Foundation Flashcards

(483 cards)

1
Q

What is the smallest distance between 2 points that can be seen my a light microscope?

A

0.2 um

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2
Q

What are the steps that occur before examining material with a microscope?

A
Fixation
Sectioning 
Paraffin embedding 
Further sectioning 
Staining
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3
Q

What is involved in fixation of a tissue?

A
  • Removal of tissue from body

- addition of fixative i.e formaldehyde

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4
Q

How do fixatives work?

A

They chemically cross link molecules to lock them in place

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5
Q

What is the most commonly used fixative?

A

Formaldehyde aka formalin

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6
Q

What are the properties of formalin?

A
  • antimicrobial

- toughens tissue

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7
Q

Describe what happens in paraffin embedding?

A
  • tissues are dehydrated in alcohol

- alcohol is then replaced with xylene which mixes well with paraffin

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8
Q

What is the result of paraffin embedding?

A

Stiffens tissues so they can be sectioned thinly

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9
Q

Describe the steps involved in sectioning after tissue has been embedded in paraffin?

A
  • paraffin sections are cut via a microtome
  • thickness is 5-15 um
  • sections are rehydrated via solutions of xylene and alcohol
  • sections are put on glass
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10
Q

Describe haematoxylin staining.

A

Blue/purple stain. Binds to acidic or anionic compounds (-ve charge) ie phosphate groups on nucleus acids(RNA, DNA).

Tissues are described as being basophilic

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11
Q

Describe the eosin stain

A

Pink/orange. Binds to cationic components ie binds to positively charged amino groups of proteins(intra or extra cellular).

Tissue components are described as being acidophilic or eosinophilic

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12
Q

What are the functions of blood?

A
  • transport
  • defence
  • haemostasis
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13
Q

Describe some properties of plasma.

A
  • aqueous
  • made up of: water, protein, salts, lipids, sugar
  • in eqm with extracellular fluid
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14
Q

Name the 3 main types of plasma proteins

A
  • coagulation proteins
  • albumin
  • globulins
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15
Q

Haematocrit equals

A

RBC volume/ blood volume

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16
Q

Normal haematocrit.

A

45%

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17
Q

Describe the features of RBCs.

A
  • biconcave disc
  • 7.2um diam
  • NO nucleus
  • NO organelles eg mitochondria
  • contains haemoglobin
  • transports O2 and CO2
  • life span = 120 days
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18
Q

What does the term amphophilic mean?

A

Substances that stain with both acidic and basic dyes. Eg cytoplasm of cells that produce a lot of protein that have lots of RER

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19
Q

What are 3 main staining techniques used in histology?

A
  • H&E
  • special histochemical stains
  • immunochemistry
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20
Q

What are the 4 basic tissue types?

A
  • connective tissue
  • epithelia
  • muscle
  • neural tissue
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21
Q

What does the term parenchyma mean?

A

Functional cell

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22
Q

What goes the term stroma mean?

A

Support tissue

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23
Q

What are the classifications of connective tissue?

A
  • embryonic connective tissue
  • connective tissue proper
  • specialised connective tissue
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24
Q

Connective tissue proper is further classified into what?

A
  • loose CT

- dense CT: regular and irregular

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25
List examples of specialised connective tissue.
- cartilage - bone - adipose tissue - blood - haemopoietic tissue - lymphatic tissue
26
What are the components of blood?
- Fluid(plasma) | - cells
27
What are reticulocytes?
Immature RBCs. They are released into the blood in this form.
28
What are some features of reticulocytes?
- larger than mature RBCs - no nucleus - still has some organelles and RNA - <1% of circulating RBCs
29
When do reticulocyte numbers increase?
Following haemorrhage or haemolysis
30
What are normoblasts?
Immature nucleated RBCs
31
Describe some features of platelets
- no nucleus - 2-4 um in diam - cell fragments - come from megakaryocytes - contain granules which release their contents - life span = 8-10 days
32
How do WBCs leave blood vessels?
Via diapedesis
33
Describe some features of neutrophils.
- Motile - 3 diff types of granules (MPO, lysozyme, collagenase) - 3-4 joined lobed nucleus - phagocytic - degranulate - life span = several days - involved in acute inflamm - rarely found in normal tissues - contain Barr body in females
34
What are the prominent features of granulocytes?
- multi lobated nucleus | - granules
35
Types of granulocytes.
- neutrophils - eosinophils - basophils
36
Describe some features of platelets
- no nucleus - 2-4 um in diam - cell fragments - come from megakaryocytes - contain granules which release their contents - life span = 8-10 days
37
What are the 2 types of white blood cells?
- granulocytes | - mononuclear leukocytes
38
What are the types of mononuclear leukocytes?
- lymphocytes | - monocytes
39
Types of granulocytes.
- neutrophils - eosinophils - basophils
40
What is the other name for neutrophils?
Polymorphonuclear leukocyte
41
Describe some features of eosinophils.
- bilobed nucleus - large specific granules - exocytose granules - involved in allergic rxn and rxns against parasites - dense eosin stain
42
Describe some features of basophils.
- bilobed nucleus - large granules containing histamine - similar to mast cells - degranulate - least common
43
Describe some feature of lymphocytes.
- smallest WBC - larger than RBC - round densely stained nucleus - thin rim of cytoplasm
44
What are the 3 main types of lymphocytes?
B cells T cells NK cells
45
Describe some features of monocytes.
- largest WBC - oval/bean shaped nucleus - pale nucleus - more cytoplasm than lymphocytes - precursors of macrophages
46
What are some roles of bone marrow?
- site of haemopoiesis - removal of old RBCs - Imm function (B cell differentiation)
47
Red bone marrow is..
Active and haemopoietic
48
Yellow bone marrow is...
Not active and is adipose tissue
49
All cells are generated from one pluripotential progenitor cell called:
Haemopoietic stem cell
50
Haemopoiesis is tightly controlled via
- growth factors | - microenvironment
51
What does a full/complete blood exam tell us?
``` Info about -RBCs -haemoglobin conc -numbers of diff types of cells -Electrolytes -proteins -enzymes Etc ```
52
What are prions?
Infectious proteins
53
Do prokaryotes have a nucleus?
No
54
Describe the appearance of a prokaryotic chromosome.
Single closed circle of ds DNA DNA is looped and supercoiled
55
Do prokaryotic cells have membrane bound organelles?
No
56
Do prokaryotic cells have ribosomes?
Yes 70S
57
Do eukaryotic cells have ribosomes?
Yes 80S
58
How do prokaryotic cells replicate?
Via binary fission
59
The prokaryotic cytoplasmic matrix is packed with what?
Water and ribosomes
60
Can bacteria carry extrachromosomal DNA?
Yes they can carry one or more plasmids
61
Describe a plasmid.
- Circular, supercoiled piece of dsDNA - replicates independently of chromosome - variable size and copy number
62
Describe the bacterial genome
Single circular ds DNA with plasmids
63
What is the main characteristic of viruses?
DNA or RNA and a protein coat
64
How does E. coli acquire new genes?
Horizontally by - plasmids - transposons - integrons - bacteriophages - pathogenicity islands
65
Describe the basic steps in the gram stain procedure.
- stain with blue dye (all bac is blue) - decolourise with alcohol (-bac become invisible, +kept blue dye) - stain with red dye
66
Functions of bacterial cell walls
- rigid layer - gives cell shape - protects against osmotic lysis - protects against harmful substances
67
The shape and strength of bac cell walls comes from what substance?
Peptidoglycan
68
Describe the cell wall of gram + bac
- thick peptidoglycan layer - contains lipoteichoic and teichoic acid - p membrane - retains blue/purple dye
69
Describe the cell wall of gram ? bac
- Outer lipopolysaccharide layer - thin peptidoglycan layer - periplasmic space - p membrane Prevents entry of bile salts and some antibacterials
70
LPS can act as a what?
Endotoxin
71
What type of cell is a bacterial cell?
Prokaryotic cell
72
What type of cell is a fungi?
Eukaryotic cell
73
What are the 2 main types of fungi?
- yeasts (single cell) | - moulds (filamentous)
74
What type of cell is a parasite?
Eukaryotic cell
75
List the key components of bac.
- cytoplasmic membrane - cytoplasmic matrix - ribosomes - genome - cell wall
76
Do prokaryotes and eukaryotes have an endoplasmic reticulum?
Prok no endoplasmic reticulum | Euk have a endoplasmic reticulum
77
What are the 3 primary layers in the early embryo?
- ectoderm - mesoderm - endoderm
78
Where is collagen type I found?
Connective tissue proper Bone Tendon Ligament
79
Where is collagen type II found?
Cartilage | Intervertebral disc
80
Where is collagen type iii found?
Forms reticular fibres
81
Where is collagen type IV found?
Basement membrane.
82
Where is collagen type VII found?
Anchoring fibrils linking to the basement membrane
83
Describe the collagen present in tendons and ligaments.
Type I | Highly organised
84
Describe the function of reticulin fibres.
Thin fibres that provide a delicate supporting framework in certain tissues. Eg bone marrow and liver.
85
Describe the features of elastin.
- branching fibres or sheets - provides elasticity - central core of elastin with surrounding network of fibrillin micro fibrils. - stains black with special dyes
86
Where is elastin found in high concs?
Aorta Lungs Skin
87
What is Marfan syndrome?
Inherited disease of fibrillin 1
88
From what embryonic layer is epithelium derived from?
All 3 layers (endoderm, ectoderm, mesoderm)
89
What is ground substance?
Viscous, clear substance that has a high water content. Often not seen on H&E stains.
90
What are the main components of ground substance?
- glycosaminoglycans (GAGs) | - glycoproteins
91
What are GAGs?
Long unbranched polysaccharides that attracts Na and with it water because of its negative charge.
92
What are the main GAGs found in ground substance?
``` Hyaluronic acid (not linked) Proteoglycans (linked to proteins) ```
93
What are glycoproteins?
Glycosylated proteins that are involved in the regulation of deposition and orientation of fibres. They are the LINKS between cells and matrix.
94
Name some glycoproteins present in ground substance.
Fibronectin Fibrillin Laminin
95
What are the roles of ECM?
- structural network - metabolic regulatory role - mechanical support - cell growth and differentiation - GFs
96
Connective tissue is derived from what cell in which layer?
Derived from multi potent mesenchymal stem cells in the mesoderm
97
Muscle is derived from what embryonic layer?
Mesoderm
98
Neural tissue is derived from what embryonic layer?
Ectoderm
99
Explain what connective tissue is.
Large continuous compartment between and within organs. There are few cells to a large amount of ECM (fibres and ground substance)
100
What is the function of connective tissue?
It functions to provide support, strength, metabolic, defence and space filling.
101
Connective tissue fibres are produced by what cell?
Fibroblasts
102
What are the 2 main types of fibres in connective tissue?
- elastin | - collagen
103
Describe collagen fibres.
- most abundant - flexible, strong - wavy - 3 polypeptide alpha chains that form a triple helix - requires vitamin c for formation
104
What are wandering cells?
Lymphocytes Eosinophils Plasma cells Basophils
105
What are the main cell types that make up bone?
- Osteoid (collagenous type I matrix) that becomes mineralised - osteoblasts - osteocyte
106
Describe the cell types that make up basement membrane
mainly ECM - collagen IV - heparan sulphate - structural glycoproteins (laminins, fibronectin)
107
What is another name for basement membrane?
Basal lamina | External lamina
108
What are resident cells
- fibroblasts, myofibroblasts - macrophages - mast cells - mesenchymal stem cells - adipocytes
109
What is the function of fibroblasts?
Responsible for the synthesis of ECM. They are elongated cells with nuclei
110
Describe macrophages
Phagocytic cell that cleans up debris.
111
Describe mast cells
They contain granules containing histamine that are released during inflammation
112
What is the function of connective tissue proper?
- links and supports organs - exchange of nutrients - tough but flexible
113
Describe the lipid present in white adipose tissue
One main droplet in the cytoplasm
114
Describe the lipid present in brown adipose tissue
Multiple lipid containing vesicles
115
What are the main cell types present in cartilage?
- mainly proteoglycan ground substance - collagen type II - chondrocytes
116
What is the main type of cartilage?
Hyaline
117
Define homeostasis
Maintenance of constant internal environment
118
Fever is characterised by
- Increase in temp set point | - synthesis of PGE2
119
Explain why chills occur during fever
Heating mechanism activated as set point rises (shivering)
120
Explain why crisis occurs during fever?
Cooling mechanism activated as set point falls (sweating)
121
Control systems normally operate on what time of feedback?
Negative feedback
122
What does the term regulated variable mean?
The thing you wish to control
123
What does the term sensor mean?
The means of measuring the regulated variable
124
What does the term set point mean?
The value you'd like the regulated variable to be
125
What does the term comparator mean?
Means of comparing the regulated variable with the set point
126
What does the term effector mean?
Means of restoring the regulated variable to the set point
127
Name some situations that can change the set point
- circadian variation - ageing - in response to persistent changes in ambient levels
128
Where are the central temperature sensors located and what is their function?
-hypothalamus -spinal cord Detect warmth
129
Where are the peripheral temperature sensors located and what is their function?
-skin Detect cold and warmth Good for early warning of changes in ambient temp
130
What are the characteristics of the innate Imm system
- rapid - no memory - recognised shared molecular patters (PAMPS, DAMPS) - inherited in the genome
131
Naive T and B cells migrate from the blood to lymph nodes via
High endothelial vessels (HEV)
132
B cells are found in which part of lymph nodes?
Cortex
133
T cells are found in what part of lymph nodes?
Paracortex
134
Naive lymphocytes return to the blood from LN via
Efferent lymphatic and the thoracic duct
135
What cell links the innate and adaptive systems?
Dendritic cell
136
Name some components of the innate system
- physical barriers - antimicrobial chemicals - complement - epithelial cells, phagocytes, NK cells - cytokines
137
What are the characteristics of the adaptive Imm system?
- recognises Ags - slow - memory - requires gene rearrangement
138
Name some components of the adaptive Imm system
- lymphocytes - abs - cytokines
139
Name some examples of PRRs
TLR NLR RLH
140
What is a cytokine?
A protein secreted by cells that affects the behaviour of nearby cell bearing the appropriate receptors
141
What is a chemokine?
A secreted protein that attracts cells bearing the appropriate receptors
142
What are the 2 groups of chemokine receptors?
CCR | CXCR
143
Lymph nodes sample Ags from where?
Skin and internal tissues
144
The spleen samples Ags from where?
The blood
145
Describe some characteristics of acid fast bac
- thick waxy walls - peptidoglycan base layer - layers of arabinogalactan, mycolic acid and lipid - resists drying and harsh chemicals and antibiotics - slow growth due to slow nutrient uptake
146
Where can strict aerobes grow?
In O2
147
Where can strict anaerobes grow?
In an environment without O2
148
Where can facultative anaerobes grow?
With or without O2
149
Can aerotolerant anaerobes survive in O2?
Yes
150
Where do microaerophils grow best?
In low concs of O2
151
Describe bacterial flagella
- thin, long, hollow helical filaments - flagellin protein - locomotion
152
What is the O Ag?
LPS
153
What is the H Ag?
Flagella
154
Describe bac pili (fimbriae)
- hair like appendages - pilin protein - attaches to other cells - sex pili= plasmid transfer - on most gram -ve bac
155
Describe bac capsules
-polysaccharide -antigenic can't be washed off -makes colonies appear large and shiny -visualised by -ve staining -protects against dehydration and phagocytosis
156
Describe bac endospores
- resistant dormant structures - resistant to heat, UV, dedication, chemicals and stains - sporulation occurs when there is a lack of nutrients and moisture
157
The term fermentation means that the final electron acceptor is:
An organic compound
158
The term respiration means that the final electron acceptor is:
Oxygen
159
The term anaerobic respiration means that the final electron acceptor is:
Inorganic compound
160
What are the diff types of epithelial tissue?
- surface epithelium | - glandular epithelium
161
What is the function of surface epithelium?
Lines surfaces and lumina
162
What is the function of glandular epithelium?
Involved in secretion
163
What are some functions of epithelium?
- protection - barrier - absorption - secretion - receptors
164
List the different types of surface epithelium
- simple squamous - simple cuboidal - simple columnar - pseudostratified columnar - stratified squamous - stratified cuboidal - other stratified - transitional/urothelium
165
Where is simple squamous epithelium found?
- mesothelium - endothelium - lining of alveoli - lining of glomeruli
166
Where is simple cuboidal epithelium found?
- thyroid follicles | - renal tubules
167
What is the function of adherens junctions?
Forms strong attachments between cells via linking cells cytoskeleton's
168
What are some other names for gap junctions?
Nexus or communicating junctions
169
What is a hemidesmosome?
A modified desmosome that links epithelium to basement membrane and underlying connective tissue
170
Where does a surface columnar layer overlie a myoepithelial layer?
- breast - sweat glands - salivary glands
171
Where does a surface columnar layer overlie a basal layer?
Prostate
172
Where is transitional/urothelium found?
- renal pelvis - ureters - bladder
173
Describe microvilli
- short - most epithelia have a few - if numerous= striated/brush boarder - increases SA - contains cytoskeleton elements (actin)
174
Describe cilia
-long, finger like projections -core of microtubules -allows movement in waves Eg respiratory tract, Fallopian tubes
175
What components hold zonula adheren junctions together?
- cadherin protein links the 2 cells tog | - plaque/anchoring proteins
176
What components hold hemidesmosomes together?
Integrin binds to laminin which then links epithelial cells to underlying connective tissue (collagen VII)
177
What are the 4 main types of cell adhesion molecules?
- cadherins - integrins - selectins - immunoglobulin superfamily
178
Where is dense regular CT found?
- tendons - ligaments - aponeuroses
179
What does the term mucosa mean?
The layer closest to the lumen. It comprises of lamina propria=surface epithelium and underlying CT And Muscularis mucosae=layer of smooth muscle
180
What does the term serosa mean?
The layer furthest from the lumen. Aka serous membrane. It comprises of surface mesothelium, basement membrane and underlying CT
181
Serous cells often form what..
An acinus (a secretory unit)
182
Describe the staining of serous acini
Basophilic at base | Acidophilic at apex
183
What are the 2 types of glandular epithelium?
Exocrine | Endocrine
184
Where do you find simple tubular glandular epithelium?
Colon
185
Where do you find simple coiled glandular epithelium?
Sweat glands
186
Where do you find simple branched tubular glandular epithelium?
Stomach
187
What are the main substances that exocrine glands secrete?
Proteins Lipids Glycoproteins
188
What is serous secretions?
Protein in aqueous medium | Eg salivary glands
189
What is mucous secretions?
Glycoprotein in aqueous medium. | Eg respiratory, GIT, cervix
190
What are goblet cells?
Mucous secreting cells packed with membrane bound mucous droplets. Note: the nucleus and organelles are displaced basally. Mucous is none staining in H&E
191
What are the 2 types of glandular epithelium?
Exocrine | Endocrine
192
What is mucous secretions?
Glycoprotein in aqueous medium. | Eg respiratory, GIT, cervix
193
Define: virus
Subcellular genetic elements. | Obligate parasites
194
What type of capsid symmetry do the poxviruses have?
Complex symmetry. They also encode their own proteins for replication (which is rare for a virus)
195
What virus has multi shelled capsids?
Rotaviruses. It makes they very hardy, and able to survive passage through the GIT
196
Describe the types of viral genomes
ss OR ds DNA ss OR ds RNA Can be linear, circular or segmented
197
Describe the further types of ssRNA
+ve sense (like mRNA) | ?ve sense (complementary to mRNA)
198
Describe the different ways to classify viruses
By - families - genera, species, type
199
How are viruses classified into families?
Via - type of nucleus acid genome - strategy of replication - virion morphology
200
What is a distinguishing feature of the DNA virus family?
There are no helical DNA viruses
201
What is a distinguishing feature of the RNA virus family?
All helical RNA viruses have an envelope
202
What are enteric viruses?
Viruses acquired by ingestion of material contaminated with faecal that are localised to the intestinal tract. Eg rotavirus, astrovirus
203
What are respiratory viruses?
Viruses acquired by inhalation if droplets that are then localised to the resp tract. Eg rhinovirus, adenovirus
204
What is a capsid?
Protective protein shell surrounding the viral genome.
205
What are arboviruses?
Viruses that you acquire be being bitten by an infected insect. Eg orbivirus, flavivirus
206
What are sexually transmitted viruses?
Acquired by sexual activity. They cause genital lesions(papillomavirus, herpesvirus) or systemic disease(HIV).
207
What are hepatitis viruses?
Viruses that target the liver. Can be spread by the enteric route or blood or sexually
208
What are some methods of viral detection?
- direct visualisation by EM - viral cultivation - viral Ag detection - host ab detection - viral gene detection
209
What is an important source of new viral diseases in humans?
Zoonoses (species jumping)
210
How do you make a specific aetiological diagnosis of an infection?
- demonstrate organism/components/products - isolate microorganism - demonstrate a serological response
211
Name the techniques used to detect viral Ags
- latex agglutination - solid phase assay - immunohistochemistry - capture assay
212
How do you detect viral nucleic acid?
Via - hybridisation - PCR
213
How do you detect other components of viruses?
- whole genome sequencing | - intact cell mass spect (aka MALDI-TOF)
214
Name some techniques used to demonstrate a serological response in a patient.
- tube agglutination (Widal test) - solid phase assay - immunoblot (Western blot)
215
What are clusters of capsid protein subunits called?
Capsomers
216
What indicates a recent or past infection?
``` Recent = high levels of specific IgM Past= rising titre (increasing levels if ab) ```
217
What is a nucleocapsid?
A capsid that is closely associated with the viral nucleus acid.
218
What is a viral envelope?
Lipid membrane derived from host cell membrane, surrounding the viral capsid.
219
What is the name for a virus without an envelope?
Nacked virus
220
What are expressed on the outside of viral particles?
Surface glycoproteins
221
What is a viral matrix?
A protein layer connecting the capsid and envelope glycoproteins.
222
How can we visualise viruses?
Via transmission electron microscopy or X-ray crystallography
223
What are the types of capsid symmetry?
- icosahedral capsid symmetry - helical capsid symmetry - complex capsid symmetry
224
Define: necrosis
Accidental cell death that induces an inflammatory response
225
Define: apoptosis
Programmed/regulated cell death that eliminates unwanted/unrepairable cells with minimal host inflamm response b/c apoptotic bodies form.
226
List the aetiology/causes of necrosis
- hypoxia/anoxia - microbial infection - drug/toxin induced injury - physical trauma
227
What is ischaemia?
Hypoxia induced by reduced BF, most commonly due to mechanical arterial obstruction. Death of cells occurs in 20-30mins!
228
What is infarction?
Death of tissue due to loss of blood supply most often as a result of arterial occlusion.
229
Injury can be
- sub lethal | - reversible
230
Describe the Pathogenesis of necrosis.
- loss of p membrane integrity (depletion of mitochondrial ATP) - leakage of enzymes - protein synthesis fails - cell swelling, nuclear dissolution, membrane rupture - inflamm response triggered (cell debris is removed by enzymatic digestion and macrophages, tissue repair occurs)
231
Describe some mechanisms of cell injury
- mitochondrial damage (decreased ATP and increased ROS) - entry of Ca (increased mitochondrial permeability and activation of enzymes eg proteases) - membrane damage (via proteases) - protein misfolding - DNA damage
232
Describe why reperfusion can cause injury
Reperfusion causes mitochondria to produce ROS which damage DNA, modify proteins leading to misfolding or breakage, and cause phospholipid damage.
233
Is apoptosis energy dependent or independent?
Energy dependent. Ie ATP processes are still preserved.
234
Describe the nuclear changes evident in necrosis
- pyknosis (n shrinkage) - karyorrhexis (n fragmentation) - dissolution of nucleus
235
Where does coagulative necrosis occur?
Enzymatic dissolution of tissue can occur in solid organs (EXCEPT the brain)
236
Where does liquefactive necrosis occur?
Digestion of dead cells thereby transforming tissue into a viscous liquid mass or cavity occurs in the brain.
237
Describe caseous necrosis
- seen in necrotising granulomatous inflammation due to tuberculosis - cheese like appearance - note: tissue dissolution via enzymes is more advanced than coagulative necrosis but not enough to liquefy the tissue
238
Describe the histology of necrosis
Increased cytoplasmic eosinophilia b/c of damaged protein and loss or rRNA
239
What are the two pathways of apoptosis?
- intrinsic/ mitochondrial pathway | - extrinsic/ death receptor pathway
240
List the causes of apoptosis
- DNA damage - accumulation of misfolded proteins - viral infections - immunological rxns
241
Describe the general steps in apoptosis
- signalling - execution - degradation - phagocytic
242
Describe the morphology of apoptosis
?cells shrink ?nuclear chromatin condenses ?formation of apoptotic bodies ?phagocytosis of apoptotic bodies via macrophages
243
Describe the features/function of skeletal muscle
- aka= voluntary/somatic/striated muscle - attaches to bone to allow movement - Giant, multinucleated cells - note the nuclei is pushed to the periphery of the cell
244
Describe the features/function of cardiac muscle
- only in the heart - also striated muscle - single cells connected into a network - can contract spontaneously
245
Describe the features/function of smooth muscle
- spindle shaped (fusiform) - smaller diam than skeletal muscle - associated with hollow viscera, vv, hair follicles - sustained contractions - central nucleus - peripheral organelles - NO myofibrils or sarcomeres or t tubules - has dense bodies
246
Muscle contraction is initiated by what?
A neural AP
247
What is the function of desmosomes in cardiac muscle cells?
-reinforce joining of myofibrils
248
What is the function of gap junctions in cardiac muscle cells?
gap junctions on longitudinal section (runs parallel to myofibrils) electrically couple cells and coordinate AP
249
Describe the contraction of smooth muscle
- dense bodies are scattered throughout each cell and are connected together via actin and myosin overlapping filaments - contraction draws dense bodies together - cell shortens/shrinks
250
Describe the amounts of muscle regeneration in the different muscle types
- regeneration capacity varies - high plasticity of smooth muscles - limited regeneration by skeletal muscle via satellite cells - no regeneration of cardiac muscle cells
251
Name 3 other contractile cells
- myoepithelial cells - myofibroblasts - pericytes
252
Describe myoepithelial cells
They surround some exocrine glands. When they contract via actin/myosin they squeeze out gland contents Eg surround mammary glands
253
Describe myofibroblasts
Fibroblasts normally make CT. When CT is injured, scar contained activated fibroblasts which become myofibroblasts. Myofibroblasts pull edges of wounds closed.
254
Describe pericytes
They extend around capillaries and regulated capillary blood flow
255
Name the 3 layers of CT that surround axons
Epineurium Perineurium Endoneurium
256
The cytoskeleton of skeletal muscle is organised into what?
Myofibrils | note: they are not an organelle b/c they are not membrane bound
257
What does epineurium surround?
Wraps the Whole nerve
258
Contrast the features of type I, IIa and IIb skeletal muscle fibres
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259
What does endoneurium surround?
Wraps individual axons
260
What is a Schwann cell?
- type of glial cell - helps axons survive - myelinates axons (wraps around multiple times)
261
What is a Node of Ranvier?
A gap between myelinated sections of an axon. It increases speed of conduction b/c APs jump node to node.
262
What is a ganglia?
Collections of neurons outside the CNS. It includes sympathetic (sensory) and parasymp (autonomic motor) dorsal root ganglia. Satellite cells (glial cells) are present too.
263
What are myofibrils made up of?
Sacromeres
264
Describe the basic structure of a sarcomere
Each sarcomere has overlapping thick (myosin) and thin (actin) filaments. Z discs are also present which anchor the thin filaments and form a boundary with the next sarcomere.
265
What is the sliding filament mechanism?
- sarcomeres shorten (not the thick or thin filaments) | - sarcomeres are in series therefore the whole myofibril shortens overall leading to muscle contraction
266
What specialised organelle do skeletal muscles have?
Sarcoplasmic reticulum which wraps around each myofibril and which is rich in Ca2+ ATPases
267
What are T tubules?
- Structures that surround each myofibril. - Note there are 2 T tubules for each myofibril. - Their function is to conduct the muscle AP down into the muscle cell to the SR because they penetrate down between sarcomeres.
268
What is an important feature of how cardiac muscle cells communicate?
?individual cells are joined by intercalated discs
269
What are the components of cardiac muscle intercalated discs?
- fascia adherentes - desmosomes - gap junctions on longitudinal section
270
What is the function of fascia adherentes in cardiac muscle cells?
-Join myofibrils
271
Name the 5 cardinal features of acute inflammation?
``` Redness Swelling Pain Heat Loss of function ```
272
Describe the vascular response that occurs during acute inflammation
- transient arteriolar constriction - arteriolar, capillary and venular dilation - increased vascular permeability - vasocongestion (All involve endothelial activation)
273
Function of endothelium
- semi permeable barrier - cells linked by junctional complexes - synthesises basement membrane - prevents blood clotting - vascular tone - resistant to leukocyte adhesion - GFs, cytokines - replenished by progenitor cells
274
How does the endothelium prevent blood clotting?
Via the compounds nitric oxide and prostacyclin
275
How does the endothelium control vascular tone?
Via the compounds nitric oxide, prostacyclin, endothelin
276
Integrin on rolling leukocytes binds to what molecules on the activated endothelium?
P selectin and E selectin
277
Describe oedema
Abnormal increase in interstitial fluid
278
Describe hyperemia?
Active process of vasodilation which results in increase of blood in vv. eg in inflammation and exercise
279
Describe vasocongestion
Passive process due to reduced outflow of blood from a tissue
280
When does transudate form?
With - increased hydrostatic P - reduced plasma oncotic P Note vascular permeability is normal
281
When does an exudate form?
When there is - increased vascular permeability - impaired lymphatic drainage
282
What are the diff types of acute inflammatory exudate?
- purulent/suppurative - fibrinous - serous
283
Name some examples of suppurative/purulent exudate.
``` (Bac infections) Lobar pneumonia Bacterial meningitis Abscess Perforated diverticulitis Generalised acute peritonitis ```
284
Name some examples of fibrinous exudate
Fibrinous pleuritis Fibrinous pericarditis Acute appendicitis
285
Name some examples of serous exudate
Blister | Pleural effusion
286
What are the two main types of inflammation?
Acute | Chronic
287
Describe acute inflammation
- earliest response - rapid onset - non specific - short duration Features: neutrophils, exudate, vasodilation, macrophages, variable necrosis
288
What is the aim of acute inflammation?
- mediate local defenses - destroy infective agents - remove debris
289
Describe chronic inflammation
- later response - long duration weeks to years) Features: macrophages, lymphocytes, plasma cells, fibrosis/scarring, immune response
290
What are some causes of acute inflammation?
- infections - trauma - foreign material - burns - infarction
291
List some non?receptor targets for drugs
- ion channels - enzymes - carrier molecules - DNA - osmotic Pressure - direct actions
292
Receptors are the sites of actions of what?
- neurotransmitters - hormones - 2nd messengers - drugs
293
Define: receptor
a biological macromolecule/complex that binds another molecule and initiates/modulates signalling or effector activity within a cell
294
Define: ligand
a molecule that binds to a receptor
295
Define: binding site
the site where ligands bind to binding molecules/targets
296
Define: agonist
a ligand that binds to a receptor and activates it. It has affinity and efficacy
297
Define: antagonist
a ligand that binds to a receptor without activating it. It has affinity but NO efficacy
298
What are the main classifications of receptors?
- Ligand gated ion channel receptors - GPCR - Kinase linked receptors - Nuclear receptors
299
Describe the features of ligand gated ion channels
- agonist binds directly and regulates the opening of an ion channel - the opening of the ion channel induces hyperpolarisation or depolarisation - time= msec
300
Name an example of a ligand gated ion channel and its features
Nicotinic receptors - 5 subunits - Ach binds to alpha subunit - Na channel opens - Na entry--> AP or Ach receptor
301
Describe the features of GPCRs
- 7 TMS - alpha helices - mostly on cell surface - linked to an effector via G proteins - most common type
302
Describe the time scale of GPCRs
seconds
303
Name 2 examples of GPCRs
Muscarinic receptor | ACh receptor
304
Describe the mechanism of GPCR activation
ligand binds and activates G proteins. G proteins can be inhibitory or stimulatory. G proteins inhibit/activate effectors which then produce 2nd messengers. These 2nd messengers can cause Ca2+ release or protein phosphorylation
305
Describe kinase linked receptors
- usually tyrosine or serine linked - agonist binds to extracellular domain - receptor often dimerises - this activates enzymatic activity of the cytoplasmic domain - auto and protein phosphorylation - causes gene transcription - ligand is often large peptides
306
Name 2 examples of kinase linked receptors
Growth hormone receptor | cytokine receptors
307
Describe nuclear receptors
- often found intracellularly - (lipid soluble) ligand enters cell - activates intracellular receptor - causes gene transcription
308
Describe the time scale of kinase linked receptors
hours
309
Name 2 examples of nuclear receptors
oestrogen receptor | glucocorticoid receptor
310
Describe the time scale of nuclear receptors
hours
311
Define: pharmacokinetics
the study of the movement of drugs into, within and out of the body and factors affecting this
312
Define: pharmacodynamics
the study of the drugs pharmacological effect/clinical effects
313
Name a drug that has a narrow therapeutic window
phenytoin (digitalis)
314
Name a drug that has a relatively wide therapeutic window
paracetamol
315
What is the therapeutic window
the range in which you can give a drug that will illicit a beneficial effect but not an adverse effect. i.e. it is the window between the minimum effective conc and the minimum toxic conc.
316
What does isoprenaline act as?
beta?1 and beta?2 agonist
317
What does prenalterol act as?
beta?1 selective agonist
318
Define: affinity
the ability of a drug to bind to its target
319
Define: pharmacological efficacy
the ability of the drug once bound, to activate the receptor
320
Full agonists have what type of efficacy?
high efficacy
321
Partial agonists have what type of efficacy?
low efficacy
322
Define: clinical efficacy
the strength of the beneficial effect
323
Name some well known partial agonists
- salbutamol (b2-adrenoceptors) - buprenorphin (opiate R) - sumatriptan (5-HT1 R) - pindolol (b-adrenoceptors)
324
Define: potency
how much of a drug is required to produce a particular effect. measured by EC50
325
Over stimulation of a receptor by its ligand often causes what
receptor desensitisation
326
List the functions of epithelial cells in innate immunity
- physical barrier - dry, no moisture - fatty acids - commensals - microbicidal & inhibitory molecules
327
How do commensals protect against infection?
- produce toxic metabolites - bacteriocins/antibiotics via PAMPS on commensals (raises threshold for infection) - compete for binding sites - control the dev of MALT
328
What are the 4 end results of complement activation
- inflammation via increased BF, permeability, mast cell degran - chemotaxis - opsonisation - lysis via MAC
329
Describe the main steps in the general complement cascade
- activation of complement proenzymes - proteolysis of C3--> C3a & C3b via C3 convertase - C3b covalently attaches to pathogens surface or abs already bound - bound C3b interacts with other molecules to form C5 convertase - C5 convertase cleaves C5-->C5a & C5b - eventual MAC formation and lysis
330
List Kochs Postulates
- organism is found in all patients with the disease - distribution corresponds to lesions - cultivate outside host for several generations - reproduce the disease in other species - demonstrate a specific imm response
331
What must pathogens do to infect mucosal surfaces?
- overcome competition from commensals - move through mucus - resist mucosal defences - adhere
332
How do bacteria adhere to host cells?
via surface proteins - fimbriae - non-fimbriate adhesins
333
What do bacteria adhere to on host cells?
host cell glycoproteins
334
Describe the evidence for fimbriae in virulence
- experiments testing virulence of fimbriate and non-fimbriate bac. The non?fimbriate bac (eg ETEC) cause a lower amount of infection/disease in piglets than fimbriate bac. Therefore we assume fimbriae is essential for infection and virulence - test virulence via giving anti-fimbrial antibodies. If virulence/disease doesn't occur then we assume fimbraie is essential
335
What are the 2 routes of entry of bacteria into host tissues?
- through cells via pathogen-mediated endocytosis | - between cells
336
What bacterial surface proteins are involved in pathogen?mediated endocytosis?
invasins
337
What is an example of a bacteria that uses invasin to penetrate epithelial cells?
Yersinia | gram -ve rod
338
List some strategies employed by bacteria to overcome phagocytosis
- direct evasion via leukocidins, anti-inflammatory toxins and enzymes, and surface anti-phagocytic structures e.g. capsules - interfering with opsonins
339
How do capsules enhance virulence?
- electrostatic repulsion - resemble host components - mask underlying structures
340
What are caspules made out of?
polysaccharides
341
What is the evidence for capsules in virulence?
- test virulence of capsulated and unencapsulated bacteria e.g. strep pneumonia. Unencapsulated bac is avirulent - Anti-capsular antibodies via passive or active immunisation
342
How do antibodies overcome capsules?
IgM and IgG binds and then fixes complement (classical complement pathway). Ig coated bac can then bind to C3b receptors and ig receptors on phagocytes
343
Name 2 examples of bacteria with capsules?
- streptococcus pyrogenes | - meningococcus group B
344
List the bacteriocidal mechanisms of phagocytosis
- lysosomal enzymes and defensins - ROS - reactive nitrogen intermediates (NO)
345
List some strategies used by intracellular pathogens to resist killing by phagocytes
- inhibit respiratory burst - prevent phagolysosome formation - escape from phagosome - resist bactericidal systems e.g. acid fast bac (thick waxy cell wall)
346
List some strategies that enable pathogens to overcome adaptive immunity?
- direct immunosuppression - expression of weak Ags - Ag diversity - Ag modification (changing Ags during infection)
347
List the stages of infection of a host cell by a pathogen
- colonisation - invasion - multiplication - tissue damage
348
List three mechanisms which occur during bacterial infection which result in tissue damage
- direct toxicity by bacterial toxins - cytokines - immunopathology
349
What are the 2 main types of bacterial toxins?
- exotoxins | - endotoxins
350
Describe the features of bacterial exotoxins
- secreted - toxin is a protein - variable resistance to heat - high antigenicity - can be neutralised by Ab - toxoids can be made - very high potency - highly specific mode of action
351
Describe the features of bacterial endotoxins
- produced by dying cells - not secreted/part of cell wall - toxin is LPS - highly heat resistant - variable antigenicity - no neutralisation by Ab - toxoids can be made - moderate potency - non specific mode of action
352
what does cytotoxic mean in relation to bacterial toxins?
Toxin kills the cell
353
what does cytotonic mean in relation to bacterial toxins?
Toxin stimulates the cell e.g. lock jaw
354
Name some examples of extracellular acting toxins that act on intact host cells
- haemolysin | - leucocidins
355
Name some examples of extracellular acting toxins that act on the extracellular matrix
- hyaluronidase | - collagenase
356
What are 2 examples of cytotoxic toxins?
- diphtheria toxin | - shiga toxin
357
What are 2 examples of cytotonic toxins?
- cholera enterotoxin | - heat stable enterotoxin
358
What are the 2 main classes of intracellularly acting toxins?
- simple (not very common) | - bi-functional (A?B type)
359
What is the function of the Ig Fc domain?
- mediates effector functions - activation of classical complement pathway - delivery of Abs through compartments
360
The heavy chain V?region is comprised of what gene segments?
V,D,J
361
The light chain V?region is comprised of what gene segments?
VJ
362
Which gene segments are joined first in VDJ recombination?
DJ first
363
The TCR alpha chain is comprised of what gene segments?
VJ
364
The TCR beta chain is comprised of what gene segments?
VDJ
365
What are the 4 main processes that generate diversity?
- Variable region splicing - junctional diversity - combinatorial diversity - somatic hypermutation
366
Describe junctional diversity
- inserting or deleting nucleotides at the time of joining the V(D)J segments - makes the greatest contribution to diversity - can result in insertion of stop codons, frameshifts etc. - mediated by the enzymes TdT and exonucleases
367
What are the names for a B cell when it is undergoing development in the bone marrow?
early lymphoid progenitor--> common lymphoid progenitor--> pro-B cell--> pre-B cell --> immature B cell
368
What is the role of Flt3L on the bone marrow stromal cells?
Binds to Flt3 on early lymphoid progenitors and promotes the expression of IL-7 R
369
SCF on bone marrow stromal cells binds to what on pro?B cells?
cKit
370
What stabilises the u chain when it is expressed on pro?B cells?
a light chain analogue
371
In what order do antibodies class switch?
IgM--> IgG--> IgE--> IgA
372
Where and when does isotype switching occur?
in secondary lymphoid tissues after encounter with Ag
373
What determines the isotype produced?
the microenvironment (i.e. cytokines produced by CD4T, TFH, NKcells)
374
What cytokine causes B cells to isotype switch to IgA?
TGF-beta
375
What cytokine causes B cells to isotype switch to IgE?
IL-4
376
What cytokine causes B cells to isotype switch to IgG?
IFN-gamma
377
Isotype switching involves changing what part of the Ig?
the constant region on the Fc portion
378
Is isotype switching reversable or irreversable?
irreversable because it involves looping out intervening C segments
379
Describe the shape of IgA
forms a dimer that is linked by a J-chain
380
Describe the shape of IgM
forms a pentamer that is linked by a J chain
381
What antibodies are good at neutralisation?
IgG, IgA
382
What antibodies are good at opsonisation?
IgG, IgA
383
What antibodies are involved in antibody dependent cytotoxicity?
IgG
384
What antibodies are involved in degranulation?
IgE
385
What antibodies are involved in complement activation?
IgM (most potent) | IgG, IgA
386
What is antibody dependent cellular cytotoxicity?
- when an Ab binds to a target cell via its variable region - Ab binds to NK cell via Fcgamma receptor - crosslinking results in NK cell killing
387
Describe the process involved in active transport of IgA across mucosal surfaces
- secreted IgA binds to poly Ig receptor - transport of IgA bound to receptor across cell - IgA is secreted into the lumen with part of secretory component from the receptor still attached - this secretory component protects the Ab from degradation
388
Describe affinity maturation
- the process where a B cell increases its affinity for a particular Ag as the immune response progresses. - it requires T cell help - As Ag levels decrease, B cells with mutations that result in high affinity BCRs are selected for
389
Where is MHC class I found?
on all nucleated cells
390
Where is MHC class II found?
on APCs
391
What are the diff types of MHC I?
HLA-A, -B, -C
392
What are the diff types of MHC II?
HLA-DR, -DP, -DQ
393
MHC class I presents what sort of Ag?
- short peptides 8-11 aa long - cytosolic/intracellular derived peptides - peptides are degraded via a prtoeasome and transported to the ER via peptide transporter TAP
394
MHC class II presents what sort of Ag?
- long peptides 10-30 aa long - extracellular derived peptides - peptides are endocytosed and degraded in an endosome
395
Describe the structure of MHC class I
made up of alpha chains (1-3) and beta-2-microglobulin
396
Describe the structure of MHC class II
-alpha chains (1-2) and beta chains (1-2)
397
Where are MHC polymorphisms localised to?
the antigen binding cleft
398
What chains in MHC class I vary the most?
alpha 1 and alpha 2 chains
399
What chains in MHC class II vary the most?
alpha 1 and beta 1 chains
400
What type of MHC class needs to be associated with an invariant chain when it is in the ER?
MHC class II
401
What is cross presentation?
When peptides derived from the class II processing pathway are process and presented to the class I pathway
402
What does a superantigen do?
- can bind to MHC II and one or more Vbeta chains on TCRs - they do not rely on the antigen binding site - therefore can activate large numbers of T cells and therefore result in large amounts of non-specific activation
403
What MHC classes do naive B cells express?
only MHC I
404
What MHC classes do activated B cells express?
MHC I and MHC II
405
What happens when a DC is activated in a tissue which causes it to mature and migrate to LNs?
- loss of anchor molecules - increased expression of IL-7R - upregs MHC II and I - increased ag processing - increased adhesion molecules - secretion of chemokines and cytokines (IL-12, IL-2) - loose capacity to capture ag - expression of co-stim molecules (CD80/86)
406
What are the 3 signals that are required for T cell activation?
- TCR binding to peptide + MHC - Co-stimulatory molecules (CD28 on T cells binds to CD80/86 on DCs) - Cytokines (shapes T cell differentiation)
407
What happens to a T cell that lacks the second and third signal?
T cell becomes anergic
408
What are the different CD4 T cell subsets?
- Th1 - Th2 - Th17 - TFH - Tregs
409
In the presence of IL?12 CD4 T cells differentiate into what?
Th1
410
In the presence of IL?4 CD4 T cells differentiate into what?
Th2
411
In the presence of IL-6/IL-21/IL-23/ TGF-beta CD4 T cells differentiate into what?
Th17
412
In the presence of IL-6 CD4 T cells differentiate into what?
TFH
413
In the presence of TGF-beta CD4 T cells differentiate into what?
Treg
414
What cytokines do Th1 cells secrete?
IFN-gamma | IL-2
415
What cytokines do Th2 cells secrete?
IL-4 IL-5 IL-13
416
What cytokines do Th17 cells secrete?
``` IL-17A IL-17F IL-6 IL-21 IL-22 ```
417
What cytokines do TFH cells secrete?
IL-21
418
What cytokines do Treg cells secrete?
TGF-beta | IL-10
419
Differentiate between T dependent and T independent responses
T dependent - protein Ags - higher order isotypes - higher affinity Abs - memory T- independent - polysaccharide/lipids/repetitive structures Ags - IgM - low affinity Abs - no memory
420
When a CD4 T cell is activated by a DC via peptide and MHC what does it upregulate?
CD40L
421
What marker does Ag specific B cells downregulate in order to leave the LN?
CXCR5 (IL-5) | aka homing marker
422
What marker does Ag specific B cells upregulate in order to leave the LN?
CCR7 (IL-7)
423
What is a germinal centre?
site of intense B cell stimulation (proliferation and affinity maturation) by TFH cells and FDC (which provide a source of Ag for affinity maturation)
424
What are the effector mechanisms of Th1 cells?
- IFN-gamma activates macrophages and enhances their microbial killing - IFN-gamma causes B cells to produce complement fixing and neutralising Abs - TNF activates neutrophils
425
What are the effector mechanisms of Th2 cells?
- IL-4 causes B cells to produce neutralising IgG Abs and IgE - IL-5 activates eosinophils to combate helminth/allergic rxns - IL-13 causes macrophages to have an alternative activation involved in tissue repair
426
Do become activated CD8 T cells must interact with what?
Ag presented in MHC I on DCs AND activated CD4 T cells
427
List the ways cytotoxic CD8 T cells kill infected cells
- perforin (punches a hole in the cell) and granzyme (activates apoptosis) - FasL binding to Fas on target cell which activates apoptosis
428
Activated CD8 T cells express what cytokines?
- IL-2 - IFN-gamma - TNF-alpha
429
For T cells to move out of the circulation they must express what molecules on their cell surface?
VLA-4 CCR5 CXCR3
430
What distinguishing feature does the 5' end of the sugar?phosphate backbone have?
a free phosphate group
431
What distinguishing feature does the 3' end of the sugar?phosphate backbone have?
a free OH group
432
The term exon stands for?
Expressing regions
433
The term intron stands for?
Intervening regions
434
The 5' promotor sequence of a gene often contains what?
TATA box
435
What does it suggest when a gene has multiple promotors?
It can make alternative forms of the protein (i.e. diff sizes or expression in diff cell types)
436
What enzymes are involved in DNA replication?
- helicase (unwinds DNA) - RNA polymerase (makes short RNA primer) - DNA polymerase (extends from primer with DNA - DNA ligase joins fragments tog
437
During transcription RNA polymerase uses what strand of DNA to synthesise mRNA?
non-coding (anti-sense) strand as a template
438
What are the 2 main sources of variation?
- genetic factors | - environment
439
What are the 2 main causes of variation?
- mutations | - sexual reproduction
440
What is a silent mutation?
where there is no change to aa
441
What is a missense mutation?
change to aa
442
What is a nonsense mutation?
creates a stop codon, usually results in a truncated protein or mRNA degredation
443
What is a polymorphism?
when there is at least 2 or more relatively common alleles of a gene in a pop
444
First cousins are what degree relatives?
3rd degree relatives
445
What are first cousins once removed and what degree relatives are they?
When mums erin or morgan have a kid. The kid would be a 4th degree relative
446
What are second cousins and what degree relatives are they?
If I had a kid and erin or morgan had a kid they would be second cousins and they would be 5th degree relatives
447
What is reduced penetrance?
Reduced penetrance when some individuals with a particular genotype don't have the associated phenotype. e.g. inherited BC
448
what is incomplete dominance?
a heterozygotes phenotype is intermediate between two homozygotes. eg achondroplasia (short limbed dwarfism)
449
What is variable expressivity?
variable expressivity is when some individuals with a particular genotype have a phenotype with varying severity. e.g. polydactyly
450
Name some examples of autosomal dominant disorders
Huntingtons disease | Polydactyly
451
Name some examples of autosomal recessive disorders
``` sickle cell disease thalasaemia albinism phenylketonuria Tay sachs disease ```
452
What is genetic heterogeneity?
where more than 1 gene can cause the phenotype. ie diff people can have diff geneotypes but still display the same phenotype. e.g. hearing impairment
453
Describe X?linked recessive inheritance
females are often carriers. there is no father?son transmission. e.g. Haemophilia A, Duchenne muscular dystrophy
454
What is X linked dominant inheritance?
- less common - twice as common in females cf males - males are hemizygous e. g. rickets
455
Describe mitochondrial inheritance
Mitochondrial DNA is passed through the maternal line. Fathers therefore do NOT pass on their mitochondrial genes e.g. myoclonic epilepsy
456
What is multifactorial/complex mean in relation to genes?
the environment and genes plays a role
457
What does polygenic mean?
``` more than one gene causes the trait e.g. height spina bifida anencephaly cleft palate ```
458
Name some mediators of acute inflammation that cause vasodilation
- histamine - prostaglandins - NO
459
Name some mediators of acute inflammation that cause increased vascular permeability
- mast cells - serotonin (platelets) - bradykinin - leukotrienes (cell membranes)
460
Name some mediators of acute inflammation that cause endothelial activation
- TNF | - IL-1
461
Name some mediators of acute inflammation that cause chemotaxis
- complement components - bac components - chemokines - leukotriene B4
462
Name some mediators of acute inflammation that cause tissue damage
- neutrophil granule contents - ROS - NO
463
Name some mediators of acute inflammation that cause pain
- prostaglandins | - bradykinin
464
Name some mediators of acute inflammation that cause fever
- IL1 - IL6 - TNF - prostaglandins (PGE2)
465
Functions of prostacyclin (PGI2)
- vasodilation | - inhibits platelet aggregation
466
Functions of thromboxane (TXA2)
- vasoconstriction | - promotes platelet aggregation
467
Functions of PGD2 and PGE2
- vasodilation | - increased vascular permeability
468
Functions of leukotrienes
- vasoconstriction - bronchospasm - increased vascular permeability
469
What are the major components of granulation tissue?
- inflammatory cells - new blood vessels - fibroblast migration and proliferation - deposition of ECM
470
Distinguish between healing by primary intention and healing by secondary intention
Healing by primary intention involves narrow closely opposed edges and results in less dead tissue, less granulation tissue and less scarring. Healing by secondary intention occurs in larger wounds and results in a larger amount of scar tissue and granulation tissue.
471
Define: juxtacrine
between adjacent cells that are in contact. it involves gap junctions
472
Define: autocrine
signal is released by a cell that acts on the same cell TYPE or the SAME cell
473
Define: paracrine
between nearby cells of a DIFFERENT type
474
Define: endocrine
signal/hormone goes into the blood as the target is far away
475
What are the 4 main outcomes of acute inflammation
- resolution - healing by repair - abscess formation - chronic inflammation
476
What are some factors that influences healing
- foreign material - infection - BF - extensive necrosis - Radiation - movement - size, location and type of wound - nutrition - immune impairement
477
What role does CD21 play in the immune system?
It's the complement (C3b) receptor Aka CR2 It can bind to complement opsonised to a bacteriums surface that has already been bound my the BCR, thereby enhancing the response.
478
How do resident macrophages and epithelial cells combat intercellular pathogens and stop their spread to nearby cells?
- activation of PRRs cause the release of inflammatory cytokines (type I interferons: IFN alpha and beta) - these up regulate MHC I expression - and block the translation if viral mRNA in nearby cells
479
Do APCs constitutively express high levels of CD80/CD86?
No, they express them when they are activated through PAMPS/DAMPS binding to PRR
480
Where is CD40L expressed?
On activated T cells only after they have been activated by APCs
481
Why will a polysaccharide vaccine not work for a child under 2?
Because they do not have very good T independent B cell mechanisms. Instead you conjugate a protein onto the polysaccharide so the protein can be broken down into peptides which can be presented in MHC II and then presented to T cells.
482
What is a defining feature of macrophages in chronic inflammation?
They fuse together and become multinucleated
483
Describe granulomatous inflammation
It develops in response to persistent or non degradable Ags. It is characterised by epitheliod macrophages (with elongated, foot shaped nuclei) that fuse together to form multi nucleated giant cells. Lymphocytes, fibroblasts and necrosis can also be present.