Integrate Immune Response

1. Naive T-cells are activated by strong signaling from APCs; weak signaling or interactions with immature APCs induces T cell anergy.

-CD4+ and CD8+ cells are stimulated by IL-2 acting as an autocrine or paracrine factor to induce proliferation and/or maturation. -expose to IL-4 drives CD4+ Th cells towards Th2 function while continues exposure to IL-2 in the absence of IL-4 drives CD4+ Th cells towards Th1 function. Th2 cells support humoral immunity by producing IL-4, 5, 10.-Th1 cells support cellular immunity by producing IL-2 and IFN-gamma. -IFNgamma produced by activated Th1 cells inhibits the activation of Th2 cells-TGFbeta produced by activated B cells inhibits the activation of Th1 cells (cross inhibition between the humoral and cellular arms)

-T-cell activation is solely dependent on the interaction with mature APCs.

-Naive T-cells can only be activated by weak signaling from APCs.

-IL-4 drives CD4+ Th cells towards Th1 function while IL-2 exposure leads to Th2 function.

2. Which molecule stabilizes synapse and enhances signaling in T cells?

TCR alone

-in addition to MHC-TCR interactions, co-receptors must be ligated at the immunological synapse in order to obtain a complete activation.-B7 (CD80/86) is upregulated on APC (dendritic cells and macrophages) in response to TLR stimulation-Co-binding of MHC-II/TCR with B7/CD28 on CD4+ cells results in cytokine release characteristic of Th1 or Th2 responses (Th2-IL-4 IL-5 IL-10) (Th1-IFNgamma and IL-2)-Co-binding of MHC-I/TCR with B7/CD28 on CD8+ cell results in cytokine release characteristic of Tc cells (and of Th2 cells), which leads to activation of macrophages (cellular response) and inhibition of humoral responses.

B cell receptor

CD4 molecule

Co-receptors, specifically B7 (CD80/86), play a crucial role in stabilizing the synapse and enhancing signaling in T cells, in addition to MHC-TCR interactions. The correct binding of MHC-II/TCR with B7/CD28 on CD4+ cells or MHC-I/TCR with B7/CD28 on CD8+ cells results in specific cytokine release and cellular responses, which is essential for complete T cell activation.

Explanation

Co-receptors, specifically B7 (CD80/86), play a crucial role in stabilizing the synapse and enhancing signaling in T cells, in addition to MHC-TCR interactions. The correct binding of MHC-II/TCR with B7/CD28 on CD4+ cells or MHC-I/TCR with B7/CD28 on CD8+ cells results in specific cytokine release and cellular responses, which is essential for complete T cell activation.

3. What is the activation mechanism for Tc cells in the periphery without concomitant recognition between Tc TCR and MHC-I?

Tc cells in the periphery can be activated solely through the interaction of CD28/B7 receptors.

This activation mechanism allows Tc cells with appropriate specificity (initially activated in the lymph node by APCs presenting relevant peptides)to be fully activated at sites of inflammation. Peripheral activation produces more Tc cells and/or induces Tc cells to express high levels of cytotoxic factors.-Engagement of Tc TCR and MHC-1 without co-receptor activation or without supporting cytokine signaling induces Tc anergy or Tc cell death. Apoptosis of Tc cells is initiated by engagement of CD95/CD95L (Fas/FasLigand) in the absence of CD28/B7

Activation of Tc cells in the periphery is not possible without direct engagement of Tc TCR and MHC-I.

IFN-gamma and IL-2 do not play a significant role in the activation of Tc cells in the periphery without TCR recognition.

Peripheral activation of Tc cells without direct TCR recognition of MHC-I is an important mechanism that allows for enhanced Tc cell responses at sites of inflammation. This process is mediated by the presence of IFN-gamma and IL-2, which promote the full activation and proliferation of Tc cells in the periphery.

Explanation

Peripheral activation of Tc cells without direct TCR recognition of MHC-I is an important mechanism that allows for enhanced Tc cell responses at sites of inflammation. This process is mediated by the presence of IFN-gamma and IL-2, which promote the full activation and proliferation of Tc cells in the periphery.

4. How are B cells initially activated?

B cells are initially activated by interacting with Th1 cells instead of Th2 cells.

B cells are directly activated by antigen binding to the BCR surface receptor.

-Bound antigen is endocytosed and presented on MHC-II for recognition by Th2 cells expressing appropriate TCRs. -An initially activated B cell becomes fully activated by the engagement of appropriate co-receptors found on the B-cell and on the Th2 cells (eg: CD40 on the b-cell and CD40L on the Th2 cell) in the context of TCR binding to MHC-II. Full B-cell activation is also supported by the production of Th2 cytokines (IL-4,5,10)

MHC-I is responsible for presenting antigens to B cells for activation.

B cells are not directly activated by antigens binding to the BCR surface receptor. The interaction involves presenting the antigen on MHC-II for recognition by Th2 cells. Additionally, the interaction is not with Th1 cells, but with Th2 cells. MHC-I is responsible for presenting antigens to CD8+ T cells, not to B cells.

Explanation

B cells are not directly activated by antigens binding to the BCR surface receptor. The interaction involves presenting the antigen on MHC-II for recognition by Th2 cells. Additionally, the interaction is not with Th1 cells, but with Th2 cells. MHC-I is responsible for presenting antigens to CD8+ T cells, not to B cells.

5. What is the structure where signaling occurs between B-cells and T-cells, APCs and T-cells, or Tc cells and targets?

The Golgi apparatus

The endoplasmic reticulum

-development of the immunological synapse in initiated by adhesion molecules which form an adhesive plaque that connects interacting cells. Signaling molecules are subsequently recruited to the adhesive plaque, initially surrounding it and then migrating toward the center of the plaque to form a unique signaling domain. -the mature immunological synapse between APCs (including B-cells) and T-cells in characterized by a central signaling domain surrounded by adhesive proteins. The immunological synapse between Tc cells and target cells is characterized by a central signaling domain adjacent to a membrane patch specialized for fusion of lytic granules; both the signaling domain and the secretory domain are surrounded by adhesive proteins.

The plasma membrane

The immunological synapse is a structured domain of signaling molecules and adhesion molecules localized within a lipid domain enriched in specific lipids and glycolipids, where signaling between immune cells occur.

Explanation

The immunological synapse is a structured domain of signaling molecules and adhesion molecules localized within a lipid domain enriched in specific lipids and glycolipids, where signaling between immune cells occur.

6. In an integrated immune response, what leads to coordinated activation of humoral and cellular immunity to the same pathogen challenge?

Suppression of immune response through downregulation of cytokine production.

Activation of innate immunity through toll-like receptor pathways.

Direct activation of TCR signaling on B-cells by antigens.

In an integrated immune response, clonal selection of B-cells plays a crucial role in activating both humoral and cellular immunity. B-cells expressing BCRs that bind antigens containing peptides capable of activating TCR signaling on Th1 and Th2 cells enable this coordinated response.

Explanation

In an integrated immune response, clonal selection of B-cells plays a crucial role in activating both humoral and cellular immunity. B-cells expressing BCRs that bind antigens containing peptides capable of activating TCR signaling on Th1 and Th2 cells enable this coordinated response.

7. Example of coordinated T/B cell response: -Antigen A, derived from a specific pathogen, initiated the activation of B-cells expressing BCRs that recognize Antigen A. -Antigen A is also endocytosed into APCs and presented on MHC-II to Th cells that express TCRs which bind peptides derived from Antigen A. -Activated Th2 cells support the continued activation of B-cells that recognize Antigen A since these activated B-cells present peptides on MHC-II that are recognized by Th2 TCRs at an immunological synapse, eventually leading to the cytokines that stimulate macrophage and granulocyte attack on pathogen. So, the same pathogen induces B-cell activation and Th cell activation on cells that possess BCR or TCRs with overlapping binding specificity.

The activation of Tc cells expressing TCRs capable of recognizing peptides derived from antigen A, presented in the context of MHC-I, is not relevant to the coordinated T/B cell response described.

Activation of B-cells expressing BCRs that recognize Antigen A and Th cells expressing TCRs that bind peptides derived from Antigen A occurs independently and does not involve any coordinated response.

B-cell activation and Th cell activation do not occur simultaneously and do not involve any interaction between the two cell types.

Taking this example further, APCs also activate Th1 cells that support the differentiation of Tc cells expressing TCRs capable of recognizing peptides derived from antigen A presented in the context of MHC-I. Therefore, Tc activation is most perinent to viral infection of intracellular pathogens in which viral or pathogen proteins are presented on infected cells, leading to the formation of an immunological synapse between Tc and the target cell.

In the described scenario, the coordinated T/B cell response involves the activation of B-cells recognizing Antigen A and Th cells binding peptides from Antigen A, leading to a series of interactions that support the immune response against the pathogen.

Explanation

In the described scenario, the coordinated T/B cell response involves the activation of B-cells recognizing Antigen A and Th cells binding peptides from Antigen A, leading to a series of interactions that support the immune response against the pathogen.

8. Activated Tc cells engage target cells through TCR/MHC-I interactions and kill by two mechanisms, both of which converge on apoptosis.

3. Activated Tc cells kill target cells through bacterial phagocytosis.

4. Activated Tc cells induce target cell death by releasing histamines.

1. Perforin-dependent: lytic vesicles fuse at the secretory site of the immune synapse to release perforin and granzymes. Perforin is a pore-forming protein that allows granzymes to enter the target cell. Granzymes are serine proteases that cleave pro-caspases to their active, apoptosis-inducing forms.1. Fas-dependent target cell death: activated Tc also express CD95L (Fas ligand) on their surface which can engage with CD95 on target cells to induce apoptosis through direct caspase activation.

2. Activated Tc cells engage target cells through BCR/MHC-I interactions.

The correct answer explains the mechanisms through which activated Tc cells kill target cells to induce apoptosis by engaging through TCR/MHC-I interactions and utilizing perforin-dependent and Fas-dependent pathways.

Explanation

The correct answer explains the mechanisms through which activated Tc cells kill target cells to induce apoptosis by engaging through TCR/MHC-I interactions and utilizing perforin-dependent and Fas-dependent pathways.

9. What are the mechanisms involved in target cell death for Perforing-dependent and Fas-dependent pathways?

Perforing-dependent pathway involves the release of cytokines, while Fas-dependent pathway causes cell lysis.

Perforing-dependent pathway leads to necrosis while Fas-dependent pathway induces autophagy.

Perforing-dependent pathway triggers inflammation in the target cell, whereas Fas-dependent pathway inhibits cell division.

Both Perforing-dependent and Fas-dependent pathways are involved in apoptotic cell death, which is a highly regulated process of programmed cell death crucial for development and maintenance of homeostasis in multicellular organisms.

Explanation

Both Perforing-dependent and Fas-dependent pathways are involved in apoptotic cell death, which is a highly regulated process of programmed cell death crucial for development and maintenance of homeostasis in multicellular organisms.

10. How is the killing potential of Tc cells enhanced by the direct action of cytokines on target cells?

TNFalpha and INF-gamma are released by activated Tc cells.-TNFalpha binds to target cells expressing the TNFalpha receptor and induces cells death. -INF-gamma upregulates the expression of MHC-I and CD95 target cells, enhancing the lytic and Fas-mediated death pathways.

IL-4 and IL-10 are released by activated Tc cells, which suppress the immune response by inhibiting cell death pathways.

GM-CSF and IL-6 are released by activated Tc cells, which promote cell proliferation and survival rather than inducing cell death.

IL-2 and IL-12 are released by activated Tc cells, which activate B cells rather than directly induce cell death.

The correct answer explains how TNFalpha and INF-gamma released by activated Tc cells directly enhance the killing potential through different mechanisms on target cells.

Explanation

The correct answer explains how TNFalpha and INF-gamma released by activated Tc cells directly enhance the killing potential through different mechanisms on target cells.

11. Example of an integrated immune response, dermal infection:step1: innate immune detection of pathogen pattern (via TLR) activates Langerhans cells (dermal dendritic cells), which begins to produce cytokines and chemokines that 1. alter cell adhesion molecule expression on vascular endothelial cells (increased E-selectin expression) 2. enhance granulocyte extravasation.

Step2: The detection of pathogen pattern does not activate Langerhans cells in the immune response.

Step2: The immune response in dermal infection is solely mediated by adaptive immune cells.

Step2: extravasation of granulocytes (neutrophils, monocytes) provides first response. Granulocytes bring to bear lytic enzymes and ROS poduction to manage pathogen invasion. Monocytes differentiate into active macrophages in reponse to local pro-inflammatory cytokine environment, proving additional support for killing and phagocytosis of pathogen and expanding the number of activated antigen presenting cells at the site.

Step2: Langerhans cells directly attack the pathogen to eradicate it.

12. Step 6: Th2 cells activated peripherally or by interaction with APCs in the lymph node form immunological synapses with naive, pre-activated, or memory B cells. If signaling is of appropriate strength, the B-cell is driven to plasma cell fate which produces circulating antibody.

Step 7: B cells activated in lymphoid follicle by T-dependent antigen initiate peripheral immune response or differentiate into memory B cells.

Step 6: Th2 cells activated peripherally or by interaction with APCs in the lymph node form immunological synapses with naive, pre-activated, or memory B cells. If signaling is of appropriate strength, the B-cell is driven to plasma cell fate which produces circulating antibody.

Step 8: Plasma cells in lymphoid follicle and tissues secrete antibody which is vital for neutralizing the antigen.

Step 9: Feedback inhibition by antibody reduces B and T cell activity once the antigen is cleared.

This question and answer set outlines the steps involved in the immune response, specifically highlighting the activation and function of Th2 cells interacting with B cells. The incorrect answers provided in the multiple-choice options relate to other steps in the immune response process, but do not directly address the formation of immunological synapses between Th2 cells and B cells.

Explanation

This question and answer set outlines the steps involved in the immune response, specifically highlighting the activation and function of Th2 cells interacting with B cells. The incorrect answers provided in the multiple-choice options relate to other steps in the immune response process, but do not directly address the formation of immunological synapses between Th2 cells and B cells.

13. How does circulating immunoglobulin enhance pathogen clearance and limit its ability to move beyond the initial site of inflammation?

By inhibiting the immune response against the pathogen.

By inducing pathogen proliferation.

By promoting pathogen evasion of the immune system.

Circulating immunoglobulin enhances pathogen clearance by opsonization and complement fixation, while also limiting the ability of the pathogen to move beyond the initial site of inflammation.

Explanation

Circulating immunoglobulin enhances pathogen clearance by opsonization and complement fixation, while also limiting the ability of the pathogen to move beyond the initial site of inflammation.

14. What is the capital of France?

London

Rome

Berlin

Paris is the correct answer as it is the capital city of France. London is the capital of the United Kingdom, Rome is the capital of Italy, and Berlin is the capital of Germany.

Explanation

Paris is the correct answer as it is the capital city of France. London is the capital of the United Kingdom, Rome is the capital of Italy, and Berlin is the capital of Germany.

15. What processes may be involved in the activation of tissue-specific APCs during epidermal infection?

Direct killing of pathogens by neutrophils

Release of histamine by mast cells in response to infection

Activation of B cells in the bloodstream

During epidermal infection, tissue-specific APCs may be activated through multiple processes including transport of pathogen molecules across the epithelial layer, presentation of pathogen molecules on MHC-I of epithelial cells, or direct detection of pathogen in the lumenal space by APC processes that insinuate themselves between epithelial cells. The activation of B cells in the bloodstream, direct killing of pathogens by neutrophils, and release of histamine by mast cells are not directly involved in the activation of tissue-specific APCs in this context.

Explanation

During epidermal infection, tissue-specific APCs may be activated through multiple processes including transport of pathogen molecules across the epithelial layer, presentation of pathogen molecules on MHC-I of epithelial cells, or direct detection of pathogen in the lumenal space by APC processes that insinuate themselves between epithelial cells. The activation of B cells in the bloodstream, direct killing of pathogens by neutrophils, and release of histamine by mast cells are not directly involved in the activation of tissue-specific APCs in this context.

16. Why does the influenza virus persist in the human population despite effective immune responses?

The influenza A virus exists as multiple serotypes which are defined by the amino acid sequence of their Hemagflutinin (H or HA) and Neuraminidase (N) coat proteins. -HA binds cell surface sialic acid resiudes on glycoproteins of host cells and is essential for entry and fusion of the virus with cellular membranes.-Neuraminidase is an enzyme that cleaves sialic acid allowing newly budded virus to be release from the host cell membrane

Influenza only affects individuals with compromised immune systems.

The influenza virus mutates too rapidly for the immune system to keep up.

The influenza virus is not impacted by the immune system's response.

The influenza A virus's ability to evolve multiple serotypes, each with unique Hemagglutinin (H) and Neuraminidase (N) proteins, allows it to evade immune responses and persist in the human population.

Explanation

The influenza A virus's ability to evolve multiple serotypes, each with unique Hemagglutinin (H) and Neuraminidase (N) proteins, allows it to evade immune responses and persist in the human population.

17. How does influenza avoid complete eradication through antigenic variation?

-Drift results from mutation in coding sequence and produces new epitopes unfamiliar to the host (antigenic variation)-Shift results from reassortment of genetic components in hosts infected by more than one serotype or species of virus (cross-species) -cross-species infections with influenza are common for many species pairs. Of particular epidemiologic interest, transfer from swine to human and swine to bird are common but bird to human is rare.

Antigenic variation only occurs in laboratory settings.

Antigenic variation reflects changes in the surrounding environment.

Antigenic variation is mainly caused by the host's immune system response.

18. What allows for the reassortment of influenza genes producing a new virus with alpha2,6 binding specificity and increased virulence?

-Intermediate hosts that possess both bird and human HA ligands (swine) could allow the reassortment of influenza genes producing a new virus with alpha2,6 binding specificity (human targeted) and increased virulence (a general characteristic of bird flu)-the sialic acid binding pocket of the devastating 1918 H1N1 virus is more similar to the H5N1 HA bird flu virus than it is to the H3N2 human virus. -evolving bird flu viruses may be only a mutation (or two) away from becoming a human pandemic virus, like the 1918 H1N1 virus that claimed 25 million lives and reached into every corner of the globe.

H3N2 human virus having alpha2,6 binding specificity

Birds presenting alpha2,3 linked sialic acid

1918 H1N1 virus being less similar to H5N1 HA bird flu virus

The correct answer explains how intermediate hosts like swine play a crucial role in allowing the reassortment of influenza genes, leading to the emergence of new viruses with specific binding specificities and increased virulence.

Explanation

The correct answer explains how intermediate hosts like swine play a crucial role in allowing the reassortment of influenza genes, leading to the emergence of new viruses with specific binding specificities and increased virulence.