Week 4 Flashcards
1
Q
Enterococcus faecalis
A
Gram positive Cocci
Normal flora in gut
Highly resistant, including vancomycin
2
Q
Gram Positive Cocci
A
Strep. pyogenes (group A)
Strep. pneumoniae
Strep. viridans (normal flora)
Staph. aureus Staph epidermidis (normal flora)
Group B beta-hemolytic strep: Strep. agalactiae
Enterococcus faecalis
3
Q
Central tolerance
A
Deletion of self reactive clones of lymphocytes - negative selection
4
Q
Peripheral tolerance
A
Lymphocyte interacts with antigen –> no subsequent response
5
Q
Clonal anergy
A
T cell recognize self antigen but no Co-stimulatory signal
Functional unresponsiveness
6
Q
Regulatory T cells
A
FoxP3, CD25 - markers for regulatory T-cells
Inhibit T cell activation
Inhibit T cell effector functions
7
Q
Activation induced cell death
A
Apoptosis induced by apoptotic proteins
Death ligands
8
Q
Receptor editing (B-cell)
A
New light chain rearrangement replacing original VL chain in B cell
9
Q
Molecular mimicry
A
Normal foreign antigen response cross reacts with self antigen
(Rheumatic fever)
10
Q
Celiac disease HLA typing
A
95% DQ2
DQ8
Used for diagnostic exclusion
11
Q
Multiple Sclerosis
A
Autoimmune response against myelin sheath –> demyelination
Animal model: EAE
Transfer disease to healthy animal –> recipient gets disease
12
Q
Insulin dependent diabetes mellitus
A
Insulitis in islet cells
13
Q
Rheumatoid factor
A
Autoantibodies against Fc portion of IgG
14
Q
X-linked agammaglobulinemia
Bruton’s
A
Defect in btk gene, disrupted B cell development
Pro –> pre blocked
15
Q
Selective IgA deficiency
A
Deficiency in IgA
Anaphylactoid rxn to blood transfusion
16
Q
Hyper IgM immunodeficiency
A
Lack of CD40L (t cell help)
Elevated IgM and low/no class switching to other Ig’s
X-linked
17
Q
CVID - Common variable immunodeficiency
A
Immunoglobulin deficiency
B cell and Ig deficiency
Wide variety
Recurrent infection
Lymphoproliferative diseases
Autoimmune cytopenias
18
Q
DiGeorge syndrome
A
Thymic aplasia:
Thymus doesn’t form –> low T cell count
Hypocalcemia, congenital heart defects
19
Q
Gamma chain deficiency
A
SCID: Common gamma chain that is subunit of cytokine receptors (IL-2, 4, 7, 9, 15)
T cell and NK cell deficiency
B cell intact (but T cell count affects B cell activation)
20
Q
Adenosine deaminase deficiency
A
SCID: Severe absence of T cell function
Accumulation of toxic product that kills T cells
T, B, and NK deficiency
21
Q
Bare lymphocyte syndrome (II)
A
SCID: Lack of MHC class II expression (transcription factor defect)
No CD4+ cells –> B cells affected
22
Q
Tcell receptor Excision Circles
A
Circular genome that is lost during T cell gene rearrangement - should have large amount as child while making T cells
Screen for TREC to diagnose immunodeficiencies
23
Q
PAMPS
A
Pathogen associated molecular patterns
24
Q
DAMPS
A
Danger associated molecular patterns
25
PRR
Pattern recognition receptors
Cell surface & Intracellular
26
Familial Mediterranean Fever
Autosomal recessive
Fever and localized inflammation (skin, serosal membranes, joints)
- Neutrophil infiltration
Day-weeks
Typically resolve, risk of amyloidosis
27
FMF Genetics
MEFV: Encodes pyrin
4 functional domains
28
PYRIN domain
Domain shared by multiple proteins involved in inflammation and apoptosis
Member of intracellular PRR family
- Sense microbial products --> pro-IL-1beta to active form (NALP3)
29
NALP3 associated autoinflammatory syndromes
Mutation in NACHT domain of NALP3 = 3 autoinflammatory syndromes
Autosomal dominant
30
Familial Cold (Urticaria) Autoinflammatory syndrome
Urticaria 30min after cold exposure: IL-1 development
Fever, chill, malaise, joint stiffness, sweating, thirst
31
Muckle-Wells syndrome
Short episodes
Temp change as trigger
Urticaria-like rash: aching
Sensory neural Hearing loss
Higher risk of amyloidosis (25% in N.America)
32
Neonatal onset multisystem inflammatory disease
NOMID
Early onset (infancy)
Rash at birth
- non pruritic urticaria
- neutrophilic infiltrate
CNS disease
- non infectious meningitis
- Low IQ
Sensory anomalies
-Deafness, optic nerve atrophy
Arthropathy
- Arthritis during flares
- Bone enlargement
33
Anakinra
IL-1 blocker
Binds to IL-1R blocking IL-1a and IL-1B
34
Canakinumab
Neutralizes IL-1B
35
Rilonacept
Neutralizes IL-1B and IL-1a
36
Gout
Recurrent attacks of acute inflammatory arthritis (accumulation of uric acid)
Uric acid crystals are DAMPS and result in IL-1 buildup
37
Chronic Recurrent Multifocal Osteomyelitis
CRMO
Recurrent lytic bone lesions with swelling and pain
Fevers, inflammation can spread to tissues
38
CRMO treatment
NSAIDs
Steroids
TNF-inhibiting agents
39
TNF receptor associated periodic syndrome
TRAPS: Autosomal dominant
Long duration of inflammation and fever
Migratory erythematous rash
Myalgias
Conjunctivitis, periorbital swelling
TNF binds --> initiate inflammatory response --> receptors don't shed and inflammatory response continues
40
TRAPS treatment
Etanercept: TNF receptor analog
41
PFAPA
Common in children
Regular occurring fevers, early age of onset
Cyclic
Aphthous stomatitis, lymphadenitis, pharyngitis
Normal growth and development
42
Cyclic Neutropenia
Inherited form caused by ELA2 gene mutation
21 day cycle
ANC
43
Severe inflammatory diseases: Cyclic/non cyclic
| Resolve/do not resolve by puberty
Non cyclic
Do not resolve by puberty
44
Omenn syndrome
2 weeks-3 months
Many symptoms: Erythroderma, alopecia, diarrhea, lymphadenopathy, opportunistic infections
Normal IgG
High IgE
Low IgA, IgM
Maternal T cells remain, expand and GVHD
RAG disorder
BMT therapy
45
Allergic Rhinoconjunctivitis epidemiology
20million americans
10% children, 10-30% adolescents/teens
46
Quick relief medications for asthma
Bronchodilator: Albuterol, xopenex, maxair
47
Long acting bronchodilators
Salmeterol, formoterol
12hr bronchodilation but no anti inflammatory effect
48
Anti inflammatory medications for asthma
Oral corticosteroids, inhaled corticosteroids, leukotriene blockers
Decrease airway inflammation - long term use results in improved disease control
49
Telodendria
Branching at end of axon
50
Epineurium
Death connective tissue surrounding nerve
51
Perineurium
Surrounds bundle of nerve fibers
52
Endoneurium
Loose connective tissue, surrounds individual nerve fibers
53
Function of multipolar neurons
Motor
54
Function of bipolar neurons
Special sensory
55
Function of unipolar neurons
Sensory system
56
4 functions of glial cells
1. Surround neurons and hold them in place
2. Supply nutrients and oxygen
3. Insulate one neuron from the other
4. Destroy and remove dead neurons
57
Oligodendrocyte
Form myelin sheath in CNS
58
Astrocytes
Induce blood brain barrier phenotype
Maintain chemical environment for generation of nerve impulses
Scaffolding
Scar formation
59
Microglia
Phagocytes of CNS
Microglial nodule when virus infects
60
Ependymal cells
Cuboidal to columnar cells arranged in single layer that possess microvilli and cilia
Line the ventricles of the brain and central canal of the spinal cord.
61
Sympathetic opthalmia
Ag sequestration in eye --> damage leads to released Ag --> Tgcells activated and attack antigen in both eyes
62
IFN-gamma and autoimmune diseases
IFN-gamma induces MHC class II molecules to be presented ---> MHC II may present sequestered AG which can induce a response
63
Goodpasture's syndrome
Type II hypersensitivity
Abs bind to type IV collagen on basement membranes of kidney and lung
64
Classic neurotransmitters
Contained in small vesicles, located in active zone
65
Dense core vesicles
Contain neuropeptides
Located further back from active zone
66
Synapsins
Vesicle associated proteins
Tether vesicle to cytoskeleton
67
Docking complex
Voltage gated Ca channel and additional proteins
68
Vesicle storage and release
Vesicles sequestered in storage compartment and releasable compartment
Ca influx moves storage vesicles to release zone, with help of Rab3A
69
Fusion pore
Similar to gap junction, opening associated with electrical signal
Much faster response
70
Synaptic vesicle recycling
Vesicles release neurotransmitters --> Fused membrane coated in dynamin and clatharin --> taken to early endosome and recycled
71
Ionotropic receptor
Ligand gated receptor
Direct receptor channel coupling
72
Metabotropic Receptor
G protein mediated receptor channel coupling
Second messenger mediated receptor/channel coupling
73
End plate potential
EPP: evoked in muscle cell and triggers PSAP and muscle contraction
Super threshold for muscle contraction, safety factor
150-200 quanta released
74
MEPP
Miniature end plate potential
Constantly happening, spontaneous release of ACh
Many MEPPS can result in AP
75
Myasthenia gravis mechanisms
1. Bind to ACh receptor and block binding and receptor activation
2. Promote endocytosis of ACh --> AChR degradation
3. Destroy Postsynaptic surface, less AChR's
76
Lambert-Eaton Myasthenic syndrome
Presynaptic disease
Reduction of Voltage gated calcium channels (Immune attack)
Weakness improves with activity
Treat with aminopyridines
77
Clostridial neurotoxins
Botulinum toxin A: Botox
Botulinum toxin B: Myobloc
- weaken nerve muscle 4-6months
Bind and cleave SNAP 25 (docking zone protein)
78
Clostridium tetani
Passes retrograde along nerve fibers
Inhibits inhibitory neurons that control spinal motor neurons and brainstem excitability
Attacks synaptobrevin
79
Wired transmission
Direct connection between pre and post synaptic neurons
80
Volume transmission
Release site of neurotransmitter is some distance from target cell
Slower onset, longer effect
81
CNS cessation of neurotransmitters
Diffusion
| Re-uptake into glial cells and synaptic terminal
82
Retrograde neurotransmitter
Messenger that goes from post synaptic cell to presynaptic cell and induces further neurotransmitter release
83
LTP requirement
Protein synthesis
84
Pre-synaptic inhibition
Inhibitory neuron contacts the terminal of a second presynaptic neuron
Released NT by inhibitory neuron depresses calcium current --> reduces NT release by presynaptic cell
85
Presynaptic facilitation
Facilitating neuron enhances release of NT by other presynaptic neuron
86
Squamous metaplasia: Smokers
Ciliated columnar --> stratified squamous
87
Desmoplasia
Way connective tissue respond to neoplasms
Collagenous stroma laid down by desmoplastic fibroblasts
88
Nicotine
AChR agonist
89
Physostigmine
AChE inhibitor
90
D-tubocurarine
Competitive inhibitor of AChR
91
Tetrodotoxin, Saxitoxin
Blocks Voltage gated Sodium channels
92
Conotoxin
Blocks Voltage gated calcium channels
93
Succinylcholine
AChR agonist
Inactivates end plate sodium channels, desensitization of AChR
94
Organophosphate compounds
Irreversible inhibition of AChE
95
4 mechanisms of Calcium level regulation in nerve terminal
1. Binding to proteins (calmodulin)
2. Na symport channel
3. Active transport out
4. Sequestration
96
EPSP
Fast - ionotropic receptors that pass NA and K
Inward current = depolarization of postsynaptic membrane
Magnitude proportional to amount of NT released
97
IPSP
Fast - ionotropic GABA and Glycine receptors
Increase Cl- conductance into cell (hypoerpolarization)
Or increased K permeability = hyperpolarization
98
ATP depletion
Reduced Oxygen - ischemic damage
Mitochondrial damage
Failure of Na/K pump
Disruption of translational machinery
Shift to anaerobic glycolysis --> decrease in pH
99
Elevated cytosolic Ca2+
External: failure of Ca pump
Internal: release from mitochondria/ER
Enzyme activation
Disruption of mitochondria membrane potential
100
Oxidative stress
Reactive oxygen species: Superoxide, H2O2, hydroxyl radical
ROS scavengers: Vit C and E
Enzymes - superoxide dismutase, catalase, glutathione peroxidase
101
Loss of membrane integrity
ATP depletion
Increased Ca
Increased protease activity
102
Protein misfolding
Unfolded protein response activated
Unresolved = apoptosis
103
Genotoxic stress
p53 transcription factor activation
Cell cycle arrest
Apoptosis
104
Necrosis
Damage exceeds repair capacity
Cells swell, leaky membranes, nuclear changes
Due to energy failure
105
Coagulative necrosis
Injury causes protein denaturing - infarct
106
Liquefactive necrosis
Hydrolytic enzyme release
Focal infections, brain infarcts
107
Caseous necrosis
Focal infection and immune response
TB, histo
Granuloma
108
Fat necrosis
Focal destruction of fat
| Acute pancreatitis
109
Gangrenous necrosis
Dry: ischemia, distal limb
Wet: Superimposed bacterial infection
GasL Deadly form, anaerobic bacterial infection
110
Apoptosis
Intrinsic: Injury to mitochondria induced
Extrinsic: Growth factor trigger
111
Necroptosis
Hybrid of necrosis and apoptosis
TNFR ligation
112
Pyroptosis
Self destruct
Capase-1
Pro-inflammatory signals released
113
Neonatal diabetes mutations
Kir6.2
SUR1
114
Kir6.2 mutation
Decrease ability of ATP to bind to K-ATP channel
No insulin release
115
SUR1 mutation
Increase Mg2+ and ADP to bind
Stops ATP binding
116
Myotonia Congenita
Defect in Cl- conductance, slow repolarization after AP --> chance for repeated AP's and thus constitutive muscle contractions
117
Bladder metaplasia
Transitional --> Squamous
Stones
118
Esophagus metaplasia
Squamous --> Columnar
Reflux
119
Dysplasia
Pre-neoplastic change
Cellular atypia: Aberrant mutation, enlarged nuclei, nuclear hyperchromasia
