T cells Flashcards

Question

Who are the main players in a viral infection?

Answer 1

• Type I IFN (alpha/beta) are important anti-viral cytokines, they can inhibit or slow viral replication • Natural Killer Cells recognize and kill infected cells and tumor cells by their absence of MHC class I • Virus-specific CTLs directly kill infected cells

Answer 2

Type II: plays a role in the immune response against intracellular pathogens, it is mainly secreted by T cells Type I: potent antiviral effects and they are an effect of PRR activation

Answer 3

It will based itself off the nature of the infection After that, the cell- mediated response is dominated by one of the T cell subsets

Answer 4

- Cross-regulation is the control between two or more effects by the release of substances and their concentration EX: TH1/TH2 cross regulation • Master transcriptional regulators commit T cells to one subset or the other • T-Bet, a master transcriptional regulator, suppresses TH2 pathway gene expression • GATA3 suppresses TH1 pathway gene expression

Answer 5

The Decision Point is the balance between two subsets EX: Th17 and Treg -The key cytokine for the differentiation of the subset is TGF-beta Taking in account the beneficial outcomes of each aspects, a balance between the two subset is ideal - Normal state could favor the development of iTreg population to keep inflammation down - infection (leading to IL-6 production) would stimulate more antibacterial TH17 differentiation

Answer 6

Homing is the process by which lymphocytes are directed to a specific sites to perform their functions. The consequences: • TH1, TH2 and TH17 leave the lymph node and migrate to the site of infection while TFH stays in the lymph node to activate B cells • Effector T cells express molecules that target specific tissues depending on the site of infection • Where effector T cells travel i partly determines by which lymph node they get activated

Answer 7

The Th1 cell recognizes pMHC class II on the surface of the macrophage, it will then use CD40L to bind to CD40, once the connection established the Th1 will secrete IFN-gamma leading to a boost in antimicrobial activity in the macrophage due to the secretion of TNF-alpha from the macrophage

Answer 8

Some pathogens persists in macrophages, they inhibit the fusion of the phagosome and the lysosome which prevents the acidification as the lysosomal proteases cannot be activated.

Answer 9

• MH1 macrophages = function induced in the context of Th1 and have a boost to their antimicrobial mechanisms • TFN-alpha secreted leads to autocrine signaling sending survival signal to the macrophage • CD40L binding activates macrophages and increases expression of IL-12 (part of signal 3 for Th1 cells) • TNF-alpha and IFN-gamma increase expression. Of MHC class I and II, CD40, B7 molecules, IL-12. All these molecules contribute to the further activation of of Th1 cells • IFN-gamma from CTLs can also activate M1 macrophages

Answer 10

Killing infected macrophages • Can happen in case of chronically infected macrophages • Th1 cells recognize pMHC-II on infected macrophage • FasL on Th1 cell bing Fas on infected cells which triggers apoptosis • Bacteria released can be phagocytosed by freshly recruited macrophages • LT-Beta (lymphotoxin beta) is a tumor necrosis factor (TNF)-C and it helps with killing tumor or infected cells Help CD8+ T cells • Th1 cell can secrete IL-2 and stimulate CD8+ T cell proliferation and differentiation • Would occur in the secondary lymphoid organ (lymph node) • CTLs kill infected macrophages through the recognition of pMHC I Increase differentiation of monocytes in bone marrow • Th1 cells secrete IL-3 and GM-CSF, which circulate in the blood and act on precursors in the bone marrow (endocrine effect example) • GM-CSF= Granulocyte- macrophage colony-stimulating factor Change expression of adhesion molecules on neighbouring endothelium to recruit more macrophages • Th1 cells secrete cytokines that induce these changes Recruitment of macrophages by chemotaxis • Th1 cells secrete chemokines CCL2 that attract macrophages to the site of infection

Answer 11

• The chronic infection often comes from bacteria (ex. M. Tuberculosis) being resistant to anti-microbial effect of macrophages • The resistance leads to the formation of a granuloma (a core of infected macrophages) - Surrounded by a layer of activated macrophages and a layer of Th1 cells - Centre often becomes necrotic. This necrotic center comes from cells dying due to a lack of oxygen and the cytotoxic effect of the activated macrophages

Answer 12

Promote cell turnover and mucous production (weep in the weep and sweep) • Il-13 can increase mucus production by goblet cells and increase turnover of epithelial tissue -> this helps the clearance of parasites bc they will have a harder time adhering to the surface Enhance worm expulsion (sweep in the weep and sweep response) • Il-13 can stimulate smooth muscle cells to contract -> can lead to worm expulsion Recruit and activate M2 macrophages • IL-4 and IL-13 are important for M2 macrophage activation • M2 macrophages = alternatively activated macrophages • M2 macrophages aid tissue repair and participate in worm killing and expulsion • M2 macrophages can form granulomas to entrap worms • M2 macrophages can also release toxic mediators directly onto the worm by antibody-dependent cell-mediated cytotoxicity (ADCC) • ADCC is the killing of antibody-coated target cells by Fc cells- Most ADCC is mediated by NK cells Eosinophil activation • IL-5 ; activates, recruits and enhances eosinophil differentiation • Eosinophils granules contain major basic protein (MBP), which can kill parasites • IL-4 and IL-13 lead to IgE generation • IgE antibodies bind antigens on parasites, eosinophils express receptors that recognize the Fc portion of the IgE, this allows eosinophils to specifically target pathogen and degranulate to kill its target Mast cell activation • Cytokines activate mast cells. Mast cells granules contain histamines and other molecules which can increase vascular permeability, intestinal motility and recruitment of inflammatory cells • IgE antibodies coat parasite, mast cells express receptors that recognize the Fc portion of IgE • Basophils: can secrete Il-4 and IL-13, can activate goblet cells, allow vasodilation. Binds to IgE and release histamines

Answer 13

Asthma and allergies

Answer 14

• Can sometimes clear the pathogen (or not leading to chronic infection) • Reduce worm burden by Weep and Sweep • Facilitates tissue repair • IgE antibodies are important or immune response against Helminths

Answer 15

1. IgE antibodies interact with antigen 2. IgE antibodies binds to mast cells or basophils and induce degranulation • Granule contents released include histamine, proteases, chemokines • Act on surrounding tissues and cells to cause symptoms such as vasodilation, inflammation

Answer 16

• Allergens can enter the host via mucosal tissues and can induce Th2 response. • IL-4 and IL-13 can induce IgE generation • Allergies are initiated by an interaction between an IgE antibody and an allergen- which can cause rashes • Free circulating IgE is usually very low in concentration in blood serum -> hampered studies on the antibody • Healthy individuals make IgE only in response to parasitic infections

Answer 17

- Il-17 is a pro-inflammatory cytokine (prolong inflammation can cause serious damage) • The responses of Th17 are involved in inflammatory diseases, including autoimmune diseases such as Psoriasis, Inflammatory Bowel Disease, Asthma, Rheumatoid Arthritis, Multiple Sclerosis • Therapies targeting IL-17 are currently being studied and soem have already been approved for clinical use

Answer 18

Induce production of antimicrobial peptides • IL-17 and Il-22 can induce epithelial cells to produce more antimicrobial peptides • Can contribute to killing/slowing replication of bacteria Increase epithelial turnover (mucosal immunity) • IL-22 increases division and shedding of epithelial cells • This can hinder bacterial growth Induces other cells to produce G-CSF • IL-17 acts on stromal and myeloid cells • These cells secrete G-CSF (Granulocyte colony-stimulating factor)(a cytokine working in an autocrine fashion) • G-CSF enters circulation and targets bone marrow precursors to differentiate into neutrophils Induce other cells to secrete chemokines • IL-17 acts on stromal and epithelial cells These cells • These cells secrete chemokines and these chemokines will attract neutrophils. The neutrophils can kill bacteria and fungi by phagocytosis, formation of NETs and release of granules (degranulation) Attracts more Th17 cells • Th17 cells secrete a chemokine that recruits additional Th17 cells resulting in the increase of the type 3 response leading of an increase of the overall effects Other effects • IL-17 can induce macrophages to secrete pro-inflammatory cytokines such as IL-beta and TNF-alpha- illustration of the impact that Th17 cells have due to their different pro-inflammatory effects

Answer 19

• IL-17 is targeted using monoclonal antibodies (antibody produced by a single clone of B lymphocytes) • Two ways : formation of an antibody that blocks the signaling from the IL-17 receptor - IL-17 receptor antagonist or antibody that binds to IL-17 to prevent it to interact with its receptor- Anti-IL-17 neutralizing antibodies

Answer 20

• IL-21 promotes differentiation an d proliferation of B-cells • Type 1(IFN gamma), Type 2 (IL-4) and Type 3 (IL-17) will determine what type of antibodies will be form depending on the threat • TFH cells interact directly with B cells • In responses to all types of pathogens

Answer 21

• Majority of effector T cells die (at least 90%), leaving behind antigen-specific memory T -cells • memory cells respond with heightened reactivity to a subsequent exposure to the same antigen- meaning that the immune system system will be stronger the second time it is infected (response more robust and effective)

Answer 22

After 10-14 days

Answer 23

Treg cells may also help to put an end to the response by releasing inhibitory cytokines (restoration of epithelial integrity)

Answer 24

Clonal contraction is the process by which the immune system stops cloning B and T cells since they are no longer needed Newly generated B and T cells are lost at the end of the primary immune response Cells die by apoptosis after the Ag is cleared

Answer 25

Intrinsic pathway (cell programs its own death) • Also called Death by neglect • ILR2 alpha and other cytokine receptors expression is transient (impermanent-last for a little bit) • Lack of signaling through these receptors-> absence of survival signal-> apoptosis Extrinsic pathway • Triggered by Fas-FasL • Involves CTLs • Leads to apoptosis

Answer 26

• PD-1 can be expressed on activated T cells • binds PDL-1 (expressed by many cells) and PDL-2 (on APCs during inflammation) • PD-1 signaling Dow-regulates T cell activation/proliferation and function • Marker of T cell exhaustion -> occurs in chronic diseases • Blocking PD-1 or PDL-1 or even CTLA-4 are targets of some cancer therapies

Answer 27

• Down-regulates T cells activation, proliferation, survival: - CTLA-4 binds to B7.1/B7/2 with higher affinity than CD28 and shuts down signaling pathways, preventing excessive and uncontrolled immune responses • induced within 24h after activation, peaks 2-3 days post-stimulation - CTLA-4 found intracellularly-> phosphorylation allows it to be expressed on the membrane - post-translational regulation

Answer 28

One CTLA-4 molecule can bind to two B7 molecules, binding sequesters B7 and prevents binding to CD28 In some cases, CTLA-4 can strip B7 molecules from antigen-presenting cells and remove them from APC surfaces • CD28 is expressed by naive T cells but surface expression of CTLA-4 is induced after activation of naive T cells (after receiving signal 1 and 2)- this process makes activated T cells less sensitive that naive T cells stimulation by APCs and restricting IL-2 production • Prevents overgrowth of lymphocytes

Answer 29

Natural • Thymus derived • Selected for high affinity for self peptides but to dampen the immune response to them • Express TCR, CD4. IL2R alpha and CTLA-4 • They are unable to provide Il-2 so they rely on other cells • Express FoxP3 Induced (adaptive) • Arise in the periphery from CD4+ T cells • express TCR, CD4, IL2R alpha and CTLA-4 • Express FoxP3 (some exceptions)

Answer 30

T reg cells negatively regulate immune responses • Deplete local area f stimulating cytokines: Express IL2R alpha (CD25) chain -> sequester IL-2 • B7 sequestration by CTLA-4 - Inhibit APC activity by reducing co-stimulatory molecule expression and pro-inflammatory cytokine secretion -reduce T cell differentiation and activation • Produce immunosuppressive cytokines (IL-10 and TGF beta) • Direct kill T cells through granzymes and met

Answer 31

• T cells are specific to peptides that are mainly dangerous non-self • Tregs are specific to pepetides that are self or are on-self -nTreg recognizes self-peptides:MHC-> arises in thymus -iTreg recognizes peptides:MHC (could be self or commensal Ag) -> arises in periphery • Majority of autoreactive T cells are deleted in the development process in the thymus • Tolerance: preventing an immune response against self-proteins • if a Treg recognizes its p:MHC on an APC-> APC presenting self-peptide • T Regs secrete cytokines that will inhibit neighbouring and potentially autoreactive T cells that recognize other self-peptide:MHC being presented by the same cell from getting activated

Answer 32

IL-10: inhibits production of Th1 and Th17 cytokines TGF-beta: inhibits T cell proliferation and inhibit the development of and function of Th1 and Th2

Answer 33

Tcm- Central memory T cells * Reside in/travel between secondary lymphoid tissues * Are rapidly reactivated by second Ag exposure * Can differentiate into several subset types depending on cytokine environment Tem- effector memory T cells * Travel to/between tertiary tissues (other tissues) * Contribute better to first line defenses-can interact with local APCs * Shift right back into effector functions on second Ag exposure-it will travel for many years within the body and will eventually die Trm- permanent residents of previously infected tissue * Respond upon reinfection * CD8+ Trm found in multiple tissues (CD4+ are harder to locate so they are harder to study)

Answer 34

90+ leaves behind antigen specific memory T cells

Answer 35

We can use the surface markers to broadly distinguish naïve, effector and various memory T cells subset in mice

Answer 36

* Less requirements for activation+ expresas unique set of receptors * Different surface adhesion molecules, costimulatory receptors * No need for strong co-stimulatory signal or cytokines- Memory T cells have large expression of CD28 * Still require ocntact with p:MHC but more sensitive to stimulation and respond more quickly * They become effector upon reactivation

Answer 37

The results showed that Memory CD8+ T cells still require the help of CD4+ T cells for longevity

Answer 38

Cytokines (IL-7, IL-15) Notch1 Strength of antigen interaction

Answer 39

IL-7: Pro-survival cytokine which can lead to increased expression of Bcl-2, an apoptotic factor IL-7R alpha: Downregulation in expression during the differentiation of effector T cells. *Is required by cells destined to become memory T cells

Answer 40

T cell development occurs in the Thymus *Developing T cells are known as thymocytes

Answer 41

*Cortex and medulla *Cortical epithelial cells in the Cortex *Medullary epithelial cells in the medulla *Thymocytes in both Cortex and Medulla *Macrophages *Cortical DCs

Answer 42

* T cell precursors enter the thymus as double negative (DN) cells, They do not express CD4 OR CD8 1. Double negative 2. Double positive (DP express both CD4 and CD8) 3. Single positive (SP-express either CD4 or CD8)

T cells Flashcards

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