Week 6 Flashcards
1
Q
What are the four classic presentations to look for while taking a physical examination?
A
Rubor, calor, tumor, dolor
Redness, heat, swelling, pain
2
Q
What is crepitus and what causes it?
A
Crunchy sounding due to microbes that produce gas. Clostridium proferengens causes this
3
Q
What is fluctuance?
A
Fluid filled
4
Q
What is purpura?
A
Micro-breaks in capillaries that look like bruises
5
Q
What is bullae?
A
Blisters
6
Q
Name six other diseases that can mimic SSTI’s
A
Gout-build up of uric acid Thrombophlebitis Deep vein thrombosis Contact dermatitis (skin exposed to some kind of chemical it doesn't like(allergy)) Drug eruption Foreign body reaction
7
Q
What is folliculitis?
What bacterial are most likely to cause folliculitis?
A
Folliculitis is a minor infection associated with friction and sweat gland activity
Staph aureus Pseudomonas aeruginosa (hot tub folliculitis)
8
Q
What is acne? What bacteria is a common cause?
A
Inflammation of hair follicles with their associated sebaceous glands
Propionibacterium acnes - within sebum, trapped in follicles/glands (S. Aureus is also a common cause)
Hormones and organic acids produced by p. Acnes contributes
9
Q
What are soft tissue abscesses? What are its symptoms?
A
Any breach in skin
Local superficial cellulitis, bacteria necrose/liquefy tissue, pus formation (cell debris and WBCs)
Fluctuant, tender, erythematous nodule with surrounding erythema
10
Q
What is the most common cause for soft tissue abscesses? Who is at most risk for polymicrobial infections?
A
Staph. Aureus (including MRSA)
IV drug users, oral, rectal, Volvo-vaginal are often polymicrobial
11
Q
Why is it that systemic antibiotics aren’t always helpful for the treatment of soft tissue abscesses? What should you do instead?
A
Systemic antibiotics aren’t always helpful because they wont penetrate into the abscess.
Incision and drainage is necessary to get rid of the source of infection
12
Q
What is a furuncle (AKA boil)? Are furuncles commonly recurrent?
A
Abscess in the area of a hair follicle
These are commonly recurrent
13
Q
What is the difference between a furuncle and a carbuncle?
A
Carbuncles are a grouping of furuncles and the infection spreads into the subcutaneous tissue
14
Q
What is the most common cause for necrotizing fasciitis?
A
Group A strep
15
Q
What is Fournier’s gangrene?
A
Polymicrobial infection causing necrotizing fasciitis of genitals and perinuem 😳😵
16
Q
What is one of the hallmark symptoms of necrotizing fasciitis?
A
Pain our of proportion to exam findings
17
Q
Name some examples of dermatophyte fungi
A
Tinea cruris, corporis
Ringworm
Nail infections - onychomycosis
Occurs in keratinized layers of skin/nails
18
Q
What are the three genera of dermatophyte fungi that cause SSTIs?
A
Trichophyton
Microsporum
Epidermophyton
19
Q
What is the most common type of fungal infection in humans?
A
Candida albicans
Usually occurs in warm, moist environments. Treatment is topical antifungals, systemic antibiotics if severe
20
Q
Name three types of infections caused by candida albicans and where they occur
A
Diaper rash
Intertrigo - on skin due to bad hygiene
Thrush - oral cavity
21
Q
What is erysipelas? What is it caused by?
A
Rapidly spreading infection of group A strep in the deep dermis. Causes rubor, calor, tumor, dolor
Treatment is penicillin
22
Q
What is cellulitis? What causes it? What is the treatment?
A
Infection of the subcutaneous tissue. Usually due to group A strep, but may also be caused by staph aureus, or gram negatives in immunocompromised individuals
Treatment is systemic antibiotics (cant use topical because its too deep)
23
Q
What four factors increase the risk of wound infections?
A
Higher number of organisms
Higher virulence of organisms
Poor circulation near wound
Poor general health
24
Q
True or false… nearly all of the population are carriers for staph aureus
A
False. About 10-30% of the population carries staph aureus, especially in the anterior nares
25
Staphylococcus aureus can secrete ___ toxin into ____ tissue to cause scolded skin syndrome (usually in ___)
alpha
Subcutaneous
Infants
26
Staph aureus can also cause exfoliatin, which is...
Bullous impetigo
Yellow blisters over extremities and/or face
27
What is staph toxic shock syndrome (TSST-1)? What causes it?
Causes desquamation of the skin (peeling)
Can be caused by super absorbent tampons or excessive gauze post surgery
28
What does the staph toxin, enterotoxin do?
Causes food poisoning (diarrhea, vomiting)
Note that the toxin just has to be present in the food, not necessarily the microbe, in order to cause food poisoning
29
```
What does each staphylococcal toxin cause?
Alpha toxin
Exfoliatin
TSST-1
Enterotoxin
```
Alpha toxin - scolded skin
Exfoliatin - bullous impetigo
TSST-1 - toxic shock syndrome
enterotoxin - food poisoning
30
MRSA strains acquire the ___ gene which...
MecA
Makes new penicillin binding proteins with reduced affinity for b-lactams
Makes it resistant to ALL B-lactams
31
What are the drugs of choice for MSSA?
Anti-staphylococcal penicillins such as nafcillin and oxacillin
Cephalosporins
32
What are four risk factors for getting MRSA? What is the treatment?
Close skin-skin contact
Crowded living conditions
Poor hygiene
IV drug use
Treatment: trimethoprim-sulfa, doxycycline, vancomycin, linezolid, daptomycin
33
What are some complications post-group a strep infection?
Strep A primes our immune system against certain antigens that resemble antigens on our heart valves and other locations, causing autoimmune disorders. It can lead to rheumatic fever or glomerulonephritis
Differences in the M protein
34
Name the two streptolysins and what they do?
O and S
cytotoxic
Lyse leukocytes, tissue cells, and platelets (which helps the microbe evade the immune system)
35
Name the two pyrogenic exotoxins of group a strep and what they do
A and B
These are "superantigens"
These hijack a normal APCs reaction to stimulate a large number of T cells, causes massive dysregulatd cytokine respone, and causes severe systemic illness (shock)
36
Name three inflammatory enzymes of group a strep and what they do.
Streptokinase: a protease
Hyaluronidase: degrades carbohydrates and breaks down CT
DNAse - degrades DNA
37
Describe clostridium perfringens
Anaerobic, spore-forming, gram positive rods
Found in soil and human colon
Produces hydrogen and CO2 gas to cause gas gangrene***
Has multiple exotoxins (neurolytic toxin destroys WBCs)
Rapidly fatal
38
What is pasteurella multocida?
Gram negative rod
Transmitted through animal bites
39
Describe pseudomonas aeruginosa
Gram negative rod
Prototypical non fermenter
Can cause hot tub folliculitis, secondary infection after burns*, necrotizing fasciitis.
40
Describe vibrio vulnificus
Gram negative rod
Found in salt water environments (colonizes shell fish)
Causes fever, sepsis, hemorrhagic bullae
Associated with iron overload and cirrhosis
Somewhat rare. Infection spreads rapidly. Can cause liver damage
41
What is mycetoma?
Madura's foot
Bacterial infection often due to actinomyces or nocardia or fungal infection due to lots of different types of molds
42
What causes sporotrichosis?
Sporothrix schenckii
*rose gardeners disease
43
True or false.. one of the best strategies to diagnose SSTIs is through pus
True
44
Hemotogenous, monomicrobial osteomyelitis is often due to what kind of bacteria?
Staphylococcus aureus
Coagulase negative staphylococci
Gram-negative rods
45
Bone infections due to periodontal issues are ____ spread
Contiguous
46
Name the three sources for osteomyelitis
Hemotogenous (through the blood stream) - typically monomicrobial
Contiguous spread (prolonged exposure nearby) - typically polymicrobial
Direct inoculation (result of trauma)
47
Where is hemotogenous osteomyelitis most likely to occur in children and adults?
Children - long bones
Adults - vertebrae
48
What is sequestra?
Separated dead bone
49
In hematogenous osteomyelitis, the infection lands in the _____, then spreads to the _____, which can result in ____
Inter-medullary canal
Cortical bone
Lifting of the periosteum
50
What is an involucrum?
When the infection in a bone pushes the periosteum out and causes NEW BONE to form between the periosteum and the old bone
51
Name the four stages of the anatomical classification of osteomyelitis
Stage 1 - medullary osteomyelitis. confined to the medullary cavity
Stage 2 - Superficial osteomyelitis. Involves only the cortical bone
Stage 3 - localized osteomyelitis. Involves both cortical and medullary bone but does not involve the enter
Stage 4 - diffuse osteomyelitis. Involves the interest thickness of the bone, with loss of stability
52
Why is it that you can treat stage 1 osteomyelitis with antibiotics but not stage 2, 3, or 4?
In stages 2, 3, and 4, a biofilm forms and requires physical removal. Also, in stage 3 and 4, the infection cuts off the blood supply so it is difficult to get the antibiotics to the site.
53
What are the differences between the acute and chronic classifications of osteomyelitis?
Acute - infection prior to development of sequestra. Usually less than 2 weeks
Chronic - infection after sequestra have formed. Involves Formation of involucrum, bone loss, and sinus tract formation
54
What are the clinical presentations acute osteomyelitis?
gradual onset over several days
Dull pain/local tenderness
Warmth, erythema, swelling
Can present as septic arthritis (bacterial infection in a joint coming from the bone (common on the superior tibia)
55
What are the clinical presentations of chronic osteomyelitis?
Mild pain over several weeks
May have localized swelling or erythema
Draining sinus tract
56
What are some characteristics that help in the diagnosis of chronic osteomyelitis?
Suspected based on chronic, poorly healing wounds, DM, vascular disease, decubitus ulcers, or in the presence of underlying hardware
57
Typically, radiographs/MRIs only help so much in the diagnosis of osteomyelitis. Laboratory tests such as WBC count, ESR/C-reactive protein, blood cultures are nonspecific. What is the best way to specifically diagnose osteomyelitis?
Culture of bacteria from bone.
Biopsy+pathology with inflammation and osteonecrosis.
However... note that if you are somehow able to diagnose the disease without culture, there is no need for biopsy
58
True or false... intravenous antibiotic administration is the best way to treat acute osteomyelitis
False... both intravenous and oral therapy work equally well. (However you should consider the oral bioavailability of the antibiotic and its ability to penetrate bone)
59
What is the treatment for acute osteomyelitis?
3-6 week treatment with antibiotics. (Surgery may or may not be indicated)
60
What is the treatment for chronic osteomyelitis?
3-6 week treatment of antibiotics + surgery
Greater role for surgery due to necrotic bone and the lack of antibiotic penetration to devascularized bone
61
Odontogenic infections can spread ____ to the jaw (oral aerobes and anaerobes)
Contiguously (not hematogenously)
This is relatively rare
62
Which is more susceptible to osteomyelitis, the mandible or maxilla? Why?
Mandible
Because it has thinner cortical plates and is less vascularized
63
What portion of the mandible is most susceptible to developing osteomyelitis? How is it developed?
Lingual aspect in the molar region
Periosteum is penetrated with chronic infection with the formation of mucosal or cutaneous abscesses and fistulae
64
What are some risk factors for osteomyelitis of the jaw?
Dental infection, compound fracture, malignancy, irradiation, DM, steroid use
65
What are the symptoms of osteomyelitis of the jaw? What is the treatment?
Mandibular pain, anesthesia or parasthesia on affected side. Lymphadenopathy, can progress to trismus (locked-jaw)
66
What is the leading cause of arthroplasty failure? (Joint replacements)
Prosthetic joint infections
Failure rate is 10-20%
PJIs lead to need for more surgery, antimicrobials, more rehab, etc.
67
What is the biggest risk factor for PJIs?
Surgical site infection not involving joint prosthesis
68
What type of bacteria are the most likely culprits of PJIs?
Gram positive cocci (65%)
This includes...
Staph aureus
Streptococcus spp.
Enterococcus spp.
69
Aerobic gram negative bacilli cause about ___% of PJIs. Name two species that are likely culprits
6
Enterobacteriaceae
Pseudomonas aeruginosa
70
Describe the pathogenesis of PJIs
Skin organisms inoculate at time of implantation
Some seed in the blood, but more importantly, a small number adheres to the implant forming a protective biofilm that evades immune system and antimicrobials
71
If a PJI occurs within the first __ months of surgery, the infection was most likely introduced during surgery
3
72
Late PJIs occur > ____ years after surgery and are due to...
1-2 years
Hematogenous seeding or late manifestation of surgical infection
73
What is the treatment for PJIs?
SURGERY + antimicrobials
74
Name 5 surgical management options for PJIs
Debridement and retention
Two stage exchange
One stage exchange (during a single procedure, everything is taken out then new stuff is put back in)
Resection arthroplasty with arthodesis (fusion)
Amputation
75
What antimicrobial is recommended for either a 1 stage exchange or debridement and retention?
Rifampin (for 2-6 weeks)
76
Why is rifampin not recommended in a 2 stage exchange? How long should you wait for re-implantation?
Rifampin is not recommended because the prosthetic material is removed in this method
6 weeks - 3 months
77
True or false... prophylactic antibiotics are recommended for dental procedures in patients with prosthetic joints
False! Dental procedures do not cause PJIs and prophylactic antibiotics don't prevent it
78
Prophylactic antibiotics are indicated for patients who have prosthetic joints and ____
Are severely immunocomprimised or have a history of PJIs
79
What mycobacteria defenses make it exceptionally difficult for antimicrobials to do their jobs?
Cell wall is thick, hydrophobic, and rich in mycolic acid
Cell membrane has efflux pumps that pumps out harmful chemicals such as antibiotics
Some species can hid inside host cells
80
True or false... TB is the 2nd leading killer of adults in the world with 2 million TB deaths a year
True
81
What is the prophylactic treatment of choice for a latent/asymptomatic primary TB infection?
Isoniazid for 9 months
82
What is the treatment of choice for an overt/active TB infection?
2 with 4, then 4 with 2
2 months treatment with combination of (RIPE) rifampin, isoniazid, pyrazinamide, ethambutol
Then 4 months with rifampin and isoniazid
83
How do you treat an overt active TB infection that is an intracellular organism?
Treat with RIPE for 12 months + azithromycin
**restrict the use of pyrazinamide to only the first two months because it is hepatotoxic
84
Reactivated (resistant) TB is a greater risk in hat kinds of patients?
Immunosuppressed, HIV-positive, other "high risk patients
85
What is the rule of 5s for TB?
In otherwise healthy patients infected with TB...
5% risk of reactivation in first 2 years
Then a 5% lifetime risk of reactivation
High risk patients have a 5% + 5% risk of reactivation each year
86
True or false... secondary tuberculosis always reactivates in the lungs
False... it may also reactivate in lymph nodes, joints, kidney, CNS..
87
What is the treatment of choice for secondary TB?
RIPES
2 months treatment with combo of rifampin, isoniazid, pyranzinamide, and STREPTOMYCIN
Then 4 months with rifampin and isoniazid
88
Second line drugs such as ___ can be added to overcome drug resistance when treating secondary TB
Bedaquiline
89
What are the clinical uses for Isoniazid?
Prophylaxis of TB
Effective in combo for treating TB
90
What is Isoniazid's mechanism?
Decreases mycolic acid synthesis
It is a prodrug that must be activated by the bacterial enzyme, Kat G.
Then, an activated complex is formed that blocks a key substrate and enzyme in mycolic acid synthesis
**KatG activation of isoniazid also produces free radicals such as NO
91
Name three adverse effects of isoniazid.
Hepatotoxicity
INH can cause a pyridoxine deficeincy so always administer with vitamin B6 to maintain heme synthesis and prevent neurotoxicity
Disulfuram-like reaction (avoid alcohol 72 hours before and after use)
92
What is the clinical use of pyrazinoamide? True or false.. it is also a prodrug
Treatment of ACTIVE TB
True, pyrazinamide is a prodrug
93
What is the mechanism of pyrazinamide?
Inhibits mycolic acid synthesis
Net effect is that pyrazinoic acid accumulates inside the granulomas
Bacterostatic
94
Pyrazinamide requires a ___ pH to be activated. Pyrazinamide is an essential part of the treatment of TB ___
Acidic
Meningitis
95
What are some adverse effects of pyrazinamide?
Hepatotoxicity (if used for longer than two months).
Increases uric acid (gout)
Rash
Contraindicated in pregnancy - can cause fetal harm and infertility in nonpregnant patients
96
What is the clinical use for ethambutal?
Treatment of ACTIVE TB
97
What is the mechanism of ethambutal?
Obstructs the mycobacteria cell wall formation
Decreases carbohydrate polymerization by inhibiting aribinosol transferase
98
True or false... ethambutal crosses the blood brain barrier
True
99
Name three adverse effects of ethambutal
Ocular toxicity
Color blindness
Ocular neuritis (swelling of optic nerve leading to blindness)
100
What are some adverse effects of streptomycin?
Ototoxic
Nephrotoxic
Avoid during pregnancy
101
Azithromycin should be added to the combo treatment in cases of ___
Mycobacterium avium
102
What is the clinical use for bedaquiline?
Multi-drug resistant TB
103
What is the mechanism of bedaquiline?
Inhibits mycobacterial ATP synthase
| Long half life
104
What are two adverse effects of bedaquiline?
Common side effects include nausea, vomiting, arthralgias (joint pain), and headache
** can cause prolonged QT syndrome, so be very careful with patients with arrhythmias
105
What is the drug of choice for treatment of both TB and leprosy?
Rifampin
106
What is the drug of choice for prophylaxis of leprosy? (Can also be used for prophylaxis of pneumocystis jiroveci)
Dapsone
107
What is the mechanism of Dapsone?
Competes with PABA to inhibit dihydrofolate synthesis in bacteria
108
What are three adverse effects of Dapsone?
Hepatotoxicity
Hemolysis
Cross-sensitivity if allergic to sulfonamides
109
Most of traveller's diarrhea is caused by ___ and is treated by ___
E. Coli
Rifaximin is the drug of choice for treating traveller's diarrhea due to E.coli
110
Ciprofloxacin is the drug of choice in treating traveller's diarrhea due to...
Campylobacter jejuni
Salmonella
Shigella
111
What is the drug of choice for treating pseudomembranous colitis?
Metronidazole
112
How long does the induced innate immune response last?
Hours to days
113
True or false... dendritic cells, neutrophils, and macrophages can do phagocytosis. However only macrophages and dendritic cells are APCs
True
114
True or false.. neutrophils die after phagocytosis
True
115
What three innate immune cells respond to parasites such as helminths and are also involved in allergic responses?
Mast cell
Eosinophil
Basophil
116
What are two ways in which cells communicate that they are infected, damaged, or diseased?
Interferon response
Altered MHC expression
117
What are three pro-inflammatory signaling mechanisms?
Cytokines
Eicosanoids
Acute phase response
118
Most tissues have resident macrophages. Name the resident macrophages of the following tissues...
Brain
Bone
Liver
Skin
Brain: microglia
Bone: osteoclasts
Liver: kupffer cells
Skin: langerhans cells
119
What are the effector mechanisms of macrophages?
Phagocytosis
Cytokine release
Degranulation
Antigen presentation
120
How does intracellular recognition work with NK cells?
Recognizes changes at the surface of human cells that are caused by viral infection
121
Most of the macrophage receptors are involved in phagocytosis. Except for ___ which can be involved in phagocytosis but function mainly in signaling and driving the inflammatory response
TLR (toll-like receptors)
122
What ligands do the lipopolysaccharide receptors bind?
LPS!!! (And some other stuff like peptidoglycan)
123
What ligand binds to the mannose receptor?
LPS, CPs and ManLam
124
What are the similar agents in phagolysosomes and granules in macrophages and neutrophils
Both macrophage and neutrophil phagolysosomes have...
Low pH, superoxide, hydrogen peroxide, NO, lysozyme, cathelicidin
125
What are some differences between the produce of phagolysosomes between macrophages and neutrophils?
Macrophages: macrophage elastase-derived peptide
Neutrophils: alpha defensins, lactoferrin, bacterial permeability inducing protein.
Note that macrophages do not have any "competitors" like neutrophils do
126
Name the external and internal TLRs
External: 1, 2, 4, 5, 6
Internal: 3, 7, 8, 9
127
```
Name what TLRs read each of the following extracellular antigens...
Diacyl lipopeptides
Triacyl lipopeptides
Flagellin
LPS
```
Diacyl lipopeptides - 2, 6
Triacyl lipopeptides - 1, 2
Flagellin - 5
LPS - 4
128
What TLRs detect the following antigens internally?
DsRNA
SsRNA
CpG DNA
DsRNA - 3
SsRNA - 7
CpGDNA - 9
129
TLR10 homerdimerizes and heterodimerizes with ___ and ____
TLR 1 and 2
130
What antigen does TLR-9 detect? Is this bacterial or viral?
TLR-9 detects CpG DNA, which is bacterial DNA or DNA viruses
131
TLR activation requires ____
Dimerization. (Like tyrosine receptor kinase)
Dimerization will allow signal transduction to occur
132
In the Nf-kb pathway, a complex of ___, ___, ___, and ____ is assembled on the macrophage surface
TLR4
MD2
CD14
LPS
133
Once the complex is assembled on the macrophage surface, ____ binds to TLR4 and activates ___ to phosphorylate ____ which leads to the phosphorylation and activation of ___
MyD88
IRAK4
TRAF6
IKK
134
IKK phosphorylates ___, leading to its degradation and the release of ____, which enters the nucleus
IkB
NF-kB
135
Upon entering the nucleus, NF-kB activates transcription genes for...
Inflammatory cytokines which are synthesized in the cytoplasm and secreted via the ER
136
What are NOD receptors?
Nucleotide-binding oligomerization domain
Recognize degraded intracellular PAMPs and DAMPs (microbial toxins, viruses, cell stress proteins) (often from phagocytosis)
137
What happens upon activation of NOD receptors?
They induce cytokine expression and release
Form inflammasome
Cooperate with TLRs
138
What is an inflammasome?
They activate and promote cytokine release
Have proteolytic activity to cleave procytokines into their fully functional form.
Enhance other inflammatory signals
Has a checkpoint function
139
True or false... cytokines are mostly soluble, have mostly paracrine and autocrine signaling functions, consist of interleukins, chemokines, and others
True
140
What are the six families of cytokines based on receptor morphology?
```
Class 1
Class 2
Interleukin 1
Interleukin 17
TNF (tumor necrosis factor)
Chemokines
```
141
True or false... cytokines only affect immune tissues
False.. they also affect non-immune tissues
142
What are some common intracellular signaling pathways induced by cytokines?
JAK-STAT (most common)
MAPK
NF-kB
143
Name 5 proinflammatory cytokines that macrophages release
Il-1B
TNF-a
IL-6
CXCL8
IL-12
144
What are the local and systemic effects of IL-1B?
Allows cells to enter diseased area by activating vascular endothelium, increasing access of effector cells, causing local tissue destruction, and also activates lymphocytes
Systemic: fever and causes production of IL-6
145
What are the local and systemic effects of TNF-alpha?
Activates vascular endothelium, increases vascular permeability to allow increased entry of igG, complement, and cells, and allow fluid drainage to lymph nodes
Systemic: fever, mobilization of metabolites, septic shock syndrome
146
What are the systemic and local effects of IL-6?
Local: lymphocyte activation, increased antibody production
Systemic: fever, induces acute-phase protein production
147
What are the local effects of CXCL8?
Chemotactic factor recruits neutrophils, basophils, and T cells to site of infection
148
What are the local effects of IL-12?
Activates NK cells, induces the differenation of T cells into T helper cells
149
Inflammatory cytokines have systemic effects? What are these effects and where do they occur?
Liver: activation of complement
Bone marrow: neutrophil mobilization
Hypothalamus: increased body temp.
Fat/muscle: protein and energy mobilization to increase body temp.
Dendritic cells: TNF-alpha stimulates them to migrate to lymph nodes and activate the adaptive immune system
150
What does Il-6 signaling do to the liver?
Stimulates the liver to increase its production of induced innate immune system proteins, like complement
151
Describe the process once leukocytes are initiated by cytokines to get to the tissues
Cytokines cause dilation of blood vessels
Endothelium expresses adhesion molecules which stick to leukocytes
Leukocytes extravasated to site of infection
Blood clotting occurs in the vessel
152
Extravasation depends on ___, ____, and ____. Describe what each does.
Chemokines: chemoattractants
Adhesion molecules: teather leukocytes to endothelium of vessel. Upon binding, proteases are released
Proteases: opens basement membranes with MMPs and Elastases
153
Excessive plasma TNF-a can cause ____. What is this?
Septic shock syndrome
This causes all of the vasculature in the body to become leaky
Often initiated by blood borne infection
Systemic extravasation and neutrophil invasion
Vascular collapse
Rapid, multi-organ failure
154
What are the effector mechanisms of neutrophils?
Phagocytosis
Degranulation
Extracellular traps***
Cytokine release
155
Granules serve to functions, what are they? What are the four neutrophil granule types? Which is released first?
Phagocytosis and degranulation
Azurophil granules -released first
Specific granules
Gelatinase granules
Secretory granules (these are released to damage the pathogen)
156
Other than granules, what is another way that the pathogen is killed within the phagosome of neutrophils?
Oxidative burst and pH dropping
157
What are the three types of neutrophil extracellular traps?
Non lytic (by release by mitochondrial DNA)
Non-lytic (by vesicular mechanism)
Lytic
**note that the non-lytic traps are mobile
*also note that traps are important in the vascular, to keep the infection from spreading
158
Natural killer cells are large cytotoxic lymphocytes that kill ____ by responding to ___, ___, and ___. Unlike neutrophils, NK cells go through bone marrow education for functional receptor patterns and do not die after killing.
Diseased self cells
Interferons, MHC class 1, and unique stress ligands
159
Altered or absent ___ on self cell surface will stimulate a negative signal, leading to granule release and death of the cell
MHC class 1
160
Virus-infected cells will ___ their interferon release, which will cause what three things?
Increase
Induce resistance to viral replication in all cells
Increase expression of ligands for receptors on NK cells
Activate NK cells to kill virus-infected cells
161
TLR-3 in endosome binds ___ and signals via __ to induce____ gene expression
DsRNA
TRIF
IFN (interferon)
162
TLR-7 in endosome binds ___ and signals via ___ to induce ___ expression
SsRNA
MyD88
IFN
163
Describe how cells detect viral infections
Viral replication in cytoplasm produces uncapped RNA
RLR (retinoic acid inducable gene -like receptor) binds to viral RNA and induces MAV (mitochondrial antiviral signaling protein) and dimierizes
Dimerization initiates signaling pathways that activate IRF3 and NF-kB
IRF3 causes synthesis and secretion of type 1 interferons
NF-kB causes synthesis and secretion of inflammatory cytokines
164
Interferons are cytokines that can do what four things? They are released by what cells?
Reduce viral replication
Prevent cell division
Induce apoptosis
Activate NK cells, T cells, and macrophages
Released by diseased/stressed cells such as intracellular infection or cancer. Also released by leukocytes
165
Describe how interferons activate NK cells, and what the NK cells do.
Virus infection of cells triggers interferon response
Type 1 interferon drives the proliferation of NK cells, then differentiation into cytotoxic effector cells
NK cells then signal the affected cells to undergo apoptosis
166
Explain how macrophage and NK cells are bidirectionally regulated
Macrophage activated by virus recruits NK cells
NK cells synapse with the macrophage
Nk cells proliferate and differentiate.
NK cells tell the macrophage to continue phagocytosis
167
Explain how NK cells regulate DC recruitment of adaptive immunity
Dendritic cells locally activate NK cells. This also acts as a checkpoint on adaptive immune function
* large NK response = DC presentation limited (DC cells actually killed)
* small NK response = DC are activated to initiate adaptive immune system
168
True or false... granulcytes such as mast cells, eosinophils, and basophils are predominant in tissues but rare in the blood. They degranulate when activated. Responsible for initiating type 1 hypersensitivity (allergic response)
True
Also note that the first time you are exposed to an antigen, mast cells dont do anything. They become more sensitive over time
169
What is a onychomycosis?
Fungal infection of the nails
170
Once staph is on the skin how may it access deeper tissues in the skin?
Through skin appendages or trauma
171
Which drug used to treat TB revs up cyp450? Why is this significant?
Rifampin
This will increase the metabolism of drugs such as oral contraceptives. ...May result in pregnancy... whoops!
