Cell-mediated immunity: activation and functions of T cells Flashcards

1
Q

Types of cells involved

A
  • cytotoxic T cells : kiling of infected or transformed cells
  • Helper T cells (Th effectors): cytokine production, activation of macrophages
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2
Q

Activation of T lymphocytes

A
  • required recognition of Antigen presented on MHC molcules by dendritic cells
  • activation occurs in secondary lmyphoid Organs
  • protein Antigens that cross eoithelial barriers or are produced in tissues are captured by DCs and transported to lymph nodes
  • Antigens that enter circulation may be caputred by DCs in the Spleen
  • After Antigen capture, DCs begin to mature and migrate to the T cell zones of peripheral lymphoid Organs
  • in lymphoid Organs: DCs present Peptides in association with MHC II molcules to naive CD4+ cells and Peptides displayed by MHC I molecules to CD8+ cells
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3
Q

Phases of T cell responses

A

Antigen recognitin by T cells includes:

  • cytokine IL2 secretio, particularly in CD4+ cells
  • clonal Expansion as a result of cell Proliferation
  • Differentiation of activated T cells into effector cells

Effectors CD4+ helper cells Respons to Antigen by producing cytokines that have several Actions:

  • recruitment and acrivation of leukocytes
  • activation of B lymphocytes

Effectors CD8+ CTLs Respons by killing other cells

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4
Q

Role of adhesion molecules in T cell activation

A
  • adhesion molecules stabilize APC-T cell interaction
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5
Q

Role of co-Stimulators in T cell activation

A
  • resting APCs Expresses no co Stimulators and Fails to activate naive T cells
  • Antigen recognition without co Stimulators may make T cells anergic
  • microbes and kytokines produced during innate Responses activate APCs to express co Stimulators, such as B7 molecules
  • APCs become capable of activating T cells
  • B7 on APC is recognized by CD28 on T cells
  • Activated APCs also produce cytokines such as IL12, which stimulate the differentation of naive T cells
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6
Q

T cells recognize ligands on APCs

A
  • MHC/Peptide complex
  • CD4 or CD8 molecules are co receptors of TCR
  • Adhesion molecules
  • Cytokines
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7
Q

Role of IL2 in T cell activation

A
  • after activation, T cells produce the cytokine IL2 –> express high Levels of the functional IL2 receptor
  • IL2 drives the Proliferation, which can result in marked Expansion of antigen-specific clones
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8
Q

Types of Th effector cells

A
  • TH1: secretes IFN-γ and mediates defense against intracellular microbes
  • TH2: secretes IL4, IL5, which favor eosinophil, mast cell-mediated immune reactions against helminths
  • Th17: promotes Inflammation and mediates defense against extracellular fungi and bacteria
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9
Q

Th cells promote Differentiation of CD8+ cells into CTL effectors

A
  • Th cells secrete cytokines that stimulate the Differentiation of CD8+ cells
  • Th cells express CD40 Ligand which binds to CD40 on APCs and activates them to stimulate Differentiation of CD8+ cells
  • Differentiation involves Acquisition of the machinery to perform target cell killing: development of membrane-bound cytoplasmic granules that contain proteins (perforins and granzymes)
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10
Q

Memory T cells

A
  • maintenance of Memory cells is dependenent of cytokines such as IL7
  • -> promote the Expression of antiapoptotic proteins adn stimulate low Level cyclin
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11
Q

Types of T cell mediated immune reaction

A
  • CD4+ T cells recognize Antigens of microbes and produce cytokines that activate the phagocytes to kill the microbes and stimulate Inflammation
  • CD8+ recognize Antigens of infected cells and kill These cells
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12
Q

Migration of effector T cells at site of infection

A
  • activated T cells migrate through Endothelium that is activated by cytokines
  • activated endothelial cells express adhesion molecules and effector T cells express their ligands
  • Chemokines Play additional roles in the Migration of T cells through walls
  • T cells that specifically recognize Antigen are activated and retained
  • T cells that do not Encounter the Antigen either die or return to the circulation
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13
Q

Activated macrophages

A
  • produce Enzymes that catalyse Generation of toxic substances in phagolysosomes (ROS, NO, proteases)
  • TH1 effectors activate the same microbe killing mechanism as in case of innate immunity
  • permanent immune Response can induce chronic Inflammation –> delayed hypersensitivity reaction
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14
Q

function of Th2

A

Stimulation of IgE and eosinophil mediated reactions against helminthic infections

  • helminths are too large to be phagocytosed
  • secrete IL4, IL5, and IL13 –> eradicating helminths
  • activate macrophages for tissue repair
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15
Q

Function of TH17

A
  • secrete cytokines that recruit leukocytes, mainly neutrophils
    Th17 cytokines stimulate:
    –> local production of chemokines
    –>production of antimicrobial Peptides (defensins)
    –>promote epithelial barrier functions
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16
Q

regulatory T cells

A

suppress or downregulate induction and Proliferation of effector T cells

17
Q

Functions of CTL effectors

A
  • specific recognition of target cells and delivery of proteins that induce cell death
  • resulats in the release of granule contennst through the area of contact (immunologic Synapse)
  • Contents deliver lethal hit to target
  • death occurs during next 2 to 6 hours
18
Q

CTL-mediated killing mechanism

A
  • cytotoxic proteins include granzymes and perforin
  • Granzymes A, B, C are serine proteases that cleave proteins (including caspases) and initiate apoptosis
  • Perforin is membrane-perturbing molecule –> polymerizes and forms aqueous pores in the target cell membrane through which granzymes enter
  • Serglycin serves to assemble a compley containing granzymes and perforin
  • Fas Ligand on Surface that binds to the death receptor