Lecture 2 Flashcards
What is inflammation
Where in the body can inflammation not occur?
Response or vascularized tissues that delivers leukocytes and molecules of host defense from circulation to the sites of the infection and cell damage in order to eliminate the offending agents
Cartilage also doesn’t have blood vessels supplying it
Inflammation can occur everywhere cuz there is blood supply to every part of the body. But there are two places that are not supplied with blood vessels . The testes in males and the cornea in the eye.
State the five cardinal signs of inflammation
Redness-rubor(due to presence of many red blood cells at the site)
Heat-Calor(due to presence of many red blood cells at the site)
Swelling-tumor (due to leakage of fluid into tissues from blood vessels cuz the blood vessels have become leaky)
Pain-dolor(pain cuz of the swell in which will compress the nerve endings there and also due to release of prostaglandins during inflammation)
Loss of function -functio laesa (all the above lead to loss of function)
The upper four are due to changes in the blood vessels supplying the site where the inflammation is to take place and the last one is due to the first four.
Who is the founder of pathology
Who discovered phagocytosis?
Rudolf virchow (1821-1902)(he brought about inflammation)
Phagocytosis-
Elie Metchnikoff (1845-1916)
The name “Elie Metchnikoff” is the French transliteration of his original Russian name, Илья Ильич Мечников (“Ilya Ilyich Mechnikov”). In English, he is often referred to as Elie Metchnikoff, but “Ilya Mechnikov” is also correct and commonly used,
What are the components of inflammation?
Inducers-infectious agents and pathogens,immune cells,foreign body causing tissue damage
Sensors- cells in body that pick up or sense the inducers in the body(mast cells,dendritic cells,macrophages)
Mediators-the sensors release mediators which effect certain responses within the body and bring an effect on the target tissues(TNF,IL-1,IL-6,CCL2,CXCL8,Histamine,Bradykinin,Eicosanoids)
Target tissues
State four causes of inflammation
● Infections
● Tissue necrosis(remember that apoptosis won’t lead to inflammation cuz it’s a programmed cell death)
● Foreign bodies
● Immune reactions
All immune cells have pattern recognition receptors. Example is Toll like receptors (TLRs)
What is PAMP?
What is DAMP?
Which is found in necrotic cells?
Which is found with infectious agents?
What is the main function of this PAMP AND DAMP
What is the end result of the function of PAMP AND DAMP in inflammation?
What is the function of Toll like receptors?
Between PAMP and DAMP, which do Toll like receptors recognize more?
These are made to identify PAMPs (Pathogen-Associated Molecular Patterns. These are found with infectious agents) and DAMPs (Damage-Associated Molecular Patterns. These are usually found in necrotic cells). The PAMPS AND DAMPS are molecules that play crucial roles in the immune system by alerting the body to the presence of infections or cellular damaged.
This entire thing leads to events which affect nuclear synthesis of certain inflammatory cytokines inside the cell that got into contact with the infectious agent. This leads synthesis of inflammatory cytokines which are released into the surroundings
Toll like receptors are like intracellular proteins in the cell and it transmits the information (signal transduction) it gets when it comes into contact with either PAMP or DAMP depending on the agent causing the inflammation. This leads to signals entering the nucleus of the cell causing promotion of synthesis of inflammatory cytokines.
So infectious agent-PAMP-Toll like receptors recognize PAMP-this leads to inflammatory cytokines release
TLR recognize PAMPS more than DAMPS while NOD Like receptors (NLR) recognize both PAMPS and DAMPS more
ocation
- NLRs (NOD-like receptors):
- Intracellular: NLRs are located within the cytoplasm of cells, where they detect intracellular pathogens and cellular damage.
-
TLRs (Toll-like receptors):
- Extracellular and Endosomal: TLRs are found on the cell surface and within endosomal compartments. They recognize extracellular and endosomal PAMPs.
State the steps of inflammatory reaction
Recognition (TLL and NLR recognizing PAMPS or DAMPS)
● Recruitment(recruitment of cells which will help in inflammatory pathways. This leads to synthesis of mediators or inflammatory cytokines. Mediators will cause recruitment of leukocytes which will try to remove the pathogens )
● Removal-the recruited leukocytes remove the pathogens
● Regulation-regulate their activities at the site of inflammation
● Repair-initiate repair of the tissue
I hat are the components of acute inflammation
Note:there is brief vasoconstriction in acute inflammation followed by a longer period of vasodilation
Vascular component;Dilation of small vessels leading to increase in blood flow. There is also stasis in blood flow
Cellular component: Increased permeability of the microvasculature enabling plasma proteins and leukocytes to leave the circulation.
Emigration of leukocytes from the microcirculation of their accumulation in the focus of injury and their activation to eliminate the offending agent. The stasis of blood allows wbcs to come out and align themselves on the inner endothelium of blood vessels.
So when they come and align, they roll by selectins and then adhere to the endothelium lining by integrins. The adhesion makes them tightly bound to the lining so that blood won’t move them from there and they’ll have enough time to respond to the cytokines to know where they’re going to.
So
The increased blood vessel permeability causes increased gaps in the endothelial lining so that the leucocytosis can move through these gaps
And into the tissue. This is transmigration or diapedesis.
When they go into the tissue, they follow the signals and get to the site of infection. This is chemotaxis
State four differences between acute and chronic inflammation
Onset
Acute Fast: minutes or
hours
Chronic Slow: days
Cellular infiltrate:
Acute-Mainly neutrophils
Chronic-Monocytes/macrophages and lymphocytes
Tissue injury, fibrosis:
Acute- Usually mild and self-limited
Chronic-Often severe and progressive
Local and
systemic signs:
Acute-Prominent
Chronic -Less
Inflammation is more in acute than in chronic.
How is transudate and exudate formed?
In inflammation you have more of exudate.
Exudate is high in protein
Some cases, you may have transudate. The transudate is believed to just be a step toward exudate in inflammation cuz transudate is seen when there is dilation of the blood vessels without increased permeability of the blood vessel but once the vessels enlarge more, there is increased permeability and leukocytes, complement proteins,cytokines,etc seeping out of the blood vessels and into the site where the wound is.
Transudate and exudate are two types of fluid that can accumulate in body cavities, often as a result of different pathological processes. Here are the key differences:
-
Origin:
- Transudate: Formed due to systemic factors that alter the balance of pressures within blood vessels, such as increased hydrostatic pressure or decreased oncotic pressure. Common causes include heart failure, liver cirrhosis, and nephrotic syndrome.
- Exudate: Results from inflammation, leading to increased vascular permeability. Causes include infections, malignancies, autoimmune diseases, and trauma.
-
Protein Content:
- Transudate: Low protein content (usually less than 3 g/dL).
- Exudate: High protein content (usually more than 3 g/dL).
-
Cell Count:
- Transudate: Low cell count.
- Exudate: High cell count, often containing inflammatory cells.
-
Specific Gravity:
- Transudate: Low specific gravity (less than 1.012).
- Exudate: High specific gravity (greater than 1.020).
-
Appearance:
- Transudate: Clear and pale.
- Exudate: Cloudy or turbid, often with a yellowish color.
-
LDH (Lactate Dehydrogenase) Levels:
- Transudate: Low LDH levels.
- Exudate: High LDH levels.
These differences help in diagnosing the underlying cause of fluid accumulation and guide appropriate treatment.
What are the vascular changes in acute inflammation
Immediate vasoconstriction
● Vasodilation
● Increased permeability
What are the cellular events changes in acute inflammation
What helps in converting hydrogen peroxide to becoming a harmful ROS?
NADPH helps convert hydrogen peroxide to hypochlorite ion which makes it become more harmful.
NADPH is essential for the initial production of superoxide, which is subsequently converted into hydrogen peroxide and then into hypochlorite(converted to hypochlorite by myeloperoxidase(, a powerful antimicrobial agent, during the immune response.
Recognition
● Emigration (from margination to diapedesis) and chemotaxis
● Phagocytosis
● Killing and degradation
When there is a pathogen, TLL recognize these. Mast cells are recruited and release histamine and kinins which will cause the vascular events that occur in inflammation(vasodilation and increased permeability of vessels). Histamine and kinins also activate the endothelial lining. This activation causes activation of selectins (P and E selectins are in the endothelial lining and L selectin is on leukocytes)
The macrophages that also recognize these cells with the pathogen begin to release inflammatory cytokines(TNF alpha and IL 1).
Transmigration- movement of leukocytes through the endothelial lining to the tissues. They must first break the basement membrane to do this using colagenase.
Movement to site of infection is indicated by IL 8.
Certainly! Here’s a bit more detail:
- Recognition: Immune cells, particularly macrophages and dendritic cells, recognize harmful agents like bacteria or damaged cells through receptors on their surface that detect foreign or abnormal molecules.
- Emigration and Chemotaxis: Upon recognition, immune cells migrate from the bloodstream to the affected tissue. They are guided by chemical signals released by the damaged tissue and inflammatory mediators. This directional movement is called chemotaxis.
- Phagocytosis: Once at the site of injury or infection, immune cells engulf and ingest the foreign invaders or cellular debris through a process called phagocytosis. This involves the formation of pseudopodia that surround and internalize the target.
- Killing and Degradation: Inside the immune cell, the engulfed material is enclosed within a membrane-bound vesicle called a phagosome. This phagosome then fuses with lysosomes, organelles containing enzymes that degrade the engulfed material. Additionally, reactive oxygen species and other toxic substances are produced within the phagosome to kill pathogens.
These cellular events work together to eliminate the source of injury or infection and initiate tissue repair.
Cellular Events in Acute Inflammation
Acute inflammation is a rapid and early response to injury or infection, characterized by a series of specific cellular events:
1. Vascular Changes: • Vasodilation: Increased blood flow to the site of injury, leading to redness (erythema) and heat. • Increased Vascular Permeability: Endothelial cells retract, allowing proteins, fluids, and leukocytes to escape from the bloodstream into the tissue, causing swelling (edema). 2. Leukocyte Recruitment: • Margination and Rolling: Leukocytes (mainly neutrophils) move to the periphery of the blood vessels (margination) and roll along the endothelial surface. • Adhesion: Leukocytes firmly adhere to the endothelial cells via interactions between integrins on leukocytes and adhesion molecules on the endothelium. • Transmigration (Diapedesis): Leukocytes squeeze through gaps in the endothelial lining to enter the tissue. • Chemotaxis: Leukocytes migrate towards the site of injury or infection in response to chemical signals (chemokines). 3. Leukocyte Activation and Phagocytosis: • Activation: Once at the site, leukocytes become activated by various signals (e.g., microbial products, cytokines). • Phagocytosis: Activated leukocytes, primarily neutrophils, engulf and digest pathogens, debris, and dead cells. • Release of Mediators: Leukocytes release various enzymes, reactive oxygen species, and other mediators that contribute to the destruction of pathogens but can also cause tissue damage. 4. Resolution: • In acute inflammation, the response typically resolves once the inciting stimulus is eliminated. Neutrophils undergo apoptosis, and macrophages clear the debris, promoting tissue repair
What are the chemical mediators(not cytokines) in acute inflammation (state five)
What’s the difference between chemical mediators and cytokines
Histamine-released by mast cells
● Arachidonic acid metabolites-contribute to prostaglandin,leukotrienes release
● Platelet-activating factor-the blood in the leaking blood vessels will try to clot due to the leaking in the blood vessels to prevent excessive loss of blood cells
● Cytokines and chemokines
● Complement system
● Kinins-released by mast cells and when released,the kinins release histamines and prostaglandins
● Neuropeptides
Key Differences
• Nature: Cytokines are proteins or glycoproteins, whereas chemical mediators can include a broader range of molecules, such as lipids, amines, and small peptides. • Function: While both are involved in the immune response, cytokines are more specifically involved in regulating and signaling immune cell activities, whereas chemical mediators encompass a wider range of functions, including directly causing vasodilation, increasing vascular permeability, and mediating pain and fever. • Source: Cytokines are predominantly produced by immune cells (like macrophages, T cells, and B cells), while chemical mediators can be produced by a variety of cells and tissues, including endothelial cells, platelets, and the liver (in the case of plasma proteins).
In summary, cytokines are a specific group of chemical mediators that play a central role in immune signaling and regulation, while chemical mediators as a whole encompass a broader array of molecules involved in various aspects of the inflammatory and immune responses.
Why is tuberculosis very difficult to handle?(with regards to what the bacteria does)
Prevents fusion of lysosome and phagocyte to form phagolysosome.
Phospholipase breaks down cell membrane to produce arachidonic acid.
This acid is broken down into either cyclooxygenase or lipooxygenase.
Which pathway produces prostaglandins D,I and E?
Which produces luekotrienes?
Cyclo produces prostaglandins. The prostaglandins cause the pain in inflammation cuz theyre further broken down into substance P(Substance P is a neuropeptide involved in transmitting pain signals and in regulating inflammation)
Lipo produced leukotrienes
