answer 20

Innate immune cells | Differentiation of Th17 cells

Answer 21

There is alpha and beta type I IFN. Synthesized by most cells infected by a virus. In the lymph node, release of these cytokines cause virally infected cells to become more susceptible to killing by NK cells and increases the resistance of unaffected cells to infection by interfering with viral replication (paracrine effect) and makes them more vulnerable to CD8 killer T cells (autocrine effect)

Answer 22

It is made by NK, Th1, and cytotoxic T cells. Required to activate infected macrophages to kill intracellular pathogens, causes infected cells to become more vulnerable to killer cells and increases resistance to viral replication in uninfected cells.

Answer 23

Innate: IFN alpha and beta, TNF-alpha, and IL-12 NK cell mediate killing of infected cells via IFN-gamma Adaptive: T cell mediated killing of infected cells via IL-2 IL-12: from macrophages stimulate NK cell to produce IFN-gamma which makes NK cell to become more cytotoxic.

Answer 24

Th1: IFN-gamma, IL-12 made by NK, CTL, innate immune cells Th2: IL-4, made by mast cell and basophils --> humoral (B cells make Ab) Th17: IL-1 and IL-23 made by innate immune cells. These secrete proinflammatory cytokines Cytokines can suppress one direction or another. For example, IL-10 inhibits antigen processing by dendritic cell and macrophages so they don't make IL-12. NK cells are not activated and cant make IFN-gamma so Th1 is prevented.

Answer 25

Th1: IFN-gamma, IL-12 made by NK, CTL, innate immune cells Th2: IL-4, made by mast cell and basophils --> humoral (B cells make Ab). Th17: IL-1 and IL-23 made by innate immune cells. These secrete proinflammatory cytokines Cytokines can suppress one direction or another. For example, IL-10 inhibits antigen processing by dendritic cell and macrophages so they don't make IL-12. NK cells are not activated and cant make IFN-gamma so Th1 is prevented.

Answer 26

Alternative RNA splicing

Answer 27

- Multipotent progenitor cell: germline - Common lymphoid progenitor: germline - Early pro-B cell: both alleles, HC rearrangement (DJ) - Late pro-B cell: VDJ rearrangement HC - Large pre B cell: HC rearranged, invariant LC - Small preB cell: LC rearrangement - Immature B cell: IgM expression with both HC and LC arranged - Mature B cell: IgD and IgM expressed (occurs in bone marrow or in periphery)

Answer 28

A surrogate chain bound to HC or beta chain to ensure appropriate BCR and TCR respectively. Occurs during large pre-cell development or double negative development of T cell. These receptors are mainly intracellular but some are on cell surface.

Answer 29

It gives the cell twice the opportunity to get a productive rearrangement of HC since so many B cells are lost in development. There are more cell lost between the pro-B to pre-B transition than the pre-B to immature B cell. The LC rearrangement has greater variability.

Answer 30

No more rearrangement of other allele allowed to prevent variations in receptor that functions appropriately. RAG proteins are involved in gene arrangement

Answer 31

Mature B Cell Apoptosis Anergic B cell Clonally Ignorant

Answer 32

A chemical in the lymphoid tissue that positively signals B cell growth and survival in 2ndary lymphoid tissue.

Answer 33

Negative and positive selection of T and B cells in bone marrow and thymus. Self peptide is again tested in 2ndary lymphoid tissue - B cells

Answer 34

- B-1 Cells: produce in fetus (mouse fetal liver) are primitive, called CD5 B cells, are good cells to react with Ag first since it has low specificity. Produces IgM, reacts with Carbs Ag, polyspecific Ab (paratope binds with many motifs) has little junctional diversity, they are the B cells that protect the pleural and peritoneal cavities, self-renewing with little or non memory dvmpt - Marginal Zone B Cells: found in spleen, produces IgM and mainly deals with encapsulated bacteria responding both to carb and protein antigen. No memory associated here and long lived cells - Conventional B Cells: produce after birth, extensive diversity, located in secondary lymphoid tissue, replaced from bone marrow, produce IgG more, respond mainly to protein Ag, has memory

Answer 35

CDR1/2 - see MHC | CDR3 - sees peptide, has a lot of junctional diversity

Answer 36

Positive Selection is bias towards MCH | Negative Selection towards peptide

Answer 37

Thymic t.f that commits incoming T cell from bone marrow to T cell lineage

Answer 38

Double Negative (CD3,4,8) DN3 Stage: gamma,delta CD3+8-9- or alpha beta CD3+4+8+ (large active double positive) Small Resting Double Positive: alpha beta CD3+,4+, 8+ Small Resting Single Positive 20% become iNKT cell, 20% gamma delta, and 60% CD4+ or CD8+ Gamma delta cells see mucosal surface and skin

Answer 39

Cortex: immature thymocytes, macrophages and does positive selection via cortical epithelial cells Medulla: mature thymocytes, medullary epithelial cells, macrophages and DC cells of bone of marrow origin and does negative selection via bone marrow derived DC and macrophages Hassall's Corpuscles: sites of cell destruction Cells enter at corticomedullary junctions. DN3 cells reside near subscapular region.

Answer 40

If a complete gamma delta TCR is formed before a successful beta chain gene rearrangement, the thymocyte receives signals through gamma delta receptor shutting off rearrangement of beta gene. Signaling through this receptor induces strong activation of Erk committing cell to gamma delta lineage. Weaker Erk activation via the pre-T cell receptor in comparison with the gamma delta receptor leads to alpha beta lineage commitment.

Answer 41

Autoimmune regulator - gene allows epithelial cells and macrophages to express tissue specific Ag. The thymus gets greater opportunity to purge from its repertoire self reactive T cells. Not complete though since there is a group of sequestered antigens - important for autoimmunity

Answer 42

A transcription factor forkhead found in a population of T cells that have a strong binding at the negative selection phase to the self MHC/peptide complex. They are CD4 cells that become regulatory T cells.

Answer 43

There are differences in affinity of weak interactions that allow cells that are selected in positive selection to survive negative selection.

Answer 44

A self reactive B or T cells could get activated if a raging infection is causing proinflammatory cytokines to form. These cytokines can act as signal 2 even if they are not being produced by APCs. You need 3 signals to activate T cell. But in autoimmune conditions, this can break.

Answer 45

Both are transmembrane proteins with 2 polypeptide chains. Class I - HLA-A, B, and C The alpha3 domain and beta2 microglobulin pair to form platform and the two alpha (alpha1 and 2) form the antigen binding groove. Class II - HLA-DR, DQ, and DP The alpha2 and beta2 form the platform and alpha1 and beta1 form the Ag binding groove. Antigenic binding site consists of a beta sheet floor walled by two alpha helices and carry 8-25 AA long peptides. Class I peptides are short 9-11 aa and class II are longer and extends out of the groove.

Answer 46

Loss of class I or II expression due to absence of transcriptional activator CIITA. This is a severe combined immunodeficiency syndrome.

Answer 47

Class I - via ER and Golgi | Class II - invariant chain and endocytic pathway

Answer 48

Chromosome 6 The beta 2 microglobulin for Class I is on chromosome 15.

Answer 49

- Polygeny and Polymorphism (many alleles compared to Kappa which only has 3 alleles) - alters diversity of binding site. - Inherited in Mendelian fashion, no rearrangement of genes - Codominant expression - 1/4 chance that a 2nd sib will share the same alleles - A person can express up to 6 different class I and class II molecules because of 2 alleles at each loci of 3 different molecules. - Inherited as a haplotype - b/c the HLA genes are all localized (haploidentical: children that share 1 haplotype) - true unless recombination occurs.

Answer 50

Peptides that bind a specific MHC molecule share structural features called a motif (formed by specific AA). These features allow the peptide to fit into the groove of that MHC molecule.

Answer 51

NK cells can detect loss of MHC class molecules when virally infected or tumor cells lose HLA expression. There is immunoselective pressure to survive. They may be invisible to T cells but not NK cells.

Answer 52

It is a drug that can cause hypersensitivity reaction in patients that have the specific HLA allele - B57:01. The drug binds to the antigen binding groove of this HLA molecule and when the cell introduces self peptide, it is pushed out of the groove and causes a conformation of the cell that is recognized as foreign to the T cell.

Answer 53

- Ankylosing Spondylitis - Multiple Sclerosis - Rheumatoid Artheritis - Celiac Disease - HIV/AIDS - homozygous patients since they express fewer HLA molecules - Transplantation Alloantigens (graft rejection & graft vs. host disease) - TCRs can recognize more than MHC-peptide complex as long as they appear physically and chemical similar called TCR cross reactivity. An antigen specific TCR from a transplant recipient can recognize a foreign MHC holding a self peptide on the transplanted tissue causing allorecognition - memory T cells do this.

Answer 54

T cell bound, Heterodimer associated with CD3 (signaling) contains alpha and beta polypeptide chains bound by disulfide bonds, TCR has variable (N terminal) and constant regions, TCR affinity is low, TCR cytoplasmic tails is short so not designed for signaling. Needs adhesion molecules and signaling assistance. It resembles an Ig Fab fragment recognizing MHC peptide complex. Signaling: CD3 and CD28 Adhesion: CD4, CD8, LFA1, CD11a

Answer 55

Alpha - chromosome 14 | Beta - chromosome 7

Answer 56

``` Alpha = 1 V + 1 J Beta = 1 V + 1 D + 1 J ``` D + J interacts w/peptide and V interacts with MHC Constant Region does not confer any effector functions. - Beta locus rearranges first in thymus - Beta stops rearranging, cell becomes CD4+ or CD8+ - Alpha locus rearranges - TCR expressed on cell surface with CD3 - Single positive selection

Answer 57

Combinatorial + Junctional Diversity but no Hypersomatic Mutation

Answer 58

- Marker for T/B cell clonality - single T/B cell expansion vs polyclonal - Stage tumors (ex. acute leukemia = less mature cells) - Presence of excision circles to indicate reconstitution of IS in patient receiving hematopoietic stem cell transplant

Answer 59

Burkitts Lymphoma - oncogene MYC translocation from 8 to 14, region Ig HC locus - unregulated B cell growth CML - translocation of BCR on 22 to ABL region of 9 leads to tyrosine kinase product that activates cell cycle - uncontrolled WBC growth (esp. granulocytes)

Answer 60

Bacterial toxins interacts with TCRs, crosslinks MHC and TCR stimulating T cell nonspecifically. The MHC Class II is utilized. 2-20% of T cells activates vs 1/10,000 for Ag.

Answer 61

Within the variable region of the HC and LC, there are HVR or CDRs (loops) and framework regions (beta pleated sheets) which are conserved. The HVRs from one HC and one LC combine together to form an antigen binding site.

Answer 62

Kappa LC - Chromosome 2 Lambda LC - Chromosome 22 (4 subclasses) with different Constant regions coding for subclasses HC - Chromsome 14 The size of B cell repertoire of antigen binding site is limited only by the # of B cells found in the body at any one time.

Answer 63

Mutations in RAG genes

Answer 64

True, somatic recombination is not passed onto offspring.

Answer 65

Junctional and combinatorial diversity - the differences in flanking sequences of kappa, lambda HC restrict rearrangement to within the same gene LC (kappa): V+J segment form the HVR (CDR3) which participates in the interaction with antigen. There are 40J each is preceded by a S and is followed by 5 alternative J exons. The S segment plays a role in transporting chains to the outside of the cell. The C region is the framework region of LC. LC (lambda): same except that there are slightly 4 different constant regions specifying the 4 subclasses. Each constant region is preceded by a J segment. HC: includes D segment, so we have V,D and J (D&J first then V along with its S is spliced next to D&J. The constant region is divided into several exons each specifying one of the constant region domains (so 9 total) and one for the hinge region. mRNA processing controls HC carboxy terminal through choice of exons (Se for short tail in secreted form and M for cytoplasmic and transmembrane region of membrane bound)

Answer 66

Mu then delta, mu is next to V/D/J exons. RNA processing results in longer transcript for delta HC.

Answer 67

Occurs in the germinal centers of peripheral lymphoid tissue. It targets the V region of both HC and LC genes. Occurs at 1 bp/1000 base compared to 1 to every 10^10 bp in avg cells. Occurs after antigen encounter - affinity maturation.

Answer 68

- Activation of B cell w/Ag generates signals that induce the process of somatic hypermutation and isotype switch. There is a downregulation of IgD. There are switch sequences preceding the constant region encoding each class and subclass of HC except delta. Another DNA rearrangement occurs that alters the class HC constant region. The rearranged HC VDJ segment is spliced next to one of the other C regions exons downstream of delta. - IgM becomes IgG, E or A and is mediated by switch sequences through influence of cytokines that specify what class to use. There is no switch sequence btw mu and delta constant regions b/c the distance btw exons is too short - RNA splicing allows for expression of IgD. - There is no alteration of the LC

Answer 69

Immunodeficiency associated with failure of T help with switch. The CD40-CD40 ligand defect is occurring which is involved in help for the B cell.

Answer 70

Prevents a B cell from expressing a mixture of antibodies even with 2 loci expressing kappa, 2 for lambda and 2 HC loci. The rearrangement of other LC or HC loci will halt once a functional gene is generated.

Answer 71

Production of single B cell clone used in diagnosis, imaging, therapy, research. They are made via hybridoma technology. Ag in mice --> produces short lived Ab, fuse with immortalized mouse myeloma cells pretreated to eliminate production of own Ig. This will produce indefinite and long lived source of Abs specific to Ag used. -Recombinant DNA tech can help make more humanized forms, this will eliminate response to foreign Ab, increase stability, increase effectiveness, and have 2 different Ag binding arms (Fv fragment - HC V region linked to a LC V region)

Answer 72

-Mab - monoclonal Ab Target: tu(m) = tumor, li(m) = lymphocyte, me(l) = melanoma Source: xi = chimeric, zu = humanized, o = mouse, a = rat Ex. Rituximab and Basiliximab

Answer 73

IgG1 vs IgM - Mol Form: monomer vs pentamer - Serum level: 9 (75-85) vs 1.5 (5-10%) - T1/2: 21 vs 10 days - IgM better complement - Placental transfer and Fc phagocytic binding vs 1st Ab made by B cell

Answer 74

- Block major portal of entry for more pathogens, protects newborn - Found in secretions (saliva, tears, breast milk and mucus) - Found as monomer in serum and cell surface (nodes and spleen) but dimer in secretions (2ndary lymphoid tissues under mucosal surfaces). The dimer is held together by S-S bonds and J chain. - Has a high rate of synthesis - IgA secreted: binds to a receptor on epithelial cells called polyIg and is internalized. It is transported through epithelial cells and dumped into secretion, but portion of polyIg receptor stays attached as a secretory component. - IgA1 and IgA2: IgA1 hinge region is sensitive to proteases made by respiratory pathogens. IgA2 is not sensitive. A1 is prodominant in serum and A2 in mucosal secretions - No activation of complement - role is neutralization and not opsonization - Serum level: 3 (7%) (IgA1) 0.5 17% (IgA2) - t1/2 - 6 days - Fc phagocytic binding

Answer 75

- No hinge region with 4 constant region domains - Shortest serum half life - Low synthesis rate - Allergy and parasitic infections - Has high affinity to Fc receptors on mast cells, basophils and eosinophils - Monomer - Serum Level 5x10^-5 (0.019%) - t1/2 = 2 days (IgE half life on mast cell > serum) - Causes hypersensitivity reactions (hay fever, hives, anaphylactic shock) when IgE bound to FcR on basophils and mast cells. Killing of parasites via eosinophils

Answer 76

Isotypic - response to species specific determinants on the constant regions of HC and LC. Ex. horse anti-snake venom antibodies to treat snake bites in humans Allotypic - response to allelic differences of either the variable or constant regions of HC and LC within a species. Ex. transfusion and multiple pregnancies Idiotypic - response to the variable region, specifically the antigen binding site of an Ab. It's significance is seen in controlling the immune response by removing Ab once they are no longer required.

Answer 77

- IFN-gamma and CD40 ligand is the primary response to activate macrophages and kill intracellular pathogen, make cytokines that promote opsonizing Ab. - Fas ligand and TNF-beta - IL-2 - IL-3 and GM-CSF trigger production of granulocytes and macrophages in bone marrow - CCL2 to recruit macrophage accumulation - TNF alpha and beta activates endothelium to induce macrophage binding and exit from blood vessel at site of infection

Answer 78

-IL-4 activates B cell -IL-5 and 6 cause B cell differentiation -CD40L/CD40 interaction is 2nd signal for B cell activation. -IL-10, TGF-beta are suppressive for Th1 responses and control activated macrophages reducing tissue damage Cytokines secreted by Th2 cells are anti-inflammatory cytokines

Answer 79

- IL-10 and TGF-beta are inhibitory cytokines secreted by regulatory T cells. Limit effector T cell proliferation and play a role in tolerance. They are anti-inflammatory - IL-7 and Il-15 prolong survival of memory T cells and are made by many non T cells

Answer 80

- Sensitivity of cell to cytokine may change over time - IL-7 receptors are expressed early in dvmp while IL-2 receptor later in dvmpt. - Naive T cells have a low affinity IL-2 receptor (beta and gamma chains) but activation induces high affinity receptor where alpha is incorporated. (IL-2 receptor is CD25) - Cytokine receptors use the JAK/STAT pathway to signal inside cell

Answer 81

Mutations in the gamma chain of IL-2 receptor affect receptors for other cytokines. The common gamma chain is encoded in the X chromosome so males are mostly affected. The result is a decrease in NK, T and nonfunctional B cells (due to lack of T cell help)

Answer 82

-Cyclosporine, tacromilus all inhibit calcineurin which activates transcription of IL-2. IL-2 is very important for adaptive immune response -Monoclonal antibodies to IL-2 (Basiliximab) -Rapamycine inhibits signaling through IL-2 receptor -G-CSF to mobilize hematopoietic stem cells for donation by aphresis -

Answer 83

Role in allergy and adaptive immunity - contribute to Th2 IgE responses via IL-4 production and antigen presentation to CD4 T cells.

Answer 84

Innate lymphoid cells (ILCs) differentiate from haematopoietic stem cells, via an ID2+ precursor cell, under the influence of cytokines such as interleukin-7 (IL-7), IL-15, IL-23, IL-25 and IL-33. These signals induce the expression of transcription factors that promote the differentiation of the various ILC subsets (group 1, 2 and 3 ILCs) and induce their expression of signature cytokines. The cytokines secreted by ILCs promote important physiological responses, such as wound healing, tumour surveillance and protection against infections. However, ILC-derived cytokines can also promote immunopathology in diseases such as asthma and IBD.

Answer 85

Large granular lymphoid like cells, function against intracellular infections, they lack antigen specific receptors. Important for viral infections.

Answer 86

The TCRs of iNKT cells are not very diverse and recognize lipids and glycolipids presented by CD1. iNKT cells have antibody receptors and can release cytotoxic granules. They also release large quantities of cytokines. Invariant NK cell – bridges both innate and adaptive immunity,

Answer 87

Outermost Cortex - B cell organized into lymphoid follicles or germinal centers Paracortex (Deep) - T cell and dendritic cells Medulla - macrophages and plasma cells (medullary cords) Lymph comes in carrying Ag via DC cells or macrophages to the node by way of afferent lymphatic vessel and leave by efferent lymphatic vessel. Naive lymphocytes enter the node from the bloodstream through specialized post capillary venules and leave with lymph through the efferent lymphatic.

Answer 88

``` Red pulp (site of RBC destruction) interspersed with lymphoid white pulp surrounding a central arteriole. PALS - surround central arteriole and contains T cells Follicular Zone - B cells, germinal center is surrounded by B cell corona --> marginal zone --> peri-follicular zone. ``` Blood carrying both lymphocytes and Ag flow from trabecular artery --> central arteriole --> smaller BV to white pulp.

Answer 89

Contains numerous B cell follicles with germinal centers. T cells occupy the areas btw the follicles (T cell dependent areas) Sub-epithelium Dome - layer btw surface epithelium and follicles, contains dendritic cells, T and B cells. Have no afferent lymphatics and the antigen enters directly from the gut across a specialized epithelium called microfold (M cells) - there is efferent lymphatics though and lymph leave through here. The M cells lack microvilli and mucus and appear as sunken area on the epithelial surface.

Answer 90

Dendritics Cells - only one to activate naive T cell (acts first as macrophage but then matures to APC which has Ag and costimulatory signals) Macrophages B lymphocytes

Answer 91

To activate a T cell, 3 signals are required: 1. Ag 2. Costimulatory signals 3. Cytokines

Answer 92

CD4+ T cells are the most numerous > CD8+ > B cells and NK cells

Answer 93

An antigen can react with a B cell or T cell receptor but cannot initiate an immune response de novo. This distinguishes btw immunogen and antigen. An immunogen will initiate an immune response de novo. They contains PAMPs (DAMPS) but antigen will interact with TCR and BCR. T cell see antigen held by MHC molecules. All immunogens are antigens but not all antigens are immunogens.

Answer 94

BCR: C terminus of molecule has no cytoplasmic tail, it cannot transduce signal into interior of the B cell, it needs accessory molecules called co receptors. It has IgB and Igalpha which have cytoplasmic tails. ITAMS motifs – these coreceptors incorporate with the BCR that transduces signal to interior of the cell. Contains 2 paratopes. TCR: It has no cytoplasmic tail – poor transducing signal. You have heterodimers called CD3 which are coreceptors for the T cell receptor signal complex. They require crosslinking like the B Cells – have the same ITAMS. Only 1 binding site (paratope)

Answer 95

Foreigness - greater the phylogenic distance btw 2 species, the greater the antigen disparity Molecular Size - > 100 kDa Chemical Composition & Heterogeneity - primary, 2ndary, tertiary and quaternary org contribute to immunogenicity.

Answer 96

- Ability to be degraded/metabolized. Only B cells can recognize native antigens/immunogens. T cells see it processed - Structural organization - Solubility/accessibility - an antigen must be able to form a colloidal suspensions to be accessible to APC, particulate substances are more potent as a result for phagocytic cells. - D- Amino Acids are poor immunogens than L AA. Human immune system can't recognize these conformation of bacterial cell walls.

Answer 97

High Zone: Lymphocytes respond to antigen on cell surfaces complexed to MHC antigens. If the antigen presenting cells are overwhelmed with excess antigen, lymphocytes bind to free antigen which prevents them from getting the second signals they need to become activated. It is overcome as the excess antigen is removed by phagocytes and serum proteases. The antigen concentration is reduced to a stimulatory level Low Zone: Doses of antigen just below that which will induce an immune response also produce tolerance (low zone tolerance). In this case the Th cells seem to be permanently inactivated, so recovery does not occur for several months; i.e., until the Th cells have been replaced by the thymus.

Answer 98

Substances that enhance immunogenicity. Do not form stable linkages with immunogen, convert soluble antigens into particulate, are used in vaccines, can contains PAMPs (bacterial products) Ex. Tetanus Toxoid Ex 1: Complete Freunds, oil in water emulsion with dead mycobacteria, activates T cell via TLR, highly toxic Ex 2: Alum(OH), enhanced up take by APCS, but delayed release of Ag, very low toxicity Ex 3: Immune Stimulatory Complexes (ISCOMs), matrix of Quil A(amphipathic glycoside) containing viral proteins, delivers Ags to cytosol, induce cytotoxic T cells, low toxicity

Answer 99

- DC SIGN (binds sugars of pathogens) - TLR - ICAM-1 and LFA-1: cell adhesion molecules after DC cell is no longer phagocytic - MHC Class II - Costimulatory Signals: B7.1 and B7.2 which deliver signal 2 to naive T cell. - Release of cytokines = signal 3

Answer 100

An epitope is 15-22 AA. About 75-120 hydrogen bonds bind an epitope to paratope. Number of antibody molecules that can bind to a molecule of Ag at one time defines the Antigen's valence (spatial limits) - The cell can display epitope in multivalent or multideterminant fashion. Multivalent: displays multiple epitopes that are identical or different. Multideterminant: displays structurally different epitopes - Epitopes can immunodominant (most potent epitope) , subdominant or cryptic (an epitope, i.e. neoantigenic that is exposed by conformation change of Ag like HIV-1)

Answer 101

B cells: -Interaction with Ag involves binary complex of membrane Ig and Ag -It binds soluble Ag -No need for MHC -Ag can be protein, polysaccarhide or lipid -Epitope is accessible, hydrophilic, mobile containing sequential or nonsequential AA T cells -Interaction with Ag involves ternary complex of TCR, Ag and MHC -No binding of soluble Ag -MHC required -Ag is mostly protein, but some lipids and glycolipids -Epitope is internal linear peptide, hydrophobic and bound to MHC

Answer 102

It means that there is no absolute specificity btw them. The # of peptides generated exceeds the # of T cells. The T cell can recognize these peptides. The tighter the fit the greater the complementarity and higher the affinity for signaling. Cross reactivity can occur as a result of this concept leading to autoimmune conditions. -Ag and Ab are held together by noncovalent forces, you can separate the two via changing pH or ionic abilities.

Answer 103

Intrinsic affinity: The goodness of fit between an epitope and paratope Functional affinity: The increase of affinity resulting from valency, i.e., 2 or more epitope – paratope intereactions Avidity: the average functional affinity of a population of antibody molecules recognizing the same epitope

Answer 104

- Small organic molecule that do not provoke Ab when injected by themselves, Ab are raised against them if they are covalently attached to a protein carrier. - The carrier does not need to be an immunogen but the same carrier must be used in priming and challenge - Anti hapten Ab formed to penicillin allergies when components attache to proteins in blood. - By itself, byproduct of penicillin degradation does not induce an immune response. The compound once attached to RBCs or other proteins in blood then cause IS b/c it is seen as foreign. - Antibodes are formed to the protein carrier+hapten but not to the hapten

Answer 105

Macrophage, Th1 Inflammation; increase permeability and activate vascular endothelium; dendritic cells to secondary lymphoid tissue; fever; mobilize metabolites; mobilize neutrophils

Answer 106

Th1 | Activate endothelium to attract macrophages to site

Answer 107

T cell | Activate B cells to make antibody; activate macrophages to kill intracellular pathogens

Answer 108

T cell | Apoptosis following immune response and during T cell development

Answer 109

Any cell infected by virus | Increase resistance to viral infection; increase susceptibility to killing via ag presentation; activate NK cells

Answer 110

Any cell infected by virus | Increase resistance to viral infection; increase susceptibility to killing via ag presentation; activate NK cells

Answer 111

``` Th1, cytotoxic T, NK Activate macrophage to kill intracellular pathogen; increase resistance to viral infection; increase susceptibility to killing via ag presentation; differentiation of Th1 cells; interfere with Th2 differentiation; class switch specificity ```

Answer 112

Fibroblasts, monocytes | Neutrophil development and differentiation in marrow

Answer 113

Monocyte development and differentiation in marrow

Answer 114

T cells, macrophages | Granulocyte and monocyte differentiation in marrow

Answer 115

Stromal cells | B and T cell development in marrow

Answer 116

``` Regulatory T cell, Th2, monocytes, chondrocytes Suppression; interfere with Th1 differentiation; class switch ```

Answer 117

Macrophage | Chemotaxis of neutrophils to site of infection

Answer 118

Th1 | Macrophages move to site of infection

Answer 119

Dendritic cells, Stromal cells, HEV | Homing in lymph node of B, T, dendritic cells

MIM Flashcards

(145 cards)