Essay writing Flashcards
metabolism definition?
Here’s a concise paragraph that incorporates the key information from your lecture notes in a way that’s easy to memorize and use in an exam:
Metabolism encompasses the chemical reactions that provide energy (catabolism) and biosynthetic precursors (anabolism) necessary for cellular function. Glucose metabolism begins with glycolysis, a rapid anaerobic process that generates ATP, NADH, and key biosynthetic intermediates such as glucose-6-phosphate (for nucleotide synthesis via the pentose phosphate pathway) and 3-phosphoglycerate (for amino acid biosynthesis). Pyruvate, the end product of glycolysis, can enter the TCA cycle under normoxic conditions, generating NADH and FADH2, which feed electrons into the electron transport chain (ETC) for efficient ATP production via oxidative phosphorylation (OXPHOS). Fatty acid oxidation (FAO) also supplies acetyl-CoA for the TCA cycle, yielding high ATP output. Additionally, glutaminolysis provides an alternative source of TCA intermediates, while anabolic pathways such as the pentose phosphate pathway and fatty acid synthesis contribute to nucleotide, lipid, and cholesterol biosynthesis, crucial for cell growth and proliferation. Together, these interconnected pathways ensure the energy and building blocks required for immune cell function.
things that I forgot to include?
Forgot to talk about how PEP reduces Nfat in tumour microenvironment and the moonlight function of GAPDH
Forgot effector cells use glutoaminolysis too
Forgot IL-4 and IL-13 induce STAT6 that produces PPAR and PXR
forgot the wider reading about akt-mTOR
introducing mtor?
The mechanistic target of rapamycin (mTOR) is a central regulator of cell growth and metabolism, integrating signals from nutrients, energy, and growth factors to modulate processes such as protein synthesis, cell proliferation, and metabolic reprogramming, playing a crucial role in both immune cell activation and differentiation.
introducing how amp levels affect mtor?
“During metabolic stress, elevated AMP levels activate AMPK, which inhibits mTOR signaling and promotes autophagy (as mtor promotes anabolic metabolism and inhibits autophagy induction Kim et.al 2015), a process crucial for maintaining cellular homeostasis. In immune cells, such as macrophages, autophagy is involved in degrading intracellular pathogens, including bacteria, by engulfing them in autophagosomes. Similarly, epithelial cells rely on autophagy to control the replication of intracellular bacteria, highlighting the importance of mTOR regulation in both immune defense and cellular integrity.
writing effective conclusions? for example in an essay about the complement system + immunometabolism?
Restate the thesis:
The complement system is an essential component of the innate immune response, which plays a crucial role in defending the body against pathogens.
Summarize key points:
This system consists of three main pathways: classical, lectin, and alternative. Through the activation of C3 and C5 convertases, complement proteins mediate immune cell recruitment, opsonization, and the formation of the membrane attack complex, all of which contribute to pathogen elimination. However, excessive activation of the complement system can lead to tissue damage and chronic inflammation, as seen in conditions such as autoimmune diseases.
Final thought:
While the complement system is critical for immune defense, understanding its regulation is essential to prevent damage to healthy tissues, highlighting the need for therapeutic approaches that target complement activation in pathological conditions.
Restate the thesis:
Immunometabolism is a dynamic field of study that explores how immune cells adapt their metabolic processes to respond to pathogens and inflammation.
Summarize key points:
Immune cells, such as macrophages and T cells, rely on various metabolic pathways, including glycolysis, glutaminolysis, and oxidative phosphorylation, to fuel their effector functions. These metabolic shifts not only support immune cell activation but also contribute to disease progression, as seen in chronic inflammatory conditions and cancer.
Final thought:
By understanding the interplay between metabolism and immune function, we can better target immune responses for therapeutic purposes, offering new avenues for treating inflammatory diseases, cancer, and immune-related disorders.
opsonisation?
Opsonization is a crucial process in the immune system where pathogens are marked for enhanced recognition and phagocytosis by immune cells. This occurs when complement proteins, such as C3b, bind to the surface of pathogens. The C3b molecule serves as an opsonin, which is a molecule that promotes the engulfment of pathogens by phagocytes. When C3b binds to a pathogen, it effectively ‘tags’ it, making it more easily recognized by immune cells, such as neutrophils and macrophages, through specific complement receptors. On neutrophils, the main receptor for C3b is CR1 (Complement Receptor 1), which recognizes and binds to the C3b opsonin on the pathogen surface. This binding facilitates the process of phagocytosis, where the neutrophil engulfs and destroys the pathogen. Additionally, neutrophils also have other complement receptors like CR3, which binds to C3dg, another cleavage product of C3b, and helps further enhance the immune response.
complement link to inf?
To effectively link the complement system to acute inflammation, it’s important to focus on the key roles that complement activation plays in initiating and amplifying the inflammatory response. Here’s a suggested explanation:
The complement system plays a central role in the initiation and amplification of acute inflammation. Upon activation, complement proteins, such as C3a and C5a, act as anaphylatoxins, which are powerful mediators of inflammation. These molecules bind to specific receptors on immune cells such as mast cells, basophils, and neutrophils, triggering their degranulation and the release of inflammatory mediators like histamines, cytokines, and chemokines. These mediators increase vascular permeability, leading to edema (swelling) and recruitment of immune cells to the site of infection or injury. C5a, in particular, is known for its potent ability to attract and activate leukocytes like neutrophils and macrophages, enhancing their ability to phagocytose pathogens and contribute to tissue repair. Additionally, the C3b fragment facilitates opsonization, marking pathogens for enhanced phagocytosis by immune cells, further promoting tissue defense. In this way, the complement system serves as both a trigger and an amplifier of the acute inflammatory response, ensuring that immune cells are rapidly recruited and activated to combat infection or tissue damage.
Targeting of complement
Mimicking host proteins - CD59-like (negative regulator of complement, prevent mac assembly), B burgdorferi, hijacks negative regulator. ?
Hijacking negative regulators – Factor H - Neisseria meningitidis
Secretion of proteases – C3/C5 cleavage, P aeruginosa
Secretion of evasion molecules - C3/C5 inhibition, S aureus
anchor residues of mhc wider reading?
original by wiezorek et.al (2017): the occupation of defined pockets by peptide side chains (anchor residues P2 or P5/6 and PΩ in MHC class I and P1, P4, P6, and P9 in MHC class II) The type of interactions of individual peptide side-chains with the MHC depend on the geometry, charge distribution, and hydrophobicity of the binding groove. In MHC class I, the binding groove is closed at both ends by conserved tyrosine residues leading to a size restriction of the bound peptides to usually 8–10 residues with its C-terminal end docking into the F-pocket (7–9). In contrast, MHC class II proteins usually accommodate peptides of 13–25 residues in length in their open binding groove, with the peptide N-terminus usually extruding from the P1 pocket (10).
chatgpt explained ver: Peptide side chains and anchor residues: The peptide that binds to the MHC molecule has different amino acids at certain positions that anchor it to the MHC groove. These anchor residues are the critical amino acids in the peptide sequence that interact with specific pockets in the MHC molecule, securing the peptide in place.
Anchor residues in MHC Class I: In MHC class I, these anchor residues are typically located at positions P2 (second amino acid), P5/6 (fifth or sixth amino acid), and PΩ (the last amino acid at the C-terminal end of the peptide). These positions are crucial for the peptide to fit properly into the MHC class I binding groove.
Anchor residues in MHC Class II: In MHC class II, the anchor residues are at positions P1, P4, P6, and P9. These residues interact with specific pockets in the MHC class II molecule to stabilize the peptide.
NK wider reading
Alternatively, recent studies have shown that human and mouse gzmB released by NK cells could also directly cleave and activate gasdermin E (GSDME) in a caspase-independent manner, promoting pyroptotic cell death (9, 124). Pyroptosis is an inflammatory cell death modality regulated by the GSDM family. GSDMs are activated by cleavage, forming a transmembrane pore that contributes to IL1 family cytokine release and, in addition, disturbs intracellular ion homeostasis, resulting in cell death (Labrada et.al 2022)
role of m1 in inflammation?
chronic inf definition
hypersensitivity
“Macrophages, particularly M1 macrophages, thrive in the hypoxic environment induced by tissue injury and contribute to inflammation through the release of cytokines
Chronic inflammation arises when acute inflammation fails to resolve, often due to persistent irritants or infection, leading to a shift from innate to adaptive immune responses. B cells, T cells, and macrophages work together in a cycle of inflammation that can lead to tissue damage if unresolved
Excessive inflammation is often the result of hypersensitivity reactions, where the immune system responds too strongly or inappropriately. In type I hypersensitivity, excessive mast cell degranulation leads to conditions such as asthma. Type II hypersensitivity involves antibody-mediated destruction of cells, as seen in autoimmune diseases. Type III hypersensitivity results from immune complex deposition, while type IV hypersensitivity involves T cell-mediated responses, leading to conditions like rheumatoid arthritis.”
acute inf !!
Acute inflammation is triggered by various stimuli, including infections (bacteria, viruses), physical injury, or chemical damage. When tissue is damaged, the immune system recognizes signals from the damage (called DAMPs — damage-associated molecular patterns) or from pathogens (PAMPs — pathogen-associated molecular patterns).
Coagulation and Clot Formation:
The initial response to injury is the formation of a blood clot (hemostasis), which reduces blood loss. This process involves the activation of the clotting cascade (involving proteins like fibrinogen turning into fibrin). The clot not only helps stop bleeding but also serves to trap pathogens and prevent them from spreading. This happens almost immediately after injury.
After Coagulation:
Vasodilation and Increased Permeability:
After coagulation, the next key step in the acute inflammatory response is vasodilation — the widening of blood vessels near the injury site. This is triggered by pro-inflammatory mediators, like histamine, bradykinin, and prostaglandins, which are released by cells like mast cells and injured tissue cells.
The increase in blood flow is responsible for the symptoms of redness (rubor) and heat (calor). Increased vascular permeability follows, meaning the blood vessels become more “leaky.” This allows immune cells, proteins, and nutrients to exit the blood vessels and enter the affected tissue.
Exudation and Swelling:
The increased permeability results in the leakage of exudate — a fluid rich in proteins like fibrinogen, complement proteins, and immunoglobulins. The exudate helps dilute toxins, and white blood cells (leukocytes) start to move toward the injury site, which is called chemotaxis. The exudate also contributes to swelling (tumor), which is the result of fluid accumulation in the tissue.
Arachidonic acid is released after cell membrane damage. It is a precursor for many inflammatory mediators:
Prostaglandins (via COX pathway) contribute to vasodilation and pain.
Leukotrienes (via 5-LOX pathway) are involved in attracting immune cells (like neutrophils) to the site of inflammation and promoting vascular permeability.
So, arachidonic acid is part of the process that amplifies the inflammatory response and contributes to tissue damage if uncontrolled. It’s key in regulating the balance between pro-inflammatory and anti-inflammatory mediators.
types of tumour antigens?
cyclin-dependent kinase 4: cell-cycle regulator. muated oncogene in tumours e.g: melanomas
beta-catenin: relay in signal transduction pathway: muated in melanoma
caspase-8: regulator of apoptosis. mutated in squamous cell carcinoma
surface ig/idiotype: specific ab after rearrangement in b cell clone. mutated in lymphoma
germ cell: MAGE-1 AND MAGE-3: normal testicular proteins. germ cells. of melanoma, breast, giloma
abnormal gene expression: HER-2 a receptor tyrosine kinase in breast and ovary cancer.
Wilm’s tumour: TF- leukemia
abnormal post-translational modification
how to describe GAPDH moonlight function?
Glucose metabolism elements…. as transcriptional and post-transcriptional regulators
of the adaptive immune response.
explain lytic synapse formation
T cell polarization plays a critical role in the formation of the lytic synapse, as it helps to direct the cytotoxic machinery of the T cell (such as cytolytic granules) toward the target cell in a focused and efficient manner. This process ensures that the cytotoxic T cell (CTL) delivers its lethal hits to the target cell and avoids damaging surrounding healthy cells.
Here’s how T cell polarization fits into the explanation of lytic synapse formation:
- Initiation of the Immune Synapse and Polarization:
When the T cell interacts with the antigen-presenting cell (APC), the initial immune synapse is formed through interactions between the TCR and MHC molecules on the APC. As the TCR is engaged by the peptide-MHC complex, signaling cascades are triggered, leading to T cell activation.
LFA-1-ICAM-1 interactions: Non-specific adhesion molecules such as LFA-1 on the T cell interact with ICAM-1 on the APC. This strengthens the physical contact between the two cells and helps to establish the synapse.
Filopodia formation: Filopodia (thin, finger-like projections of actin filaments) form and interdigitate with the APC, creating tight contacts where the TCR-MHC interaction occurs.
2. T Cell Polarization:
Once TCR engagement occurs, the T cell undergoes polarization, which is the reorganization of its internal structure to focus on the target cell. This polarization is crucial for targeted delivery of cytotoxic molecules to the synapse.
F-actin reorganization: Upon activation, F-actin (the filamentous actin) undergoes reorganization. The T cell’s actin cytoskeleton is polarized, and lamellipodia (flat extensions of actin filaments) move toward the synapse’s periphery. This process helps the T cell create a functional immune synapse by directing the cytoskeletal components towards the synapse and supporting the movement of cytolytic granules to the site of action.
Centrosome and microtubule reorganization: The centrosome, which organizes microtubules, shifts toward the immune synapse from the back of the T cell. The microtubule-organizing center (MTOC) guides the movement of cytolytic granules along microtubules towards the synapse. This is the polarization of the centrosome, and it ensures that the granules are positioned correctly to be released at the contact site.
The granules contain perforin (a pore-forming protein), granzymes (proteases that induce apoptosis), and other molecules necessary for killing the target cell.
Focused delivery: The polarization of the centrosome ensures that the cytolytic granules are concentrated at the immune synapse, forming a lytic synapse. This focused delivery of cytotoxic molecules is essential for targeted killing of the infected or cancerous cell while minimizing damage to surrounding healthy tissues.
- T Cell Actin Depolymerization and Granule Release:
As part of polarization and synapse formation, the T cell also induces actin depolymerization in specific regions to allow the granules to move efficiently to the synapse and be secreted.
Granule release: Cytolytic granules dock at the plasma membrane, and a targeted fusion occurs. This fusion is facilitated by the formation of synaptic pores, allowing the release of perforin and granzymes into the target cell.
Perforin creates pores in the target cell membrane, and granzymes enter through these pores to induce apoptosis in the target cell.
T cell cytotoxic activity: The release of these cytotoxic molecules results in the killing of the target cell, which is often a virus-infected or tumor cell.
- Incorporating Polarization into Lytic Synapse Formation:
So, to fit T cell polarization into the overall process of lytic synapse formation:
Initial synapse formation: LFA-1-ICAM-1 and filopodia form the initial contacts between the CTL and APC.
TCR engagement and signaling: This activates downstream pathways, including those that lead to the polarization of the T cell.
F-actin reorganization and centrosome polarization: The T cell polarizes by reorganizing its actin cytoskeleton, moving the centrosome and microtubules towards the immune synapse, which directs granules toward the synapse.
Actin depolymerization and granule release: The targeted release of cytotoxic granules, including perforin and granzymes, is facilitated by actin depolymerization and directed fusion with the synaptic membrane.
This entire process ensures that the T cell can focus its cytotoxic machinery on the target cell, allowing for the specific killing of infected or cancerous cells while minimizing collateral damage to healthy cells. Polarization is a key step in ensuring that the T cell is highly efficient in this targeted immune response.
