Cell-Mediated Immunity and T Lymphocytes
10 Questions
0 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to Lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the primary function of APCs in the generation of a useful cell-mediated immune response?

  • To produce costimulators
  • To capture and concentrate antigens in specialized lymphoid organs (correct)
  • To activate T cells directly
  • To recognize and respond to microbial antigens

Which type of T cells respond to antigens from the endosomal compartment?

  • Naive T cells
  • CD8+ CTLs
  • APCs
  • CD4+ helper T cells (correct)

What determines the selectivity of T cells responding to antigens from the endosomal and cytosolic compartments?

  • The type of antigen presented
  • The location of the antigen in the lymphoid organ
  • The expression of costimulators on APCs
  • The specificity of the CD4 and CD8 coreceptors for class II and class I MHC molecules (correct)

What is the reason for T cells to respond to microbial antigens but not to harmless proteins?

<p>T cell activation requires costimulators induced on APCs by microbes (D)</p> Signup and view all the answers

What is the primary function of costimulators in the immune response?

<p>To enhance T cell activation in response to microbial antigens (C)</p> Signup and view all the answers

What is the mechanism by which T cells recognize antigens from the cytosolic compartment?

<p>Through the recognition of class I MHC molecules (D)</p> Signup and view all the answers

What is the purpose of the segregation of extracellular and intracellular protein antigens for display by class II and class I MHC molecules?

<p>To ensure that T cells respond to microbial antigens but not to harmless proteins (D)</p> Signup and view all the answers

What is the role of naive T cells in the immune response?

<p>To recirculate through lymphoid organs and find antigens (D)</p> Signup and view all the answers

What is the result of T cells responding to antigens from the endosomal compartment?

<p>Activation of CD4+ helper T cells (D)</p> Signup and view all the answers

What is the primary function of MHC molecules in the immune response?

<p>To present antigens to T cells (B)</p> Signup and view all the answers

Study Notes

T Lymphocytes and Cell-Mediated Immunity

  • T lymphocytes perform multiple functions in defending against infections by various kinds of microbes.
  • They play a major role in cell-mediated immunity, which provides defense against infections by intracellular microbes.
  • Cell-mediated immunity is necessary to eliminate infections that occur inside cells, such as those caused by viruses and some bacteria.

Phases of T Cell Responses

  • Naive T lymphocytes recognize antigens in peripheral lymphoid organs, which initiates proliferation and differentiation into effector and memory cells.
  • Effector cells perform their functions when they are activated by the same antigens in peripheral tissues or lymphoid organs.
  • The responses of naive T lymphocytes to cell-associated microbial antigens consist of a series of sequential steps, including:
    • Antigen recognition
    • Cytokine secretion and receptor expression
    • Clonal expansion
    • Differentiation into effector and memory cells

Antigen Recognition and Costimulation

  • The initiation of T cell responses requires multiple receptors on the T cells recognizing ligands on antigen-presenting cells (APCs).
  • The T cell receptor (TCR) recognizes MHC-associated peptide antigens.
  • CD4 or CD8 coreceptors on the T cells recognize MHC molecules on the APC and help the TCR complex to deliver activating signals.
  • Adhesion molecules strengthen the binding of T cells to APCs.
  • Costimulators, such as B7-1 and B7-2, on APCs promote the responses of T cells to antigens.
  • Cytokines amplify the T cell response and direct it along various differentiation pathways.

Role of Adhesion Molecules and Costimulation

  • Adhesion molecules, such as integrins, on T cells recognize ligands on APCs and stabilize the binding of T cells to APCs.
  • The binding of T cells to APCs must be stabilized for a sufficiently long period to achieve the necessary signaling threshold.
  • Costimulation ensures that naive T lymphocytes are activated fully by microbial antigens and not by harmless foreign substances or self-antigens.

Inhibitory Receptors of T Cells

  • Inhibitory receptors, such as CTLA-4 and PD-1, are critical for limiting and terminating immune responses.
  • These receptors function to terminate responses of activated T cells and prevent immune responses against self-antigens.
  • Genetic deletion or blockade of these molecules can result in systemic autoimmune disease.

Stimuli for Activation of CD8+ T Cells

  • The activation of CD8+ T cells is stimulated by recognition of class I MHC-associated peptides and requires costimulation and helper T cells.
  • The initiation of CD8+ T cell activation often requires cytosolic antigen from one cell (e.g., virus-infected or tumor cells) to be cross-presented by dendritic cells.
  • The differentiation of naive CD8+ T cells into fully active cytotoxic T lymphocytes (CTLs) and memory cells may require the concomitant activation of CD4+ helper T cells.### Helper T Cells and CD8+ T Cells
  • Human immunodeficiency virus (HIV) kills CD4+ but not CD8+ T cells, which is likely the explanation for the defective CTL responses to many viruses in HIV patients.
  • CD8+ T cells can respond to some viruses without the help of CD4+ T cells.

Biochemical Pathways of T Cell Activation

  • T cell activation leads to protein synthesis, differentiation, and effector functions.
  • Antigen recognition triggers several biochemical mechanisms, including:
    • Kinase activation
    • Adaptor protein recruitment
    • Production of active transcription factors
  • The TCR complex, CD4/CD8 coreceptors, and CD28 coalesce at the center of the immune synapse, while integrins move to the periphery.
  • The immune synapse is required for optimal induction of activating signals in the T cell.

Signaling Pathways

  • CD4 and CD8 coreceptors facilitate signaling through the protein tyrosine kinase Lck.
  • Lck phosphorylates ITAMs (immunoreceptor tyrosine-based activation motifs) in the CD3 and ζ chains.
  • The phosphorylated ITAMs in the ζ chain become docking sites for the tyrosine kinase ZAP-70.
  • ZAP-70 phosphorylates various adaptor proteins and enzymes, leading to additional signaling events.
  • The major signaling pathways linked to ζ-chain phosphorylation and ZAP-70 are:
    • Calcium-NFAT pathway
    • Ras- and Rac-MAP kinase pathways
    • PKCθ-NF-κB pathway
    • PI-3 kinase pathway

Calcium-NFAT Pathway

  • NFAT (nuclear factor of activated T cells) is a transcription factor that is present in an inactive form in the cytoplasm of resting T cells.
  • NFAT activation and nuclear translocation depend on the concentration of Ca2+ ions in the cytosol.
  • The signaling pathway is initiated by ZAP-70-mediated phosphorylation and activation of phospholipase Cγ (PLCγ).
  • PLCγ catalyzes the hydrolysis of PIP2, generating IP3, which binds to IP3 receptors on the ER membrane, stimulating the release of Ca2+ from the ER.

Ras- and Rac-MAP Kinase Pathways

  • These pathways are initiated by ZAP-70-dependent phosphorylation and accumulation of adaptor proteins at the plasma membrane.
  • The pathways lead to the activation of distinct MAP kinases (ERK and JNK), which induce the expression of the transcription factor AP-1.

PKCθ-NF-κB Pathway

  • PKCθ is activated by diacylglycerol, which is generated by PLC-mediated hydrolysis of membrane inositol lipids.
  • PKCθ acts through adaptor proteins recruited to the TCR complex to activate NF-κB.
  • NF-κB is released from its inhibitor IκB and moves to the nucleus, promoting the transcription of several genes.

PI-3 Kinase Pathway

  • PI-3 kinase phosphorylates the membrane phospholipid PIP2 to generate PIP3.
  • PIP3 is required for the activation of Akt, which has many roles, including stimulating the expression of antiapoptotic proteins and promoting survival of antigen-stimulated T cells.

T Cell Functional Responses

  • T cell activation leads to the secretion of cytokines, such as IL-2, which act on the T cells themselves and on other cells involved in immune defenses.
  • Cytokines are produced by effector T cells and serve diverse roles in host defense.
  • IL-2 is produced by activated CD4+ T cells and stimulates the survival and proliferation of T cells.
  • The IL-2 receptor is a three-chain molecule, and its expression is increased on activated T cells.

Clonal Expansion

  • T lymphocytes activated by antigen and costimulation begin to proliferate, resulting in the expansion of antigen-specific clones.
  • The magnitude of clonal expansion is remarkable, especially for CD8+ T cells.
  • The expansion of CD4+ T cells is 100- to 1000-fold less than that of CD8+ cells.

Differentiation of Naive T Cells into Effector Cells

  • Some of the progeny of antigen-stimulated, proliferating T cells differentiate into effector cells whose function is to eradicate infections.
  • Effector cells of the CD4+ lineage acquire the capacity to produce different sets of cytokines.
  • Effector cells of the CD8+ lineage acquire the ability to kill infected cells.

Development of Memory T Lymphocytes

  • A fraction of antigen-activated T lymphocytes differentiates into long-lived memory cells.
  • Memory cells survive even after the infection is eradicated and antigen is no longer present.
  • Memory cells can be found in lymphoid organs, peripheral tissues, and the circulation.

Migration of T Lymphocytes in Cell-Mediated Immune Reactions

  • T cells at different stages of their lives have to migrate in different ways.
  • Naive T cells migrate between blood and secondary lymphoid organs through HEVs (high endothelial venules).
  • HEVs are lined by specialized endothelial cells that express carbohydrate ligands that bind to L-selectin.### Migration of Naive T Cells
  • Naive T cells migrate through blood vessels in a multistep sequence similar to other leukocytes
  • Engagement of L-selectin with HEV (high endothelial venules) allows chemokines to bind to CCR7 on T cells
  • CCR7 transduces signals that activate LFA-1 (leukocyte function-associated antigen 1) on naive T cells, increasing binding affinity for ICAM-1 on HEV
  • Firm adhesion and arrest of rolling T cells occurs, followed by exit into the T cell zone of the lymph node

Egress of T Cells from Lymph Nodes

  • Sphingosine 1-phosphate (S1P) plays a key role in T cell egress from lymph nodes
  • S1P levels are higher in blood and lymph than inside lymph nodes
  • S1P binds to its receptor, reducing expression on circulating naive T cells
  • When a naive T cell enters a node, S1P receptor expression increases, and the cell exits the node through efferent lymphatic vessels following the S1P gradient

Activation and Differentiation of T Cells

  • Activated T cells do not express CCR7 or L-selectin, preventing re-entry into lymph nodes
  • Effector T cells migrate to sites of infection, expressing adhesion molecules and chemokine receptors that bind to ligands on vascular endothelium
  • Naive T cells do not express ligands for E- or P-selectin or receptors for chemokines produced at inflammatory sites, preventing migration into sites of infection

Site-Specific Immune Response

  • Homing of effector T cells to a site of infection is independent of antigen recognition, but lymphocytes that recognize antigens are preferentially retained and activated at the site
  • Chemokines produced by macrophages and endothelial cells stimulate motility of transmigrating T cells
  • Effector T cells that leave the circulation and recognize microbial antigens presented by local tissue APCs become reactivated and contribute to killing microbes

Decline of the Immune Response

  • After an infection is cleared, the immune response subsides, and the system returns to homeostasis
  • Survival and proliferation of T cells are maintained by antigen, costimulatory signals from CD28, and cytokines like IL-2
  • Once the infection is cleared, stimulated T cells die by apoptosis, and the response subsides within 1-2 weeks

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Quiz Team

Description

This quiz covers the role of T lymphocytes in defending against infections by intracellular microbes and their function in cell-mediated immunity. Learn how T cells help eliminate microbes that find a haven inside cells.

More Like This

Cell Biology and Immunology Quiz
60 questions

Cell Biology and Immunology Quiz

UserFriendlyLepidolite13 avatar
UserFriendlyLepidolite13
Phagocytosis Process: Cellular Defense
55 questions
Immunology and Cell Biology Quiz
50 questions

Immunology and Cell Biology Quiz

BountifulAntigorite3696 avatar
BountifulAntigorite3696
T Cell Biology and Cellular Immunology
48 questions
Use Quizgecko on...
Browser
Browser