Immune System Part 1 Flashcards
Categories of Immunity
(2)
Innate
Only recognizes self vs. non-self and requires no previous experience to pathogen to fight it (with same intensity and speed regardless of # of encounters)
Adaptive (Acquired Immunity)
Part that learns, responds to pathogens more intensely and efficiently with more exposure “acquired immunity”
Overview of Immune System
- Cells of the Immune System (3)
- Organization of the Immune System (2)
- Molecular Communication in the Immune System
- WBC (leukocytes), Cytokines that allow for communication between immune cells, Surface markers
- The Lymphoid System, The Reticulo-endothelial System (RES) - where are cells located, activated, and where they travel
Innate Immunity Components
(3)
- The Front line of Host Defense
-
Second Line of Defense: The Inflammatory Response
- Acute Inflammation: Events and Mediators
- Induced (Systemic) Innate responses to infection
- Tissue Repair and Chronic Inflammation
Components of Innate and Adaptive Immunity
- A______
- Innate Immunity (4)
- Adaptive Immunity (2)
- Antigen
-
Innate
- Structural/Chemical Barriers
- Phagocytic/Scavenger Cells
- Inflammation
- Plasma Protein Systems (ie Complement System)
-
Adaptive
- B Lymphocytes (Antibody mediated immunity)
- T Lymphocytes (Cell-mediated immunity)
Innate and Adaptive Immunity (Notes)
-
Pathogens
- _______ (pink dot) = occupies ______ space
- _______ (black line) = genetic material in the form of DNA or RNA is _____ space/parasites that can’t replicate on their own, needs a host to make copies of itself
- P______ worms, Pro_____, F_____
- Prion =
-
Antigens =
- HLA’s =
- Pathogens
- Bacteria = extracellular
- Virus = intracellular
- Parasitic, Protozoa, Fungus
- Proteins that can replicate themselves by interacting wtih other proteins by causing that protein to mimic its shape
- Surface identity markers - that allows you to identify a specific pathogen (self. vs. non self)
- Protein that is most dissimilar from person to person
Innate and Adaptive Immunity (Notes)
-
Innate Immunity =
- Chemical Barriers =
- Scavenger Cells =
- Inflammation =
- Plasma Proteins =
-
Adaptive Immunity =
- B Lymphocytes =
- T Lymphocytes =
- Effector Cells =
- What is the relationship between Innate and Adaptive Immunity
- Fights pathogens with same efficacy and speed no matter how many encounters, needs no previous experience
- Skin, mucous membranes, our microbiome
- Neutrophils, Macrophages, etc.
- “Big hammer” powerful but causes some tissue damage
- Comprises the Complement System “Probably the most important” can destroy pathogens whether we’ve had previous experience with them (also used by adaptive immunity)
- learns and gets better at fighting pathogens with every subsequent encounter
- Antibody mediated immunity
- Fights pathogens that occupy intracellular space
- Recognizes infected or abnormal host cells and target them for removal
Interconnection of the two - innate has to trigger adaptive immune responses and adaptive can use components of the innate system to target particular pathogens with specificity (Innate = weapons, Adaptive = soldiers who use those weapons)
Cells of the Immune System
Cells of the Immune System are pretty much what blood cell? Also known as?
-
Pluripotent Hematopoietic Stem Cell =
- Lymphoid Progenitor Cells (3)
- Myeloid Progenitor Cells (3) - (5)
- One cell that is produced by both lymphoid and progenitor cells?
WBC (Leukocytes)
- Origin cell found in red bone marrow found in trabecular long bones (hip bones) (long bones of arms and legs are actually yellow bone marrow composed mostly of fat) that gives rise to both lymphoid progenenitor and myeloid progenitor cells
- B cell, T cells, NK cells
- RBC, Platelets, Granulocytes (Neutrophils, Eosinophils, Basophils, Mast cells, Monocytes)
- Dendritic Cells
Cells of the Immune System
- Hematopoietic stem cells go through Differentiation process -> ______ cell -> _______ differentiated cell (most _______ mature, but loses ability to _____)
- Function of B cells?
- Function of T cells?
- Function of NK Lymphocyte?
- Function of Dendritic Cells? How?
- secondary, terminally, functionally, replicate
- Part of adaptive immune system, B cells more for bacterial infections
- Part of adaptive immune system, T cells more for viral infections
- Part of our innate immune system ->like T cells v important in fighting intracellular (viral) infections but does so NONspecifically bc no specificity in innate system
- Phagocytic cell produced by both lymphoid and myeloid progenitor cells -> primary job is initiating adaptive immune responses
- Found in connective tissue throughout the body and do this thing called extracellular drinking (takes sips of ECF frequently) - and if they happen to trap a pathogen they go find cells necessary to trigger adaptive immune response
Myeloid Cells
(6)
-
(2) are the primary phagocytic cells that engulf pathogens and destory them in intracellular vesicles, a function they perform in both innate and adaptive immune responses
- (1) can also present antigens to T cells and activate them
- (1) are phagocytic when they are ______ and can take up pathogens, after maturing they act as ___-_____ cells to __ cells initiating adaptive immune responses
- Function of other myeloid cells =
- Eosinophils =
- Basophils =
- Mast cells =
Macrophage
Dendritic Cell
Neutrophil
Eosinophil
Basophil
Mast Cell
-
Neutrophils, Macrophages
- Macrophages
- Dendritic Cells (immature), Antigen presenting to T cells (mature)
- Primarily secretory and release contents of their prominent granules upon activation via antibody during adaptive immune response
- Involved in attacking large antibody-coated parasites (WORMS)
- Function is less clear
- Trigger local inflammatory response by releasing substances that act on local blood vessels
The Granulocytes
(6)
These cells are all _____
Neutrophils
Eosinophils
Basophils
Mast Cells
Monocytes -> Macrophages
Inducible: bone marrow can be induced to make more when needed for ongoing infection
Named dt large Granules
Neutrophils
=
(3) Mechanisms
One of three scavenger cells - first cells to migrate to area of inflammation or infection, found in circultion “riot police that break into house”
- Release Reactive Oxygen species
- Release Lysosomal enzymes
- Phagocytize Bacteria
They cause a huge mess then eat up that mess and die
Macrophages
=
- Circulating Macrophages
- Tissue Macrophages
2nd group of 3 phagocytic SCAVENGER cells that migrate to area and are much more smart and precise, clean up mess and eat dead neutrophils, and if they ingest a pathogen will go and trigger adaptive immune response
- AKA monocytes
- Scattered throughout the body and live in connective tissue, epithelial barriers, mucous membranes (where pathogens enter/infection)
- starts off at monocytes -> no active infection -> left bone marrow -> migrates to tissue -> turned into macrophages and stayed dormant “guards at the door” some stay dormant for decades ie liver tissue macrophages
Basophils
=
Filled with histamine and pro-inflammatory mediators
Identical in function to mast cells - only diff is mast cells live in tissue
Eosinophils
=
2 conditions
Rise under 2 major conditions, granules filled with chemical mediators that degrades the plasma membrane of whatever its trying to kill
- Parasitic worm infection
- Allergic Response
Mast Cells
=
Mast cells are also filled with histamine and inflammatory mediators -> located in tissue but always close to circulation
Monocytes
=
Immune cells produced by bone marrow that when activated turns into macrophages
Dendritic Cells
=
3rd Phagocytic Scavenger Cell
“like the spy” bc doesn’t have any actions that attack pathogens, it just sits in tissues and constantly takes samples of ECF to trap foreign antigens -> if it traps then will travel towards adaptive immune system
Overview of Inflammatory Response (Notes)
- 1st wave of cells =
- 2nd wave of cells =
- Both neutrophils and macrophages release (2) but also
- Eat up dead _____, cellular ____, and _____ that might be there
- Then they determine if inflammatory response needs to go down and trigger ________
- Neutrophils
-
Macrophages
- Reactive oxygen species and Lysosomal enzymes
- neutrophils, debris, pathogens
- Trigger healing
Where are Cells Found?
- Resident in Tissue =
- In Circulation =
- Circulating numbers induced to _____ during infection
- Dendritic Cells, Mast Cells, Macrophages
- Neutrophils, Eosinophils, Basophils, Monocytes
- Increase
Lymphocytes
=
(3)
- Derived from?
- Involved in?
Cells that comprise the adaptive Immune System
-
B Lymphocytes
- Bone marrow derived (formed in bone marrow)
- Antibody mediated immunity
-
T Lymphocytes
- Thymus derived (formed in bone marrow)
- Cell mediated immunity
-
NK Cells
- Part of innate immunity - v important for viral infections (they fight with NON-specificity)
Surface Markers
=
- B Cell Surface Markers (2) =
-
T Cell Surface Markers (2) =
- CD4 =
- CD8 =
Therefore, if an adaptive immune response is triggered - Antigen presents to ____ cell -> which then activates appropriate ____ or ____ cell that is needed to fight that infection
Identify the lymphocyte and determine is function and specificity
- Igm and IgD: antibodies (looks like a Y) where the antigen binding site resides and tells you what pathogen this B cell is destined to fight
-
CD4 and CD8: Determines T lymphocyte Function
- Helper T cells -> helps Coordinate, regulate, and control all adaptive immune responses “general of the army”
- Is our Suppressor, Cytotoxic T cell which Kills abnormal cancer cells or virus infected host cells
CD4 cell -> activates B cell or CD8 T cell
The Thymus
Which cells are thymus derived?
Which cells are bone marrow derived?
T cells form in the bone marrow then migrate to thymus gland to mature “Thymus derived T cells”
B cells form and mature in the bone marrow
The Distribution of Lymphoid Tissues in the Body
- Lymphocytes arise from stem cells in the? And differentiate in the central lymphoid organs (2)
- They migrate from these tissues and are carried in the bloodstream to the peripheral or secondary lymphoid organs (5)
- The peripheral lymphoid organs are the sites of lymphocyte _____ by antigen, and lymphocytes recirculate between the blood and these organs until they encounter specific antigens.
- T cells receive survival signals from ______ cells in the periphery, whereas the source of survival signals for B cells it thought to be in the lymphoid ______.
- Lymphatics drain extracellular fluid from the peripheral tissues, through the LN and into the _____ duct, which empties into the left _____ vein.
- This fluid, kown as lymph, carries _____ taken up by DCs and macrophages to the lymph nodes and recirculating lymphocytes from the LN back into the blood.
- Lymphoid tissue is also associated with other muchosa such as ____ lining (not shown in pic)
- Bone Marrow -> Bone Marrow, Thymus
- LN, Spleen, Lymphoid Tissues asctd with Mucosa (Gut asctd Tonsils, Peyer’s patches, Apeendix)
- activation
- Dendritic, Follicles
- Thoracic, Subclavian
- antigens
- Bronchial
Organization of the Immune System (Notes)
2 Tissue Types
Definitions
- Lymphoid Tissue = any structure where lymphocytes form, mature, reside, and atc
- Reticular Tissue = Connective tissue, endothelial barriers, mucous membranes
Lymphoid Tissue
-
Primary Lymphoid Structures =
- (2)
-
Secondary Lymphoid Structures =
- Examples:
- Which are all _____ through lymphatic vessels
- Where B and T Lymphocytes are ______ (ie. we eat alot of pathogens so GI tract)
- As fluid passes through LN/everything -> it interacts with all of the lymphocytes so if you need to activate one of those lymphocytes, its going to get _____ there
- Structure where lymphocytes form, mature, or reside and act
- Bone Marrow, Thymus
- Where lymphocytes live and get activated
- Spleen, LN, Adenoids, Tonsils, Heart, Kidney, Appendix, Thoraci Duct, Skin, GI tract (Peyer’s patches), Resp tract etc
- connected
- Stored
- antigens get trapped
Reticular Endothelial Tissue
- Where (3) live
- Even lymph nodes contain connective tissue so LN also have _____ and _____ cells
- Tissue macrophages, Dendritic Cells, Mast Cells
- macrophages, dendritic cells
Overview of the Immune System
- Pathogens gain entry how?
- Pathogen is detected how?
- Phagocytic cells intiate an _______ response (more phagocytic cells are ____ to the area)
- Phagocytic cells _____ antigen to ______ cell, how?
- T helper cell intiates an _______ immune response
- Activates (1) OR (1)
- Encountering or Breaking Epithelial Barrier
- Pathogen is detected by
- Tissue phagocytic cells (macrophages/dendritic cells)
- Peripheral lymphoid tissue phagocytic cells (via lymph fluid)
- Spleen phagocytic cells (via blood)
- By circulating B lymphocytes
- Inflammatory, recruited
- Present antigen to Helper T cell
- Directly in lymphoid tissue/spleen
- Phagocytic cell migrates to lymphoid tissue
- Adaptive
- Cytotoxic T cells OR B lymphocytes
Different Groups of WBCs, Where they are formed and live out their days
(5)
Macrophages, Dendritic Cells, Mast Cells
Neutrophils, Eosinophils, Basophils
T Lymphocytes (Pre + Mature “Naive”)
B Lymphocytes (Mature “Naive”)
NK Lymphocytes
Tissue Macrophages, Dendritic Cells, and Mast Cells
Formed where?
Live where?
Bone marrow and enter circulation early in development and migrate to these potential sites of infection
Skin, Brain, Liver, LN, Spleen, MALT, Respiratory Tract, Gut, Thymus, and others
Neutrophils, Eosinophils, and Basophils
Formed where? Live where?
Constantly produced by bone marrow throughout our lives and enter circulation where they live out their days in the circulation and get replaced by new cells
T Lymphocytes
Formed where? Live where?
Pre T lymphocytes formed in bone marrow -> migrate to thymus to mature, get their CD4 or CD8 marker and T cell receptor and leave thymus gland into blood stream - but are called naive T lymphocytes bc never encountered the pathogen they are programmed to fight
In circulation briefly then migrate to secondary lymphoid tissue where they live out their days
B Lymphocytes
Form where? Live where?
Unique Characteristic =
B cells form and mature in the bone marrow where they get their B cell receptor and surface markers -> leave bone marrow and enter circulation as mature but again naive B lymphocytes where they again migrate to secondary lymphoid tissue and live out their days
More constantly produced than T lymphocytes so when they migrate to secondary lymphoid tissue will occasionally encounter the pathogen they are programmed tof ight (“meeting your soulmate in preschool”) - not the most common way but does happen
NK Lymphocytes
Form where? Live where?
NK lymphocytes form and mature in bone marrow
Leave bone marrow and occupy 2 spaces
- Mature NK cells in circulation
- Mature NK cells in secondary lymphoid tissue
Again will fight viral infections in a nonspecific way
Overview of the Immune System
- Pathogens gain entry how?
- Pathogen is detected how?
- Phagocytic cells intiate an _______ response (more phagocytic cells are ____ to the area)
- Phagocytic cells _____ antigen to ______ cell, how?
- T helper cell intiates an _______ immune response
- Activates (1) OR (1)
- Encountering or Breaking Epithelial Barrier
- Pathogen is detected by
- Tissue phagocytic cells (macrophages/dendritic cells)
- Peripheral lymphoid tissue phagocytic cells (via lymph fluid)
- Spleen phagocytic cells (via blood)
- By circulating B lymphocytes
- Inflammatory, recruited
- Present antigen to Helper T cell
- Directly in lymphoid tissue/spleen
- Phagocytic cell migrates to lymphoid tissue
- Adaptive
- Cytotoxic T cells OR B lymphocytes
- Phagocytic cell takes that antigen in and go finds a helper*
- T cell to initiate adaptive immune response*
Secondary Lymphoid Structures
= Where B and T cells ____ and get ______ makes lots of ____ of itself and initiates an attack on the pathogen
- First experience with pathogen -> immune attack will be a bit ____
- Subsequent encounters -> attack will be very _____
live and get activated, copies
- sluggish
- fast
Lymph Nodes
- Found throughout the body at ______ points on lymphatic vessels
- Every LN has an a_____, v____ and _____ vessels that carry lymph fluid into and ____ vessels carrying lymph fluid out (and fluid has to pass through all of the tissue of the node itself)
Zones of the LN
- Medullary Cords (red) =
- Paracortical Area (blue) =
- Primary Lymphoid follicle (white) =
- Germinal Centers (yellow) =
- bifurcation
- artery, vein, afferent, efferent
- packed with macrophages + dendritic cells
- mostly T cells
- mostly B cells
- where cells that are activated enter and start replicating (ex. T or B cell will replicate in these centers)
Spleen
- Similar makeup as __
- Blue is __ cell area, Yellow is __ cell area, and Germinal center where cells are ______
Types of Tissue
- Red pulp =
- White pulp =
- LN
- T cell, B cell, replicating
- part of spleen that traps and processes rbcs
- lymphatic tissue located between artery that perfuses spleen and blood that drains away from spleen (so blood has to pass through white pulp)
Peyer’s Patches in Small Intestine
Similar makeup again, T cell area, _____ B cell area, and Germinal Center
follicle
Molecular Communication in the Immune System
Cytokines =
Pro-Inflammatory Mediators (3)
-
One way Cytokines are used to create a response
- What are the cells that live in our bloodstream? and they are all ______ = constantly produced by bone marrow
- During a bacterial infection, what do cytokines do?
Cell derived chemical mediators responsible for communication between immune cells (Cyto means cell)
IL1, IL6, TNF Alpha
- Cytokines
- Neutrophils, Eosinophils, Basophils, Monocytes - INDUCIBLE
- Act on bone marrow to trigger increased production of neutrophils
Ex) injured cell releases cytokines that will trigger mast cells to begin inflammatory process or when body has ongoing infection, cytokines communicate with bone marrow to trigger increase wbc production (pretty much anything going on the immune system going to be signaled and responded to by release of cytokines)
Routes of Infection for Pathogens
1st Line of Defense
- Mucosal Surfaces
-
- External Epithelial
-
- *
- Mucosal Surfaces
- Airway (flu)
- GI tract (contaminated food and water salmonella)
- Reproductive tract (HIV)
- External Epithelia
- External surface (Physical contact ie Athletes foot)
- Wounds and Abrasians
- Insect Bites (Vector that gets it across the epithelial like instects that inject ie Ticks)
Frontline of Defense: Barriers
(3)
Examples of each (3) (5) (1)
- Mechanical Barriers
- Tight Junctions
- Flow of air or fluid across barriers to prevent lingering of pathogens
- Mucus and Cilia
- Chemical Barriers (reduce pathogenic microbial proliferation)
- Low pH in stomach
- Fatty Acids
- Digestive enzymes in stomach
- Lysozyme (salivary enzymes) in saliva
- Antibacterial peptides
- Microbiome
- Natural flora and microorganisms that live in our body
Second Line of Defense
=
Steps
- Damaged tissue releases _____ increasing ____ flow to the area
- Histamines cause capillaries to _____, releasing ______ and _____ factors into the wound
- Phagocytes _____ bacteria, dead cells, and cellular debris
- _____ move out of the capillary to ____ the wounded area
Inflammation
- Histamines, blood
- leak, phagocytes, clotting
- Engulf
- Platelets, seal
Inflammation Summary
I____ or _____ of a _____ triggers inflammation (how?)
- Injured tissue releases ______ that activate ______
- Injury activates ____ Cells which release?
- Macrophages detect/_____ pathogen then release?
- Activated ______ stimulate _____ cells to release?
- ________
- Vasodilation, Increased permeability (redness, heat, edema), Delayed Vascular Stasis
- _____ ______
- Chemotaxic migration of leukocytes to area
- ______ of ______
- Pathogens phagocytized or destroyed via ________ killing
- Phagocytic cells carry ____ through ____ fluid to the nearest?
Injury or Presence of a Pathogen
- cytokines -> macrophages
- Mast cells -> pro-inflammatory mediators
- ingests -> pro-inflammatory mediators
- Macrophages -> Mast Cells -> pro-inflammatory mediators
- Vascular
- Cell Migration
- Attack of Pathogens
- extracellular
- antigen -> lymph -> lymph nodes
How Macrophages are Inflammatory Mediators
Activated Macrophage Secretes a range of Cytokines
Key ones to focus on are? and their functions?
- 3.
- IL1 = activates mast cells
- TNF alpha = causes vasodilation and increased capillary permeability
- IL6 = important for the systemic inflammatory response
Things that Activate Mast Cells
(4)
- Injury
- Interleukin 1 (coming from macrophage or straight from injured cells)
- IgE (allergies)
- Complement Proteins (C3a and C5a)
2 Things that Happen When we activate Mast Cells
(2)
Definitions
- Degranulation: Immediate response - of all the mast cell’s secretory granules, it releases all of the stuff in its granules (an immediate response)
-
Synthesis of Leukotrienes and Prostaglandins: Long term response - make the inflammatory response painful (prostaglandins)
- vascular effects -> increased permeability -> exudation
Degranulation
What is secreted? and what are their effects?
(3)
- Histamine -> Vascular effects -> dilation, increased permeability -> exudation (potent vasodilator to increase permeability)
- Neutrophil chemotactic factor -> attracts neutrophils to site -> phagocytosis
- Eosinophil chemotactic factor -> attracts eosinophils
Vascular Events Location
Where do vascular events during inflammation happen?
Flow of blood?
_____ surrounds capillary bed
Microcirculation: capillaries, arterioles, venules
Arterioles -> capillary beds -> Drains into venules
Tissue
Events of Transmigration
(3)
Migration to site
Adhesion
Transmigration
General Cell-derived Chemical Mediators Table
(Use as reference guide)
2 inflammatory mediators that cause the most damage (2)
2 major cells that release these are? (2)
- Reactive Oxygen Species
- Lysosomal enzymes
Neutrophils and macrophages
Cytokines (3)
Plasma Protein System (3)
Specific Pathways for Complement Activation
(3)
All three pathways will activate (1) critical step that will activate the whole cascade
- Classic Pathway
- MB-Lectin Pathway
- Alternate Pathway
C3
Classic Pathway
The only pathway we knew for a very long time
Involves the activation of the ____ complement protein C_ by
- Binding ______ to the pathogen
- Binding to a _______ (2)
- Binding to an ______
first complement protein C1
- Directly binding to the pathogen surface by encountering it in the bloodstream
- Binding to a protein (CRP, MBL) - proteins produced by liver during systemic inflammatory response, go off and try to bind to any pathogens in circulation, make activation of C1 easier) already attached to pathogen’s surface
- Binding to an antibody attached to the pathogen (so your body mounts an adaptive immune response against the pathogen and produces antibodies that attracts C1
- Main takeaway, back to last slide on ways to activate complement
- Presence of pathogen can activate complement bc can directly bind to complement proteins
- As part of systemic inflammatory response bc CRP and MBL make it easier
- As part of adaptive immune response bc the antibody attached to pathogen can activate it
MB Lectin Pathway
=
Involves MBL attaching to pathogen surface and activation of proteins farther down in complement cascade (similar to MBL involved in activating C1 just activating other complement proteins)
Alternate Pathway
=
Involves direct activation by binding of C3 to pathogen surface
The Kinin System
- Activated Clotting Factor ____ synthesizes
- _________ which converts ______ to _____
- Kinins then have 4 effects =
- Factor XII (XIIa)
- Kalikrein, Kinongens -> Kinins (Bradykinin)
- 4 effects
- Stimulate complement system
- Promote localized vasodilation and increased capillary permeability
- Activate pain receptors (along with prostaglandins)
- Act as chemotaxins - to draw more neutrophils and macrophages to the area
The Kinin System (Notes)
Another plasma protein system that intersects with the clotting system
- Activated by ______ and potentiates inflammation by producing more inflammatory _____
- Inflammation -> _____ arrive and release _____ -> triggers blood ____ and convert inactivated kininogens to active Kinins
- Kallikrein =
- Kinins =
- (2) both cause the pain asctd with inflammation
- Bradykinin also produces?
- inflammation -> mediators
- neutrophils, Kallikrein -> blood clots
- activated form of factor 12 which is the first protein in the clotting cascade
- (similar in structure to bradykinin)
- Bradykinin and Prostaglandins
- Secondary area of pain (that’s larger than the primary area ie skin around a cut also tender - zone of pain that protects against maniupulation of the damaged part) allodynia
The Clotting Cascade
3rd Plasma Protein system
- Intrisic Pathway = damage to?
- Extrinsic Pathway = damage to?
- Starts with activation of?
- Wherever you start, end point is a single reaction of inactive _____ to active _____ -> which converts ______ (individual strings of spaghetti) to ______ (spaghetti clumps)
- What does fibrin do?
- What does thrombin do?
- Blood vessels
- Tissues (outside vessels)
-
Kallikrein (Factor 12)
- Prothrombin -> Thrombin, Fibrinogen -> Fibrin
- Traps rbc and wbc to create Bloot clots
- Form the clot and enhances inflammation via Protease activated receptor-> edema
What is this a picture of?
Interconnected FIBRIN that creates meshwork - to suspend rbc’s and other blood born cells to turn blood from liquid to gel like state
Leukotrienes and Prostaglandins
Role in Inflammation =
Biosynthesis of Leukotrienes and Prostaglandins
- Arachidonic Acid =
- Arachidonic Acid interacts with either
- 2 forms of ______ to produce ______
- 2 forms of ______ to produce ______
Inflammatory mediators that are produced by all types of cells (when damaged)
- Substance that all forms of leukotrienes and prostaglandins are derived from and is produced by our cell membrane phospholipids
- interacts with
- Cyclooxygenase -> Prostaglandins
- Lipoxygenase -> Leukotrienes
Few Tools to Reduce Inflammation
What are 2 major ones and how do they work?
Steroids: most potent anti-inflammatory durgs that act by blocking phospholipase - synthesis of arachidonic acid -> blocks leukotrienes and prostaglandins…however have so many SE
NSAIDs (aspirin, indomethacin): block cyclooxygenase (COX1 and COX2) however also have so many SE (ulcers/bleeding)
Interactions of Some Inflammatory Mediators
No need to memorize - just shows the events of inflammation is all ______
No matter who starts the inflammatory response -> it all potentiates very ___
interconnected
quickly
Systemic Inflammatory Response (Acute Phase Response)
- Example Respiratory Infection
- Triggers local inflammatory response
- As infection gets larger, size of inflammatory response gets larger and larger - release of 3 key cytokines (3)
- Once their _____ become high enough start to do what?
- IL1, IL6, TNF alpha
- concentrations become high enough start to bind to distant receptors and trigger systemic effects
Targets of IL1, IL6, TNF alpha
(5)
Effects
- Hypothalamus: our body’s thermostat -> cytokines will raise temp and induce fever (decreases changes of viral/bacterial replication) + sickness behavior (fatigue, malaise - which is protective bc forces you to rest)
- Bone Marrow: increase production of wbcs
- Fat and Muscle: increase breakdown of protein and fat to increase body temp and feed fever (why we feel achy)
- Dendritic Cells: to migrate to nearest LN -> bc if dendritic cell has trapped that pathogen will initiate adaptive immune response ASAP
-
Liver: increase production of acute phase response proteins (which help trigger complement system to attack pathogens)
- CRP (C reactive protein), MBL (mannose binding lectin)
Sepsis
= presence of bacteria in the ______ (bacteremia) - an exaggerated _____ inflammatory response and activation of innate immunity
- When bacteria exit tissue and interact with targets in the bloodstream -> activates a large immune response (_ _ _ _)
- LPS = lipopolysaccharides which are part of bacteria cell ____
bacteria in bloodstream, exaggerated systemic inflammatory response
- SIRS
- wall
Sepsis
Activation of (4)
- Endothelium (inner lining of blood vessels): triggers inflammation and coagulation when interacting with bacteria and LPS
- Circulating Neutrophils: will release free radicals, cytokines, and trigger inflammation in circulation
- Circulating Monocytes
- Complement System
Sepsis Effects
_ _ _
(4)
DIC
Hemorrhage dt running out of clotting factors (most often intracerebral or GI bleed)
- Coagulation
- Fever
- Systemic Vasodilation (drop of BP and shock)
- Capillary Leak -> decreased perfusion to organs -> organ failure -> more tissue injury -> more inflammation (potentiating vicious cycle)
Responses to Viral Infection
Infected cell detects ____ stranded RNA ->
Host cell releases (2) ->
- Host cell produced ____ that ____ viral RNA and block production of viral protein
- Host cell increases production of _____ (better _____ _____)
- Activates ___ cells -> which then ____ virus infected cells and releases (1) which potentiates the effects of interferon a and B
- these cells can also be activated by (1)
double stranded RNA
Interferon a and B
- enzymes, degrade
- MHC1 (better antigen presentation)
- NK cells -> Kills, Interferon y
- Macrophage-derived cytokines
Interferons (Notes)
Important for ____ attack of virus infected cells
- Double stranded RNA is ____ found in our genes but is common component of _____ cycle of viruses so our first clue that we are infected is the host cell detects double stranded RNA -> release of interferon alpha and beta
- Activates ___ cells to kill virus in infected cell
- White its waiting for NK cells it does (2) things
- NK cells also release interferon y (gamma) to?
- How does the NK cell recognize that this is an infected cell?
- Can NK cells eradicate the virus completely?
Innate
- never, replication
- NK cells
- host cell produces enzymes that degrades viral RNA and increases production of MHC1 for better antigen presentation
- potentiate effects of interfern alpha and beta
- MHC1 helps it recognize that this is a host cell and the viral antigen attached to the MHC1 helps NK cell recognize that its infected
- NO, NK cells stem the rise in viral rapid replication and make it plateau to hold it at a particular replication rate, buys enough time for CD8-T cells to come in and eradicate the virus completely
Outcomes of Acute Inflammatory Response
(3)
Resolution
Fibrosis +/- Abscess
Chronic Inflammation
Resolution
- Clearance of (3)
- _______ of injured cells
- Function?
- injurous stimuli, mediators, and acute inflammatory cells
- Replacement
- Returns to normal
Undergoes healing that replaces injured cells -> tissue looks like nothing ever happened, is IDEAL, completely healed and normal function restored
Fibrosis
=
Abscess
=
Loss of function, scar formation
When certain bacteria colonize the area and are difficult to clear, causes continuous cycle of recruitment and death of neutrophils - pus = dead neutrophils -> the abscess can eventually celar as well as cause a scar
Chronic Inflammation
Caused by?
What happens is? “_____ ______”
- A_____
- Mononuclear cell ____
- _____ (scar) and ____ of function
Persistent Injury: ie. viral infections, chronic/autoimmune infections, HTN, hyperglycemia dt DM, smoking, HLD
“Frustrated Repair”: Active inflammation and Attempted healing occurs simultaneously
- Angiogenesis
- infiltrates
- Fibrosis, loss of function
Fibrosis of skin is diff, but in chronic inflammation you can get fibrosis of artery walls -> athersclerosis
Two types of Healing
Primary Intention
Secondary Intention
- Minimal tissue loss, clean closely apposed wound edges
- Involves sealing (epithelialization) and wound shrinkage (contraction)
- More tissue damage - open wounds
- Involves more extensive and prolonged epithelialization, scar formation, and contraction
Healing by First vs. Second Intention
- First Intention
- Reconstruction phase:
- Maturation phase:
- Second Intention
- Reconstruction phase:
- Maturation phase:
- Neutrophils -> Macrophages that continue inflammation -> 2nd wave of macrophages that turn off inflammatory response triggers healing (reconstruction phase)
- Healing macrophages: release cytokines that cause tissue regeneration, healing
- Wound tightens up and mature
- Reconstruction phase takes longer with a larger wound (more susceptible to infection -> more likely to leave a true scar)
- Large amounts of granulation tissue and wound contraction
Another Flow Chart of Healing
Example of ______ -> chronically inflamed liver will cause _____ of liver (which is the definitionof cirrhosis) - and liver loses its ____ -> have to take away ___ before liver becomes fibrotic
Cirrhosis -> fibrosis -> loses function -> alc
What is the immune cell responsible for switching inflammatory response to a healing response?
By releasing what ____ factors
Macrophages
growth factors
In chronic inflammation macrophages are going to release both inflammatory and healing mediators -> frustrating both processes and resulting in fibrosis
Persistent recruitment to and/or immobilization of Macrophages at site will cause ____ sets of mediators to be released concurrently leading to “_____ _____“
both
“frustrated repair”
Persistent Stimulus (Chronic Inflammation)
Development of fibrosis in chronic inflammation. The persistent stimulus of chronic inflammation activates _____ and _____, leading to production of ____ factors and _____, which increases the synthesis of _____. Deposition of collagen is enhaced by decreased activity of m_______.
macrophages, lymphocytes -> growth factors,cytokines -> collagen, decreased activity of metalloproteinases = decreased collagen degradation
