Innate Immunity - Inflammation and Wound Healing Flashcards
1
Q
What is the body’s first line of defense ?
A
Innate Immunity (AKA natural/innate)
2
Q
Is it worse to have damage to a single cell or to multiple cells ?
A
Multiple cells - damage to a single cell can be easily repaired while damage at the level of multiple cells or tissues or organs can result in disease and potentially the death of the individual
3
Q
Innate immunity consists of what kind of barriers ?
A
Physical, biochemical, and mechanical barriers
4
Q
Innate immunity contains barriers and what other line of defense?
A
Inflammation
5
Q
Group of microorganisms within the body that can protect us from pathogens
A
Normal flora or Normal Microbiome
6
Q
If surface barriers are breached, The second line of defense is …………………
A
The inflammatory response
7
Q
The inflammatory response does what ?
A
It protects the body from further injury, prevents infection of the injured tissue and promotes healing
8
Q
What is the third line of the body’s defenses ?
A
adaptive Immunity
9
Q
Unique about adaptive immunity
A
It is a specific response - it is a relatively slower response but is targeted to the pathogen
it also involves memory
10
Q
When are the natural defenses of innate immunity in place ?
A
At birth
11
Q
What kind of cells provide the first line of defense as physical barriers ?
A
Tightly packed epithelial cells of the skin and of the linings of the gastrointestinal, genitourinary and respiratory tracts
12
Q
Epithelial cells secrete what kind of substances to aid in defense?
A
Mucus, saliva, sweat, tears and earwax
13
Q
Lysozyme
A
An enzyme contained in sweat, tears, and saliva
that attacks the cell walls of gram positive bacteria
14
Q
Microbes of the Normal Microbiome colonize what areas of our body ?
A
Skin, mucous membranes of our eyes, upper and lower Gi tracts, upper respiratory tract, urethra and vagina
15
Q
Benefits of Normal Microbiome
A
Produce enzymes that aid in digestion, produces usable metabolites such as vitamin K and vitamin B, defends against pathogens through antibacterial factors
16
Q
Danger of prolonged use of broad spectrum antibiotics
A
Can alter the normal microbiome, decreasing its protective activity and lead to an overgrowth of pathogenic microbes
17
Q
What are opportunistic microorganisms ?
A
Those that are normally a part of the normal microbiome but that can cause disease if the individuals defenses are compromised
18
Q
Inflammation is programmed to response to ………………..
A
cellular or tissue damage
19
Q
Is inflammation a specific or nonspecific response ?
A
Nonspecific
20
Q
Inflammatory response- where does it occur ?
A
In any tissues with a blood supply (vascularized)
21
Q
Is the inflammatory response rapid or slow ?
A
It is a rapid response
22
Q
The inflammatory response depends on what ?
A
Cellular and chemical components
23
Q
Signs of acute inflammation
A
Redness, swelling, pain, heat , loss of function
24
Q
Rubor
A
redness
25
Erythema
Redness
26
Steps of inflammation
1) Dilation of blood vessels and increased blood flow
2) Leakage of plasma proteins
3) Leukocyte (neutrophil) recruitment and migration
27
Dilation of blood vessels and increased blood flow leads to
erythema and warmth
28
Leakage of fluid from the vessels to the injured tissue area leads to ......................
edema of the area
29
What are the three plasma protein systems ? What are they essential for ?
The complement system, the clotting system and the kinin system. They are needed for an effective inflammatory response in order to contain and destroy bacteria
30
The complement cascade system consists of what ?
A large number of proteins that constitute about 10% of the total circulating serum protein
31
The cascade system activates _____ and ____________. This results in a variety of molecules that are ___________, _________________ or ________________
C3 and C5; opsonins; chemotactic factors; anaphylatoxins
32
How many different pathways can the complement system be activated by ?
3 - classical, alternative and leptin pathways
33
What is the clotting system ?
A group of plasma proteins that when activated sequentially form a blood clot
34
What is the final product of the kinin system ?
Bradykinin
35
What does Bradykinin do ?
Causes dilation of blood vessels, acts with prostaglandins to induce pain, causes smooth muscle cell contraction and increases vascular permeability
36
Physical barriers
Skin, GI, GU, respiratory tract
37
mechanical barriers
dead skin cells, coughing, sneezing, vomiting
38
Biochemical barriers
mucus, sweat, saliva and earwax
39
Inflammatory process is caused by
infection, tissue necrosis ,trauma, physical/chemical injury, ischemia
40
Adaptive immunity can be divided between
Cell mediated and Humoral mediated immunity
41
Difference between infection and inflammation
Inflammation is a response to tissue injury that aims to restore health and promote healing
Infection is a failure of inflammatory defenses and involves invasion of host tissues by disease causing agents, colonization and multiplication and the reaction of host tissues to organisms and the toxins they produce
42
Goals of Inflammatory process
Limit and control the inflammatory process
Prevent and limit infection and further damage
Initiate adaptive immune response - brings more macrophages and lymphocytes to the site of injury
Initiate healing
43
The plasma protein systems are __________
interdependent. Activation of one can activate the other
44
Granulocytes consist of
Neutrophils, basophils and eosinophils
45
Neutrophils are
the first responder's to inflammation/infection, are highly mobile
46
BANs
immature neutrophils
47
Segmented neutrophils are
mature neutrophils
48
A shift to the left
refers to an increased number of BANs in circulation, commonly found in patients with acute bacterial infection
49
An elevation in BANs and WBC could indicate an
acute bacterial infection
50
Do BANs have an effect on fighting infections ?
No because they are immature
51
Eosinophils respond to
allergic reactions and help control inflammatory mediator release
52
Basophils
respond to allergic reactions where IgE is present
53
agranulocytes
monocytes and macrophages
Monocytes mature into the macrophages
produce prostaglandins
have longer phagocytic reactions than granulocytes
54
T cells mature in the
thymus
55
B cells mature in the
bone marrow
56
Plasma cells develop from the
B lymphocytes
57
Leukocytosis
elevated levels of WBC's, mostly neutrophils
58
phagocytosis
where one cell ingests another - Primarily the job of granulocytes (neutrophils, basophils, eosinophils) and monocytes
59
Inflammation - think about ___________ and ________
leukocytosis and phagocytosis
60
Cytokines
are another response to inflammation and infection
small, low MW signaling proteins produced during all phases of the immune response - Primarily made by T cells and macrophages (lymphokines/monokines) and act primarily on other immune cells in response to presence of viral or bacterial infection
61
Cytokines can be
pro inflammatory and anti-inflammatory
62
Mast cell degranulation
immediate release of chemotactic factors that attract neutrophils and eosinophils
63
Histamine
increases permeability of vessels
64
Leukotrienes
induce smooth muscle contraction, constricts pulmonary airways, increases microvascular permeability
65
Prostaglandins
induce vasodilation, induce fever, increase vascular permeability, chemotaxis, and pain by direct effects on nerves
66
Platelet Activating Factor
Activates platelets
67
Cyclooxygenase pathway (COX) leads to
Synthesis of prostaglandins and thromboxane
68
thromboxane
VCPF
causes vasocontriction, bronchoconstriction and promotes platelet function
69
Lipoxygenase pathway
Synthesis of leukotrienes
| Constricts pulmonary airways
70
Corticosteroids prevent the release of ____________
arachidonic acid - this would reduce inflammation
71
arachidonic acid
no production of leukotrienes, prostaglandins and thromboxane
72
Primary phagocyte within the blood
Neutrophil
73
Phagocytosis steps
Production of adhesion molecules
Margination (pavementing)
- Adherence of leukocytes to endothelial cells
Diapedesis (emigration)
- Emigration of cells through the endothelial junctions
Chemotaxis
- Leukocytes are attracted and accumulate at the site
```
Adherence
Engulfment
Phagosome formation
Fusion with lysosomal granules
Destruction of the target
```
74
Acute Inflammation
Self-limiting
Local manifestations—result from vascular changes and corresponding leakage of circulating components into the tissue
Heat, swelling, redness, pain
Exudative fluids
75
Serous exudate indicates
early inflammation- it is watery and has low protein
76
Fibrinous exudate indicates
Thick, clotted exudate: indicates more advanced inflammation, large amounts of fibrinogen
77
Purulent exudate indicates a
bacterial infection
78
Hemorrhagic exudate
contains bloood and indicates bleeding and a severe leakage of red cells from capillaries
79
Systemic Manifestations of Acute Inflammation
Fever, Leukocytosis, increased plasma protein synthesis (proteins can be proinflammatory or anti-inflammatory)
80
Chronic Inflammation
lasts longer than 2 weeks- Often related to an unsuccessful acute inflammatory response
Characterized by pus formation, purulent discharge, and incomplete wound healing
81
Other causes of chronic inflammation
High lipid and wax content of a microorganism
Ability to survive inside the macrophage
Toxins
Chemicals, particulate matter, or physical irritants
82
Temperature raising responses
vasoconstriction
shivering
piloerection
increased metabolism
83
Temperature reducing responses
vasodilation
sweating
increased ventilation
84
Pharmocologic treatment of fever
Antipyretic medications
NSAID’s (non-steroidal anti-inflammatory drugs)
Aspirin
Ibuprofen (Motrin, Advil, etc)
```
Antipyretic only (Not anti-inflammatory drug)
Acetaminophen (Tylenol)
```
85
How do Antipyretic medications reset the temperature set point ?
By blocking the activity of COX (and prostaglandins)
86
Agents of Infection
Bacteria
Fungi
Virus
Parasitic
87
Staphylococcus aureus
```
Life threatening
Major cause of nosocomial infection
Common on normal skin and nasal passages
Opportunistic
Biofilms associated with colonization
Secretes exotoxins
Antibiotic resistance is a major problem
```
88
biofilms consist of
mixed species of microorganisms - this makes it harder to fight against certain bacteria
89
bacteremia
bacteria are present in the blood
90
septicemia
infection in the blood
91
Bacteremia and Septicemia are both results of the
failures of the body's defense mechanisms
92
DIC
Disseminated Intervascular Coagulation - we have used up all of our clotting factor so we start bleeding - perhaps from the eyes or the site of an IV. This can happen when endotoxins are released from the blood because of bacteremia
93
Gram negative organisms produce
endotoxins that release the TLR-4. This triggers the septic syndrome to start.
94
SIRS
systemic inflammatory response - fever, tachycardia, tachypnea, leukocytosis)
95
SIRS + bacteremia =
sepsis
96
IF we dont treat our patients with fluids, oxygen, get cultures and antibiotics then sepsis can ___________ into a bigger issue. What can result ?
Vasodilation, hypotension, tissue inflammation, tissue hypoperfusion
97
More severe Sepsis results in
myocardial depression, worsening hypoperfusion (cold shock) increase in lactic acid >2
98
Septic shock has lactic acid levels greater than
4
99
Viruses can live on their own. True or false?
False- viruses hijack other cells and depend on these cells for replication. It is not capable of independent production
100
Viral Invasion and Replication Steps
```
Attachment
Penetration
Uncoating
Replication
Assembly
Release
```
101
Antigenic drift
refers to a virus than can change yearly. The influenza virus undergoes antigenic drift leading to new strains
102
Characteristics of Fungi
Large microorganisms with thick, rigid cell walls without peptidoglycans (resist penicillin and cephalosporins)
Eukaryotes
Exist as single-celled yeasts, multicelled molds, or both
Reproduce by simple division or budding
Pathogenicity
Adapt to host environment
Wide temperature variations, digest keratin, low oxygen
Suppress the immune defenses
Usually controlled by phagocytes, T lymphocytes
103
Most common cause of fungal infections
Candida Albacans
Opportunistic
Found in normal microbiome of skin, GI tract, vagina
Localized infection if overgrowth occurs
Disseminated infection if immunocompromised
May involve deep infection
High mortality rates
104
Factors for Infection: Communicability
Ability to spread from one individual to others and cause disease: measles and pertussis spread very easily; HIV is of lower communicability
105
Factors for Infection: Infectivity
Ability of pathogen to invade and multiply in the host
| Involves attachment to cell surface, release of enzymes, escape of phagocytes, spread through lymph and blood to tissues
106
Factors for Infection: Virulence
Capacity of a pathogen to cause severe disease; for example, measles virus is of low virulence while rabies virus is highly virulent
107
Factors for Infection: Pathogenicity
Ability of an agent to produce disease
| Success depends on communicability, infectivity, extent of tissue damage, and virulence
108
Factors for Infection: Portal of entry
Route by which a pathogenic microorganism infects the host
109
Factors for Infection: Toxigenicity
Ability to produce soluble toxins or endotoxins, factors that greatly influence the pathogen’s degree of virulence
110
Role of Biofilm in common infections
Bacteria prefer to stick to and colonize environmental surfaces
Biofilm is a structured community of bacteria
Access to nutrients- elimination of wastes
Intracellular signaling and communication
Implicated in as much as 80% of infections
Locations:
Dental plaque, catheter infections, implanted medical devices
111
We dislike foley catheters because of _________
biofilms
112
Treating Infectious diseases
Antibiotics, antifungals and antivirals
113
Requirements of medications and actions take to fight and eliminate infection
Organism must be susceptible to concentrations of drug at infected site
Dose and route of administration must result in adequate levels of drug at infected site for sufficient time
Local factors must not interfere with drug activity
Host defenses must facilitate microbial clearance
Adjunctive therapies (such as surgical drainage of abscess) must be used when necessary
114
Antibacterial drugs consist of
Narrow spectrum antibiotics: target few types of bacteria
Broad spectrum antibiotics: target many types of bacteria
Anti-mycobacterial drugs
115
Antiviral drugs consist of
Antivirals
| Anti-retroviral
116
Classifications of Antibiotics by mechanism of action
```
Inhibits bacterial cell wall synthesis
Inhibits protein synthesis
Inhibits nucleic acid synthesis
Interrupts metabolic pathways
Disrupts cell membrane permeability
Inhibits enzymes important in microorganism’s function
```
117
A patient might be on several antibiotics because
of the range of actions that these antibiotics may take towards the invading bacteria
118
Bactericidal
drug actually kills bacteria
119
Bacteriostatic
drug inhibits bacterial reproduction so host defenses can kill
120
Selective Toxicity
Drug is toxic to microbe but not to human host
121
Organism Sensitivity
Drug is toxic to the microorganism causing the infection. Culture and sensitivity testing will determine this.
122
If someone comes in with a infection, the best thing we can do is
get a culture and sensitivity. Culture will let us know what antibiotic bacterium is sensitive to
123
Tests for identifying infecting microbe can be
rapid or take days depending on the test
124
Frequently therapy is initiated with ____________ antibiotics and then switched to a more specific ______________ when the organism is identified.
broad spectrum; antibiotic
125
We worry about _____________ resistance.
Antibiotic
126
Antibiotic resistance is caused by
```
Genetic mutations
Inactivation of antibiotic
Penicillin resistance
Modification of target molecule
Increasing active efflux of antibiotic
Caused by:
Lack of compliance with therapeutic regimen
Overuse
Destruction of normal microbiome
```
127
Adverse effects of antibiotic therapy
Normal gut flora are killed - diarrhea and can pave the way for colonization with pathogenic bacteria (clostridium difficile )
Supra-infection: Infection with a second (antibiotic resistant) organism that occurs during antibiotic therapy.
Pseudomembranous colitis: bowel is colonized with Clostridium difficile, producing a severe diarrhea that is sometimes fatal.
Allergy – most common with the penicillins (up to 7%)
Cross over allergy > Cephalosporins (cousin to penicillin) (small 1%)
128
Supra infection
Infection with a second (antibiotic resistant) organism that occurs during antibiotic therapy
Pseudomembranous colitis: bowel is colonized with Clostridium difficile, producing a severe diarrhea that is sometimes fatal.
129
Allergy is most common with
penicillins
130
Cross over allergy
allergic to one drug means one may be allergic to another drugs "cousin"
Cephalosporins (cousin to penicillin) (small 1%)
131
We can identify a pathogen through
culture, gram stain
132
What is the important principle of antimicrobial selection and administration ?
Match "drug with bug"
133
Antibiotics should be given
around the clock. We need the higher, consistent levels in order to kill the bacteria
134
Synergistic
Antibiotics work well with each other
135
In some instances, antibiotic resistance is discouraged by _____________
combinations
136
In some instances, antibiotic resistance is discouraged by _____________
combinations
137
Ways to decrease risk for antibiotic based infections
don't take antibiotics to prevent illness
washing hands
follow directions
do not request antibiotic for flu or cold
finish course
do not take left over antibiotics
138
With a "shift to the left" what are we worried about ?
BANS level are usually 0-4%. With increased levels we are looking at acute inflammatory response or acute infection.
139
What is chemotaxis ?
Chemotaxis is the movement of an organism in response to a chemical stimulus.
Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment.
a chemically induced signally process that leads to the migration of WBC
140
Margination of WBC refers to
an accumulation of WBC near the vessel wall
141
chemotaxis occurs after
a WBC has left circulation via the process of diapedesis
142
diapedesis
WBC squeezes through the vessel wall
143
diapedesis gives rise to
chemotaxis as chemical signals direct the WBCs to the site of injury
144
What is hyperemia ?
an excess of blood in the vessels supplying an organ or other part of the body.
145
Corticosteroids, NSAIDS and acetylsalicylic acid act to inhibit various steps in what pathway?
The cyclooxygenase pathway and the Lipoxygenase pathway
146
When cells are activated by injury, the arachidonic acid in the cell membrane is rapidly converted to produce what substances ?
Prostaglandins, thromboxane and leukotrienes
147
Prostaglandins are considered pro-inflammatory and are potent ____________ contributing to increased __________ and ________
vasodilators; blood flow; edema formation
148
Prostaglandins- do they dilate or constrict vessels ?
Dilate vessels
149
Arachidonic acid is important because
it produces Prostaglandins and thromboxane and leukotrienes, all which play important roles in the inflammatory response
150
roles of Prostaglandin
vasodilator
sensitizing pain receptors to arousal by stimuli
stimulate temperature regulating area of hypothalamus, helping to produce fever
151
Thromboxane roles
powerful vasoconstrictor
platelet aggregating agent
causes brief vasoconstriction and skin pallor at the injury site and promotes clot formation
152
Leukotrienes
form the slow reacting substance of anaphylaxis, which constricts smooth muscles of bronchi, causing narrowing of the airway, and increases capillary permeability leading to airway edema
- stimulate chemotaxis
153
Histamine role
causes vasodilation and increased capillary permeability
154
A biochemical substance that attracts leukocytes to the site of inflammation is a(n):
chemotactic factor
155
Leukotrienes act like histamine and cause smooth muscle contraction, ________________ vascular permeability, and chemotaxis.
Prostaglandins cause increased vascular permeability, chemotaxis, and pain.
Adhesion molecules increase the _____________ between cells.
increased; stickiness
