TEST 2: Inflammation

Question 1

What is the immune system?

Answer 1

A diverse collection of disease fighting cells in the blood, lymph, tissues, and organs throughout the body

-Lymphatic system:
-adenoids/ tonsils
-thymus
-bone marrow
-bronchus associated lymphoid tissue
-axillary lymph nodes
-intestine/ Peyers patches
-spleen
-inguinal lymph nodes
-appendix

Question 2

$ Benefits of acute inflammation

Answer 2

-Acute inflammation:rapid and localized response that aims to eliminate the cause of cell injury and initiate repair process
-triggers the release of growth factors and cytokines to promote tissue repair/ regeneretion
-helps isolate and contain pathogens
-primes the adaptive immune system for pathogen recognition

Question 3

$ Drawback of chronic inflammation

Answer 3

-Prolonged, systemic inflammatory response that persists over a longer period
-can lead to progressive tissue damage and fibrosis, impairing organ function
-may trigger autoimmune disease
-contributes to insulin resistance, dyslipidemia, cardiovascular risk
-associated with DNA damage, cell mutations, increased risk of cancer

Question 4

Key components of immune system

Answer 4

1. Blood
2. Lymphatic system
3. Solid organs (thymus and appendix)
4. Bones

Question 5

How the blood helps the immune system

Answer 5

-WBC’s are the primary cells of the immune system and are categorized into neutrophils, lymphocytes monocytes, eosinophils, and basophils (each has a specific role in immune response)

Question 6

How the lymphatic system helps the immune response

Answer 6

1. Lymph nodes: bean shaped structures that filter lymph fluid and trap pathogens
2. Tonsils and Adenoids: tissues at the back of the throat that help prevent infections from entering the body
3. Spleen: acts as a blood filter, removing old or damaged RBC’s and helping to fight infections
4. Peyer’s patches: are found in the intestines and are part of the gut- associated lymphoid tissue, helping protect against pathogens in GI tract

Question 7

How solid organs help the immune system

Answer 7

1. Thymus: located behind the breastbone, thymus plays a critical role in the development and maturation of T lymphocytes
2. Appendix: recent studies suggest may play a role in immune function and gut health

Question 8

How bones help the immune system

Answer 8

Bone marrow: spongy tissue found in the center of bones that is responsible for producing all blood cells

Question 9

Innate immunity barriers

Answer 9

• first line of defense
  -layers of protection: skin/ mucous membranes, cells and secretory molecules (low pH of stomach acid and urine), ciliary activity
  -this response is always at work

Question 10

Innate immunity inflammatory response

Answer 10

-Second line of defense
-vascular response, plasma protein response, and cell mediated response
-able to respond immediately to invasion

Question 11

Key roles of the immune system

Answer 11

1. Protect against pathogens (B and T cells, macrophages, dendritic cells that work together to recognize and target specific pathogens)
2. Isolate and remove foreign substances (dendritic cells capture and present foreign antigens to other immune cells for recognition/ response)
3. Immune surveillance: dynamic process where cells constantly survey the body for abnormal cells (NK cells detect and eliminate aberrant cells before they develop into tumors; cytotoxic T cells can recognize/ destroy cancer cells)

Question 12

Inflammatory response

Answer 12

A key component of the innate immune response and is triggered in response to tissue damage, infection, or threat.
-During inflammation, blood vessels dilate, allowing immune cells to reach the site of injury/ infection quickly (helps to contain and eliminate pathogens)

Question 13

$ Inmate and adaptive immunity interaction

Answer 13

-The innate system provides immediate, generalized defense against a wide array of threats, and also is responsible for priming the adaptive immune response.
-Innate immune cells present antigens to adaptive immune cells, activating them and guiding their specific responses to pathogens.

Question 14

Stages of inflammatory response

Answer 14

1. Stage 1: recognition and triggering stage
2. Stage 2: Inflammatory mediator release
3. Stage 3: immune cell activation and phagocytosis
4. Resolution and tissue repair

Question 15

Stage 1: recognition and triggering of inflammatory response

Answer 15

-At the onset of inflammation, immune cells recognize danger signals such as pathogen-associated molecular patterns (PAMP’s) or damage- associated molecular patterns (DAMP’s) through pattern recognition receptors (PRR’s)
-This recognition initiates a cascade of events leading to the release of pro inflammatory mediators like histamines, prostaglandins, and cytokines.
-initial vascular changes like vasodilation and increased permeability are crucial for promoting the influx of immune cells to the affected site.
-these cells play a pivotal role in eliminating pathogens and activating the adaptive immune response

Question 16

Stage 2: inflammatory mediator response in inflammatory response

Answer 16

-Inflammatory mediators like TNF, interleukins, and chemokines, are release by immune cells and contribute to amplification of inflammatory response. They orchestrate the recruiting and activity of more immune cells, enhancing defense.
-The balance between pro and anti inflammatory mediators is crucial for ensuring an effective but controlled response, preventing excessive tissue damage but still fighting the threat

Question 17

Stage 3: inflammatory mediator release in inflammatory response

Answer 17

-Neutrophils and macrophages play key roles in engulfing and destroying pathogens through phagocytosis. This not only eliminates the immediate threat but generates signaling molecules that regulate immune response and tissue repair.
-Concurrently, the activation of T and B cells occurs, leading to a tailored and specific response against pathogens that are invading, forming immunologic memory for future encounters

Question 18

Stage 4: Resolution and tissue repair in the inflammatory response

Answer 18

-When the threat is neutralized and the immune system under control, anti inflammatory mediators (including growth factor beta and interleukin 10) dampen the inflammatory cascade, promoting the clearance of immune cells and initiation of tissue repair
-Tissue repair involves the regeneration of damage through proliferation of fibroblasts, deposition of collagen, and angiogenesis.
-Regenerative phase aims to restore normal tissue structure and function while minimizing scar formation

Question 19

$ Vascular response to inflammation

Answer 19

-Inflammation characterized by rapid and dynamic changes in blood vessels that facilitate immune cell recruitment to the area of injury by:
-Vasodilation: relaxation of blood vessel walls to increase blood flow to site (triggered by histamine and prostaglandins creating redness/heat)
-Increased vascular permeability: permeability of blood vessels is enhanced, allowing immune and plasma proteins to move out of the blood stream into the tissues; is crucial for delivery of immune cells to infection)
-Formation of edema: leakage of fluid from blood vessels from the increased permeability and results in accumulation of fluid into the tissues (edema helps dilute toxins and provide a fluid environment for cells to work effectively)

Question 20

Cell Mediated response to inflammation

Answer 20

-Neutrophils, monocytes, and macrophages are responsible for:

1. Phagocytosis: engulfs and destroys pathogens, debris, foreign particles
2. Cytokine production: releasing signaling molecules (cytokines and chemokines) regulates inflammation, immune cell recruitment, and coordination of immune response.
3. Tissue repair: secrete growth factors that promote cell proliferation, collagen synthesis, and angiogenesis.

Question 21

$ Plasma protein response in inflammatory response

Answer 21

1. Complement cascade
2. Clotting cascade
3. Kinin cascade

Question 22

$ Mast cells

Answer 22

-Found In connective tissues close to blood vessels and areas exposed to the environment (lungs/ GI tract)
-Activated/ released in response to:
Heat, chemicals, immune activation
-Job is to release products by degranulation (Histamine 1 and 2,
Neutrophils, eosinophils) and synthesis of new mediators (leukotrienes, prostaglandins, platelet activating factors)

Question 23

$ Purpose of the complement cascade

Answer 23

1. Pathogen recognition and Opsonization: helps identify and tag pathogens for elimination; recognizes unique molecular patterns on pathogens and coats them with complement proteins (usually C3b). Opsonization enhances phagocytosis.
2. Inflammation: helps trigger and amplify the inflammatory response.
3. Direct pathogen killing: can directly lyse pathogens through the formation of membrane attack complex (MAC), which creates pores in the pathogens membrane (particularly effective against certain bacteria and enveloped viruses)
4. Clearance of immune complexes: aids in clearance of immune complexes that are formed by antigens and antibodies; can bind to these complexes and remove them (helps prevent autoimmune reactions)
5. Modulation of immune responses: interact with other components for the immune system. Integrates with other immune pathways (coagulation cascade and adaptive immune response) to coordinate effective defense.

Question 24

$ Complement Cascade

Answer 24

Antigen-antibody complex—> complements activated—>
Induction of mast cell degranulation—>
Releases histamine —>
Leukocyte chemotaxis—>
Opsonization —>
Cell lysis

Question 25

Phases of the complement cascade

Answer 25

1. Initiation: activates the complement cascade in response to pathogen or antigen-antibody complexes (identifies and marks a target for destruction) 2. Amplification phase: enhances the complement response, rapidly increasing the Opsonization and inflammatory processes. 3. Cascade convergence phase: integrates the different pathways activations and amplifies complement response. MAC formation initiates the direct killing of pathogens 4. Terminal phase: MAC insertion into pathogen membranes disrupts their cell integrity and causes lysis.

Question 26

$ Four key roles of clotting cascade in inflammation

Answer 26

Are proteins that form a blot at the site of injury/ inflammation 1. Prevents spread to adjacent tissue: helps contain injury site but forming a mesh like clot of fibrin, platelets, protein; physically blocks the spread of pathogens/ toxins/ damaged parts (limiting the extent of tissue damage) 2. Traps antigen at the site for removal: makes it easier for macrophages to access and remove unwanted elements (facilitating clearance of pathogens and promoting tissue cleaning). 3. Stops bleeding: prevents excessive blood loss, seals off damaged vessels and smut inning homeostasis (crucial for preventing further damage) 4. Provides a frame for repair/ healing: fibrin mean formed as a result of the clotting cascade provides a structural scaffold for tissue repair/ healing (fibroblasts and endothelial cells).

Question 27

$ Kinin cascade major functions

Answer 27

1. Vasodilation (widens the blood vessels leading to increased blood flow and increases vascular permeability) 2. Leuko chemotaxis (process by which WBC’s, leukocytes, are attracted to and migrate towards the site of inflammation in response to chemical signals and are directed towards the injury) -Both are actions of bradykinin (potent chemoattractant for leukocytes)

Question 28

$ Role of Kinin cascade

Answer 28

-Primary protein in bradykinin -Causes: -vasodilation -increased vascular permeability -smooth muscle contraction -nerve cell stimulation (pain) -leukocyte chemotaxis -Is short acting and rapidly degrades

Question 29

$ Cell mediated response

Answer 29

-After injury, cell mediated responses facilitates blood clotting and the passage of cells and fluid to injured tissues (relies on a mix of RBC, plt, WBC) -Two parallel processes: 1. Cellular receptors (recognize paternal of cell damage and trigger complement cascade) 2. Cellular products (send messages and coordinate inflammatory process)

Question 30

$ White blood cells: Leukocytes (agranulocytes) *** Check this one

Answer 30

-Neutrophils: early responders that phagocytize and eliminate pathogens -Monocytes (macrophages): initiate the plasma protein responses, engage in long term healing and cleanup (deception on severity of infection) -Eosinophils: involved in parasitic infections and allergic reactions x regulate the mast cell response -Basophils: contribute to B cell antibody response and associated with allergic reacgions -Natural Killer cells: granulocyte free cells that target infected cells, particularly virus infected cells and some cancer (are leukocyte adjacent)

Question 31

Leukocyte role in phagocytosis

Answer 31

-Complement cascade brings leukocytes to site of inflammation -Once there: they recognize the antigen using Opsonization, engulf the antigen, fuse it to lysosome granules, and destroy the antigen -It relies on oxygen uptake by the cells to generate the reactive oxygen species (necrosis triggering mechanism to the on switch) -once adequate phagocytosis has occurred, serum inhibitors turn off the destructive mechanism -Monocytes are part of the long term defense and healing

Question 32

How RBC’s (erythrocytes) function in the cell mediated response

Answer 32

-function: Transport oxygen to the tissues and play a role in cellular respiration -Cell mediated response: while not directly involved in immune responses, their function in oxygen transport supports overall metabolic needs during inflammation

Question 33

Platelets (thrombocytes) role in cell mediated response

Answer 33

-Function: essential for blood clotting and Hemostasis (prevent excessive bleeding at injury site) -Cell mediated response: contribute to the formation of blood clots which helps seal damaged blood vessels, control bleeding, and provide temporary scaffold for cell migration during tissue repair

Question 34

Mast cells role in cell mediated response

Answer 34

-Function: tissue resident immune cells that contain granules rich in inflammatory mediators (ie histamine) -Cell mediated response: play a key role in the immediate inflammatory response by degranulating and releasing histamine (and other vasodilators). This leads to Increased vascular permeability, vasodilation, and characteristic symptoms of inflammation: swelling, redness, itching.

Question 35

$ Cytokines main functions

Answer 35

-Are a diverse group of proteins that create a Chemical communication network -Mediate immune response to ramp up or slow down (act locally but have systemic effects) -Produced by cells of the acquired immune system in response to specific antigens

Question 36

$ 4 key cytokine classes

Answer 36

1. Interleukins 2. Tumor necrosis factor- alpha (TNF-a) 3. Interferons 4. Chemokines

Question 37

$ Interleukins

Answer 37

-Are produced by macrophages and leukocytes -local effect: Alter adhesion molecule expression, Act as a signaling molecule to bring leukocytes to an area of inflammation -systemic effect: getting bone marrow to make more leukocytes (usually IL-2) -Have pro- inflammatory (IL-1 and IL-6) or anti- inflammatory (IL-10) properties that help balance the immune responses

Question 38

$ Tumor Necrosis Factor Alpha

Answer 38

-Primarily produced by macrophages, mast cells in response to injury/ infection -Local response: increase endothelial cell adhesion, starts chemokine production, promotes apoptosis -Systemic response: fever, weight loss, septic shock, cache is from increased metabolic demand, tissue damage in sepsis or autoimmune diseases -PRO INFLAMMATORY ONLY

Question 39

$ Interferons

Answer 39

-Primarily produced by virally infected cells, dendritic cells, and natural killer cells -Local role: help inhibit viral replication in infected cells by stimulating antiviral proteins -Systemic role: induce antiviral state in nearby cells, enhancing immune surveillance against viruses -PRO INFLAMMATORY

Question 40

$ Chemokines

Answer 40

-Produced by macrophages, fibroblasts, and endothelial cells in response to inflammation or infection -Local role: regulate leukocyte migration to the site of inflammation by acting as a chemoattractant (in response to pro inflammatory cytokines) -Systemic role: coordinate cell recruitment and activation systemically during inflammation (associated with cancer growth) -PRO INFLAMMATORY

Question 41

Balance in inflammation

Answer 41

-Pathophysiologic: deficient inflammatory response—>infection -Hyperactive: autoimmune disease, allergies, alloimmunity

Question 42

$ Acute inflammation

Answer 42

-Rapid, localized response to injury or infection S/s: Fever (triggered by IL-1, pyrogens act on hypothalamus to control temp) redness, heat swelling, pain -Causes increased vascular permeability (leading to influx of immune cells) -Tissue repair and resolution of inflammation occur once threat is gone -Well regulated, self limiting responses aimed at restoring tissue homeostasis -Synthesis of plasma proteins (acute phase reactants—> CRP, fibrinogen, ferritin) -Elevated WBC count, increase in immature bands, called “left shift”

Question 43

$ Cytokine Storm

Answer 43

-Is an exaggerated and uncontrolled systemic inflammatory response where too many cytokines are released too quickly (usually pro-inflammatory interleukins, TNF, interferons) -Can be triggered by severe sepsis, autoimmune disorders, transplants -Hallmark symptom is very high fever -wide range of symptoms: multi-organ failure, rashes, pulm edema, renal failure, coagulopathy, AMS, hypotension

Question 44

$ Acute Inflammation vs. cytokine storm

Answer 44

Acute: -Localized response triggered by tissue damage or infection -Presents as swelling, redness, heat -Part of body’s normal defense mechanism and is self limiting Cytokine Storm: -A systemic and dis regulated immune response resulting in uncontrolled inflammation -Systemic manifestations with severe complications -lacks control and regulation leading to excessive inflammation and tissue damage

Question 45

$ Chronic Inflammation

Answer 45

-Damages cells and weakens immune system (less robust responses) -Associated with chronic diseases: -Peridonitis (chronic gum disease) -Obesity (metabolic dysfunction) -DM (insulin resistance) -Alzheimer’s (neuro inflammation) Frailty -Mediators: dietary factors (phytochemicals, antioxidants increase), more diverse gut microbiome -Consequences: body may struggle to adequately fight disease/ infections OR may lead to autoimmunity, allergies, chronic pain

Question 46

$ Phagocytosis in the immune response

Answer 46

-Is the process that involves removing the offending antigen -Works by: 1. Chemotaxis (process where immune cells are guided to the site of infection/ inflammation) Complement cascade plays a significant role in attracting attracting the leukocytes to the injury where they begin phagocytosis 2. Opsonization (process of labeling pathogens with molecules that enhance their recognition and ingestion) 3. Lysosomes (aid in digestion and breakdown of engulfed material during phagocytosis) 4. Cell injury and apoptosis (phagocytic cells engulf apoptotic cells and debris)

Question 47

Inflammation and chronic pain

Answer 47

-Acute pain may transition to chronic pain from unresolved inflammation -Often involves a dysregulated inflammatory response -In chronic pain states, pro- inflammatory mediators continue to be released, sensitizing pain pathways, altering neural signaling, an repeating the perception of pain -Can cause actual neuro plastic changes over time (amplifies pain signals)

Question 48

BP (Lecture)

Answer 48

-SNS contributes to blood pressure regulation (promotes cardiac contractility + HR = CO) (also controlled arteriolar vasoconstriction (PVR) -SNS responds to Catecholamines (Epi and NorEpi) -SNS stimulates RAAS