Immunology, exam 3

αβ T cells

CD4+ and CD8+ with T helper and T cytotoxic Ag processed and presented in context of an MHC molecule

9.- The majority of cells found at tick bite sites are: A) NK cells B) T cells C) Dendritic Cells D) Basophils

D) Basophils

Central Tolerance

Negative selection that eliminates auto-reactive T or B lymphocytes during their development clones if they possess self reactive antigen receptors with anything greater than a low antigen affinity Occurs in the primary lymphoid tissues where the lymphoid cells mature.

Ig Effectors

Neutralization Opsonization Complement Fixation Antibody Dependent Cellular Cytotoxicity Antibody mediated degranulation

Cortico-medullary junction

Where does negative selection take place?

Hemophagocytosis

the phagocytic destruction of red blood cells)

TNF-alpha

contributes to systemic anaphylaxis which cytokine is particularly important in maintaining granulomas? -mediates septic shoc upregulates IL-1 and IL-6

Caspase

recruited by death domain adaptor protiens, 8 cleaves 3 with leads to apoptosis

KIR

(Killer cell immunoglobulin-like receptors) present on NK cells through which the cells' cytotoxic activity is controlled. Family contains both activating and inhibitory receptors.

21. Which of the following B cells, having recognized its antigen, & now presenting it with MHC-II, is most likely to become a plasma or memory cell? (a) B cell moves from the primary focus into the medulla of a lymph node (b) B cell interacts move from the primary focus into a germinal center (c) B cell develops into a cell that is secreting antibody but still expresses (d) B cell remains in the primary follicle. surface antibody as well.

(b) B cell interacts move from the primary focus into a germinal center

19. A strain of mice is unable to produce CTLA-4. These mice are experimentally challenged with a viral pathogen. You expect to see: (a) The mice die, because they are unable to mount a cell-mediated (b) The mice die, because of a fatal over-proliferation of T-lymphocytes (c) The mice live because Cell mediated immunity is unimpaired. Humoral (d) The mice live but all immune response would be primary. No memory is response immunity, however, would be adversely affected. generated.

(b) The mice die, because of a fatal over-proliferation of T-lymphocytes

22. If a macrophage is unable to undergo an effective respiratory burst following phagocytosis: (a) It will down regulate MHC II (b) It will down regulate B7 (c) It may migrate to a secondary lymphatic, where it may be activated by (d) No adaptive response would be possible (e) It would undergo anergy IFN-gamma.

(c) It may migrate to a secondary lymphatic, where it may be activated by IFN-gamma.

20. You discover a new interleukin, IL-33, which appears, in the lab at least, to cause antibody class switching to IgA. You want to see if you can detect this cytokine in vivo. So you challenge experimental animals with soluble bacterial antigen. Where is the most likely place to detect this cytokine in vivo, assuming it works like other cytokines involved in class switching? (a) blood (b) thymus (c) lymph node medulla (d) lymph node secondary follicle, surrounding a germinal center (e) the MALT

(d) lymph node secondary follicle, surrounding a germinal center

23. Red blood cells have a complement receptor termed CR1. Suppose an individual was lacking this receptor. Which of the following problems might they have? (a) an inability to mount an inflammatory response (b) an inability to mount a granulomatous response (c) an inability to respond to viral infections (d) greatly decreased activation of NK cells (e) an accumulation of immune complexes in the kidneys, resulting in nephritis.

(e) an accumulation of immune complexes in the kidneys, resulting in nephritis.

28.- The Switch regions A) Are found within the exons of all IgH genes B) Are recognized by the enzyme TdT C) Are recognized by the enzyme AID D) Are found in the V segments of light chains and heavy chains

C) Are recognized by the enzyme AID

6.- Mutations in AIRE give rise to: A) Tumors B) Graft rejection C) Autoimmune polyglandular syndrome I D) Nude mice

C) Autoimmune polyglandular syndrome I

14.- Antibody dependent enhancement of dengue results in: A) Death B) Enhanced production of antibodies C) Binding of virus and delivery to macrophages D) Protection against all 4 serotypes

C) Binding of virus and delivery to macrophages

26.- If an immature B cell recognizes a multivalent self molecule in the bone marrow, the B cells undergoes: A) Anergy B) Apoptosis C) Clonal deletion or receptor editing D) Clonal expansion

C) Clonal deletion or receptor editing

18.- Cytotoxic lymphocyte activity: A) Can be measured by western blot B) Can be measured by PCR C) Is measured by the chromium 51 release assay D) Is measured by the thymidine accumulation assay

C) Is measured by the chromium 51 release assay

35.- Follicular T helper cells A) Play a major role in antibody class switch in the bone marrow B) Play a major role in positive selection C) Play a major role in antibody class switch in the germinal centers of lymph nodes D) Are CD8 T cells with cytotoxic activity

C) Play a major role in antibody class switch in the germinal centers of lymph nodes

16.- During B cell development: A) The light chain rearranges first B) The pro-B cell has surface expression of rearranged IgM C) The light chain rearranges after successful rearrangement of the heavy chain D) The VpreB receptor is expressed in mature naïve B cells

C) The light chain rearranges after successful rearrangement of the heavy chain

30.- Th2 T cells are formed A) When signal 3 is IFN gamma B) When signal 3 is TGF-B C) When signal 3 is IL-4 D) When signal 3 is IL-6

C) When signal 3 is IL-4

FCγRIII

CD16 is a low affinity Fc receptor.surface of natural killer cells, hese receptors bind to the Fc portion of IgG antibodies which then activates the NK cell for antibody-dependent cell-mediated cytotoxicity.

IL2Rα

CD25, Interleukin 2 rec on activated t or t helper cells activation marker on dendritic cells

Fas

protien receptor which binds to FasL on a virus infected cell so CTLs can see and kill it, binding begins apoptosis cascade

CD40L, CD40

CD40 on B cells and CD40L on activated helper T cells are co-stimulatory molecules whose interaction is required for the proliferation and class switching of antigen activated naïve B cells

LFA1

receptor on post stimulation molecules that binds the Ig cell adhesion molecule ICAM-1 on the APC causing cell-cell adhesion CD8 interacts with... on T cells

13.- Class switch recombination: A) Changes the effector functions of T cells B) Changes the specificity of B cells C) Changes the effector functions of B cells D) None of the above

Changes the effector functions of B cells

Artemis

Creates asymmetrical hairpins in RNA repair; disfunction can lead to SCID/ Omenn's

17.- Cathepsin L is: A) Activated by low pH values within late endosomes B) Involved in peptide processing via the exogenous pathway C) A protease D) All of the above

D) All of the above

19.- Regulatory T cells are: A) A type of alpha beta T cell B) Are induced by TGF-B C) Used to be known as suppressor T cells D) All of the above

D) All of the above

22.- Superantigens: A) Induce immediate strong immune responses B) Activate between 2-10% of all T cells C) Do not required processing to bind to MHC D) All of the above

D) All of the above

27.- Lambda 5 is: A) Part of the surrogate light chain B) Similar to the C domain of a light chain C) None of the above D) All of the above

D) All of the above

31.- HLA-DM is A) Encoded within the MHC B) Upregulated by interferon C) Vital for peptide editing D) All of the above

D) All of the above

7.- Allelic exclusion is: A) A process that prevents expression of more than one heavy chain type on the surface of B cells B) A process that prevents expression of more than one light chain type on the surface of B cells C) Reinforced by the expression of the surrogate light chain D) All of the above

D) All of the above

20.- IL-17 released by Th17 T cells A) Attracts B cells B) Attracts dendritic cells C) Attracts macrophages D) Attracts neutrophils

D) Attracts neutrophils

12.- Some drugs that help with transplant success are A) Inhibitors of IL-1 receptor B) Inhibitors of TCR C) Aire inhibitors D) IL-2R blockers

D) IL-2R blockers

33.- A deficiency in TAP genes results in: A) Increased presence of MHC-II molecules on cell surface B) Increased processing of viral antigens C) Lack of transport of peptides from the ER to the cytosol D) Impaired transport of peptides from the cytosol to the ER

D) Impaired transport of peptides from the cytosol to the ER

29.- The process of positive selection: A) Converts a double positive thymocyte into a single positive mature thymocyte B) Converts a double negative thymocyte into a double positive thymocyte C) Converts a double negative thymocyte into a single positive mature thymocyte D) None of the above

D) None of the above

5.- The TUNEL technique: A) Reveals proliferating cells in tissue sections B) Reveals cytotoxic T cells C) Reveals immunological synapses D) Reveals apoptotic cells in tissue sections

D) Reveals apoptotic cells in tissue sections

The high affinity IL-2 receptor is: A) Expressed in all T cells B) Expressed in response to interferon C) Expressed in all naïve mature B cells E) Expressed in activated T cells

E) Expressed in activated T cells

Cytochrome C

release into cytosol activates apoptosis, CAD induces dna frag

Lymphotoxin

released by cytotoxic t-cells; activates enzymes in target cell which causes the DNA to fragment and kills the cell

Arginase

repair, M2 agonist IL10, IL2ra, cxcr1, cxcr2, ccl17 18 22 24 CD23, CD163, MR, SR, MHCII

Thymic selection

Elimination of T cells that don't recognize self antigens (major histocompatibility complex); similar to colonal deletion pre-T cells enter thymus; if they're able to determine non-self, they're specialized and released; ones that are not able to determine non-self are not allowed to be released; if latter are released = autoimmune disfunction

Freemartin Cows

Freemartins are the female of a dizygotic twin pair that grow up to be sterile, The females are masculinised by the male hormones. 1940s - Freemartins are tolerant to each others blood group type (Ray Owen).

RAG 1/2

Gene complex that gives rise to a protein that initiates VDJ recombination in B and T cell development. Enables TCR beta sequence rearrangement. Splice the gene for BCR rearrangement. Turned on: early pro-B cell. 2nd step in VDJ recombination.

Granzyme

Granzymes-a class of serine proteases. 5 in humans, 10 in mice. Forms a complex with sergylcin and perforin. Both are required for effective cell killing

Endogenous pyrogen

IL-1 and 6, fever

CLP

If receives IL-7, then increase cell survival, EBF1 transcription factor make Ig genes accessible

7. Consider a cell in the bone marrow, attempting to go through all the steps necessary to become a functional B cell. Generally speaking: a. the chance of correctly rearranging Heavy chain segments is more likely to be successful than rearranging light chain segments because TdT is most active during heavy chain gene rearrangement b. the chance is greater for heavy chains because of "heavy chain rescue" c. In part because light chain segments are present for both kappa and lambda light chains, light chain rearrangement is more likely to be successful. d. The likelihood of a successful rearrangement on either the heavy or light chain is approximately equal.

In part because light chain segments are present for both kappa and lambda light chains, light chain rearrangement is more likely to be successful.

Apoptotic Bodies

In the process of undergoing apoptosis the cell surface breaks up into membrane enclosed fragments called?

IL12

secreted by macs; differentiation into Th1 cells; activates NK cells; also secreted by B cells induces differentiation of CD4 T cells in TH1 cells T cell growth factor Essential for both helper and cytotoxic T cell activation, proliferation. Produced by activated CD4+ helper T cells Also called T cell-stimulating factor Produced by macrophages and dendritic cells Influences a bias in CD4+ T cells. Increases gamma interferon production Can make autoimmune disease worse May inhibit allergic responses

Type I IFN

Large family (, , , , , ) Produced by most cell types Binds to the IFNAR (Interferon alpha receptor) Expressed by the infected cell and affect neighboring cells to make them more resistant to the virus Most likely applies to Type III IFN as well

TNF

Lymphotoxin (LT) activity now known to be associated with multiple cytokines some still called LT others known as Tumor Necrosis Factor

Lytic Granules

Modified lysosomes with a mixture of cytotoxins in CD8

Hyper IgM syndrome

Mutation in CD40L on helper t or CD40 receptor on b. 2nd signal not delivered in B cell activation, so class-switching cytokines not produced. Results in recurrent pyogenic infections

CD40

Name the B-cell CD marker: • Required for class switching signals from T cells on surface, important for activating B cell causing class switch: need T helper cell to make certain cytokins, also associates with B cell, when B cell presents peptide on MHC II, T helper cell associates, makes cytokines. CD40 on B cell and CD40 ligand on T helper cell interact-important for inducing class switch in B cell

CD28

Name the T-cell CD marker: Is a costimulatory molecule in T cell activation Binds with the B7 receptor of the APC to receive a second activation signal T-cell costimulatory molecule interacts with CD80 and CD86, activates T-cells and IL-2 production

CD3

Name the T-cell CD marker: • Expressed on all T cells and is needed as a signal transducer for the T cell receptor surface marker found on thymocytes and T cells that is associated with T-cell antigen receptor; role in TCR signal transduction

Hemophahocutic lymphohistiocytosis

severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages characterised by proliferation of morphologically benign lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. It is classified as one of the cytokine storm syndromes.

SSC

side-scattered light flow cytometry

NK cells

Non T/B cells, which kills virus infected cells and some tumor cells. Important in innate immunity to viruses and other intracellular pathogens.

Antigen processing

Often the first step in an immune response, where some HLA glycoproteins bind bacterial and viral proteins, displaying them like badges to alert other immune system cells What process is involved when an antigen is in the endocytic vacuole and there is fusion with lysosomes, which contain proteases that cleave the protein antigens into peptide fragments? At what stage of an immune response do we see catabolism without synthesis of antibody, causing a decline in the levels? TH APC encounters antige the recognition, ingestion, and breakdown of a foreign antigen, culminating in production of an antibody to the antigen or in a direct cytotoxic response to the antigen. APC encounters antigen > internalizes it by endocytosis > digests it into molecular fragments > displays relevant fragments (epitopes) in the grooves of the MHC protein

Medulla

On what area of the lymph node can you locate plasma cells?

OKT 4

Ortho laboratories by Patrick Kung, from mice immunized with human T cells. OKT4 binds to ~ 55% mature T cells rarely on same as 8 T3+, T4+, T8- "helper" T cells CD3+, CD4+, CD8- are CD4 T cells

OKT 8

Ortho laboratories by Patrick Kung, from mice immunized with human T cells. OKT8 binds to ~ 45% mature T cells rarely on same as 4 T3+, T4-, T8+ cytotoxic (killer) T cells (CTLs) CD3+, CD4-, CD8+ are CD8 T cells

OKT 3

Ortho laboratories by Patrick Kung, from mice immunized with human T cells. binds to 100% mature T cells T3+CD3

IL4

Overexpression of which interleukin by Th2 cells will induce B cells to class switch to IgE? differentiation into th2 cells; promotes growth of b cells; B cell growth factors Produced by activated CD4+ helper T cells mostly. Can be produced by mast cells and NK cells Fundamental component of T cell "help" for B cells Required for isotype switch.

Perforin

Perforin-A protein stored in the lytic granules of Tc-Cells and NK cells, which on release polymerize to form pores in cell membranes which other cytotoxic proteins enter the target cell.

Type II IFN

Produced by activated CD4+ helper and CD8+ cytotoxic T cells and NK cells Primary effect to attract and activate macrophages Binds to the IFNGR

Interleukin

something that passes between leukocytes

Fc Receptors

Receptor-Cell surface receptor on macrophages and other cells in the immune system that binds the Fc protion of the antibodies. Different Fc receptors for different isotypes

Linked Recognition

Recognition-The rule that for a helper T cell to be able to activate a B cell, the epitopes recognize by the B cell and the helper T cell have to be derived from the same antigen.

TFH

Releases IL-21, IL-4, & CD40L. CD40L rescues B cells from apoptosis & promotes proliferation & IL-21 enhances differentiation of CD40L-stimulated B cells into antibody producing plasma cells; TfH also promote long-lived plasma cells & memory B cells T cells and FDC provide IL-6 and IL-21 (cyto milieu) which activates STAT3 TF; this induces Bcl-6 TF; Tfh produce IL-21

P nucleotides

Short, palindromic sequences formed by cleavage of hairpins that form at the blunt-end cut sites (where RAG cuts) Reverse-encoded nucleotides formed by single strand break in complementary strand. These are derived from the sequence itself which is cut from a different place to the end. P stands for palindromic. Added by RAG1/RAG2 Complexes and DNA Repair Proteins. asymmetrical hairpins created byArtemis, which results in template addition of nucleotides nucleotides added into the junctions between Ig gene segments during somatic recombination. TdT

MyD88

Signaling from IL-1 Receptor What are the adaptor proteins of TLR-2, TLR-7/8, and TLR-9? Severe infections by pyogenic bacteria, such as Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa bacteria, causing the production of pu

Peripheral Tolerance

Some self-reactive T and B cells escape negative selection and mature. They may be removed from the repertoire after leaving the primary immune tissue to prevent autoimmune responses in the peripheral tissues renders lymphocytes in the secondary lymphoid tissue inactive or anergic.

poly Ig Receptor

Special receptor for transporting IgA (can also recognize IgM) protects gut from attack by gut proteases j chain

Trabeculae

Supporting bundles of bony fibers in cancellous (spongy) bone. each lymph node is covered by a capsule of fibrous connective tissue that extends into the node called .

TReg

Suppress adaptive immunity CD25 suppress effector T cells. TF: FoxP3 immune tolerance, lymphocyte homeostasis, regulation of immune responses Which type of T helper cell inhibits inflammation TGF-B, IL-10 CD4 T cell that controls and limits the activities of other effector CD4 T cells

M2 Macrophage

stimulated from monocyte by I4, 6, 10, or glucocorticoids

M1 macrophage

stimulated from monocyte by IFN-gamma

IL2

support T cell proliferation, differentiation & activation Produced by Th1 cells immunosupressive drugs target this interleukin CD4 T-helper 1 -> IFgamma calls in monocytes and THF in inflammation What is CD25?

T cell activation

t cellls recognize antigens when they are bound to glycoproteins in cell membrane. Antigen presesntation-when antigen/glycoprotein combo appears plasma membrane. Glycoproteins are called MHC complex. MHC Class 1-in all nucleated cells membrane; Class 2 only in antigen presenting cells and lymphocytes. APC's; Antigen Recognition, t cell will bind to mhc protein depending on CD markers: CD8-cytoxic&supressor T cells on MHC 1; CD4-helper T cells on MHC 2; Costimulation -then a t cell binds @ second site APCs(macrophages/dendritic cells) phagocytize invaders; degrade them; present epitopes on cell surfaces bound to MHC I(on apc) or MHC II(humoral)

Tdt

Terminal deoxynucleotidyl transferase (TdT) adds nucleotides to V, D, and J region of antibody genes. Antigenic diversity. Marker of immature lymphoblasts (both B and T).

6. Although we don't know for sure, it is speculated that: a. The Pre-B receptor transmits a signal that a functional heavy chain has been made b. The Pre-B receptor transmits a signal that a function light chain has been made c. The pre-B receptor transmits a signal that causes RAG to suddenly be expressed d. The pre-B receptor transmits a signal that causes the cell to stop dividing

The Pre-B receptor transmits a signal that a functional heavy chain has been made

MHC restriction

The ability of T lymphocytes to respond only when they 'see' the appropriate antigen in association with "self" MHC class I or class II proteins on the antigen presenting cells Co-recognition, Need specific peptide and MHC molecule in order for the T cell to recongize it TCR of the CD8 T cell is specific for the complex of the peptide X with the class I molecule so the TCR does not recognize the same peptide when it is bound to a different class I molecule and it also does not recognize the class I molecule with a different peptide o T cells are MHC restricted, because they are selected in the thymus to recognize Ags as peptides displayed by self MHC molecules.

Immunological Synapse

The highly organized interface that develops between a T cell and an antigen-presenting cell (APC) or target cell it is in contact with, formed by T-cell receptors binding to antigen-MHC complexes on the APC and cell-adhesion proteins binding to their counterparts on the APCs.

Altered Self Hypothesis

The hypothesis that the T-cell receptor in MHC mediated phenomena recognises a syngeneic MHC Class I or Class II molecule after modification by a virus or certain chemicals.-- MHC restriction

Antibody dependent cell-mediated cytotoxicity (ADCC)

The killing of antibody-coated target cells by cells with Fc Recptors that recognize the constant region of the bound antibody. Mediated by NK cells that have the Fc Receptor FcγRIII on their surface

Hybridoma

the fusion of an immortal (tumor) cell with a lymphocyte to produce an immortal lymphocyte. a cell hybrid produced in vitro by the fusion of a lymphocyte that produces antibodies and a myeloma tumor cell in order to produce a continuous supply of a specific antibody.

Cortex

The outer layer of an organ, e.g. the renal cortex, the ovarian cortex, the adrenal cortex, etc.

Antigen presentation

The process by which an MHC molecule cradles a fragment of an intracellular protein antigen in its hammocklike groove, carries it to the cell surface, and "presents" the protein to an antigen receptor on a nearby T cell. MHC molecules bind and transport antigen fragments to the surface of infected cells. T cell binds both the antigen and MHC molecule. Advertises the fact the cell has a foreign molecule in it. T-cell must bind with the antigen fragment and MHC molecule in order to be effective - A macrophage or dendritic cell that ingests and degrades an antigen and subsequently places the antigenic determinant molecules on its surfaces for recognition by T-lymphocyte ___ ___ is the first step in the immune response.

FcERI

The receptor on the surface of mast cells and basophils that binds the Fc Region of free IgE at high affinity. When antigen binds this IgE and cross-links FcεRI, it causes

VDJ Recombinase

The somatic recombination of V and J, or of V, D, and J, gene segments is mediated by a lymphoid-specific enzyme, ____________, and additional enzymes, most of which are not lymphocyte specific and are involved in repair of double-stranded DNA breaks. Enzyme that mediates rearrangement process of Heavy Change gene rearrangement in Ig production and also does TCR genes. Composed of RAG-1 and RAG-2 lymphocyte specific compound

Endocytic/Exogenous Pathway

The source of the antigen is external to the cell Performed by professional antigen presenting cells Antigen phagocytosed into the cell Peptides presented by MHC class II molecules. antigen comes from outside the body so could be bacteria, bacterial toxin or foreign red blood cells. These have to be internalized so these cells are adept at phagocytosis/endocytosis. Remember class II MHC are on the surface of only a limited number of immune cells that are involved in antigen processing.

Cytosolic/Endogenous Pathway

The source of the antigen is internal to the cell Performed by all cell types in the body Antigen synthesized inside the cell Peptides presented by MHC class I molecules. important for viral infections which can happen to any cell in the body as well as intracellular bacteria. Remember class I MHC are on the surface of all nucleated cells.

Affinity Hypothesis

The specificity or affinity of positive selection must be differ from that of negative selection. Immature T cells are positively selected in such a way that only those thymocytes whose receptors can engage the peptide:self-MHC complexes mature, giving rise to self-MHC restricted T cells. Negative selection removes those thymocytes whose receptors can be activated by self peptides when complexed by self-MHC. Giving rise to a self tolerant population of thymocytes. If the specificity and affinity of positive and negative selection were the same (left) all T cells that survive positive selection would be deleted in negative selection. Only if these are different can thymocytes mature into T cells. --Low affinity interactions (negative selection) recue cells from death by neglect (apoptosis). This leads to positive selection where high affinity interactions with self peptide leads to apoptosis.

NFkB

This is the master switch to nucleus for induction of inflammation Which transcription factor is most important to the expression of TNF-alpha? activates expression of IL-8 in response to LPS

AIRE

Transcription factor that causes several hundred tissue specific genes to be transcribed by a Subpopulation of epithelial cells in the thymus, and which thus enables the developing T cell population to become tolerant of antigens that normally occur outside the thymus. Auto immune Regulator. Stimulates expression of genes from many different tissues in thymus TRANSCRIPTION FACTOR that makes thymus express all tissue specific genes (TSAs) so that all of these proteins are "seen" by thymocytes prior to migrating to periphery

TH1

Type of Th cells that act for inflammation, activating macrophages this helper T cell is "dirty" (when balancing TH1 vs. TH2) If a pathogen triggers the release of IL-12 and IFNγ from macrophages and NK cells, respectively, the TH subset will be ____. Activated in MICROBIAL INFECTIONS; Activates macrophages and PGs (prostaglandins) -> Increase in blood flow, edema and fever CD40 only works on which subset

FasL

Used by CTLs to see viruss infected cell, binding begins apoptosis cascade

pTα

the surrogate α chain that combines with the T cell receptor β chain to form the pre-T-cell receptor Nascent β chains are tested for their ability to bind to...

Medullary epithelial cells

What cells are important in mediating T cell NEGATIVE selection

TH2

What subset of CD4 helper T cells stimulate B-cell division and differentiation? Type of Th cells that activate humoral immune repsonse stimulate eosinophil mediated immunity, which is effective against parasites and is involved in ALLERGIC RESPONSES respiratory and skin allergies are predominated by ______ cell activity If a pathogen triggers the release of IL-4 and IL-10, the TH subset will be _____. Helper cell that binds B cells and activates them to divide into plasma cells & memory cells These cells produce Interleukins 4, 5, 10, 13. helper cell, type of Tcell, cell mediated, induces antiV state when secretes IFN lamda, cytokines that are antibodies that neutralize

12. Which of the following statements is TRUE, AND THEREFORE offers support for NEGATIVE selection of T-cells? a. When transgenic mice are created, causing the mice to produce T-cells with TCRs specific for a peptide coded for by a gene on the Y- chromosome, only FEMALE mice are later shown to actually have such T-cells in circulation b. When transgenic mice are created, causing the mice to produce T-cells with TCRs specific for a peptide coded for by a gene on the Y- chromosome, only MALE mice are later shown to actually have such T- cells in circulation c. Class II deficient mice DO NOT produce CD4+ T-cells d. If monoclonal antibodies are generated against MHC I, & DP thymocytes are placed with thymic tissue en vitro, no CD8+ T-cells will be produced.

When transgenic mice are created, causing the mice to produce T-cells with TCRs specific for a peptide coded for by a gene on the Y- chromosome, only FEMALE mice are later shown to actually have such T-cells in circulation

MHC class I

Which MHC class presents peptides that were produced by the cell itself or by viruses infecting the cell ? CD8+ T cells detect and destroy mutated cells so to evade the immune surveillance, tumor cell down regulate the expression of what on CD8+ T cells? are found on the surface of all nucleated cells Whose function is it to present exogenous peptides to helper T cells? Display antigens derived from extracellular pathogens. Displayed by phagocytic cells. CD4 binds to Which MHC class presents peptides TH cells ? MHC class expressed on "professional" APC, dendritic cells, macrophages, B cells

CD4+ TH

Which T cell provides signal 2 to B cells?

CD8+ Tc

Which cells are MHC1 presented to Effector Stage of CD8 CTL MHC class I recognized by

MHC class II

Whose function is it to present exogenous peptides to helper T cells? Display antigens derived from extracellular pathogens. Displayed by phagocytic cells. Class of MHC recognized by CD4 T cell receptor: Which MHC class presents peptides TH cells ? protein cell markers that present exogenous antigens; only professional APCs can present these, like macrophages, dendritic cells, some B lymphocytes What MHC class acts to remove foreign Ags from the body?

Flow cytometry

a single cell suspension is put through a tube 1 cell wide and a laser is shone at the cells as they pass through. Fluorescent antibodies to the protein of interest are mixed in with the suspension and bind to any cells with that protein (EphB2). based on the wavelength of light, the light can be separated and sent to detectors that only recognize a specific wavelength (thus, GFP can be used and only sent to green detectors

1. A B-cell in the bone marrow has just completed the production of a complete, functional B-cell receptor. This receptor recognizes a self-antigen in the marrow. The antigen is monovalent and soluble. What is the fate of this B-cell? a. it will become anergenic b. it will undergo apoptosis - also accepted for 1 point c. it will undergo allelic exclusion d. it will now have passed the "positive selection" test e. It will begin to differentiate into either a plasma or memory cell

a. it will become anergenic

Double positive

ab and go through a stage where they express both CD4 and CD8 Most thymocytes die as double positive cells but if they have TCR that can react with non-self peptide:self MHC increase their level of expression of TCR and develop in to single positive thymocytes

10.- Patients with autoimmune lymphoproliferative syndrome A) Have a defect in Fas protein B) Have decreased caspase activation and apoptosis C) Have double positive T cells in the periphery D) All of the above

above

naïve T cells

after T cells are processed they leave the thymus via the circulation and migrate to lymphoid tissue where they wait until activated by their particular antigen; what are they called now? IL-12 acts upon have t cell receptors which are immunoglobulin molecules specific for those epitopes (and can bind those epitopes) and have CD4+ or CD8+ on their surfaces, bind the MHC complexes and the epitopes CD2 Naïve T cells initially home to lymph nodes from *venules of thymal medulla* due to expression of the chemokines CCL19 and CCL2. Naïve T cells express CCR7, the receptor for CCL19 and CCL21. This initial contact between the T cell and endothelium of lymph nodes set up the opportunity for T cells to enter the lymph nodes Dendritic cells

Thymus independent Ag

an anitgen able to trigger b cells to produce antibodies w/o presense of t cells

Thymus dependent Ag

an antigen requirinh yhe presense of helper cells to stimulate antibody production by B cells

4. You are studying the antibody genetics of the zebras & you want to know if zebras rearrange kappa or lambda light chains first. Which of the following observations leads to an appropriate conclusion? a. Plasma cell is secreting Ig with kappa chains. Upon inspection, lambda genes are NOT rearranged. You conclude lambda genes are rearranged before kappa. b. A plasma cell is secreting Ig with kappa chains. Upon inspection, lambda genes are NOT rearranged. You conclude kappa genes are rearranged before lambda. c. A plasma cell is secreting Ig with lambda chains. Upon inspection, kappa chains are rearranged. You conclude Lambda genes are rearranged before kappa. d. A plasma cell is secreting Ig with lambda chains. Upon inspection, kappa chains are NOT rearranged. You conclude kappa genes are rearranged before lambda.

b. A plasma cell is secreting Ig with kappa chains. Upon inspection, lambda genes are NOT rearranged. You conclude kappa genes are rearranged before lambda.

25. Which of the following about the inactivated Salk and the attenuated Sabin polio vaccines is true? a. The Salk vaccine mimics an actual infection better than the Sabin b. The Sabin vaccine might also offer protection to unvaccinated individuals c. The Salk vaccine would only be used when the natural incidence of polio is high. d. Only the Sabin vaccine results in a high IgG titer e. The Sabin vaccine requires regular boosters, whereas the Salk does not.

b. The Sabin vaccine might also offer protection to unvaccinated individuals

3. Following the production of the pre-B cell receptor there is a period of cell proliferation during which Ig light chain gene segments are not rearranged. A consequence of this is: a. light chain rescue b. increased Ig diversity c. allelic exclusion d. B-cell anergy e. negative selection of self-reactive B-cells

b. increased Ig diversity

16. A naïve T-cell has a mutated gene for LFA-1. Although this protein is expressed, it is unable to undergo normal conformational changes. Consequently: a. this T-cell will be more likely to attack cells displaying self- peptides with MHC-1 b. this T-cell may not be able to interact with an antigen presenting cell long enough to become activated. c. This T-cell will be activated quickly, but will not be able to carry out effector functions d. this T-cell will be activated without antigen specificity

b. this T-cell may not be able to interact with an antigen presenting cell long enough to become activated.

IL10

both enhnces and suppresses immune response, suppresses inflammation Causes suppression of production of other cytokines Decreases expression of MHC class II molecules General immune suppressive effects Produced by CD4+ helper T cells Also produced by UV treated epidermal cells (keratinocytes). Clinical trials for organ transplant survival have been tried. Mostly unsuccessful? Also in asthma rheumatoid arthritis, other Th2 type diseases Successful in mice not humans Clinical trials: rIL-10 administration I.V. or S.C (subcutaneous) injections 3 times a week for 4 to 6 weeks. Gene therapy which could lead to long term IL-10 supplementation not approved for clinical trial due to side effects Reduction of red blood cells Continuous delivery Risk of increased infections, increased risk of cancer (decrease antigen presentation, T cell anergy)

8. In human kappa chain genes there are 40 V segments & 5 J segments. All forty V segments are numbered, starting with "V-1" at the 5' end. The same is true for J segments (5'--J-1, J-2, J-3, J-4, J-5---3'). Assume that segment "V-15" rearranges with segment "J-2", but the rearrangement is NOT successful. Which of the following could still be attempted, via "light chain rescue"? a. "V-20" & "J-3" b. "V-20" & "J-1" c. "V-10" & "J-3" d. "V-10" & "J-1"

c. "V-10" & "J-3"

13. Which of the following is true about T-reg cells? a. Natural T-reg cells develop in the periphery when CD4+ cells are b. Induced T-reg cells develop in the thymus when they have an c. Both types of Treg cells are characterized by the transcription d. Both types of Treg cells are characterized by their lack of CTLA-4 e. All of the above statements are true

c. Both types of Treg cells are characterized by the transcription factor Fox P3

TH17

cells that express IL-17A, IL-17F, IL-21, IL-22 TGF-beta + IL-6 make Cytokines: IL-17, 2 Distinct from Th1 and Th2 lineages, play a role in adaptive immunity protecting the body against pathogens, associated with autoimmune diseases Important in the GI tract. Will stimulate secretion of IL-17 and IL-22, which will secrete antimicrobial peptides in the gut. Will also stabilize the epithelial layer, increase mucus formation, and activate neutrophils. Osteoclastogenic Th cells, an additional effector CD4+ T cell subset

CAD

cleaves DNA in nucleus

Hypercytokinemia

cytokine storm

18. Which of the following T cells is most likely to become anergic? a. A naïve T cell recognizes its specific antigen complexed with MHC on the surface of an APC. It also binds B7 via its CD28 receptor b. An effector CTL recognizes its antigen complexed with MHC-1, but not expressing B7. c. An activated CD4 cell interacts with a B-cell, expressing antigen with MHC-2, but not expressing B7 d. A naïve CD4+ T cell interacts with its antigen through its TCR, but the presenting cell expresses no B7 e. A T cell & a B cell fail to interact via CD40L/CD40

d. A naïve CD4+ T cell interacts with its antigen through its TCR, but the presenting cell expresses no B7

14. Ficoll is a T-independent antigen. If you immunized a mouse with ficoll, which of the following is TRUE? a. The initial humoral response would be IgM. Later responses would probably be IgG b. Affinity of antibody would increase with successive responses c. Activated B cells would interact with follicular dendritic cells in primary follicles d. Little, if any memory would be established to Ficoll e. All B cells exposed to ficoll would become anergenic

d. Little, if any memory would be established to Ficoll

2. Tolerance to self- antigens expressed in the thymus is best explained by which of the following mechanisms? a. Suppression b. Anergy c. Positive selection d. Negative selection

d. Negative selection

11. Which of the following would most likely be a scenario, that ends in a thymocyte failing POSITIVE selection? a. Thymocyte (single positive-CD4+) fails to bind MHC II on the surface of a cortical epithelial cell in the thymus b. Thymocyte is now single positive CD4+ cell. It binds MHC II on a dendritic cell in the medulla of the thymus c. Thymocyte (double positive) does not bind MHC I or II on epithelial cells in the cortex d. Thymocyte (DP) binds either MHC I or II on macrophage in the cortex with high avidity

d. Thymocyte (DP) binds either MHC I or II on macrophage in the cortex with high avidity

15. The receptor to which secreted IgA binds, permitting transcytosis across the epithelium is called: a. CD28 b. Secretory chain c. FcRn d. poly-Ig R e. Fc-alphaR

d. poly-Ig R

10. A particular thymocyte is expressing its Pre-T cell receptor. This receptor binds its ligand in the thymus. Which of the following will NOT be a consequence of this binding? a. proliferation & continued development of thymocyte b. Allelic exclusion of beta-chain genes on second chromosome c. induction of double positive state d. signal to immediately begin rearrangement of alpha chain gene segments e. All of these events may occur

d. signal to immediately begin rearrangement of alpha chain gene segments

Cognate T cell

differentatied in the prensence of tleukin6 isotype switching T cells provide additional signals to B cells in the form of secreted cytokines that regulate B-cell proliferation and antibody production. In the B-cell follicle, it is the follicular helper T cell (TFH) ( Provide B-cell help for high-affinity antibody production in lymphoid follicles. TFH cells are identified mainly by their location and by the expression of certain markers, such as CXCR5 and ICOS Produce both Th1 and Th2 cytokines

Double negative

do not express CD4 or CD8--give rise to two lineages of T cells, gd and ab. gd T cells are also CD4, CD8 negative when they are mature.

9. Consider "double negative" (DN), "single positive" (SP), "double positive" (DP), & "Pre-T cells" (expressing a pre-TCR). In which order would these different thymocyte stages be seen in the thymus? a. DNSPDPPre-T b. Pre-TDNDPSP c. Pre-TDNSPDP d. DN DPSPpre-T e. DNpre-TDPSP

e. DNpre-TDPSP

24. You are observing developing B cells in different stages of development. Which of the following observations would statements is NOT accurate. a. In a late (small)-B cell, both RAG-1 and 2 are being expressed b. In a late Pro-B cell, TdT is being expressed c. In an early (large) pre-B cell, lambda 5 is being expressed d. In a late pro-B cell, VpreB is being expressed e. In an immature B cell, lambda 5 is being expressed

e. In an immature B cell, lambda 5 is being expressed

5. Which event defines the progression from a pro-B to a pre-B cell? a. Expression of Ig alpha & Ig Beta b. Increased levels of RAG-2 following a period of replication c. VJ recombination d. Successful replacement of a surrogate light chain with a light chain e. Presence of heavy chains with their associated surrogate light chains on the cell membrane

e. Presence of heavy chains with their associated surrogate light chains on the cell membrane

IL6

enhances immune response and inflammation secreted by macrophages. causes fever and stimulates production of acute-phase proteins. Made by macrophages (and other cells) in response to a number of different classes of microbial antigens. (similar to IL-1) Stimulates resting (not already activated) T cells, and other cell types Also supports growth of B cells and differentiation into plasma cells

IL1

enhances immune response and inflammation, promotes cell growth causes fever, increase in acute phase reactants and the release of IL-2 from T-cells What interleukin induces differentiation of T cells into Th1 cells and activates NK cells? Originally described as lymphocyte activating factor (LAF) by Igal Gery and Byron Waksman. Made by a large range of cell types, most importantly macrophages and dendritic cells Activates a large range of cell types, including T and B cells Along with IL-6, stimulates fever (endogenous pyrogen)

IL8

enhances inflammation, chemotactic Cytokine - chemotactic factor for neutrophils major chemotactic factor for neutrophils; *clean up on aisle 8; neutrophils are recruited by IL8 to clear infections* This is a chemokine produced by macrophages in response to IL1 and TNF (microbial product). CXCL8

17. Which of the following is TRUE about the IL-2 receptor on T-cells? f. Unactivated T cells express a dimeric form of the IL-2 receptor, consisting of beta & gamma chains b. Unactived T cells express a trimeric form of the IL-2 receptor, consisting of beta, gamma, & alpha chains c. Unactivated T cells mostly express an IL-2 receptor of relatively high affinity. Upon activation, this affinity decreases. d. Unactivated T-cells express no IL-2 receptor. Alpha, beta and gamma chains are produced only following activation.

f. Unactivated T cells express a dimeric form of the IL-2 receptor, consisting of beta & gamma chains

FSC

forward-scattered light flow cytomtery

ITAM

immunoreceptor tyrosine-based activation motifs are sequences in the cytoplasmic domains of membrane receptors that are sites of tyrosine phosphorylation and associate with tyrosine kinases involved in signal transduction. sequences contained in a CD3 complex's cytoplasmic tails that associate with Lck (lymphocyte-specific protein tyrosine kinase At what does "thing" does leukocyte-specific tyrosine kinase double phosphorylate the TCR to initiate T-cell degranulation? Tails of CD3's and TCR' BCRs are associated with ____ which activates B cell differentiation and proliferation when the BRCs crosslink upon binding to an antigen What do Ig alpha and beta have What is double-phosphorolated in CD-4 or CD-8 signaling, which leads to T-cell altered gene expression and degranulation? ZAP-70 (70zeta-chain-associated protein kinase-70 )

Self Tolerance

individuals immune system will NOT attack the normal health tissue of the body

CXCL8

inflammatory cytokines secreted by macrophages that recruit neutrophils from the blood and guide them to the infected tissue Antibody that is a CHEMOTACTIC FACTOR: recruits neutrophils, basophils, and T cells to site of infection. Also called Interleukin 8

ITIM

inhibitory receptors-receptors on the NK cells who's stimulation results in suppression of the cell's cytotoxic activity.

ICAD

inhibits CAD, cleaved by caspase 3

Hassall's corpuscles

instruct dendritic cells to nuce CD+CD25+ tregs in human thymus, tregs dependent

Neutralization

interaction of antibody with antigen that reduces or blocks the biological activity of the antigen

Thymic Involution

is one of the most dramatic and ubiquitous changes in the ageing immune system, but the precise regulators remain anonymous. However, a picture is emerging, implicating extrinsic and intrinsic factors that may contribute towards age-associated thymic involution

iNOS

killing, M1 agonist il12, TNF, IL6, IL1, IL23 CXCL8, 9,10,11,16 CCL2, 3, 5 CD80, CD86, NOS, ROS, MHCII, TLR2/4

Downly-McKinlay cells

large cells with foamy basophilic cytoplasm and fenestrated nuclei. They are mostly CD8 cytotoxic T cells Atypical lymphocytes

BID/tBID

truncated BID disruptes mitochondrial outer membrane and activated caspase-3 cleaves ICAS, releaseing caspase=activated DNAase(CAD)

IFN alpha/beta receptor

viral infections receptor

Cortical epithelial cella

what cells are responsible for the positive selection of t cells in the thymus

γδ T cells

-migrate preferentially to the peritoneal cavity, respiratory tract, and skin 5-10% of total T lymphocyte early defenses against common pathogens They likely straddle the boundary between innate and specific defense mechanisms

Plamablast

1. B cell made in bone marrow

Coordinated Model

19.32

Pluripotent Model

19.32

Pre-Ag Model

19.32

Cell Mediated Toxicity

> The binding of a virus-infected cell by an active cytotoxic T cel

Granulocytes

A group of leukocytes containing granules in their cytoplasm; neutrophils, eosinophils, basophils.

Plasma cell

A short-lived form of a lymphocyte from b cells that secretes antibodies

Monoclonal Ab

A substance, usually a protein, which can be synthsised in the laboratory in pure form by a single clone (population) of cells. These antibodies can be made in large quantities and have a specific affinity for certain target molecules called antigens which can be found on the surface of cells and those that are malignant. monoclonal antibodies are currently being investigated as a possible form of cancer treatment although their benefit has not be fully proven.

3.- Thymic cortical epithelial cells: A) Are critical for positive selection of thymocytes B) Express high amounts of TdT C) Do not express MHC molecules D) All of the above

A) Are critical for positive selection of thymocytes

24.- The secondary diversification of the antibody repertoire is: A) Dependent on AID B) Restricted to T cells C) A feature of the bone marrow and thymus D) Dependent on TdT

A) Dependent on AID

11.- The imbalance of the microbiome is called: A) Dysbiosis B) Symbiosis C) Meconium D) Sepsis

A) Dysbiosis

32.- The process known as cross presentation consists of: A) Presentation of exogenous antigens via MHC-I B) Presentation of antigens by a dendritic cell to a B cell C) Presentation of endogenous antigens via MHC-II D) Presentation of viral antigens by an epithelial cell

A) Presentation of exogenous antigens via MHC-I

Autoimmune Polyendocrine Syndrome

AIRE mutation- mutation in TF needed for medullary epithelium to adequately 'test' T cells during negative selection- mutation results in T cells that will react to self AIRE gene necessary for exposure of self-antigen in the medulla. If no Ag presented negative selection cant occur AUTOIMMUNE POLYENDOCRINE SYNDOME TYPE A: polyglandular disorder against adrenal and parathyroid glands Ovarian failure Diabetes Hepatitis Alopecia Anemia

FcRn

neonatal Fc Receptor that transports IgG from the fetus across the placenta and across other epithelia.

N nucleotides

Added at random to P nucleotides by Terminal deoxynucleotidal trasferase (TdT) enzyme NOT INHERITED, create JUNCTIONAL DIVERSITY TdT is not expressed in early prenatal period, therefore H-chain gene of B-1 cells lack

Type III IFN

Also called IL-28 and IL-29 Recently discovered (2002) Binds to the IL10R2 and IFNLR1 complex Trigger Type I-like IFN response on a restricted subset of cells

PKR

phosphorylates alpha subunit of eukaryotic translation initiation factor 2 (eIF-2 alpha) --> decrease in rate of initiation of translation IFN induced. Activated by dsRNA. kinase. Phosphorylated from activates immune response.

IL17

produced by TH17 cells (stimulates neutrophil production migration & inflammation) Family of related cytokines (IL-17A, B, C, etc.) Appear to be made by distinct CD4+ T cell subset called TH17s Pro-inflammatory Promotes inflammation and immune responses Over-activity linked to autoimmune diseases Stimulates production of a number of other cytokines (IL-6) and chemokines

IL5

promotes differenitation of B cells; enhances class switching to IgA; stimulates growth and diff of eosinophils Interleukin: IgD->IgA B cell growth factors Produced by activated CD4+ helper T cells mostly. Can be produced by mast cells and NK cells Fundamental component of T cell "help" for B cells Required for isotype switch.

Immunological Big Bang

B cells, T cells, VDJ recombination (RAG system) and MHC first appeared in evolution in jawed vertebrates

8.- One MHC class I molecule: A) Can only present one specific peptide B) Can only present a peptide of between 8-10 amino acids C) Can only present a peptide with a hydrophilic C-terminus D) Can present self and non-self peptides at the same time

B) Can only present a peptide of between 8-10 amino acids

1.- B cells, T cells, VDJ recombination (RAG system) and MHC first appeared in evolution: A) In mammals B) In jawed vertebrates (cartilaginous fish) C) In chordates D) In teleost fish

B) In jawed vertebrates (cartilaginous fish)

25.- Gamma-delta T cells are: A) The main T cell subset after birth B) Involved in skin wound healing C) As variable as alpha beta T cells D) MHC restricted

B) Involved in skin wound healing

34.- The immunoproteasome: A) Is induced by bacterial PAMPs B) Is induced by interferon C) Is induced by adhesion molecules D) Is induced by interleukins

B) Is induced by interferon

23.- During T cell development in the thymus: A) The cortex contains single positive thymocytes B) Positive selection occurs in the cortex and negative selection in the medulla C) Negative selection in the cortex occurs first D) Dendritic cells in the cortex and not in the medulla

B) Positive selection occurs in the cortex and negative selection in the medulla

21.- Beta 2 microglobulin: A) Stabilizes the MHC-II molecule B) Stabilizes the MHC-I molecule C) Is encoded within the MHC D) A and C are correct

B) Stabilizes the MHC-I molecule

4.- If a viral protein interferes with tapasin: A) The virus will be presented via MHC class-II B) TAP will not bind the peptide loading complex C) Cross presentation will be induced D) The immunoproteasome will not cleave antigens properly

B) TAP will not bind the peptide loading complex

B7

Biotin In addition to specific TCR - peptide/MHC interactions between T cells and professional "antigen presenting cells" (APCs), an antigen-nonspecific co-signal is also required for activation of naive T cells. Which of the following proteins on professional "APCs" interacts with CD28 on naive T cells, thereby delivering this required co-signal? CD8 and Dendritic cell interactions: CD28 receptor on naive CD8 binds to _____ on dendritic cell.