T Cell-Mediated Immunity Notes
T Cell-Mediated Immunity
Role of Antigen Processing and Presentation
Antigens must be presented to T cells by Antigen-Presenting Cells (APCs).
Major APCs: Macrophages, dendritic cells, and B cells.
T cells primarily identify peptides (T cell-dependent antigens).
Antigens are presented as an MHC-antigen combination:
T cells recognize the MHC and processed antigen (peptide) using separate receptors.
MHC Class I and II Binding to T Cells
MHC Class I and II engage with different subsets of T cells:
MHC Class I: Interacts with CD8 T cells.
MHC Class II: Interacts with CD4 T cells.
Importance of Two MHC Complexes
The dual presence of MHC allows activation of both branches of the adaptive immune system:
MHC Class I Presentation: Activates cytotoxic T cell pathways (effective against intracellular pathogens).
MHC Class II Presentation: Activates helper T cells and promotes antibody production (effective against extracellular pathogens).
This distinction enhances immune response as needed based on infection type.
Adaptive Immune Response Initiation
The process starts with antigen presentation:
APCs like dendritic cells encounter pathogens at the infection site.
After engulfing pathogens, APCs migrate through lymphatic vessels to regional draining lymph nodes.
In lymph nodes, they present antigens to naïve T cells, initiating an immune response.
Dendritic Cells and Antigen Processing
Dendritic cells are essential for activating cytotoxic T cells (CD8).
They can present processed peptides on:
MHC II to CD4 (Helper T cells).
MHC I to CD8 (Cytotoxic T cells).
They employ different pathways for processing antigens.
Membrane Transport Mechanisms
Phagocytosis (Cell Eating):
Cellular projections (pseudopods) engulf large particles, forming vacuoles.
Commonly used by macrophages to destroy bacteria/foreign substances.
Pinocytosis (Cell Drinking):
Plasma membrane folds inward to allow small dissolved materials to enter via vesicles.
Utilized by organisms like saprophytic fungi.
Receptor-Mediated Endocytosis:
Requires specific molecules/ligands to bind to cell surface receptors, followed by membrane folding.
Maturation of Dendritic Cells
Once at lymph nodes, dendritic cells mature and express special receptors to bind chemokines.
Chemokine signals direct dendritic cells into lymph nodes, ceasing their capacity to process additional antigens.
Interaction with Naïve T Cells
In high endothelial venules (HEVs), mature dendritic cells interact with naïve T cells:
Successful binding of T cell receptors to MHC with peptides selects and retains the T cell within lymph nodes.
Activated T cells undergo differentiation and proliferation into effector T cells, then exit into circulation.
Activation of T Helper Cells (TH Cells)
Activation Process:
Interaction of MHC-antigen complex with T cell receptors gives the first activation signal.
The second signal is from CD28 receptors on T cells binding to B7 proteins on APCs.
Differentiation of TH cells occurs based on the type of cytokines (mainly interleukins) secreted by APCs.
Activation of T Cytotoxic Cells (Tc Cells)
Activation Sequence:
Interaction of T cell receptors on CD8 cells with MHC-antigen complex on APCs.
Binding of CD28 on T cells to B7 protein on APCs.
Cytokine signals from TH1 cells, notably Interleukin-2 (IL-2).
Activated CD8 cells differentiate into T-cytotoxic and memory T cells.
T Cell Mediated Cytotoxicity: Cellular Immunity
Steps in T cell mediated cytotoxicity include:
Non-specific adhesion to target via cell adhesion molecules (CAMs).
Polarization of receptors involving cytoskeletal rearrangement.
Recognition of foreign antigens leading to the release of lytic granules.
Mechanisms of Cytotoxic T Cell Action
Granzymes are released to:
Initiate proteolytic cleavage reactions, degrade cell proteins, and activate nucleases for DNA degradation.
The process leads to formation of vesicles with cellular contents being shed.
Induction of Apoptosis by Cytotoxic T Cells
Controlled apoptosis results in:
Cell shrinkage while retaining intracellular content.
Phagocytes may engulf dying cells, facilitating clearance from the body.
Cytotoxic T Cells: Efficiency in Killing
Cytotoxic T cells have the ability to kill multiple infected cells in succession, maintaining an efficient immune response.
MORE DETAILED NOTES
Role of Antigen Processing and Presentation
Antigens must be presented to T cells by Antigen-Presenting Cells (APCs).
Major APCs: Macrophages, dendritic cells, and B cells are crucial for effective antigen presentation and immune activation. APCs process and present antigens in a way that T cells can recognize them, ensuring a tailored immune response.
T cells primarily identify peptides derived from proteins (T cell-dependent antigens).
Antigens are presented as an MHC-antigen combination:
T cells recognize the MHC (Major Histocompatibility Complex) and processed antigen (peptide) using distinct receptors specific to their subtype.
MHC Class I and II Binding to T Cells
MHC Class I and II engage with different subsets of T cells:
MHC Class I: Interacts with CD8 T cells (cytotoxic T cells), responsible for killing infected or cancerous cells.
MHC Class II: Interacts with CD4 T cells (helper T cells), which help coordinate the immune response by signaling other immune cells.
Importance of Two MHC Complexes
The dual presence of MHC molecules allows for the activation of both branches of the adaptive immune system:
MHC Class I Presentation: Activates cytotoxic T cell pathways, which are particularly effective against intracellular pathogens, such as viruses that replicate within host cells.
MHC Class II Presentation: Activates helper T cells, promoting antibody production by B cells and enhancing the activation of other immune cells, crucial for combating extracellular pathogens like bacteria and parasites.
This distinction enhances the immune response, adjusting it based on the type of infection and enhancing overall efficacy.
Adaptive Immune Response Initiation
The process of adaptive immunity starts with antigen presentation:
APCs, primarily dendritic cells, encounter pathogens at the site of infection (like wounds or tissues).
After engulfing pathogens, APCs process them into peptide fragments and migrate through lymphatic vessels to regional draining lymph nodes, where they can present the antigens to naïve T cells.
In lymph nodes, dendritic cells interact with naïve T cells to initiate a robust and specific immune response, marking the transition from innate to adaptive immunity.
Dendritic Cells and Antigen Processing
Dendritic cells play a vital role in activating cytotoxic T cells (CD8):
They present processed peptides on:
MHC II to CD4 T helper cells, which can enhance immune activity.
MHC I to CD8 cytotoxic T cells to initiate their activation.
Dendritic cells utilize various pathways for processing antigens, including cross-presentation, where they can present extracellular antigens on MHC I.
Membrane Transport Mechanisms
Phagocytosis (Cell Eating):
Cellular projections (pseudopods) engulf large particles, forming vacuoles that fuse with lysosomes for degradation.
This mechanism is commonly utilized by macrophages to destroy bacteria and other foreign substances, playing a crucial role in innate immunity.
Pinocytosis (Cell Drinking):
The plasma membrane folds inward to allow small dissolved materials to enter via vesicles.
This process is utilized by various organisms, including saprophytic fungi, for nutrient absorption.
Receptor-Mediated Endocytosis:
This process requires specific molecules or ligands to bind to cell surface receptors, leading to targeted uptake of substances, ensuring the selective capture of important proteins or pathogens.
Maturation of Dendritic Cells
Once they reach lymph nodes, dendritic cells undergo maturation, characterized by changes in morphology and function:
They express specialized receptors to bind to chemokines, which facilitate their movement into lymph nodes and enhance their ability to interact with T cells.
Maturation ceases their capacity to process additional antigens, ensuring that they can focus on presenting the antigens they have processed.
Interaction with Naïve T Cells
At high endothelial venules (HEVs), mature dendritic cells interact with naïve T cells:
Successful binding of T cell receptors to the MHC-peptide complex results in the activation and retention of T cells within lymph nodes, an essential step for clonal expansion.
Activated T cells undergo differentiation and proliferation into effector T cells, ultimately exiting the lymph nodes into circulation to perform their immune functions.
Activation of T Helper Cells (TH Cells)
Activation Process:
Interaction of the MHC-antigen complex with T cell receptors provides the first activation signal.
The second signal is delivered when CD28 receptors on T cells bind to B7 proteins on APCs, a crucial costimulatory signal necessary for full activation.
Differentiation of TH cells occurs based on the type of cytokines (primarily interleukins) secreted by APCs, which will shape the immune response depending on the pathogen type.
Activation of T Cytotoxic Cells (Tc Cells)
Activation Sequence:
Interaction of T cell receptors on CD8 T cells with the MHC-antigen complex on APCs initiates their activation.
Binding of CD28 on T cells to B7 proteins on APCs provides a crucial second signal for activation.
Cytokine signals from TH1 cells, notably Interleukin-2 (IL-2), facilitate full activation and proliferation of CD8 T cells.
Activated CD8 T cells differentiate into cytotoxic T lymphocytes and memory T cells, preparing for future encounters with the same antigen.
T Cell Mediated Cytotoxicity: Cellular Immunity
Steps in T cell mediated cytotoxicity include:
Non-specific adhesion to target cells via cell adhesion molecules (CAMs), facilitating an initial interaction.
Polarization of receptors, involving cytoskeletal rearrangement, which positions cytotoxic granules towards the target cell membrane.
Recognition of foreign antigens on target cells leading to the release of lytic granules, ultimately inducing apoptosis in the infected cells.
Mechanisms of Cytotoxic T Cell Action
Granzymes are released into target cells to initiate proteolytic cleavage reactions:
They degrade structural proteins, activate nucleases essential for DNA degradation, and induce apoptosis effectively.
This cytotoxic process results in the formation of vesicles containing cellular constituents, which are ultimately shed or phagocytosed by immune cells.
Induction of Apoptosis by Cytotoxic T Cells
Controlled apoptosis is characterized by:
Cell shrinkage while retaining intracellular content, a hallmark of programmed cell death.
Phagocytes may engulf these dying cells, facilitating their clearance from the body while ensuring no inflammatory response is triggered.
Cytotoxic T Cells: Efficiency in Killing
Cytotoxic T cells possess the capacity to kill multiple infected cells in succession, a functionality that is vital for maintaining an efficient immune response without overwhelming the host tissue.