Inflammation, Immunology and Stress Flashcards
(127 cards)
1
Q
Define Mediators
A
- facilitators which orchestrate the body’s responses
- low molecular weight proteins which are secreted by one cell for the purpose of altering either its own functions or those of other cells
- act as messangers
- activated with the onset of injury, invasion and/or stress
2
Q
What are the three main mediator categories?
A
cytokines, lymphokines, and monokines
3
Q
Where are cytokines released from and what are some examples?
A
- released from granulocytes (neutrophils, basophils, and eosinophils)
- histamine, serotonin, heparin, chemotactic factors, tumour necrosis factor, interleukins, and leukotrienes
4
Q
Where are lymphokines released and what are some examples?
A
- released from lymphocytes (b-cells and t-cells)
- tumour necrosis factor, interleukins, interferons, and chemotactic factors
5
Q
Where are monokines released and what are some examples?
A
- released from monocytes and macrophages
- interleukins, tumour necrosis factor, interferons, and chemotactic factors
6
Q
What are the common characteristics of mediators?
A
- regulate the amplitude and duration of inflammation, immune, and stress responses
- initiate their actions by binding to specific surface receptors on the target cell which then leads to a change in RNA and protein synthesis which alters it’s behaviour
- act on nearby cells of many types
- multiple physiological actions on the target cell, but can also have functional redundancy with other cells
- act as growth factors of cell division
7
Q
What are mediators dependent on?
A
- local concentration
- type of cell
- other cell regulators to which the target cell is being exposed to at the same time
8
Q
What are some cell-derived sources of mediators?
A
- tissue macrophages
- tissue mast cells
- platelets
- leukocytes (neutrophils, eosinophils, basophils, and monocytes)
- damaged cells and/or endotoxins
9
Q
Within the cell, where are mediators generated?
A
cellular lipids
intra-cytoplasmic granules
10
Q
How does injury/invasion affect the cell and what is generated by this process?
A
- causes disruption of the phospholipid bi-layer of the cell wall
- phospholipid metabolism geneartes the arachidonic acid cascade which leads to either the cyclooxygenase and lipoxygenase pathways
11
Q
What are some examples of cells containing granules?
A
- mast cells
- macrophages
- platelets
- vascular endothelial cells
- granulocytes (neutrophils, eosinophils, basophils)
12
Q
Why is degranulation important in the inflammatory response?
A
- degranulation (releasing granules into the tissue and vascular space)
- a key factor for releasing or making mediators available to initiate, promote, or control the inflammation response
13
Q
Plasma derived mediators
A
- normally circulate in the plasma in an inactive form
- primarily includes components of the three plasma protein systems: coagulation, kinin, and complement system
- triggered by the Hageman Factor and complement components
14
Q
What is meant by activation of a cascade?
A
-a series of reactions which occur in a sequential manner -responding in a cascade manner ensures a more sustained inflammation response
15
Q
What are the main physiological actions of the three plasma protein systems?
A
- vascular changes of vasodilation and increased permeability
- cellular activation, such as chemotaxis
- clot formation
- chemical stimulation of nerve endings (pain)
- destruction of foreign cells and debris (cytolysis)
16
Q
Hageman Factor
A
- activates all three plasma protein systems
- activated by several substances, including damaged cell and leukocyte products, exposed collagen, damaged endothelial cells, plasmin, and endotoxin.
- stimulates the coagulation system through activation of the intrinsic pathway
- stimulates complement system through activation of C3
- stimulates kinin system through activation of pre-kallikrein
17
Q
What are the four main functions of the complement system?
A
- vasodilation, stimulated by anaphylatoxins
- chemotaxis, especially for phagocytes
- opsonization (tagging, coating, binding) of substances to enhance phagocytosis, components are opsonin
- direct lysis of target cells due to the activity of membrane attack complexes (MACs)
18
Q
What activates the complement system and what are the two pathways?
A
- activated by hageman factor, antigen-antibody complexes, substances released from bacteria, such as endotoxin, and components of other plasma protein systems
- the classical pathway is activated by antibodies bound to specific antigens which activate C1
- the alternate pathway is acticvated by non-specific triggers, such as substances released from damaged cells and/or bacteria
19
Q
C3
A
- split into two fragments C3a and C3b by either classical or alternative pathways
- causes the release of C5a or C5b fragments from C5
20
Q
vasodilation
A
- due to anaphylatoxins, C3a and C5a
- induces mast cell degranulation, releasing mediators, such as histamine, which cause vasodilation and increased vascular permeability
- important to enhance the inflammation response
- increases nutrient delivery (oxygen, glucose, amino acids) and cellular access (neutrophils, monocytes, fibroblasts and platelets)
21
Q
chemotactants
A
C3a, C5a, and C567 attract neutrophils and monocytes/macrophages to the site for phagocytosis
22
Q
opsonization
A
- enhances phagocytosis
- bind or coat the target cell which tags the cell for destruction by phagocytosis
23
Q
cytolysis
A
- due to the formation and activity of MACs which destroy target cells, especially bacteria
- disrupt the outer membrane o the cell by drilling holes into the membrane, causing an influx of water and substances into the cell, destroying it
24
Q
Kinin system
A
- role not fully identified -produces bradykinin (an important mediator in the inflammatory response)
- also activates the complement and coagulation systems
25
Bradykinin
-three main actions include vascular changes (vasodilation and increased permeability), stimulation of peripheral nerve endings to cause pain, and probably neutrophil chemotactant
26
Clotting system
- activating factors usually circulate in an inactive form and require a stimulus to be activated
- intrinsic and extrinsic pathways, both converge into a common pathway to form a clot
- when vascular injury occurs the subendothelial structures are exposed to flowing blood. platelets adhere to the injured vessel site and to each other to form a hemostatic plug. Platelets are attracted to injured vessel walls which then cause platelets to change in shape from disks to spiny spheres, thus exposing surface receptors. vonWillebrand factor acts in bridging platelets to the injured vessel wall by binding to platelet receptors and the exposed collagen of the vessel. The platelet plug is formed.
27
What are the steps involved in hemostasis?
- platelet adherence and aggregation, forming a platelet plug
- activation of the intrinsic and extrinsic coagulation pathways
- conversion of fibrinogen to fibrin to form a stable clot
- fibrinolysis
28
Intrinsic pathway
- activated by circulating Hageman factor with damaged endothelial surface or any type of abnormal surface within the vascular system
- converges to form the common, final pathway when activated by factor X
29
Extrinsic pathways
- activated by factor III (tissue thromboplastin) released from damaged tissues or endothelium, when blood is exposed to tissue/cell debris
- converges to form the common, final pathway when activated by factor X
30
Final Clotting Pathway
- both intrinsic and extrinsic pathways converge resulting in the thrombin
- induced formation of a stable fibrin clot.
- factor X, calcium, factor V and platelets combine to form prothrombin activator complex (PAC) which converts prothrombin into thrombin.
- thrombin converts fibrinogen into fibrin and also acts with activated factor XIII to stabilize the fibrin clot
31
Activated Factor XIII
- crosslinks fibrin to firbonectin which crosslinks to collagen; binding the insoluble, stable fibrin clot to the collagen surface
- the strands of fibrin intertwine, forming a meshwork surrounding the platelet plug.
- this meshwork creates an insoluble fibrin clot to achieve secondary hemostasis
32
What are the effects of coagulation?
- preventing spread of infection and inflammation to adjacent tissues by keeping microorganisms/antigens at the site of greatest phagocytosis
- controlling bleeding by forming an insoluble, stable fibrin clot
- restoring patency of the blood vessels
- providing a framework for tissue healing and repair
33
What are the 12 Clotting Factors?
I - fibrinogen
II - prothrombin
III - tissue thromboplastin
IV - calcium
V - proaccelerin or accelerator globulin
VII - serum prothrombin conversion accelerator
VIII - anti-hemophilic factor
IX - plasma thromboplastin component
X - Stuart-Prower factor
XI - plasma thromboplastin antecedent
XII - Hageman Factor
XIII - fibrin stabilizing factor
34
Vitamin K
- essential for synthesis of these liver-derived coagulation factors
- not directly involved in clot formation
- liver requires vit. K to synthesize prothrombin, factors VII, IX, and X
- also required to help create strong calcium binding sites on their surfaces
35
Plasminogen
- activates fibrinolysis
- activated by tissue plasminogen activator (TPA released from the vascular endothelial cells in response to thrombin), urokinase (released from vascular endothelial cells and activated by macrophages), Hageman factor, factor XI, kallikrein, and thrombin, as well as lysosomal enzymes
- forms a loose bond with fibrinogen, then a tight bond with fibrin. The affinity of plasminogen for fibrin helps to localize fibrinolysis to the fibrin surface.
36
Plasmin
- breaks apart the bonds in fibrin and splits the fibrin clot to smaller, soluble fibrin degredation products or fibrin split products
- can dissolve large or small clots depending on the size of the blood vessel
- rapidly activated by alpha-2 plasmin inhibitor which limits fibrinolysis
- synthesized in the endothelium and liver
37
Fibrinolysis
- a slow process, continuing over a period of several days depending on the size of the clot; normal clot lysis occurs within 7 days of clot formation
- allows slow clearing of extraneous blood in the tissues and may re-open clotted vessels
- is normal controlled by natural regulation mechanisms
- overactivation or malfunction results in clotting and bleeding disorders
38
The action of clotting factors is balanced by the action of normal, natural anticoagulants such as:
- heparin (antithrombin II) which exerts its effects on several steps of the coagulation cascade. It inactivates coagulation factors and neutralizes thrombin
- antithrombin III which inactivates thrombin and prevents its action on fibrinogen
39
Define the inflammation response
- immediate, nonspecific response to any type of injury in vascularized (living) tissue
- normal, expected, and predictable physiological response
- does not occur in non-vascularized or necrotic tissue, however it would still be present in the surrounding tissue that is still living
40
What are the differences between acute and chronic inflammation?
Acute occurs within seconds of injury and continues until the threat of the body is eliminated. This response is normally self-limiting, lasting 8-10 days from the time of injury until healing occurs. Chronic inflammation persists for more than 2-3 weeks. May be due to an extension of acute inflammation, prolonged healing of acute inflammation, or persistence of causative antigens
41
What are the goals of the inflammation response?
- facilitate prompt movement of nutrients and cells to the site of injury to promote would healing and restoration of homeostasis
- prevent/protect against invasion of mircoorganisms
- limit the extent of the injury
- remove cellular debris
- minimize bleeding -prepare tissue for healing
42
What is the purpose of microvascular permeability in the inflammation response?
- nutrient transport to tissue cells
- cellular access to tissue injury (diabedesis, chemotaxis)
43
What is the purpose of coagulation in the inflammation response?
- prevent/minimize blood loss
- isolate/wall off injury
44
What is the purpose of cellular activation and adhesion in the inflammation response?
- phagocytosis
- respiratory burst
- microdebridement
- host protection
- wound healing
- further mediator release
45
What are the cardinal signs of inflammation and what are their causes?
Heat/Warmth (calor) - increased blood flow and increased local cellular metabolism
Redness (rubor) - increased blood flow
Swelling (tumour) - increased blood flow and increased vascular permeability; these changes allow for egress of fluid out of the vascular space and infiltration of cells
Pain (dubor) - direct effects of mediators, such as prostaglandins, norepinephrine and bradykinin; stretching of sensory nerves from edema
Loss of function (functio laesa) - replacement of parenchymal tissue (such as damaged myocardium); reflexive disuse due to pain, mechanical changes, such as when a joint swells; too painful to move or unable to move it; or development of scar tissue which contracts as it matures
46
What are the three phases of the inflammation response?
Phase 1 - vascular response -injury/invasion and vasodilation and increased vascular permeability due to release of cellular chemicals and mediators
Phase 2 - enhancement and exudate - activation of plasma protein systems, activation of acute phase proteins, and adherence of leukocytes to walls of altered blood vessels
Phase 3 - repair and regeneration - tissue healing or repair
47
What are the responses to phase 1 of the inflammation response?
- mast cell degranulation
- release of mediators as a direct response to injury which initially cause vascular changes such as a brief, transient vasoconstriction followed by vasodilation and increased permeability.
- vasodilation increases blood flow to the site which increases hydrostatic pressure
- edema resulting from changes in permeability,
- increased temperature and redness at the site due to increased blood flow through dilated vessels
- pain due to increased edema in tissues and from direct stimulation of peripheral nerve endings from mediators
48
What are the responses to phase 2 of the inflammation response?
- hemostasis with platelet activation to minimize blood loss -enhance the inflammation response through actions of chemotaxis, opsonization, direct lysis, vascular changes, and pain.
- liver releases acute phase proteins in response to mediators
- chemotactic migration through blood vessel walls to inflammation site which promotes clearing of debris by phagocytosis and initiate antibody production
- formation of exudate
49
What are the responses to phase 3 of the inflammation response
- connective tissue cells migrate
- connective tissue cells proliferate for healing by either regeneration or repair
50
What are the cellular components of the inflammatory response?
mast cells
neutrophils
macrophages
eosinophils
basophils
platelets
endothelium
fibroblasts
lymphocytes
51
What are the mediators of the inflammatory system?
interleukins
tumour necrosis factor
arachidonic acid metabolites
platelet activating factor
histamine
serotonin
52
Describe how vasoconstriction plays a role in the inflammation response
- a brief, transient period of vasoconstriction, (seconds to minutes)
- slows blood flow and promotes formation of a platelet plug to minimize blood loss
- mast cells release histamine, serotonin, and prostaglandins
- SNS triggers local release of norepinephrine
- endothelial cells release histamine, serotonin, and prostaglandin
53
What promotes vasodilation in the inflammatory response? Why is this significant?
- histamine
- prostacyclin
- serotonin
- bradykinin
- plasma activating factor
- leukotrienes
- nitric oxide
- tumour necrosis factor
- vasodilation increases blood flow thus facilitating movement of fluid, nutrients, and cells to the injury site. Vasodilation contributes significantly to each of the cardinal signs.
54
What are primary and secondary hemostasis?
primary hemostasis - activation and adherence of platelets to the injured vascular wall
secondary hemostasis - coagulation to form a stable fibrin clot.
55
Platelets
- adhere to injured tissue, altered endothelial cells, and each other to form platelet aggregates (plugs)
- limit the extent of the injury
- minimize blood loss
- release mediators
- first need to be activated (occurs within seconds of injury)
- upon activation, platelets swell, change shape, and become sticky which changes the platelet's surface receptors to increase surface area
- adhesion is enhanced by vonWillebrand Factor which activates Hageman factor
- once adhered, platelets degranulate and release mediators which promote activation, adherence, and aggregation of additional platelets to form a platelet plug or augment vasodilation and increase permeability
- the two main inhibitory mediators of platelet aggregation are prostacyclin and nitric oxide
56
Neutrophils
- granulocytes
- must be activated
- have a short life-span
- appear rapidly in large quantities at the site
- are the first leukocyte to arrive at the sit of injury, peaking within 6 hours
- are the dominant phagocyte for the first 24-48hrs
- respond very well to chemotactants released from mast cells and complement components
- release mediators such as arachidonic acid metabolites, interleukins, and plasminogen activating factor
57
Macrophages
- agranulocytes
- must be activated
- are powerful, non-specific phagocytes especially against microorganisms and cellular debris, including dead leukocytes
- have a longer life-span than neutrophils
- arrive later than neutrophils to the site of injury, peak about 24-72 hours
- respond well to chemotactants
- reside in tissue
- one of the key activators of inflammation
- release mediators such as arachindonic acid metabolites, interleukin, and tumour necrosis factor
58
What is involved in the process in which leukocytes move from the vascular to the extravascular space and consequently to the site of injury?
- activation
- margination (pavementing) ]
- adhesion
- diapedesis
- chemotaxis
- ameboid motion
59
Adhesion allows leukocytes to:
- stop flowing in the central (axial) stream and move, accumulate, and adhere to enothelial cells
- squeeze (diapedesis) through retracted endothelial cells (increased permeability)
- move (ameboid motion using pseudopods) through tissue towards the site of injury
60
Chemotaxis
Chemotactants (mediators released by damaged cells) call leukocytes to the site of injury via chemotaxis. It is a nonrandom or controlled movement of leukocytes toward the site of inflammation orchestrated by mediators
61
What are the main physiological events of Inflammation Phase II: Enhancement and Exudation?
- phagocytosis by neutrophils
- arrival of the monocytes and differentiation into macrophages
- arrival of basophils and eosinophils
- formation of exudate
- migration of connective tissue cells into the injury site
62
Phagocytosis
- the process of engulfment and destruction of microorganisms, foreign cells, and cellular debris by phagocytic leukocytes
- is the same for all phagocytes
- occurs at the site of inflammation (in the tissue or in the circulation)
- has both oxygen-dependent and independent 'killing' mechanisms
- occurs in three phases: attachment (recognition), ingestion, and digestion.
63
Lysosomal Enzymes
- released when neutrophils die and rupture
- enhances the inflammation response
- stimulates the arachidonic acid cascade, releasing mediators
- releases proteases, such as collagenase and elastase, which active the plasma protein systems
- acting as chemotactants for more neutrophils and macrophages.
- dead neutrophils and complement fragments attract monocytes to the site, enhancing inflammation
- digested by macrophages
64
Leukotrienes
- metabolite of arachidonic acid
- attract and activate more phagocytes to the injury site to participate in phagocytosis and promote healing
65
Three phases of phagocytosis
1 - attachment (recognition) phase
2 - ingestion
3 - digestion
66
Opsonization
- produces a strong bond between the phagocyte and target cell
- enhances the ability of phagocytes to recognize and adhere to it
- surface receptor sites specific to opsonins
- main opsonins for inflammation are C3b, fibronectin, and tissue necrosis factor
67
Ingestion phase
- once attached, the phagocyte engulfs the cell
- small pseudopods extend from the phagocyte's plasma membrane which internalizes the target cell
- known as phagosome when completed
- fusion of the lysosomes of the phagocyte fuse with the phagosome causing degranulation of lysosomal contents into the phagosome, creating phagolysosome
68
Digestion phase
- the phagosolysosome is digested
- two types of mediators produced during phagocytosis: oxygen derived radicals and leukotrienes
69
Oxygen-derived radicals
- toxic oxygen metabolites
- oxygen free radicals
- when neutrophils are inactive, their metabolism is primarily anaerobic glycolysis.
- when neutrophils are activated, an enzyme complex is activated and metabolism is converted to aerobic metabolism causeing consumption of large amount of oxygen thus producing oxygen metabolites
- helpful in breaking down cellular debris during the ingestion phase
- ODRs and other non-oxygen dependent contents are then injected into the phagolysosome, where they perform their microbicidal activity
70
Monocytes
- arrive within 24hrs
- adhere to the endothelium and migrate into tissues
- upon migration into tissues they differentiate and mature in macrophages which can ingest up to several hundred times before they die.
- breaks the cell down into little fragments to be picked up by the leukocytes
- important in antigen processing and provides the link between the inflammation and immune responses
71
Eosinophils
- attracted by degranulation of mast cells due to eosinophil-chemotactic factors
- migrate slowly to the injury site, within 48hrs post-injury -slower movement
72
Basophils
- release hitamine, serotonin, leukotrienes, bradykinin, chemotactic factors and heparin.
- the release of heparin is helpful to restore microcirculation at the site of injury by preventing further clot formation
73
Formation of Exudate
- due to the actions of multiple mediators responsible for vasodilation and increased permeability which alters hydrostatic pressure so fluid and cells accumulate in the interstitial space
- the main functions: 1) dilutes toxins produced by damaged cells, 2) facilitates migration of plasma proteins including antibodies and leukocytes, 3) promotes removal of debris and toxins via epithelium channels or the lymphatics, 4) provides humidity which promotes healing, 5) provides a barrier to limit the extent of the injury, 6) contributes proteins for tissue repair
74
Which cells participate in Inflammation Phase III: Regeneration and Repair?
- neutrophils
- macrophages
- connective tissue cells (fibroblasts, myofibroblasts, and angioblasts)
- epithelial cells
75
Macrophages
-release growth factors which attract epithelial cells and vascular endothelial cells essential for healing by regenerations as well as fibroblast-activating factors for proliferation of fibroblasts used in healing of tissue by repair
76
Fibroblasts
-produce most of the numerous extracellular matrix componenets including fibronectin
77
Fibronectin
- an acute phase protein
- numerous functions with wound healing: most important are formation of a scaffold, provision of tensile strength, ability to glue other substances and cells together.
78
Collagen
- 13 different collagens including skin, bone, cartilage, blood vessels, old and early scar tissue, basement membranes
- form the fibrils in the interstitial space
- initially fibroblasts synthesize one type of collagen, mainly "young or immature" connective tissue, formed temporarily in the wound, and is replaced later by another type of collagen which provides tensile strength for all tissues
79
Myofibroblasts
- smooth muscle cells and fibroblasts
- contract like muscle cells
- secrete matrix substances like fibroblasts
- contraction of myofibroblasts which occurs within first few days reduces and holds the margins of tissue in close approximation
- enables proliferating epithelial cells to cover surface loss and restore integrity of surface epithelium
80
Angioblasts
- precursors of blood vessels
- proliferate like sprouts from the numerous small blood vessels at wound margins
- these sprouts appear 2 to 3 days after incision or injury and by about a week the injury site is permeated with newly formed blood vessels
81
Regeneration
- the growth of new cells that function like the original tissue
- only those cells capable of mitosis are able to regenerate: skin, mucous membranes, and epithelial lining of organs
- macrophages release growth-factors which stimulates cell division until the damaged tissue is replaced
82
Repair
- many vital tissues are not capable of mitosis such as myocardium, skeletal muscles and nerves.
- healing occurs in these areas by replacing the lost tissue with collagen
- normal structure and function are not completely restored
- consists of the reconstructive phase and the remodeling/maturation phase
83
Reconstructive phase
- begins about 3-4 days post-injury
- fibroblast proliferation
- collagen synthesis by fibroblasts
- formation of granulation tissue
- formation of scar tissue
84
Remodeling/maturation phase
- occurs about 2 weeks post injury
- the wound has about 25% of its former strength and function.
- scar contraction by myofibroblasts completed
- capillaries in scar tissue disappear and consequently the scar changes from pink to white
- repair facilitates closure of the wound
- at about 3 months post injury the scar tissue is about 75% as strong as the uninjured tissue it replaced
85
Antigens
- foreign proteins
- do not posess HLA of 'self cells'
- large size
- complex
- need to be present in sufficient amounts
86
Antibodies
- glycoproteins produced by plasma cells in response to a specific antigen
- plasma cells have the potential to synthesize thousands, even millions of antibodies
87
Primary Immune Response
first exposure of the host to a specific antigen
88
Secondary (Anamnestic) Immune Response
- the second and subsequent exposures of the host to the same antigen
- characterized by an accelerated and stronger response due to the formation of memory cells
89
Cell-mediated Immunity
- involves the activities of t-lymphocytes
- in order to recognize an antigen, t-cells need the antigen to be presented to them by macrophages
- t-cells bind to and directly destroy antigens by releasing mediators which regulate the activities of the immune response
- especially effective against intracellular viral and fungal invasions
90
Humoral Immunity
- involves the activities of B-lymphocytes and consequent synthesis of specific antibodies to specific antigens
- these bind to form antigen antibody complexes (immune complexes)
- the immune complexes stimulate direct and indirect actions to neutralize, eliminate, or destroy antigens
- mediated through antibodies
- the presence of t-cells and macrophages facilitate the transformation of b-cells into antibody-producing plasma cells
91
Summarize the immune response
- following contact with an antigen, macrophages phagocytize it
- after ingestion, the antigen is digested by macrophages
- during digestion antigen fragments are released and expressed onto macrophages
- macrophages carry and present expressed antigen to the t-cells
- causes the release of mediators which lead to proliferation and differentiation of both T and B-cells, producing cells capable of destroying the antigen
92
What are the goals of the immune response?
- defence against invading organisms
- homeostasis with degredation and removal of damaged cells/cellular debris
- surveillance with recognition and removal of mutant or abnormal (non-self) body cells
93
How are the goals of the immune response achieved?
- recognition and binding to specific antigens
- antigen processing and presentation by macrophages to T-cells
- proliferation and differentiation of t and b-cells
- direct destruction of antigens
- phagocytosis and stimulation of inflammation components
94
Triggers of the immune response
infectious:
- viruses
- bacteria
- fungi
- parasites
Non-infectious:
- physical or chemical trauma
- invasive surgeries
- bee or snake venom
- pollens
- foods
- medications
- vaccines
- transplanted tissue/organs
- transfusions
- myocardial infarction
- neoplasms
95
lymphocytes
- originate in stem cells in the bone marrow; maturing into two distinct cell types
- migrate to specific sites to mature into immunocompetent cells
- possess the abilities of memory and specificity, providing long-lasting protection
- have specific binding receptors for specific antigens
- interact with macrophages
- secrete mediators
- do not contain granules in their cytoplasm
- have different mechanisms to destroy antigens
- stored in lymph nodes and lymphoid tissues strategically located in the body
- have long lifespans
96
T-lymphocytes
- mature in the thymus gland to become immunocompetent
- responsible for cell mediated immunity
- production main function is regulating activities of the immune response
- must interact with macrophages to recognize and destroy antigens
- have specific antigen-binding receptors
- produce mediators such as interleukin2, 3, and 4, interferons, growth factors, chemotactic factors, and macrophage activating factors
- destroy antigens directly -five main subgroups for development and continuation of cell mediated immunity
- develop memory cells -protect primarily against intracellular viruses and fungi
97
B-lymphocytes
- mature in lymphoid tissue to become immunocompetent
- responsible for humoral immunity, major function is antibody
- do not have to interact with macrophage to destory antigen
- mature into Ig-producing plasma cells upon activation
- have specific antibody-binding receptors, forming immune complexes
- 5 major classes of Ig -develop memory cells -protects primarily against extracellular bacteria
98
What stimulates the release of mediators (primarily by t-cells) for the immune response?
- infection
- inflammation
- other mediators
- antibodies
- antigens
- activation of certain cells such as T4 cells
99
What are the major effects of mediators involved in the immune response?
- increasing the production of plasma membrane proteins which increases the number of mediator receptor sites on immune cells
- proliferation and differentiation of T and B cells
- recruitement, retainment, regulation, and activation of immune cells
100
Antibody Production
- known as immunoglobulins
- proteins produced by plasma cells in response to a specific antigen
- bind with the antigen, form immune complezes to destory the antigen
- circulate in small numbers complexes to destory the antigen
- circulate in small numbers throughout the body on surveillance for specific antigens
- five major classes, each has a distinct chemical structure and function -four steps: 1) contact and recognition, 2) antibody synthesis, 3) formation of immune complexes, 4) antibody functions
101
Contact and Recognition
- first step in the production of antibodies
- at first encounter, b-cells with membrane receptors matching the antigen's receptors are stimulated to proliferate and differentiate (specificity)
- t-helper cells can contact and recognize the antigen before the b-cell can proliferate and differentiate with the help of macrophages
- sensitization only occurs once, and delays the initial response as the lymphocyte is learning about one specific antigen
102
Antibody Synthesis
- immediately following the recognition process
- b-cells proliferate and differentiate into antibody producing plasma cells
- 5 major classes of immunoglobulins
- once produced immunoglobulins are released into the circulation and extracellular fluids
103
IgG
- major immunoglobulin in the body
- responsibly for most antibody functions such as neutralization, aggulination, opsonization, complement activation
- primary immunoglobulin with secondary response
104
IgM
- first antibody produced in primary immune response
- largest immunoglobulin with most binding sites
- activates complement cascade
- increased numbers indicated active infection
105
IgA
- secretory Ig found in 'watery' type body fluids/secretions
- may protect mucosal linings from digestive enzymes
- may activate complement system
- protects against non-specific antigens
106
IgD
- often found with IgM on the surface of b-lymphocytes
- function not fully understood
- does not activate complement system
107
IgE
- least amount
- major antibody in allergies and parasitic infections
- present on basophils and mast cells as they contain surface receptors for IgE which causes degranulation and thus the release of mediators such as histamine
108
What are the main antibody functions?
- toxin neutralization and precipitation
- viral neutralization and agglutination
- opsonization of bacteria which enhances phagocytosis
- activating components of the complement system for lysis of the antigen
109
How do memory cells accelerate the immune response?
-memory cells learn the process faster with each exposure
110
T4
- t helper cells
- largest cell
- stimulates activity of other t-cells
- very efficient in organizing antigens
- responsible for interactions with macrophages and b-cells
- recruit Tc to antigen sites
- assistance required for majority of Ig synthesis
- in response to antigen recognition, secretes mediators which promote proliferation and activity of all other immune cells such as MAF, interleukin 2, colony stimulating factor, interferon, and tumour necrosis factor
111
T8
- suppressor t-cells
- role in both inflammation and immune responses
- regulated CMI and HI
- secrete mediators, such as interferon, which suppresses the proliferation and actions of t and b-cells
- keeps immune response in check by preventing overreaction
- half as many as T4 cells
112
Tc
- cytotoxic t-cells
- responsible for CMI cell destruction through the production of mediators and cytolytic enzymes
- active against intracellular viruses, tumour and donor tissue
- may also be called Killer T cells
113
Memory T-cells
- cloned to remember the same antigen with a faster and stronger response with re-exposures
- cytotoxic effects
- may remain inactive/dormant for years
- induce secondary amnaesic responses
114
Td
- delayed hypersensitivity
- produce mediators such as macrophage activating factor, macrophage inhibition and aggregation factor to attract more macrophages to phagocytize antigens destroyed by Tc cells
- activated other cells
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NK cells
- similar killing mechanisms as Tc cells, so tend to be associated with T-cells, however not directly involved in CMI HI
- directly recognizes antigen; membranes intertwine and release lytic enzymes to destroy
- do not require sensitization to antigen
- release mediators such as interleukin, interferon, and tumour necrosis factor
- have nonspecific killing mechanisms for unhealthy or abnormal self-cells infect with viruses and tumour cells; conduct 'seek and destroy' missions
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What are the three main mechanisms that occur to localize and bring the antigen and lymphocyte together, initiating the immune response?
- direct recognition and contact between lymphocutes and antigen
- antigen recognition and processing by the macrophage
- activation of t-lymphocytes to release mediators which activate b-lymphocytes and other t-cells
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Define Stress
the individuals cognitive, physiological, and psychological response to a perceived situation
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Biological Response Model of Stress
- Hans Selye - "Father of Stress"
- defined stress and a nonspecific physiological (biological) response to any demand
- three physiological changes are 1) an enlarged adrenal cortex, 2) atrophy of the thymus gland and other lymphoid tissues, 3) GI ulceration
- three stages of stress (General Adaptive Syndrome) 1) alarm stage, 2) stage of resistance or adaptation, 3) stage of exhaustion
- three components of physiological stress: 1) stressor, 2) physiological or chemical changes produced by that stresor, 3) body's adaptational responses to the stressor
- assumptions: 1) all biological organisms want to maintain homeostasis, 2) any stressor (positive or negative) disrupts homeostasis and produces nonspecific physiological responses, 3) the stress response was the body's mechanism to meet and deal with the stressor
- does not account for human's psychological responses, individual differences, choices or perceptions.
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alarm stage
- begins with any stressor or demand (positive or negative)
- triggers the SNS and pituitary gland (which secrete ACTH and ADH)
- if unable to restore homeostasis, the body continues to try and restore balance and stage of resistance occurs
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stage of resistance
- continues after the body has failed to return to homeostasis after initiation of a stressor
- mobilization of defences through release of cortisol, epinephrine, and norepinephrine to maintain homeostasis
- resistance uses a tremendous amount of energy, thus decreases further or future resistance
- illness may occur, such as infections which further decreases body resistance
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stage of exhaustion
- results from severe, persistant, chronic stressors or demands which are sustained over prolonged periods of time
- adaptation and coping are unsuccessful
- energy reserves become further depleted impairing the immune response
- physical illness common
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Transactional Model of Stress
- Richard Lazarus -the current accepted theory
- stress is the individual's cognitive, physiological, and psychological response to a situation in which the person perceives that the demand exceeds the coping skills or resources to deal with the demand
- the greater the perceived imbalance between the demands and the resources, the greater the stress experienced by the individual
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Describe the basic pathway of stress
- all stressors are perceived and processed by the mind, or the complex network of neurologic structures and transmitters
- the message is relayed to the thalamus and then to the hypothalamus
- the hypothalamus then directs numerous hormonal responses in order for the person to adapt to stressors
- norepinephrine is immediately released from peripheral nerve endings and the adrenal medulla is stimulated to release epinephrine
- both of which facilitate the shunting of blood to vital organs and cause vasoconstriction
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Goals of the Stress Response
- preparation of the body to act
- increased blood volume to maintain cardiac output and function, increased oxygen consumption and delivery, increased blood pressure, and improved oxygenation
- provision of energy
- increased catabolism, metabolism, and mobilization of free fatty acids and glucose to provide necessary energy for cellular function -restoration of the body
- increases platelet activity and fibrinogen to prevent excess loss of blood and to initiate healing if injured in fight or flight response
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cortisol
- platelet production
- fibrinogen production
- fatty acids
- amino acids
- protein catabolism
- glucose
- glucogenesis
- immune response
- alters mood
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Triggers of the Stress Response
- biogenic - stimuli which directly trigger the physiological stress response without cognitive-processing (two common ones are infection and exercise)
- psychosocial - either real or perceived stimuli which do not directly trigger the physiological response.
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Factors that alter the perception and intensity of the stressor
- magnitude and duration of stressor
- the significant or meaning of the stressor to the individual
- cultural influences
- circadian rhythms
- sleep disturbances
- stage of development/age
- previous and/or concurrent stressors (previous experience may decrease impact of the stressor by highlighting coping skills or may decrease the ability to adapt (the 'straw that broke the camel's back')
- physiologic reserve - better adaptation if young, healthy
- genetic endowment - may endow improved resistance
- speed of event - easier to adapt to gradual change
- social networks - better adaptation with adequate social support
