Foundation Block Flashcards

Question

What is the significance of red and yellow bone marrow?

Answer 1

Red BM is haemopoietic, Yellow is adipose tissue. New borns all bones are red. With age the axial skeleton is red and the proximal femur.

Answer 2

Common progenitor cell divides then differentiates. Haemopoietic stem cell -\>Pro-erythroblast -\> normalblast -\> reticulocytes As you differentiate the nucleus gets smaller until its gone.

Answer 3

Myeloid pathway that produces all the blood cells except for B, T and NK cells.

Answer 4

Neural tissue - ectoderm Muscle - mesoderm Epithelium - all three Connective tissue - multipotent mesenchymal stem cells from mesoderm

Answer 5

The connective tissue makes up a large continuous compartment of the body. Compromised of a few cells, large ECM (fibres and ground substance). It provides structure, strength, metabolic and defensive functions.

Answer 6

Fibres of connective tissue are mostly proteins produced by _fibroblasts_. The two main types are elastin and collagen (this includes reticulin type 3)

Answer 7

Collagen fibres are the most abundant, flexible, strong, Wavy under LM. Consist of three alpha-chains of polypeptide that forms helix.

Answer 8

There are 27 types but need to know: I - connective tissue proper II - cartilage, IV disc III - forms reticular fibres IV - basement membrane VII - anchoring fibrils to BM and ECM

Answer 9

It is dense connective tissue proper that has highly organised collagen.

Answer 10

Collagen type III, thin fibres and provides framework for certain tissues (bone marrow, liver). - Does not stain H&E, must use _silver_ stain

Answer 11

Elastin is made up of a core elastin and fibrillin microfibrils. It founds to provide elasticity in areas such as the aorta, lung and skin.

Answer 12

Ground substance has high water content which cannot be stained with H&E. Made up of GAG (glycosoaminoglycans - long unbranched polysaccharides) and glycoproteins. Hyaluronic acid - GAG but not linked to proteins (most abundant in loose connective tissue) - negatively charged so it attracts Na+ and stains blue. Glycoproteins involved in deposition and orientation of fibres - links cells and matrix (fibrillin, laminin and fibronectin)

Answer 13

The ECM is made up of fibres and ground substance, has various roles in support, metabolic, control of cell differentiation, binding growth factors, scaffold for cell proliferation, continual remodelling, important in haemopoiesis etc

Answer 14

There are fibroblasts found in the connective tissue. Resident cells: macrophages, mast cells, myofibroblast, adipose cells, haemopoietic cells. Wandering cells: lymphocytes, eosinophils, plasma cells, basophils etc

Answer 15

Fibroblast synthesised the ECM and has an elongated cell nuclei.

Answer 16

Nucleus, RER and collagen filaments

Answer 17

Macrophages are phagocytotic cells involved in the immune response and wound healing. Also clears up debris and very important in inflammation. Oval or bean shaped nucleus which is found towards one side of the cell.

Answer 18

These cells are similar to basophils (they are granular), that release histamines, involved in the inflammation pathway

Answer 19

Eosinophils, basophils, plasma cells and lymphocytes

Answer 20

It links and supports organs and the body, mediates nutrient transfer (must pass through this to reach cells).

Answer 21

The density refers to the density of collagen. It can be loose or dense. The thicker it is the less ground substance there is. Dense connective tissue regular: tendons and ligaments

Answer 22

These are cells that specialise in lipid storage. White has one droplet in the cytoplasm. Yellow has multiple droplets.

Answer 23

This is specialised connective tissue involved in compression and flexibility. Proteoglycan ground substance is abundant (highly negatively charged - stains very purple). Collagen type III - the cells are _chondrocytes_ Main type of cartilage is hyaline.

Answer 24

These are rigid and strong support structures of the body. Collagen type I matrix (osteoid) and the connective tissue cells are osteoblasts and osteoclasts

Answer 25

Lies between the support cells and parenchymal cells (such as epithelia). Made up of collagen VII (binds BM to underlying tissue) and reticulin. Also made up of collagen type IV, heparan sulfate and structural glycoproteins (laminin and fibronectin) Cannot see it under the LM with H&E must use different stain (methamine silver) Provides structural support, control of epithelial growth, selective barrier to nutrients, links epithelium to tissue.

Answer 26

Much smaller, no membrane bound organelles, single DNA circle, no nucleus, different ribosome size and binary fission in bacteria.

Answer 27

Cytoplasmic membrane, matrix, ribosomes, genome (chromosome with/without plasmids) and _cell wall_

Answer 28

Essential for survival which contains proteins and lipids. Allows selective interaction with environment (entry of nutrients and exit of waste). Location for many processes because proteins can be located in it (respiration or pseudo ER)

Answer 29

It is hypertonic (relatively) so water enters the cells and will cause it to burst. But the cell wall protects this from happening. Packed with ribosomes

Answer 30

No membrane, chromosome is single circular DNA, looped and super coiled. No introns or exons.

Answer 31

These are circular dsDNA supercoiled that is _independent_ of the chromosome.

Answer 32

Each cell has 4000-6000 genes but the entire 'pan-genome' has detected over 25000 genes. This implies optional genes (accessory) on top of the core.

Answer 33

Plasmids can move between bacteria, bacteriophages (viruses that afefct bacteria), pathogenecity islands, transposons, integrons

Answer 34

Protects cell lysis Consist of peptidoglycan (polymer of sugar and amino acid). Many targets for antibiotics and main component of PAMPs

Answer 35

Gram positive: The outside layer consist of the peptidoglycan Gram negative: This has three layers instead. It has an outer membrane then followed by the peptidoglycan and finally plasma membrane, Cell wall for Gram negative includes: Outer membrane and peptidoglycan

Answer 36

Teichoic acids and large amounts of peptidoglycan

Answer 37

Major feature is the outer membrane, prevents entry of bile salts and antibiotics. The outer membrane can be washed away by alcohol. Has passageway for larger molecules to pass. Contains _lipopolysaccharide (LPS)_ that stabilises outer membrane - also acts as an endotoxin (PAMPs)

Answer 38

Consists of Lipid molecule --\> core polysaccharide (repeating sugar unit). The repeating sugar units are known as O-antigens.

Answer 39

These do not respond to Gram stains because of a _thick waxy_ wall. It has a peptidoglycan base layer then many additional layers. This gives it resistance to harsh environments and antibiotics. (Also leads to slow nutrient uptake - slow growth)

Answer 40

These are circular bacteria.

Answer 41

These are bacteria that looks like rods...

Answer 42

Stain blue first then wash with alcohol then stain red.

Answer 43

Constant maintenance of internal body environment

Answer 44

These are systems that cause effect to maintain the environment. Usually uses _negative feedback_.

Answer 45

Regulated variable, sensor, set point, comparator and effector

Answer 46

Baroreceptor – physical stretch opens up ion channels so that the influx of ions sends signal about the blood pressure. Osmoreceptors: found in the brain and if there is more water coming in the difference in osmolality will be detected by the cell enlarging (water enters it).

Answer 47

Chemical - hormones Electrical - nerve impulses Fast vs slow. General vs localised response. There are systems that mix the two such as adrenal glands and kidneys (renin - sympathetic)

Answer 48

Set points can change with circadian variation, aging and response to _persistent_ changes in ambient levels

Answer 49

Sometimes two variables will contradict what the effectors will do. Such as blood pressure and body temperature while running on a hot day. The body will prioritise the blood pressure first because of the brain oxygenation importance.

Answer 50

Heart rate, stroke volume and total peripheral resistance

Answer 51

Pre and post glomerular tone and mesangial cell contraction (structure associated with the capillaries - by contracting it)

Answer 52

This is done in the hypothalamus with separate heating and cooling centres (by integrating both inputs from central and peripheral receptors)

Answer 53

Central receptors are used to detect warmth and generally found in the spinal cord. Peripheral receptors are used for both cold and warmth (typically the skin) for preemptive warning of oncoming changes in ambient temperature.

Answer 54

Sublingual, ear canal and rectal (this is the best method - least affected by ambient temperature)

Answer 55

Body heat generation + heat gained by radiation = heat loss by body

Answer 56

Radiation, conduction, convection, radiation and evaporation. Many of these are dependent on moving down a thermal gradient.

Answer 57

Sympathetic outflow to skin arterioles and sweat glands for cooling. Stimulation of motor nerves to begin shivering for heating

Answer 58

The sweating occurs sooner, more sweat volume but lower [Na+] in sweat

Answer 59

This occurs because of the change in set-point temperature induced by pyrogens (whether it may be exogenous or endogenous). Synthesis of PGE2 which is inhibited by aspirin. Shivering occurs because the body is trying to increase the temperature by trying to reach the new set point. Chills: Heating mechanisms activated as set-point rises (Shivering) Crisis: Cooling mechanisms activated as set-point falls (sweating)

Answer 60

1. Recognise self/non-self 2. Should be present since birth 3. Rapid reaction 4. Response must be appropriate for the microbe

Answer 61

There is the innate and adaptive system and yes they do communicate with each other. The variation in innate signalling will shape the adaptive response to particular microbes.

Answer 62

Innate differences: recognises PAMPs (generalised), rapid response, no memory, components include physical barrier, antimicrobial chemicals, phagocytes, NK cells and others (adaptive components: lymphocytes, antibodies and cytokines)

Answer 63

Recgonition \> effector function (innate, maybe immunity) \> immunological memory \> immune system regulation Sometimes immunopathology due to damage by or failures in the immune system

Answer 64

Pattern recognition receptors bind to PAMPs which are shared molecular patterns found on pathogens. This induces a signal cascade. These include TLR (toll like receptors) and NOD-like receptors This is the recognition system used by the _innate_ immune system

Answer 65

These are antigen receptors used by T and B cells in the adaptive immune system. It also includes antibodies generated. These receptors recognise very distinct molecular patterns that seperate from self.

Answer 66

Antibodies are immunoglobulin that binds to specific antigens. It has a constant region (for isotype - different effector) and variable region (for the specific antigen) It can be found in soluble form or bound to BCR (is the BCR)

Answer 67

All immune cells originate from the haemopoietic stem cell which differentiates into the myeloid and lymphoid progenitor. Lymphoid progenitor produces: NK, B and T cells Myeloid progenitor produces: Everything else

Answer 68

These are proteins secreted by cells that interact and affect behaviour of cells that have the appropriate receptors

Answer 69

These are secreted proteins that attract cells who have the appropriate receptors - by binding to cysteine containing receptors (CCR, CXCR)

Answer 70

May be constitutively produced or only on activation. Different concentrations lead to different effectors. Inhibition or activation of cytokines produces many outcomes.

Answer 71

Most of them are found in the blood circulation and only a few resident macrophages and dentritic cells are found in the tissues.

Answer 72

Leukocytes are first found in primary lymphoid organ which then circulate into the blood and into the secondary lymphoid organ (spleen, lymph nodes and MALT - mucosal associated lymphoid tissue). This circulation completes a whole cycle 24 hours for T cells. Some macrophages and dentritic cells move into the tissue.

Answer 73

Leukocytes from the blood into tissues by interactions with endotheliel cells. Which then bind to PAMPs on the pathogen and activate their effectors. The lymphatics carry microbes to the secondary lymphoid organs where they bind to specific antigen. Once T and B cells are ready they will re-enter the tissue through the blood circulation.

Answer 74

Lymph nodes: sample antigens from skin and internal tissues Spleen: samples antigens from blood MALT (Mucosal associated lymphoid tissue): samples antigens from mucosal tissues, about 50% of lymphocytes are here.

Answer 75

These cells act to suppress the immune system in case the system is activated for too long which may cause damage instead.

Answer 76

Flagella, fimbriae (pili), capsules and endospores

Answer 77

It is composed of thin, long, hollow helical filaments (which contain flagellin protein). Its function is to provide the bacteria with motility. It is also the determinant of the H-antigen in E.coli

Answer 78

Made of the protein pilin and its function is to attach to other cells and each other. Sex pili can transfer plasmids between bacteria.

Answer 79

These have polysaccharides extending from cell surface. It's hard to wash off and makes the colonies look shiny. Seen by negative staining. It functions to protect the bacteria from dehydration, virulence and protects against phagocytosis.

Answer 80

Bacillus are rod shaped bacteria, Gram +ve, produces spores, aerobic, causes Anthrax and is encapsulated

Answer 81

Endospores are highly resistant dormant structures that do no replicate. They are very resistant to heat, UV and chemicals. Hard to stain and sporulation occurs when growth ceases (lack of nutrients/moisture)

Answer 82

Causes tetanus, strict anaerobe, Gram +ve, Rod, capable of forming spores

Answer 83

These fall under the same family as Clostridium tetani - just that the spores are found within the cells instead.

Answer 84

Bacteria uses binary fission. The curve consists of lag phase, log phase, stationary phase (toxic substances released by the bacteria itself)

Answer 85

Passive diffusion, facilitated diffusion and active transport

Answer 86

Respiration: oxygen Anaerobic respiration: Inorganic compound (not O2) - such as sulfur oxidising bacteria Fermentation: organic compound (often when oxygen is used up)

Answer 87

Strict anaerobes, strict aerobes, facultative anaerobes, aerotolerant anerobes and microaerophiles (best in O2)

Answer 88

Top row is before the tubes are inoculated. Bottom row has been inoculated. The particular tube is looking for specific characteristics. The middle tube went from purple to yellow because acid has been produced. Gas is also trapped. This looks at the ability of bacteria to ferment glucose to produce formic acid (HCOOH). Formic dehydrogenase HCOOH —\> H2 + CO2, this gas is trapped in the tube.

Answer 89

Bombard the bacteria till it breaks down then measure the masses of the components using MS

Answer 90

Can genome the bacteria DNA to identify the exact species to allow for proper treatment

Answer 91

Phenotype - Morphology, biochemical behaviour, surface antigens Genetic make up Defined as species if \>97% related and genera if \>95% related

Answer 92

1. Microscopy a) Unstained - darkground (e.g., syphilis), phase contrast (e.g., cholera) b) Stained - Gram, Ziehl-Neelsen, capsule, spores. 2. Culture a) Indication of growth requirements, e.g. atmosphere (anaerobes); temperature; nutritional requirements; resistance to inhibitory compounds, e.g., bile salts b) Colony morphology - size, shape, pigment, texture (smooth or rough), haemolysis (e.g., Streptococcus), swarming. 3. Proteomics Identification of species-specific proteins by using mass spectrometry on intact or lysed cells 4. Genomics Determination and analysis of 16S rDNA or other sequence, including whole genome 5. Detection of structural antigens a) For rapid diagnosis: by immunofluorescence, direct agglutination or latex agglutination b) To determine serotype 6. Susceptibility to bacteriophages and bacteriocins Mainly used by reference labs to subtype certain bacteria. Will be superceded by sequencing 7. Production of toxins and other virulence determinants Mostly done by testing for virulence-associated genes. Can be determined from whole genome sequence 8. Pathogenicity for animals. Seldom done, but may be required for forensic testing.

Answer 93

There are surface epithelium (lines surfaces and lumina - e.g. skin, GI, respiratory system, kidney and reproductive tract) and glandular epithelium (involved in secretion - single cells, invagination of multiple cells forming glands, solid organs).

Answer 94

It is for protection, secretion, absorption, barrier and receptors (smell and taste)

Answer 95

The cells have a polarity: apical, lateral and basal domains. They are connected by a cell junctions and supported by a basement membrane. It is avascular (nutrients must diffuse from surrounding tissue)

Answer 96

Number of layer (simple and stratified - type is determined by top layer cells), shape of cells (squamous, cuboidal, columnar) and surface specialisation (cilia or keratinisation)

Answer 97

They are flat cells which are good for selective diffusion of nutrients in specific regions. Found in the mseothelium (lining of body cavity), endothelium, lining of alveoli, glomeruli

Answer 98

These are cells that look like cubes found in the thyroid follicles and renale tubules. These types of cells are generally used for secretion and absorption (used in many ducts).

Answer 99

These are tall cells (but not as wide) with an oval nucleus at the base. There are non-ciliated (stomach, small and large intestines, gall bladder and bile ducts, endocervix). There are also ciliated ones (fallopian tubes and bronchioles - used to move mucus around with) They mostly cover the digestive system and upper respiratory system

Answer 100

These look like if multiple cell layers are present but in reality it is just a single layer of columnar cells with cilia. This is found in the respiratory tract. - If it is non-ciliated it would be found in the epididymis and vas deferens Also involved in secretion and absorption

Answer 101

These have multiple layers of cells typicall with cuboidal cells at the base and squamous cells at the top. Keratinising: skin Non-keratinising: found oral cavity, oesphagus, anus, vagina, ecto cervix

Answer 102

These are multiple layers of cuboidal and are found on _ducts_

Answer 103

This is found in glands because the myoepithelial contraction forces the contents to come out. Salivary glands, Mammary glands (breasts), sweat glands

Answer 104

These are found on prostate

Answer 105

These have a basal layer of columnar and the top layer is umbrella cells (which is able to accomodate for changing sizes) this is found on the renal pelvis, ureter and bladder.

Answer 106

Microvilli, cilia Microvilli - increase surface area by 20 times and contain cytoskeletal element Cilia - are longer finger projections of microtubules that allow movement (found in the respiratory tract or fallopian tube)

Answer 107

From apex to base of cells Zonula occludens \> Zonula adherens \> Macula adherens (Desmosome)

Answer 108

They act to limit the passage way for what goes between cells

Answer 109

There is the zonula and the macula adherens, cadherin is a transmembrane protein where the cadherin protudes from the two cells into the gap. In the plaque there are catenins that links the cadherins to the actin (cytoskeleton). Defects in these two proteins means that the cells do not adhere well. Cancer cells dissociate and invade other parts of the body, this is why the two proteins are so important -Mechanically strong attachment between cells (links cytoskeleton)

Answer 110

These are communicating junctions (allow selective movements of molecule between cells)

Answer 111

These are modified desmosomes that links epithelial to underlying basement membrane (not cadherins it is integrins which act as TM protein)

Answer 112

TM proteins that link to other CAMs on other cells. Functions in cell adhesion, communication, cell movement and differentiation.

Answer 113

Cadherins, integrins, selectins and immunoglobulin superfamily (ICAM, CCAM, PECAM - for homotypic cell-cell adhesion)

Answer 114

Structural support, control of epithelial growth, links epithelium to underying tissue and selective barrier to nutrients. Underlying basement membrane

Answer 115

Found on the body that is exposed to the external environment (resp and GI) Has epithelium, underying connective tissue (lamina propria) and sometimes SMC (muscularis mucosae). Has glands to secrete mucus

Answer 116

These are found in the body cavity and lines the peritoneal cavities, pleural, pericardium It has surface _mesothelium_ and supportive connective tissue.

Answer 117

Exocrine secretes on the epithelium or into a duct. Endocrine secretes into the blood. These glandular epithelia can be single celled, invaginations or solid organs.

Answer 118

Simple tubular - colon Simple coiled - sweat glands Simple branched tubular - stomach

Answer 119

Lipids, proteins, mucous (glycoprotein) and serous (protein)

Answer 120

They secrete mucus from mucus droplets. Unicellular glands.

Answer 121

Serous cells are secretory units (cuboidal) which are called acini. Secretes into a lumen.

Answer 122

These are epithelial cells that can contract usually found on glands that require extra release. Mammary, salivary and sweat glands.

Answer 123

Labile cells are continuous going through the cell cycle and dividing. Stable cells are outside the cycle waiting for signals to divide.

Answer 124

It causes diarrhoea and only recent have been able to put forth a vaccination.

Answer 125

The virus may target the T-cells themselves which are essential (HIV). Viruses that incorporate their genome into our DNA also makes it very complicated to vaccine against when they go _dormant_

Answer 126

Viruses are strands of genetic elements which are obligate parasites. They are not cells. They are unable to self-replicate on their own or have motility (no metabolism)

Answer 127

Genome, capsule (protective protein shell), nucleocapsid (capsid most closely associated with the viral nucleic acid), envelope (lipid membrane), matrix (protein layer that connects the capsid and envelope glycoproteins). Genome + capsid (core component) = virus

Answer 128

Electron microscopy or use of light that have a much smaller wavelength (such as X-rays)

Answer 129

Capsids are actually _icosahedral_ capsids which means they are made up of 20 planes. The capsomers are different sized so give particles a different look. Or it can be made up of a _helical_ capsule (which is also enclosed by an envelope) usually found as the nucleocapsid.

Answer 130

These are not like the standard icosahedral and helical structures. These are much larger and complex out of all the viruses.

Answer 131

A very hardy virus because of the thick layer that allow them to survive harsher environments. Such as rotavirus surviving in the GI tract.

Answer 132

Some viruses acquire a lipid capsule by budding it off from the host cell membranes.

Answer 133

This allows us to analyse the specific shape of receptors found on viruses. Help us develop virus-receptor-antibody interactions that may lead to vaccines.

Answer 134

Classification by: type of genome, mode of replication, morphology of virion - determines family For species we look at: arrangement of genes, sizes of proteins, serological reactions and the disease it produces Useful to classify so we can predict how new viruses may behave.

Answer 135

They are also only found in RNA there are NO helical DNA viruses.

Answer 136

Enteric viruses - intestinal stract Respiratory viruses Arboviruses - through insect bites Sexually transmitted viruses Hepatitis virus

Answer 137

1. Use EM 2. Grow viruses on culture - gold standard (this is actually quite hard because of the large variations) 3. Detect specific virus proteins 4. Host serological response 5. Viral gene detection

Answer 138

Emerging infections generally are infections that appear in a population or had previously appeared but are increasing in frequency. Viruses have a very high mutation rate (Esp RNA). Zoonose (species jumping) also introduces a lot of new viruses

Answer 139

1. Make clinical diagnosis based on history and examination 2. Confirm with tests 3. Never blindly order tests

Answer 140

1. Demonstrate organism, component or product 2. Isolate the micro-organism (gold standard) --\> since presence does not imply causality (normal flora) 3. Demonstrate a serological response (immune response to that microbe)

Answer 141

Microscope can be used to identify the agents by using different stains such as: phase contrast, darkground, gram, Ziehl-Neelsen (acid fast bacteria)

Answer 142

When the component or organism is too small to detect with microscopy, EM can be used to very small particles such as viruses.

Answer 143

Antigens are first in the solution \> latex particles are attached with known antibodies\> once it recognises the antigen it will cross link it The latex particle causes clumping This process must have a particular antigen in mind.

Answer 144

This time the sample is in a solid state with antigens on it. The antibody will attach to it whilst having a label attached (the label will visual fluorescent - immunofluorescence)

Answer 145

This causes syphilis

Answer 146

It can also be used in anatomical pathology for many biopsies.

Answer 147

This is done by identifying a known antibody that binds to our target antigen. Then the typical labelling occurs.

Answer 148

In this case we use the an antibody to first clean up the sample then wash it. Then use another tagged antibody to make it fluorescent.

Answer 149

Hybridisation and PCR

Answer 150

There will be a target DNA. It must be sDNA (by melting) which is allowed to be re-anneal with a probe. The probe has a particular sequence (complementary base pairing) and labelled with a fluorescence or radioactive element.

Answer 151

The target DNA will be melted, a primer of complementary strand is attached to it. DNA polymerase is then used to extend that DNA strand until a new dsDNA is created. This process is repeated multiple of times then it is ran on a gel electrophoresis (to confirm identity). - Each strand created are of the same length. Despite a longer strand thats created, each time the primer attaches it's always at the same location. Therefore creating the same length.

Answer 152

It is important to attemp to isolate the organism before the patient has been medicated. These are then grown on a culture media.

Answer 153

Sterile site: no microbiota Site with normal microbiota Sterile site with abutting site with microbiota (sterile passes through non-sterile area)

Answer 154

Tube agglutination test (Widal test) Heat kill the bacteria so they will not infect people in the labs. The heating gets rid of many rubbish on the surface so that the O-antigen is showing easily. The tubes are diluted. Add the bacteria to each tube, there is also a control. When the bacteria binds to the antibody they clump and fall to the bottom so that you can now see the lines in the background. The first tube is a control where the bacteria is in suspension (hanging in the middle) so that we cannot see the lines)

Answer 155

Titre is the greatest dilution that will allow you see the lines

Answer 156

When you first see the patient you take serum, faeces and blood for culture (store it). Then you take a second serum and check if the antibody count is going up. We check for a four fold rise in tubes (rising titre) to see if it is a recent infection. IgM is the first type of antibody that is produced in an infection. High levels indicates a recent infection whereas IgG indicates past infection.

Answer 157

Hypoxia, trauma, drugs/toxins and infections

Answer 158

Hypoxia induced by reduce blood flow most commonly do to mechanical arterial obstruction. Timing is important in determining reversibility of tissue damage.

Answer 159

Death of tissue due to loss of blood supply because of arterial occlusion

Answer 160

The lack of mitochondrial ATP production is the key event in cellular injury. Morphological change are far slower than the immediate metabolic death/changes. 1. Reversible injury: ATP depletion so ATP pumps don't work. Cell becomes swollen. 2. Irreversible: when the cell membrane breaks, protein synthesis stop and nuclear/cytoplasm gets dissolved. Inflammation is integral in necrosis

Answer 161

Decrease ATP, increased ROS (damage to cell contents), influx of calcium ions (activate enzymes and permeability) and eventual membrane damage and rupture. Repursion of the damaged tissue can cause secondary damage because it produces ROS that affects everything in the cell.

Answer 162

Well defined demarcation because of the defined blood supply. Necrotic tissue is yellow.

Answer 163

Has ghost cells (just the outline) with the loss of its nucleus The cytoplasm stains more eosinophilic (loss of rRNA and binds to damaged protein)

Answer 164

Pyknosis: shrinkage of the nucleus and increased basophilia Karyorrhexis: this is nuclear fragmentation Then eventually complete dissolution of nucleus

Answer 165

Ghost outlines and occurs when enzyme digestion of tissues is slow. Occurs in _solid organs_ except for brain.

Answer 166

This is necrosis where the digestive enzymes work a bit faster and transfer the tissue into a viscous liquid. Only found in the brain.

Answer 167

This occurs commonly in the lungs due to tuberculosis. It has a cheese-like appearance. Amorphous granular debris with no distint cell borders. The digestive enzymes speed are between coagulative and liquefactive.

Answer 168

This is an energy dependent process. Activated by intrinsic or extrinsic pathways \> activates _executioner caspases_ to begin apoptosis. Intrinsic - mitochondrial pathway Extrinsic - death receptors (by Fas or TNF receptors)

Answer 169

DNA damage, accumulation of misfolded proteins, viral infections or immunological reactions

Answer 170

The cell will shrink, nuclear chromatin will condense, formation of cytoplasmic blebs which are apoptotic bodies (AB). Phagocytosis of the AB by macrophages

Answer 171

Skeletal, cardiac, smooth Myofibroblast, myoepithelial and pericytes

Answer 172

These are somatic, striated, multinucleated peripherally muscles that stretch the entire length of muscle.

Answer 173

Also striated, works like skeletal muscles, network of single cells instead and can spontaneously contract. Single nuclei located centrally

Answer 174

These are NOT striated, spindle shaped (fusiform), these are very good at sustaining long contractions. Centrally located elongated nuclei

Answer 175

Contraction is between the actin and myosin. Started by an AP that travels down the T-tubules which triggers SR release of Ca²⁺. This the sarcomeres to contract. Myofibril (organelles of contraction) is made up of sarcomeres.

Answer 176

The myofibres are made up of repeating sarcomeres. The sarcomeres are made up of the overlapping of actin and myosin. The Z band anchors the thin filament in the sarcomere (actin)

Answer 177

Myofibrils and sarcomeres work like skeletal muscles. It is single cells in a network. There may be mono or binucleate cells. These form interconnecting network which is joined by _intercalated discs_.

Answer 178

These are specialised cell junctions. They hold the contractile cells together as well as transfer the force conducted. Fascia adherentes join myofibrils across cell boundaries. Desmosomes reinforce join between myofibrils. There are also gap junctions on the longitudinal section of the intercalated disc (not much stress on this)

Answer 179

They function to carry electrical impulse across the cells so that they contract in coordination.

Answer 180

These are spindle shaped cells, with central nucleus but no sarcomeres, myofibrils or t-tubules. Instead of myofibrils they have _dense bodies_ (which act as Z discs) that bind to myosin and actin Not as organised as striated muscle - but very similar

Answer 181

The different chemistry in each type allows for differential staining.

Answer 182

Some muscle cells have limited regeneration (skeletal muscles - satellite cells). Cardiac muscles have none. Reasonable plasticity in smooth muscle cells as evident in atherosclerosis.

Answer 183

Myofibroblasts: close wounds Pericytes: these are found around capillaries and regulate capillary blood flow Myoepithelial cells: surround exocrine cell to aid secretion

Answer 184

They arise from the CNS, DRG and autonomic ganglia. Some are myelinated to increase transmission speed Axons are extended throughout the body

Answer 185

The axons are wrapped in connective tissue. There are epineurium (whole nerves), perineurium (bundles of axons - fascicles) and endoneurium (individual axons)

Answer 186

Schwann cells are a subset of glial cells (support). Schwann cells specific support axons. The nerves are waxy (s-shaped). These cells wrap axons in myelin.

Answer 187

These are gaps in the axons that allow electrical pulse to jump.

Answer 188

Ganglia includes DRG (sensory), sympathetic and parasympathetic ganglia. These are supported by satellite cells (glial)

Answer 189

Inflammation is the body's defense after injury has occurred and typically attracts blood cells to the site of location to deal with injury and initiate repair. May include clearing pathogens, regeneration and scarring.

Answer 190

Acute: earliest response, rapid onset, short duration, mostly _neutrophils_, fluid, protein exudate, vasodilation and macrophages, specific Chronic: is mostly macrophages, lymphocytes and plasma cells, has scarring and development of immune responses

Answer 191

Some infections, trauma, burns, foreign materials

Answer 192

Vascular response \> infiltration (exudate: cells, fluid and proteins) \> Variable necrosis

Answer 193

These PAMPs and DAMPs will be recognised by PRR on tissue macrophages, dendritic cells and epithelial cells. This leads to activation of these cells that produces cytokines and thus begin the inflammatory response.

Answer 194

Initially there will be transient arteriolar constriction. Then dilation follows soon after. There will be increased vascular permeability \> vasocongestion which is all done by endothelial activation.

Answer 195

Tight junctional complexes, synthesises underlying basement membrane, prevents blood clotting, prevents leukocyte adhesion, role in vascular tone.

Answer 196

First macrophages release IL-1 and TNFa once activated to act on the endothelial cells. They will up-regulate P,E selectins that bind leukocytes (margination). Rolling occurs until the leukocyte binds to integrins (ICAM-1 which binds to LFA-1). This is a stronger hold onto the leukocyte and stops them from rolling. PE-CAM are then involved in the diapedisis process while the leukocyte follow the chemokine signals.

Answer 197

Neutrophils have short life because of the lack organelles and anaerobic resp. They are recruited into the tissue from the blood - predominant cell for 6-72 hours. Main role is to phagocytose bacteria and break down damaged tissue. - Neutrophilia (increased amount in blood - since its released from the bone marrow)

Answer 198

Come from blood monocyte, long lived, phagocytic (microbes, tissue debris) and act as APC for humoral immunity. Secretes many chemokines that affect the adaptive immune system, endotheliel, bacteria (breaks it down), tissue destruction and stimulate repair.

Answer 199

Engulfed after it binds to the surface receptors. Kill bacteria by lysozyme or ROS (NO) pathway.

Answer 200

Heat, pain, swelling, loss of function and redness

Answer 201

Purulent, fibrinous and serous

Answer 202

This is when there is a large amount of neutrophils that infilitrate the site (pus formation). This is associated with abscess (a lot of necrosis with inflammation). Perforated diverticulitis - neutrophils in the wall of a hollow organ (gets necrosis) \> leads to enzyme release \> inflammation \> perforation in the periteneal.

Answer 203

Fibrinous exudate is produced on the serosa layer and in these causes the fibrin exudates into the periteneal. The inflamed surfaces activate pain receptors and this is healed by scarring.

Answer 204

Not many cells are found in these exudate and it is mainly fluids e.g. blisters

Answer 205

This is abnormal increase in interstitial fluid which could lead to transudate (increased hydrostatic pressure so fluid exits only - no proteins) or exudate (increased permeability)

Answer 206

There are physical, chemical and biological barriers that prevent pathogens from colonising.

Answer 207

They act as a physical barrier while also secreting enzymes that are microbicidal. As well as cytokines to signal immune system function. e.g. lysozyme, phospholipase A, B-defensins (peptides that enter the bacterial cell wall and disrupts it), pH

Answer 208

The normal flora can produce toxins, antibiotics, compete for binding site on the host, and effectively tickle the immune system via interactions with the epithelial cells PAMPs,PRRs (to induce defensins. Indirectly develops MALT.

Answer 209

Peptidoglycan, LPS and flagellin which are recognised by TLR and NLR

Answer 210

It recognises mannan (sugar) and phosphocholine which is recognised by MBL (mannan binding lectin), CRP (C-reactive protein) and C1q Ultimately activates the _complement cascade_

Answer 211

They release potent pro-inflammatory mediators \> inflammation. They are involved in chemotaxis to attract phagocytes to the site. Opsonisation to stick proteins on microbes to increase their affinity to macrophages and neutrophils They can even lyse the bacteria themselves (membrane attack complex)

Answer 212

Activation of complement proenzymes \> all pathways lead to proteolysis of C3 into C3a and C3b (C3 convertase). C3b will attach to microbial surface. C3b will interact with other molecules to form C5 convertase which cleaves C5 into C5a and C5b (forms the core of another enzyme - membrane attack complex)

Answer 213

Alternative (PAMPs), classical (C reactive protein, antibody when bound to microbe) and lectin (mannan) pathway

Answer 214

Spontaneous lysis of C3 \> C3a and C3b in the presence of PAMPs. The C3b will interact with other molecules (B,D,etc) to form C5 convertase.

Answer 215

C3b only binds to pathogen surfaces - because of charge, inhibitory molecules found on host cells C3b receptors found on phagocytes

Answer 216

IgM and IgG bound to microbes attract C1q \> recruit C1r \> forms enzyme to bind C1s which forms the complex that can then initiate the breakdown of C4,2,3. Now C4b and C2b form a C3 convertase. It produces C3b. If C4b, C2b and C3b come together it produces C5 convertase - MAC

Answer 217

The MBL is similar in structure to C1q which attaches to repeating units of mannose and other sugars on microbes. This captures _MASP-2 and activates C4._ This pathway is very similar to_ classical_ pathway now. Initiates the breakdown of C2 and C4.

Answer 218

The convertase produces C5a and C5b. By recruiting C6,7,8 we can now recruit 15 units of C9 we form a MAC (membrane attack complex)

Answer 219

They are phagocytotic to microbes as well as apoptotic and necrotic cells. Secrete many factors (chemokines, IL-1 and TNFa inflammatory mediators). Can present antigens to T cell (as well resident dendritic cells)

Answer 220

TLRs, NLRs, C-type lectins are the PRRs and it typically recognises peptidoglycans, LPS and B-glucans

Answer 221

Activated TLR will use MyD88 and TRIFs as adaptors to eventually converge the signalling pathway to the production of inflammatory mediators, chemokines and costimulatory molecules. In this case especially NFkB

Answer 222

PAMPs and DAMPs bind to _some_ NLRs which causes oligomerisation form high molecular weight complexes (recruits caspase-1 which proteolytically cleaves molecules - especially IL-1 which is a pro-enzyme). Inflammasomes are multi-molecular IL-1 activating machines.

Answer 223

The microorganism must bind to the appropriate receptors. Whether it may be antibodies, complement receptors or mannose receptors. Ingestion then occurs followed by killing.

Answer 224

1. Phagocyte binds to the opsonised organism (C3b) 2. Phagosome begins to form by engulfment 3. Phagosome and lysosome begin to fuse and form phagolysosome 4. Damage and digest the microbe

Answer 225

Acidification, antimicrobial peptides (defensins, cationic proteins), lysozymes, hydrolases, lactoferin (competitors) and toxic super oxides and toxic nitrogen intermediates (nitric oxide)

Answer 226

Phagocytose and kill a variety of microbial agents. Produce cytokines and chemokines to regulate the immune response. First line of defence against infection. Also cell lysis causes their cellular content to act as NETs (neutrophil extracellular traps) to catch bacteria.

Answer 227

By IgE loaded eosinophils.

Answer 228

NK enters cell via chemotactic signals, bind and kill altered cells. Typically detect changes in MHC I (which normally acts as an inhibitory molecule)

Answer 229

Anterior skin is more sensitive than the posterior skin. This is due to the nerves innervation. The blood supply is much more diffuse on the back.

Answer 230

From the 9% rule we can estimate to about 18% of the total skin

Answer 231

T1 vertebra - coccyx, medial border of the scapula, posterior surface of the ribs and the iliac crest.

Answer 232

T1-T12 which includes true ribs, false ribs and floating ribs.

Answer 233

The primary curve is the area of the vertebra where the fetus C-shape direction is maintained. Secondary curves are lordosis of the vertebra at specific areas. - Lordosis is found in the cervical and lumbar regions.

Answer 234

Abnormal lordosis, kyphosis (exaggeration of the thoracic region) and lateral scoliosis.

Answer 235

With the cranial shift it is a change towards the head. We may find a _cervical_ rib at C7. And a reduction in T12 rib size. Caudal shift is the other direction, so we may find an elongated rib at T12 and one at L1 (_lumbar_ ribs).

Answer 236

Superficial (deep) muscles are muscles that have one attachment to the vertebra and one to the upper limb (allows movement) Deep (intrinsic) muscles have both attachments to the vertebra.

Answer 237

Vertebra body with an epiphyseal ring around it. There is the vertebral canal (neural arch) made up of the pedical (root) and lamina (found near the spinous processes) - The shape of the canal is distinctive for lumbar. There is the spinous process and transverse process (for muscle and ligament attachment). There is the superior and inferior vertebral notch. Superior and Inferior articular processes.

Answer 238

It is similar to the lumbar but the vertebral canal is round. And has articular facets found for tubercle of ribs.

Answer 239

This is the region between the articular process above and below. This site is a common location for weakness which may lead to fractures.

Answer 240

There is fusion between sacrum and coccyx. The sacrum is a triangular bone with 5 vertebras fused. No joints, but may see pseudo joints when young. Oriented in coronal plane S1 facet surfaces. Foreminae for nerve roots and vessels in anterior and posterior (including sacral vein) Deep veins have no valves (antegrade and retrograde flow)

Answer 241

3 primary centres in the body (and each neural arch) begins about 8 weeks. 5 secondary centres at the tip of spinous and tranverse procceses and the upper and lower margins of the body (annular epiphysis). Secondary centres normally close late adolescence (begins at puberty) when vertebral growth is done. - May be source of mistake of fractures in young children.

Answer 242

The joints of the vertebra is the intervertebral discs. Make of a nucleus pulposus and annulus fibrosus. The NP is made up mostly of water which is deformable but not compressible. The annulus fibrosus pulls everything together and holds it in place. Accumulative shorterning - loss of water Annulus is in perpendicular layers. So twisting is dangerous because of 50% of the fibres out of place.

Answer 243

Anterior longitudinal ligament, posterior longitudinal ligament, interspinous ligament, supraspinous ligament, posterior longitudinal ligament.

Answer 244

The posterior longitudinal ligament and ligamentum flavum (between lamina). The ligamenets are slightly elastic to allow for movement too.

Answer 245

This is the ligament that connects the lumbar to the iliac crest. This is with the L4 lumbar which has the transverse processes coming out of the vertebral body (more support)

Answer 246

Common spinal nerve comes from the posterior and anterior roots joining together. Posterior is always sensory. Ventral root is effector. The block is the dorsal root ganglia with sensory cell bodies. Anterior horn of the spinal cord has the cell body of motor neuron. Cell bodies of sympathetic neurons in the T1-L2 Anterior ramus contains both sensory and motor neurons (goes to the front of the body wall and upper and lower limbs) Posterior ramus has sensory and motor neurons and it goes to the back and supplies to the intrinsic muscles, skin, joints (fasic). Outer third of an intervertebral disc is innervated and it can be a direct source of pain. (Also supplied with blood 1/3)

Answer 247

There are synovial joints, fibrous capsules (allows little movement), capsule supplied by branches of _posterior rami_ (also supply intrinsic muscles and overlying skin) Bones are lined with hyaline cartilage (avascular and aneural). Articular surfaces surrounded by fibrous capsules (vascular and neural supply) And synovial membrane (a membrane that lines the fibrous capsule)

Answer 248

The orientation dictates the plane that it allows movement for. - Thoracic is the coronal plane - Lumbar in the sagittal plane - L5/S1 these surfaces are shifted so they are more in the coronal phase

Answer 249

L5 is looking out into the pelvis so it runs the risk of slipping in. The iliolumbar ligament is what limits this from happening. Spondylolisis is a defect of the inter pars-articularis (prone to fractures) and Spondylolisthesis is the forward positioning of the L4-L5 and L5-S1.

Answer 250

Boundary is the vertebral body, arches, ligaments and IV disc.

Answer 251

Spinal cord which is protected by the meninges. From inside out: Pia mater, subarachnoid space, arachoid mater then dura mater. There is the extradural space with extradural fat and venus plexus (anterior internal vertebral)

Answer 252

It is the IV discs, superior and inferior vertebral notch.

Answer 253

Nerve roots are found near the superior margin of the opening. If there is a prolapse (herniation) from the nucleus proportion it would not compress the nerve root coming out and located in the superior area. But it will affect the nerve roots found near the bottom. DRG is always within the intervertebral foramen but the roots may be different (further down). Blood vessels arteries and veins.

Answer 254

The blood supplies are posterior intercostals, lumbar arteries and lateral sacral. Horizontal blood supply provides it to bones and entry into spinal cord via IV foramen. These are drained to the internal vertebral venous plexus. External -\> Internal plexus.

Answer 255

At birth the spinal cord is at L3 but the body grows faster than the spinal cord. 1st trimester - S5, 2nd trimester - S1, Birth -L3, Adult - L1

Answer 256

This is because CSF is found in these areas without running the risk of puncturing the spinal cord (nerve roots here).

Answer 257

This is the extradural space so the drugs will act directly on the nerves for pain relief.

Answer 258

This is when the spine does not close/fuse properly at L3/4 and may lead to protrusion (occulta or cystica).

Answer 259

Flexion will cause the nucleus to project posteriorly (issue for people with prolapse of IV discs) and hyperflexion may stretch the sciatic nerve. Hyperextension of the back can increase stress on the facet joints.

Answer 260

Lateral flexion is allowed by the lumbar spine but limited by the ribs.

Answer 261

Orientation of articular facets: Thoracic - permits rotation in the coronal plane Lumbar - permits flexion/extension in sagittal plane Lumbosacral - limits movement in the sagittal plane

Answer 262

Trapezius, Latissimus dorsi, rhomboids and levator scapulae Cervical myotomes migrate to the posterior aspect of the scapula and the ribs down to the iliac crest. Since myotomes originated from cervical area the innervation will be from there too.

Answer 263

Originate from cervical myotomes and are innervated by _anterior_ rami (nerves are faithful to their embryological origin.

Answer 264

The posterior rami penetrates the superficial muscles and innverates the deep muscles

Answer 265

The serratus posterior superior and inferior act on the ribs and are innervated by _anterior_ rami.

Answer 266

Erector spinae - The lateral border of erector spinae corresponds with the angle of rib (common fracture site). They run medial to lateral and are prime movers. Transversospinalis - short muscles run from lateral to medial across few vertebral segments (acts as stabilisers)

Answer 267

Prime mover involved in concentric and eccentric. They work eccentrically when we are controlling flexion. At full flexion the muscles are electrically quiet and leads to danger in lifting in flexed posture.

Answer 268

These are segmented stabilisers together with abdominal muscles (transversus abdominis) form 'corset' around trunk via lumbar fascia. Back is also strengthened through core strengthing of deep abdominal muscles. Deep muscles are stimulated which then uses lumbar fascia to stimulate deep back muscles.

Answer 269

Dorsal type skin. Superficial veins and lymphatics pass _anteriorly_ and arteries pass through muscles with dorsal rami to skin.

Answer 270

Angiosomes are vascular territories and allows for skin grafts to be taken in particular areas.

Answer 271

These are innervated by the posterior rami: which affects the overlying skin, deep back muscles and facet joints.

Answer 272

This is found posterior to the nerves and is activated when nerves are being damaged because they have the same nerve supply

Answer 273

Mechanical (such as muscle pain due to abnormal posture) and compressive type pain

Answer 274

This is caused by nerve root irritation or pinching. This is most likely caused by herniated discs or spinal stenosis (this is when the space is abnormally narrow - which may affect exiting nerves)

Answer 275

Bulge, Herniation and Extrusion which affects IV canal and foramen.

Answer 276

Posterior longitudinal ligament - causes most protrusions to be posterior lateral

Answer 277

Nerve roots are typically found in the upper part of the foramen. Lumbar disc prolapse affect nerve roots (due to narrow lumbosacral foramen, large lumbasacral disc). S1 nerve root

Answer 278

Lumbar flexion, rotation, overweight, keeping lower limbs extended

Answer 279

With age the discs will degenerate and the edges may protude to pinch on nerve roots

Answer 280

This is when bones tend to lose water and become less dense (with age). This causes overgrowth of bone producing bony spurs (osteophytes) that can extend into the foramen, narrowing them (stenosis) and compressing exiting nerve roots

Answer 281

They bind to the antigen epitope or determinant. One antigen can have many epitoptes.

Answer 282

They can be either, discontinuous (conformational)

Answer 283

Conformational shape not linear

Answer 284

B cells have a reservoir of diverse specific receptors. Each cell has multiple copies of a single specific receptor.

Answer 285

They are either bound to the surface (embedded in the B cell membrane) or secreted Ig.

Answer 286

Antibodies have heavy and light chains (2 of each). There is also the constant region and variable region. The antigen binds to the variable region. Chains are bound by disulfide covalent bonding Five different isotypes of the constant region: A, D, G, M, E (determines action of Ig)

Answer 287

Fab - variable Fc - constant

Answer 288

Fab is where the antigen binds to Fc mediates the effector functions. May include activation of classical complement cascade. Delivery of Abs through active transport to various compartments (IgA in mucus)

Answer 289

Diversity is achieved by gene rearrangement of the: Heavy chain V region: V, D and J. This V region connects to a constant (C) gene. Light chain V region: V and J Which then also connects to constant gene. - This is all done through enzyme RAG

Answer 290

1. V region 2. Junctional diversity 3. Combinatorial diversity (different pairing of light and heavy chains) 4. Somatic hypermutation (further mutate antigen after maturation)

Answer 291

DJ rearrange first, then VDJ then forms primary RNA transcript. This is then spliced to form the mRNA to be translated into the protein. Produces both IgM and IgD (both expressed on naive B cells - IgM is secreted first)

Answer 292

First somatic recombination where VJ joins first. Primary transcript is made which is then spliced into a mRNA. This is translated into 'k' light chains. 'l' light chains only rearranges if k is not successful.

Answer 293

The junctional diversity makes the greatest diversity to mediated by TdT (terminal deoxytransferase - further adds DNA at the end). Joining of different segments with deletions and insertions of nucleotides.

Answer 294

Early lymphoid progenitor cell \> common lymphoid progenitor \> Pro B cell \> Pre B cell \> Immature B cell \> mature B cell (leaves bone marrow)

Answer 295

_Flt3_ is important on the multipotent progenitor cell which begins onto the common lymphoid cell (ligand found on stromal cells). Once a common lymphoid cell it requires _IL-7_ to push this process through to produce immature B cells.

Answer 296

This is at the _large pre B cell._ Pre-B receptor will act as a checkpoint by acting like a light chain analogue which binds to H chain (allows kinases to attach - then give signals to continue maturation of B cells).

Answer 297

Check for autoreactivity, will kill cell if it is before releasing the immature B cell into circulation (IgM and IgD)

Answer 298

This is introduced in the secondary lymphoid tissue _after_ antigen binding.

Answer 299

Proliferation, affinity maturation and isotype switching (specialisation)

Answer 300

B cells change their antibody isotype after antigen encounter. IgM \> G \> E \> A Occurs in secondary lymphoid tissue after antigen stimulation. Involves irreversible recombination events. The _microenvironment_ determines the isotype produced (CD4T, TFH, NKT). - This is dependent on T-cell help Cytokines control the isotype produced. Such as TGFb (A), IL-4 (E) and IFN-g (G) There is rearrangement of C (heavy) region that gives new isotype. VDJ is untouched.

Answer 301

IgG,A - Neutralisation Opsonisation: IgG, IgA ADCC: IgG Degranulation: IgE Complement activation: IgM \> IgG and IgA IgM is pentameric increases number of binding site so can fixate complement well.

Answer 302

These are Fc receptors that bind to Ig. Different cells will have different FcR to bind to different isotypes.

Answer 303

Preventing viruses and bacteria binding to cell surfaces for infections

Answer 304

The antibody will attach to the bacterium which will now have affinity for FcR on phagocytes. (Easier recognition for phagocytosis) Also classical activation of complement. IgM and IgG will attract C1 to begin the process.

Answer 305

These form dimers which are able to actively cross the cytoplasm and excrete into a lumen.

Answer 306

B cell increases affinity for a particular pathogen. Dependent upon mutations in V region of heavy and light chains. Needs _continued_ antigen stimulation and needs T-cell help. When immune response dies down only the higher affinity surfaces are selected for survival

Answer 307

- Organism found in all patients with disease - Found in lesions - Cultivate outside host - Reproduce disease in other species - Demonstrate immune response

Answer 308

Primary pathogens will cause disease in non-immune but normal functioning immune system. Opportunistic pathogens take advantage of immunocompromised hosts.

Answer 309

Colonisation, Invasion, multiplication and tissue damage

Answer 310

Must overcome commensals, pass through mucus and resist their defences then finally _adhere_ to epithelial cells.

Answer 311

This is done through fimbriae or non-fimbriate adhesions (surface proteins). These bind to oligosaccharides found on the cell membrane.

Answer 312

The commensals actually compete for binding sites of the pathogens so that they cannot adhere. The commensals themselves are just associated (not adhered)

Answer 313

Can use fimbriated vs non-fimbriated bacteria. Done with ETEC (binding to human intestine CS3) for piglets.

Answer 314

Vaccinate the mother pig with K88 antigen (ETEC) and see if their piglets will be immune to ETEC or not?

Answer 315

They can either travel through or between the cells. Another mechanism is pathogen mediated endocytosis (initiated by invasins)

Answer 316

Yersina have invasins which will recognise particular M-cell (antigen sampling cell in intestine) integrins which will initiate endocytosis.

Answer 317

They either face host defences or find a niche location.

Answer 318

Affect phagocytes, interfere with oposinins (antibodies and complement)

Answer 319

They can secrete leukocidins (kill WBC - strep pyrogenes) Produce anti-inflammatory toxins and enzymes (Cholera toxin) Have surface anti-phagocytic structures

Answer 320

Test capsulated vs uncapsulated bacteria. Passive and active immunisation against capsule.

Answer 321

Electrostatic repulsion to prevent near cell contact. Resemble host components (contains hyaluronic acid) and mask underlying structure (e.g Meningicoccus B). It also prevents oposinisation.

Answer 322

The antibody will bind to the capsule with its Fab. If it is IgM or IgG it will then activate the complement (classical) cascade. It binds to C3b receptors on specialised phagocytes (macrophages and neutrophils)

Answer 323

Lysosomal enzymes, defensins, reactive oxygen and nitrogen intermediates.

Answer 324

Inhibit the respiratory burst, prevent phagolysosome formation, escape phagocytic vacuole, resist bactericidal systems (M.tuberculosis acid fast bacteria)

Answer 325

Direct immunosuppresion, express weak antigens, antigenic diversity and antigen modification

Answer 326

Directly from the pathogen (release of toxins), induction of cytokinesa and immunopathology (inflammation to infections).

Answer 327

Intact host cells, ECM and other host molecules (lipids,fibrin, nucleic acids,etc)

Answer 328

Cytotoxic is actually poisonous to cells. Whereas cytotonic changes functions in cells but does not actually kill it. Both change protein synthesis

Answer 329

Simple (uncommon) and Bi-functional (A-B type) A- active portion, B- binding portion. Binds to specific cells via B, A is internalised. Toxoids do not have a functional A component.

Answer 330

Toxins that have no more toxic effects but still elicit antigenic response.

Answer 331

It is to combat intracellular pathogens.

Answer 332

1. Acquire and process the antigen through MHC I and II 2. Interact with naive T cells to induce effector T cells. Adhere to T-cells, present MHC and provide _co-stimulation_ to T cells (tolerance mechanism). This is done by professional APC - macrophages, dendritic and B cells.

Answer 333

TCR can only recognise linear epitopes. Therefore they must be degraded to 8-11 AA then presented on MHC molecules.

Answer 334

It is an heterodimer of an a and B chain. Encoded by rearrangement of genes (similar to Ig) TCRa - VJ C TCRb - VDJ C NO somatic hypermutation after antigen Checkpoint - autoreactive cell removed (negative selection) and it receptor can bind to MHC (positive)

Answer 335

CD8+ T - cytotoxic that kill infected cells and neoplastic cells CD4+ T - Produce cytokines to help specialise the adaptive and innate response (cytokine is dependent on stimulus received)

Answer 336

APC must travel to lymph nodes to allow for antigen presentation via MHC.

Answer 337

I - Found on all nucleated cells II - APC Class I - HLA A, B and C Class II - HLA DR, DP and DQ

Answer 338

Bound to a3 to a2 to a1 then B2m which is not covalently bound to the cells. a2 and a1 groove forms MHC binding cleft for proteins

Answer 339

It has a B chain and alpha chain. Binding cleft is found between the B1 and a1 unit (binds slightly larger peptides).

Answer 340

MHC is co-dominantly expressed on the cells. Each cell will express 6 alleles (mother and father). The polymorphism allows you to target a larger range of antigens on a population scale (localised to the binding cleft of the molecule). Resistance/susceptibility to many diseases and transplant issues.

Answer 341

It alters the binding cleft and the anchors to hold down different antigens. Can hold different peptides as long as it has the same common anchor residues. Sometimes it may alter MHC's ability to bind to certain TCR as well.

Answer 342

The protein antigen is processed into either cytosol (class I) or endosomes (class II) Class I: Degrade antigen, uptake into ER, synthesis of Class I, Interaction of Class I with antigen, transport from ER to surface of cell. Class II: Endocytose the antigen and degrades it, Class II assembled in ER and bound to chaperone (it is unstable at peptide binding site so need pseudo ligand), transported from the ER, then associated with the peptide displacing 'li' chain and sticking on the peptide, then expressed on the cell membrane. May also be _cross presentation_ movement of MHC II to the MHC I pathway.

Answer 343

These are antigens that bind to conserved regions of MHC II B1 chains and on the chain of T receptors. This makes it able to bind non-specifically to activate T cells. Activate a large number of T cells -\> significant pathology.

Answer 344

NKT and gamma delta T cells because they have semi-invariant alpha-beta chain. Fit into MHC-1 like molcules.

Answer 345

CD4 - MHC II, CD4 stabilises the binding CD8 - MHC I, CD8 stabilises the binding

Answer 346

Macrophages: Mannose receptor and FcR -\> phagocytosis or receptor mediated endocytosis Activated B cell: receptor mediated endocytosis (via Membrane bound Ig) Dendritic cells: Take up small soluble antigens, macropinocytes (grabs little bits of environment for sampling) and receptor mediated endocytosis. Mannos and FcR too.

Answer 347

They are very good at sampling antigens but not at presenting them. Sample antigens by Mannose and FcR (macropinocytosis). Unable to migrate to lymph nodes, low levels of MHC II on membrane (it is found intracellularly with endocytic vesicles)

Answer 348

The DCs need to bind to pathogens and be in the presence of PAMPs or DAMPs (signals danger to cell). These are recognised by TLRs

Answer 349

The DCs lose anchor molecules (free to move), increase in chemokine receptor expression _CCR7_ to allow for migration of DCs to lymphatics. Also increase in secretion of cytokines and chemokines to attract _precursor_ DC and monocytes to infected site for more uptake of antigen.

Answer 350

Increase in MHC I and II on surface, increase antigen processing, increase adhesion molecules (for T cells), secrete new chemokines (attract naive T cells in lymph node), but mature DCs cannot capture antigen, expresses co-stimulatory molecules (_CD80,86_) and secrete cytokines (IL-2, IL-12)

Answer 351

At first it is low affinity binding with the adhesion molecules found on DCs (ICAM1-LFA1, CD58-CD2) which is then stabilised by the TCR-peptide interaction with MHC. This stabilisation causes a conformational change in LFA-1 to increase binding affinity -\> high affinity now

Answer 352

The first signal is the MHC peptide and TCR. The second signal isCD80/86 (DC) binding to CD28 (expressed on naive T cells) - costimulation The thrid signal is cytokine signalling. The DCs produce cytokines that will act on receptors found on the T-cell (specialise the cell for a particular response)

Answer 353

The T cell becomes anergic (inactivated) and may lead to tolerance

Answer 354

There are Th1,2,17 Treg and TFH. These all have their own effector function and are obtained by the presence of particular cytokines. IL12 -Th1 - IFN-gamma IL-2 TGFbeta -Treg - TGFbeta IL-6 -Th17 - IL-17a, IL-21, IL-22 IL-4 - Th2 - IL-4 and IL-5 IL- 6 -TFH- IL-21

Answer 355

Th1 and Th2 are potent pro-inflammatory T cells. Th2 is more geared towards parasites (IgE production). Th17 is neutrophil recruitment (damage in some autoimmunedisease) Th1 typical macrophage, antibody (IgG) Treg - controls anti-self responses

Answer 356

T dependent produces high affinity antibodies, memory and against protein antigens. T-independent produces low affinity antibodies, no memory and is against polysaccharides and most lipids.

Answer 357

Only TD shows response whereas infants cannot respond to TI.

Answer 358

It upregulates CD40L on its surface as well as co-stimulatory molecules for B-cells

Answer 359

Once the T-cell is activated with CD40L and releasing cytokines it drives the proliferation and differentiation of B cells (produces IgD and IgM). Without the CD40 you would only produce IgM. - T cell very important in isotype switching as long as the associated cytokine is present too

Answer 360

This meeting occurs in the lymph nodes (but the cells are held in separate segments. B cells - follicles T cells - paracortex Macrophages and plasma cells found in the medulla

Answer 361

DC will antigen specific T cell. B cells will increase CCR 7 and decrease CXCR5 which causes the B cells to move right and the CXCL13 to move right. T cells will decrease CCR 7 and increase CXCR5 causing it to move left. CCL21 also moves left now.

Answer 362

B cells can only stay in this site with T cell help. This is a site for intense B cell stimulation for proliferation and affinity maturation.

Answer 363

These are found in lymphoid follicles and germinal centres. Basically have a lot of antigens deposited onto it to drive B-cell activation and affinity maturation.

Answer 364

They activate macrophages, aid complement binding and opsonising antibodies and neutrophil activation. IFN-gamma for the first two. TNF is very important for neutrophil activation.

Answer 365

Production of neutralising IgG antibodies, production of IgE, eosinophil activation and alternative macrophage activation (_repair and suppression of inflammation)_ Used to deal with helminthes/allergies. Mucosal protection too by enhancing mucus secretion and tissue repair.

Answer 366

It requires more stimulatory signals than CD4 cells. Most cases need help from activated CD4 T cells. - Must still recognise antigen on DC - Activated CD4 T cells interact with APC and allow DC to induce CD8 activation _via function of CD40L_

Answer 367

1. Granular exocytosis of granzymes + perforin to activate caspase and induce apoptosis in the target cell. 2. FasL on the T cell will interact with Fas receptor on the cell to initiate apoptosis. They also do signal cytokines to set up antiviral setting - upregulate MHC I via IFN-gamma

Answer 368

Move from efferent lymphatic to circulation where levels of CCR are changed. Decrease in CCR7 makes it enter the circulation (leave lymph nodes). Increase in CXCR3 and CCR5 makes it move towards the infected site. It will also bind to similar CAM used for neutrophil infiltration.

Answer 369

1-22 based on length, 21 and 22 switched because of size later on. 23 chromosomes in humans but diploid gives 46.

Answer 370

Leading and lagging strand 5' to 3' extension. DNA polymerase. RNA primer on lagging strand - DNA polymerase digest those primers and extend. DNA ligase joins Okazaki fragments. Telomerase extends the ends. Helicase splits and unwinds the DNA. Semi-conservative DNA.

Answer 371

The RNA polymerase uses the non-coding (anti-sense) strand.

Answer 372

Gross chromosomal changes, copy number variation (amount of specific sequences of DNA), changes to DNA sequences (base pair sub, insertion, deletion)

Answer 373

1st cousins are 4 degree relatives, 2nd cousins are 5 degree relatives.

Answer 374

Reduced penetrance is when someone with the genotype do not have the phenotype

Answer 375

Heterozygote phenotype is an intermediate of the two alleles.

Answer 376

There is variable expressivity when an individual has the genotype.

Answer 377

Mitochondrial single chromosome is transferred. But it is transferred from the mother and _not_ the father.

Answer 378

Polygenic is when more than one gene causes the condition. (May be addictive to other factors)

Answer 379

A biological macromolecule that binds another molecule and begins a signalling or effector activity.

Answer 380

GPCR with 7 transmembrane proteins. Responsive to NA and Adr. Propranolol - selective antagonist (B) Isoprenaline - selective agonist (B)

Answer 381

Ligand gated ion channels, GPCR, kinase-linked receptors and nuclear receptors. Listed from shortest to longest time frame.

Answer 382

Agonists bind directly to the channel itself and regulates its opening.

Answer 383

They are linked to G-protein and may affect many different structures - ion channel, enzyme, transporter, gene transcription.

Answer 384

Mostly tyrosine and serine kinases. Ligand binds extracellularly causing it to dimerise and auto-phosphorylate. Then activates cytoplasmic enzyme (kinase)

Answer 385

Typically ligand passes cell membrane to bind to the intracellular receptor which will then regulate gene transcription.

Answer 386

Polymorphism in human receptor proteins can alter their responsiveness to drugs.

Answer 387

The closer they are the more close in structure they are. This makes it difficult for selective targeting and leads to a greater general effect.

Answer 388

It must be enough to do some good without causing too much side effects. (Every system is dose limiting - same response after a particular point)

Answer 389

It gives us an idea of what sensible dose increments should be. The larger the dose does not always give a larger effect. The steeper the curve the more sensitive it is to doses.

Answer 390

This is the window of dosage where it can produce a beneficial effect while not causing adverse effects.

Answer 391

The usable dose of a drug is limited by the side effect doses.

Answer 392

Isoprenaline (B), Prenalterol (B1?)

Answer 393

EC50 is the concentration of drug that gives 50% of its maximal effect. A partial agonist cannot elicit a maximum response from a tissue whereas a full agonst can.

Answer 394

Generally it is because it prevents overdose damage.

Answer 395

Salbutamol - B2 adrenoceptors Buprenorphin - opiate receptors (low tendency of addiction and tolerance) Sumatriptan - 5-HT1 receptors (used for migraines by vasoconstricting blood to brain - but also affects heart via vasoconstriction) Pindolol - B adrenoceptor agonist but is used as a B-blocker because it takes up receptor with partial agonist.

Answer 396

Drug affinity, receptor affinity and the intrinsic efficacy of the receptors.

Answer 397

As heart failure goes on the sympathetic stimulation rises and begins to decline until it hits the chronic stage where it begins to decrease. Seems to have resulted in desensitisation of the receptor.

Answer 398

It works by reduced receptor availability due to internalisation. A full agonists are not affected as much because of the spare receptors they have. Whereas partial agonist typically already use up all the receptors and any loss will significantly affect their activity.

Answer 399

The exudate is drained through the lymph nodes. Neutrophils do after a few days and macrophages are a major cleaner of debris.

Answer 400

There is resolution where microbes are cleared and minimal damage is done (regrowth/regeneration of dead cells). There is healing by repair which may require scarring (granulation tissue forms). Or it may lead to chronic inflammation.

Answer 401

It really depends on the tissue type (different cell regenerative abilities). Labile (continuous cycling), stable (enters when needed - liver and fibroblasts) and permanent (cardiac myocyte and nerves).

Answer 402

They are able to self-renew and are undifferentiated so they can generate different cell lineages. Embryonic: pluripotent (any cell type in the body) Adult: Generate a more limited range of cell lineages.

Answer 403

The epithelium in epithelial tissues proliferate and migrate. Fibroblasts, myofibroblasts and endothelial cells are what forms scar tissue by granulation tissue formation.

Answer 404

It is the intermediate tissue to form scar tissue. It contains macrophages and lymphocytes mainly - few neutrophils from previous infection. New blood vessels formed by degrading basement membrane - matrix metalloproteinases (MMPs) from macrophages. Migration of endothelial cells towards angiogenic stimulus, leaky at first, recruits pericytes and SMC. VEGF secreted is very important in this process. Fibroblast migrate and proliferate with various growth factors TGF-beta. Deposition of ECM also required.

Answer 405

This is when the wound is clean, edges are closely opposed without much inflammation or scarring.

Answer 406

This is where the wound will develop granulation tissue - typically larger wounds heal by secondary intention.

Answer 407

Epidermal growth factors, VEGF, FGF, TGFbeta, platelet derived growth factor. Many receptors are tyrosine kinase based. Leads to activation of transcription factors that control entry of cells into the cell cycle. - Leads to proliferation of epithelium, endothelium, fibroblasts and blood vessels

Answer 408

Juxtacrine - signalling to adjacent cell via gap junctions Autocrine: produces molecules that act on the receptor of the same cell type or same cell Paracrine: Acts on nearby cells of different cell types Endocrine

Answer 409

Sometimes it may be infection, may follow on from acute inflammation, autoimmune diseases or repeated/prolonged exposure to potentially toxic agents.

Answer 410

This is ongoing inflammation that involves tissue damage and healing at the same time. This will persist until damaging stimulus is removed. Most of the time it destroys tissues and results in scarring. E.g. atherosclerosis, tuberculosis, fibrosing lung disease, chronic hepatitis and cirrhosis and rheumatoid arthritis.

Answer 411

By this stage we expect to find macrophages, lymphocytes and plasma cells with fibrosis and scarring. May see neutrophils from acute inflammation.

Answer 412

These macrophages are foamy macrophages because it takes up lipid (large vacuole in the cytoplasm. Occurs in atherosclerosis). Macrophages phagocytose carbon (in smoking) it clumps in the cell. See the pigment in macrophages. Phagocytosis of old RBC which is then converts haemoglobulin into haemosiderin (gold brown pigment which can be seen in cells).

Answer 413

Yes they fuse together to form a giant cell

Answer 414

No it does not. If the lymphocyte was found in an area you did not expect to have a lot of may be an indication of chronic inflammation.

Answer 415

It is a differentiated B lymphocyte with a big nucleus on the side and _oval_ shaped cell - often there is a golgi apparatus next to it (clear spot). May be able to spot clock faced chromatin on the edge of the cell - stained purple-ish due to increased RNA.

Answer 416

This is the structure where B cells differentiate into plasma cells. The germinal centres are the paler areas. This is a secondary follicle where the B cells are activated and begin to differentiate.

Answer 417

Chronic Rheumatic Valve disease - Arises from throat infection that somehow induces inflammation in the heart (valves) The mitral valve is very thickened as well as the chordinae tendin. Valve scarring can cause obstruction or incompotence. Cirrhosis: Main cause is alcohol and viruses (Hep B and C) and metabolic syndromes. Nodular liver Tuberculosis: Necrosis and scarring. Tuberculosis primarily affects the lungs. Can cause significant lung destruction. Secondary TB is apparent. But the primary TB nah not show clinical signs as easily as secondary TB.

Answer 418

Cells involved - epithelioid macrophages and multinucleate giant cells (fusion of macrophages). These nuclei tend to be longer (looks like fibroblasts - but they are not they are modified macrophages). There may be lymphocytes or fibroblasts present too. Some cases there is necrosis and come up as hypereosinophilic. Granuloma is a well circumscribed collection of these cells. Granulomatous inflammation is more disorganised term.

Answer 419

Certain infections such as tuberculosis - typically intracellular infection excluding viruses. Lymphomas and deposition of irritant (endogenous or exogenous)

Answer 420

It is cell mediated response. Macrophages present antigen to CD4 T cells which release IFN-gamma: activate macrophages IL-12 - activate Th1 lymphocytes.

Answer 421

It causes fevers: exogenous/endogenous pyrogens -\> PGE2 synthesis in hypothalamus -\> resetting set point. Leukocytosis - neutrophilia in acute inflammation Increase in C-reactive protein and fibrinogen. Fibrinogen binds to RBC, rouleaux formation, sediment more rapidly - basis for erythrocyte sedimentation rate. CSR and ESR are non-specific tests for inflammation

Foundation Block Flashcards

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