Phase 1 Flashcards
Biomedical Science
Name 4 functions of skin
- Water Repellent
- Immunological Barrier
- Mechanical Barrier
- Sensation
- Synthesis of Vit D
- UV Protection
Describe the structure of skin
Three Layers; epidermis, dermis, subcutis.
Epidermis (Avascular)
- Stratum (Keratinocytes)
- Stratum Lucidum
- Stratum Granulosum
- Stratum Spinosum
- Stratum (Merkel Cells)
- Basement Membrane (Type IV Collagen)
Dermis
- Papillary Layer
Areolar tissue, connective tissue that contains dermal papilla from epidermis. Meissners Corpuscles - Light Touch.
- Reticular Layer
Dense and irregular, contains most accessory structures. Pacinan Corpuscles for deep pressure and vibration.
Subcutis
- Adipocyte rich. Padding. Vascularised.
Describe the main difference between thick and thin skin.
Stratum Lucidum exists on palms and soles of the feet. Thin layers do not contain these layers.
Name the cell types found in the epidermis and state their function.
- Keratinocytes - 95% of cells in the epidermis. Produces keratin.
- Melanocytes - produce melanin for UV protection. Transfer via projectins.
- Langerhans Cells - DCs, APC.
- Merkel Cells - Mechanoreceptors
Name the layers of the epidermis.
Epidermis (Strata Corneum, Lucidum, Granulosum,
Describe the role of skin the synthesis of Vit D
UVB photons are absorbed to convert 7-dehydrocholesterol to previtamin D3.
Describe the cell junction between the epidermis and the dermis and a pathology associated with it.
Epidermis and the dermis is joined at the dermo-epidermo junction by the interactions of Retes Ridges in the papillary layer. Hemi-desmosomes bind intermediate filaments and Focal Adhesions bind Actin Filaments.
Pathology is Epidermolysis Bullosa simplex.
Name the layers of the dermis
Papillary (superficial) and reticular (deep)
State 3 types of glands found in the dermis and name their function.
- Eccrine Glands - produce sweat
- Apocrine Glands - Scent
- Sebaceous Glands - lubricant of the hair shaft
Describe the accessory structures found in the dermis.
- Eccrine Glands - produce sweat
- Apocrine Glands - Scent
- Sebaceous Glands - lubricant of the hair shaft
- Meissners Corpuscles - Light Touch
- Pacinian Corpuscles - Deep Pressure
State the functions of the subcutaneous layer
- Fat storage, energy reserve
2. Padding
Name the type of collagen found in the skins and basement membrane
Skin - Type I
Basement Membrane - Type IV
Label the diagram (layers of the skin)
Epidermis
- Strata Corneum, Lucidum, Granulosum, Spinosum, Basale, Basement Membrane
Dermis
- Papillary
- Reticular
Subcutis
Adnexal structures
- Eccrine, Appocrine, Sebaceous glands
- Meissner and Pacinian Corpuscles
Describe superficial and deep wound healing
Superficial wound healing -
A scrape or graze, no involvement of the basement membrane. Mitotically active keratinocytes in the Basale lose BM adhesions. Migrate in leap frog or train method to form granulation tissue. Epidermal Growth Factor is released.
Basale Layer keratinocytes undergo terminal differentiation to restore lost cells.
Deep
Inflammatory phase
1. Coagulation/ haemostasis
2. Platelets secrete growth factors. WBCs are recruited. Inflammation takes place to allow vasopermeability to increase.
3. Neutrophils and Macrophages phagocytose waste. More growth factors.
(VEG-F, EGF, APF, PDGF, FGF)
Proliferative phase
- Basement membrane is reformed and keratinocytes migrate over wound to form granulation tissue (leap frog or train).
- Once formed, divide and differentiate. Granulation tissue laid down, mainly Type 3 Collagen.
- Neo-vascularisation
Remodelling phase
- Granulation tissue tissue matures to scar tissue.
- Type 3 collagen is crossed linked, swapped for type 1. More tensile strength.
Name three growth factors secreted by phagocytosis
- Vascular Endothelial Growth Factor (VEG-F)
- Angiogenesis Promoting Factor (APF)
- Platelet Derived Growth Factor (PDGF)
- Fibroblast Growth Factor (FGF)
Name the two methods by which re-epithelialisation takes place and give a brief description of each.
- Train method - a lead cell pulls following keratinocytes
2. Leap from - cells leap over one another over the wound base. Much like leap frogging or pepper potting.
Name the cell that produces collagen.
Fibroblasts
Give the effects of UV radiation
- Photoageing
- DNA Damage
- Carcinogenesis
Name the organelles and state their function
- Plasma Membrane
- Barrier to the outside environment, hosts receptors for signalling, mediates diffusion, holds other membrane receptors and channels. - Mitochondrion
- The power house of the cell (Aerobic Respiration) producing ATP. - Nucleus
- Contains the genome and is the site of transcription. - Rough Endoplasmic Reticulum.
- Hosts ribosomes for mRNA translation. - Smooth Endoplasmic Reticulum
- Calcium Store and lipid synthesis. - Golgi Apparatus
- “Sorting office” - responsible for post-translational modifications to proteins and packaging. - Lysosomes, Peroxisomes and Proteasomes.
Enzymatic degradation of lipids (L), oxidative reactions/ biosynthesis of bile/ fatty acid metabolism and detox (Perox), protein degradation (Proteasome).
What pathologies are associated with: A. Mitochondrial Damage B. Defective Lysosomes C. Microtubule Defects D. Failure of Cell-ECM junctions E. Connexin 26 Mutation
A. Damage causes the release of cytochrome C, which activate caspases, resulting in a proteolytic cascade activating DNAases, Lamin degradation and cell apoptosis. - Diabetes and Deafness (DaD).
B. Lipid build up. Neural damage. - Tay Sachs Disease.
C. Defects in dyneins in Axonemes. Leads to defunct cilia and flagellum. - Kartageners Syndrome.
D. Loss of Hemidesmosome - Intermediate Filament interaction. - Epidermolysis Bullosa Simplex.
E. Defunct connexins, leads to hearing loss.
Describe the Cell-Cell and Cell-ECM junctions and the cytoskeleton involved.
Cell-Cell
- Desmosomes - Intermediate Filaments
- Adherens - Actin Filaments
- Tight Junctions - Actin Filaments
- Gap Junctions - Connexin Channels
Cell-ECM
- Hemi-Desmosomes - Intermediate Filaments
- Focal Adhesions - Actin Filaments
Describe the cytoskeleton
A network of proteins, three types.
Microtubules, made of tubulin. Allow for push (kinesins) and pull (dyneins), these Microtubules grow and shrink from centrosomes. Allow for chromosome separation in Mitosis or movement in axonemes (cilia and flagellum).
Microfilaments made up of Actin and Myosin. Dynamic processes, such as cell shape and motility.
Intermediate filaments made up of vimentin and keratin. Provide tensile, rope like strength.
Describe the default secretory pathway.
Transcription (Nucleus), Translation (Ribosome).
Signal Recognition Particle on mRNA attaches SRP-Receptor, anchoring it and ribosome to RER. Protein is translated into the ER lumen. Signal pepsidase cleaves the protein. Transportation to the Golgi Apparatus, via the Cis-Cisterna model, is sent to the plasma membrane in vesicles. Where it is modified at the C-Terminus, it is anchored to the plasma membrane.
Proteins for the lysosome are modified with mannose-6-phosphate.
Describe the default cytosolic pathway.
Without SRP, the protein is translated into the cytosol.
Here, if destined for the Nucleus, the protein is modified with a Nucleus Translocation Signal (NLS)- moves via importing through the nuclear pore.
Mitochondrion proteins are modified with Mitochondrion Translocation Signal.
Peroxisomal proteins are modified at the C-Terminus with a three amino acid chain.
Describe Lysosomal degradation
Cytosolic proteins are taken to the vesicle by autophagy (from the ER - mannose-6-phosphate cleaved at low pH), while extracellular components are taken in by endocytosis (surface proteins) or receptor-mediated endocytosis.
An acidid pH, proteases, lipases and DNAases finish the task.
Describe proteosomal degradation.
Proteins for destruction are ubiquitilated. Useful for short-half life proteins, defective proteins and those key in metabolism.
Proteins are then cleaved by proteases and pepsidases.
Define: a. genome b. proteome c. transcriptome
a. All genetic material of an organism
b. All proteins translated from the transcriptome
c. All mRNA transcribed from Genome
Why is the proteome larger than the genome?
- Alternative mRNA splicing
- Post translational modification
(Gene splicing and epigenetics?)
Describe translation
DNA is transcribed to mRNA in the nucleus. The mRNA attaches to a tRNA via start codon AUG. tRNA anti-codon binds and pre-initiation complex binds small sub unit of the ribosome.
Translation is initiation, working from the 5’ to 3’, cessation at stop codon (varies).
Describe three post-translational modifications
- Methylation - addition of a methyl group. Example is Histone methylation in gene expression.
- Ubiquitination - addition of ubiquitin to a protein. Example is in proteosomal degradation
- Phosphorylation - addition of a phosphate. Example is phosphorylation of myosin in muscle contraction.
Outline the functions of blood
- Transport of gases (o2 and co2), plasma proteins, hormones and of waste such as urea and uric acid.
- Homeostasis - buffer of pH, restriction of flui loss.
- Immunity by WBCs.
Describe the composition of blood
- Plasma 55%
- Plasma Proteins 7% (Albumin, Globulins, Fibrinogens)
- Solutes 1% (Ions, organic waste such as urea)
- Organic nutrients like lipids, amino acids.
- Water 92% - Haematocrit 45%
- Erythrocytes 99.9%
- Leukocytes 0.5%
- Platelets 0.5%
Name the different plasma proteins and their function
- Albumins
- Osmotic Pressure
- Transport protein (such as lipids and billirubin) - Globulins
- Transport of ions, lipids, hormones
- Immunoglobulins in immunity - Fibrinogen
- Coagulation, Haemostasis
Others, such as hormones (insulin), zymogens, coagulation factors.
Name the cell types found in blood and state their function.
- Erythrocytes
- Carriage of o2 and co2. - Leukocytes
- Innate and Adaptive Immunity - Platelets
- Not technically cells. Coagulation, haemostasis.
Describe a RBC
- Also called erythrocytes
- Biconcave in shape, allows flexibility
- Anucleated with no organelles, allowing extra capacity for haemoglobin
- Life span of 120 days
- Contains molecules of haemoglobin, accounts for red colour
- Low energy demand
- Carriage of o2 and co2 (Binds haemoglobin)
Describe the platelet
- Not a cell
- Cell fragments (Megakaryocyte)
- Small
- Principle role in coagulation/ haemostasis
- Short life span 9-12 days
- Anucleated, no organelles
Describe the different WBCs and state whether their origin is lymphoid or myeloid.
- Neutrophil - Myeloid
- Most common at 65%
- Multi-lobed nucleus
- granule rich
- Innate - Lymphocytes - Lymphoid
- 2nd most common at 30%
- Large nucleus occupies most of the cytoplasm
- Differentiates into, T, B and NK types for adaptive immunity. - Monocyte - Myeloid
- Differentiates to Macrophage
- Kidney shaped nucleus (bilobe)
- 3rd most common - 8% - Eosinophils - Myeloid
- Red in colour, acidophillic.
- Bilobed nucleus
- Granule rich, cytotoxic.
- Fight parasites - Innate
- 4th most common, 4.5% - Basophils
- Blue, basic.
- Highly granulated
- Role in allergy
- less that 1%
List the WBCs in order of abundance
- Neutrophil
- Lymphocyte
- Monocyte
- Eosinophil
- Basophil
Describe the triage system and the role of the triage nurse
Triage, french for “sieve”, is a system used to prioritise patients for treatment based on medical urgency. It is commonly used in pre-hospital, A&E and military settings. It is dynamic and changes with assessment.
Multiple systems exist. In the UK, A&E’s commonly use the Manchester System defining categories as:
- Immediate (, MI)
- Very Urgent, 10 mins (Chest pain)
- Urgent, 1 hour (poison)
- Standard, 2 hours (minor injury)
- Non-urgent, 4 hours (non-acute)
The triage nurse will monitor patients, carry out obs, bloods, ECGs and aid the the triage picture. Dependant on Trust.
Define shock and list five types.
Shock is the loss of circulating blood, causing inadequate perfusion of body tissue impairing metabolic function.
- Hypovolemic
- A bleed
- Loss of sodium causing dehydration - Cardiogenic
- Acute M.I reduced cardiac output - Septic
- Systemic inflammation causing vessels to become “leaky”. Fluid migrates to tissues. - Anaphylactic
- Allergy, inappropriate inflammation causing leakage. - Spinal
- Injury causing loss of sympathetic innervation and decrease in vasomotor tone leading to hypotension (C.O cannot match compliance).
Define differentiation
The process by which a cell matures and specialises through regulated gene expression.
Define the terms:
- Totipotent
- Pluripotent
- Multipotent
- Unipotent
Totipotent - can differentiate into all cell types. Zygote.
Pluripotent - can differentiate into most cell types - blastocyst.
Multipotent - progenitor cell able to differentiate into many cell types.
Unipotent - able to mature into one cell type, such as erythroblasts.
Describe haematopoeisis and discuss it’s regulation.
- Is the production of blood cells from Haematopoeitic Stem Cells (HSCs) in the bone marrow.
- HSCs can differentiate into Myeloid and Lymphoid stem cells.
- Lymphoid Stem Cells are directed by normal control originating in the Thymus. Pre-T-Cells migrate to the Thymus to undergo selection, while Pre-B/ NK cells remain in the Bone Marrow these are acted upon by IL-7.
- Common Myeloid Progenitor cells give rise to erythroblasts (stimulated by EPO), megakaryocytes (TPO) and select leukocytes (IL-3, IL-6m GM-CSF). GM-CSF plays a large role in all cell types of Myeloid lineage.
Outline the possible fates of a stem cell.
- Self Renewal
- Quiescence
- Apoptosis
- Differentiation
Compare adult and embryonic stems cells.
(You’ll have to touch on ethics here, too)
Adult Stem Cells
- Less ethical issues
- Difficult to culture
- Less potent
- Useful for transplants
- Multipotent at best
Embryonic
- Highly emotive topic, ethical maze
- Easy to culture
- High potency
- Risk of rejection
- Pluripotent
Describe the process of haemostasis and coagulation
- The arrest of blood loss.
- Vascular phase
- local vasospasm reduces blood flow.
- Basement membrane collagen is exposed.
- Damaged endothelial cells release Endothelins (promotes growth and repair and vasoconstriction).
- Tissue Factor to initiate Extrinsic Coagulation.
- NO balance is upset with tissue damage, prostacyclin released.
- Endothelial cells become “sticky”
- Platelet phase
- Platelets stick to exposed collagen and endothelial cells.
- Platelets release granules on binding. vWF facilitates early binding and aggregation. Released in granules are: ADP, TxA2 and serotonin.
- Bound platelets express Glycoproteins II/IIb
- Prostacyclins keep this +be feedback loop in check.
- This primary haemostasis plug is formed. - Coagulation
- Initiated at the extrinsic pathway (tissue factor - PT time assesses this).
- Tissue Factor III(3) activates VII (7) to VIIa (7a).
- These combine to form TF-VIIa (3-7a).
- This in turn activates X to Xa (10 - 10a)
- Concomitant with the intrinsic pathway (contact activation).
- XII (12) is activated to XIIa (12a).
- XI (11)is activated to (11a)
- IX (9) is activated to IXa (9a)
- X is activated to Xa (10 - 10a)
Xa marks the convergence to the Common Coagulation Pathway. Xa is activated in the presence of Ca and Pl.
- Prothrombin II (2) is activated to Thrombin IIa (2a) by Va and Xa.
- IIa activates V (5) to Va (5a) and Fibrinogen I (1) to Fibrin Ia (1a).
XIIIa (Fibrin stabilising) helps cross link Ia. The stable Fibrin Clot is formed.
- Clot lysis
- by Plasmin
- TF is inhibited by TFPI
- Protein C inhibits lots of Fs.
- Antithrombin. Think.
Describe the basic structure of bacteria and their function.
- Cell Wall - A polysaccharide layer, protective.
- Plasma Membrane - phospholipids. Boundary of the cytosol.
- Plasmids - Short fragments of DNA that can be exchanged. With other CFUs.
- Mesosomes - Folded invagination of the cell wall, increasing surface area.
- Chromosomes - Genetic material, as with eukaryotic cells.
- Ribosomes - for protein translation
- Flagellum - for motility
- Pili - Hairlike appendages. Allow for adherence, can also be used in conjugation (sex pili).
State the different shapes of bacteria
- Cocci
- Single (Coccus), double (diplococci) or bunched (cocci) - Bacilli
- Rod like - Coccobacilli
- Round rod, like a rugby ball. - Spirochetes
- Spiral in structure.
Define the terms Gram Positive and Gram Negative in microbiology.
Gram Positive (Gram +ve). - Stains well in “Gram Stain”. Due to a thick peptidoglycan wall.
Gram Negative (Gram -ve) Stains poorly due to a thinner peptidoglycan wall. Usually has outer layer/ capsule holding LPS and endotoxins. Bad times.
Describe two key differences between gram +ve / -ve
+ve stains rich in Gram Stain, think peptidoglycan wall.
-ve stains poorly, thin peptidoglycan wall and hosts outer layer rich in LPS and Endotoxins.
Name two of each:
- Gram -ve Bacilli
- Gram -ve Cocci
- Gram +ve Bacilli
- Gram +ve Cocci
- E.coli and S.enterrica
- N.meningitidis and H.Influenzae
- C.Dificile and L.monocytogenes
- Staph.aureus and Strep.aureus
Define:
- Endotoxin
2. Exotoxin
- Endotoxins: a bad time. Structures found on the outer layer of gram -ve bacteria. Can be shed. Common example is LPS.
- Secreted (not shed) by bacteria, disrupting cellular metabolism
Describe basic viral structure.
- Genetic material that comes in a variety of flavours.
- Double or Single stranded DNA (dsDNA/ssDNA)
- Double or Single stranded RNA (dsRNA/ssRNA) - Capsid. Viral protein coat made up of capsomeres.
- Some contain basic enzymes, such as reverse transcriptase.
Describe the shapes of nucleocapsids
Viral.
Icosahedral. 20 triangular shapes organised to form a coat.
Helical. Rod shaped and filamentous.
Prolate. Sophisticated is shape. A cylinder flanked by two caps. Bacteriophages.
Describe the process of viral replication
- Absorption. The virus binds to a specific receptor. Such as HIV binding CD4 CCR5.
- Penetration. The viral coat fuses with the cell or is endocytosed.
- Uncoating. The viral capsid is lost, free nucleic acid is in host cytosol.
- The coup etat. Host cell metabolism halts. Viral nucleic acid is transcribed and translated using host cell organelles.
- Synthesis. Viral genome is replicated.
- Assembly. Viral products are assembled, capsomeres self-assemble around viral genome to form new virions.
- Release. Virions either bud from the host cell, or cause cell lysis.
- The virus spreads.
State the primary and secondary lymphoid glands.
a. Primary. Where lymphocytes are produced and mature; Bone marrow and Thymus.
b. Secondary. Where lymphocytes migrate to undergo clonal expansion. Lymph nodes.
Describe how lymph is formed.
Blood arrives to the capillary bed at high hydrostatic pressure.
Fluid, minus haematocrit is force through capillary gaps. As blood moves along the capillary, fluid returns due to osmotic pressure. Remaining fluid in the tissues is the lymph. It is returned to circulation via the right and left venous angle.
State 4 functions of Lymph
- Transport of lipids, fat and chyle
- Removal of excess fluid, preventing oedema
- Transport of APCs and Antigens to initiate the adaptive immune response
- Maintenance and distribution of lymphocytes.
Describe lymphopoeisis
Haematopoeitic Stem Cell, which is multipotent differentiates into either Myeloid or Lymphoid Stem Cells. Lymphoid Cells remain in the bone marrow, or migrate to the Thymus. Thymus cells undergo selection, and can be induced by APCs, while B and NK cells are influence into growth by IL-7.
Describe Lymph flow through a lymph node.
- Afferent lymphatic
- Subscapular space and cortical sinus
- Through the deep cortex and germinal centres.
- Through the paracortical area
- Through medullary cords in the medulla and out via the efferent lymphatic.
List (label) the parts of the lymph node, and the cell type prominent in each zone.
- Afferent Lymphatics
- Germinal Centres - B CELLS (proliferate and mature)
- Cortex - B CELLS
- Paracortical area - T Cells
- Medulla - Macrophages and Plasma Cells.
- Afferent Lymphatics
Describe Innate Immunity
- Physical Barriers
- The skin, and other epithelial linings.
- Secretions can support these barriers, such as sweat on the skin or secretion of mucus in the airways. A variable pH in the alimentary tract also acts to eliminate microbes.
- Immunoglobulins in secretions (IgA in saliva) - Associated Lymphoid Tissues
- around epithelial linings, such as the Peyers patches (GALT). Rich in immunoglobulins. - Innate line leukocytes
- Monocytes, Neutrophils, Dendritic Cells (phagocytic)
- These act as APCs, presenting to T Helper Cells.
- Recognise Pathogen Associated Molecular Patterns (PAMPs) and Damage AMPs via Toll Like Receptors (TLRs). Eg. TLR-4 Recognises -ve LPS.
- Immune surveillance
- Natural Killer Cells “ID Check” via MHC-I. Kill any self-cells that have gone awry (viral or cancerous). - Interleukins and Interferons (Cytokines)
- Soluble proteins. Broad usage. Such as IL-6, pyrogenic or IFN-Y, increases MHC-II expression and M.O recruitment. - Complement
- Opsonisation, Inflammation, Lysis. A cascade of proteins. Three pathways. Classical, Alternative and Lectin. C3a kick starts it all (such as by binding Fc Ab). - Inflammation
Palor, Rubor, Dolor, Tumor, Functio Laesa
- Fever
IL-1 and IL-6 encourage the release of prostaglandins in the hypothalamus, increasing core body temperature, off setting ideal growth environment for pathogens.
Explain the concept of PAMPs and TLRs
PAMPs, Pathogen Associated Molecular Patterns, are highly conserved components of pathogens. These components are fundamental to the pathogens function, so is usually expressed. They are detected by Toll Like Receptors (TLRs) on host Leukocytes. Example: Lipopolysaccharide (LPS) on -ve bacteria are detected by TLR-4.
Name five pro-inflammatory cytokines
- IL-1 - pyrogen
- IL-6 Pyrogen
- TNF-A - Vasopermability
- IL-8 - Chemoattractant of neutrophils
- IFN-Y - stimulates Macrophages
(IL-12 - Activates NK Cells)
Describe the physical barriers of the body
- Epithelium
- Mucous Membranes
- Secretions
- Ear wax
- Hair in the nose and ears
- Tears
Describe the MHC and which cells they are found on.
MHC Class I, found on all nucleases cells. Present self antigen to NK Cells and Tc Cells. Made of three alpha and 1 beta2 chains.
MHC Class II - Found on Antigen Presenting Cells (in abundance on professional APCs). Present ingested, non-self antigen to Th Cells. 2 alpha and 2 beta chains.
Name the three pathways of the complement system.
- Classical Pathway (Adaptive, C3a is activated by Ab Fc)
- Alternative Pathway (C3 binds the pathogen)
- Lectin Pathway (fungi and parasites)
Give three functions of the complement system
- Inflammation. Anaphylatoxins formed during cleavage are responsible.
- Opsonisation, another component of cleaved proteins. “Tag” microbes for more effective killing.
- Lysis. The terminal sequence of complement by the formation of the Membrane Attack Complex (MAC).
What is the equation for the activation of C3a?
C3 ——- C3a via C3 Convertase (C3bBb or C4bC2a)
Explain how NK Cells kill.
Natural position is to kill other cells, bind MHC-I. If non-self/ aberrant/ absent antigen is presented, the cell is killed by performing and granzymes.
State the functions of the Interferons
Alpha - produced by infected cells. Chemoattractant for NK Cells and phagocytes.
Beta - Produced by infected cells to stimulate anti-viral proteins in non-infected cells.
Gamma - Produced by T Cells to stimulate macrophages. (Also expression of MHC-II).
State the cardinal signs of inflammation, and how they are produced.
Rubor - Redness. Increased vasodilation
Tumor - Growth. Increased vasopermeability.
Dolor - Pain. Stretching of tissue.
Calor - Heat. Fever and blood flow.
Functio Laesa - Loss of Function, due to swelling. Restrictive and protective.
Describe the process of leukocyte extravasation.
- Chemoattraction - cytokines cause endothelial cells to express selectins. Leukocytes slow down due to vasodilation.
- Margination and Rolling Adhesion - Leukocytes bind selectins via integrins. Rolling and slowing.
- Tight Binding.
- Diapedesis. “Foot through” of Leukocyte through junctions between endothelial cells.
- The cell fully migrates.
Describe Adaptive Immunity
Active:
- Natural (Infection) or Artificial (Vaccine).
Passive:
- Natural (gaining Abs from mother breastmilk or across the placenta.)
- Active (vaccine).
Antigen Presentation.
More traditional.
- Carried out by Professional Antigen Presenting Cells (APCs) or standard APCs via Major Histocompatibility Complex Class II (MHC-II)
- APCs or free antigen travel to the lymph nodes via the afferent Lymphatics.
- Antigen is presented to CD4+ Lymphocytes (Th Cells).
- Th Cells are co-stimulated by adnexal receptors and activated. (B7 APC - CD28 ThC)
- Cytokines IL-2, IL-6 facilitate this.
- Cells undergo Clonal Expansion. The differentiation of cells to target the same epitope.
- T Cells act similarly, but react via MHC-I.
- B Cells mediate the humoral (antibody) response while T Cells either help, or facilitate the cell mediate response (cytotoxicity.)
Describe the five classes of antibody.
IgM - A pentamer. Binds a broad range of epitopes.
IgA - Dimer, found often at Lymphoid Associated Tissues.
IgD - Membrane bound, used as a receptor.
IgG - Highly specific binding.
IgE - Role not really known, targets parasites and helminths. Role in allergy.
Draw and label an IgG molecule.
- Two long chains
- Two short chains
- Joined by disulphides bonds.
- Variable, antigen binding site/ region. “Fab”
- Constant region “Fc”.
What is the function of IgE?
Allergy. Mast Cell degranulation.
Give five functions of antibodies.
- Opsonisation
- Complement Activation
- Neutralisation
- Agglutination
- Attract phagocytes
Define the term Neoplasia
A new abnormal growth, occurs due to unregulated cell proliferation.
Define the term Tumour
A growth of the same neoplasm.
Define the term Cancer
A neoplasia that has metastasised.
Define the term Cell proliferation
Cell division and reproduction
Define the term Apoptosis
Programmed cell death
Define the term hyperplasia
Increase in cell number, causing an increase in tissue size. Often early sign of neoplasia.
Define the term dysplasia
Abnormal growth/ organisation of a tissue
Define the term metaplasia
A tissue has differentiated into another tissue type/ mimics another tissue type.
Define the term Benign
A tumour that does not metastasise.
Define the term Malignant
A tumour which has invaded or metastasised. Gives rise to secondary tumours.
Define the term hypertrophy
Increase in cell size, causing increased tissue size.
Define the term labile
Not stable. Rapid cell turnover
Define the term stable
Not labile. Slow cell turn over.
Define the term permanent (cells)
No cell turn over
Define the term cell cycle
The interval between two mitotic divisions resulting in two daughter cells.
Describe the four phases of the cell cycle.
“Interphase”
- G1 phase. Mitogen dependant. The cell grows in size, proteins are synthesised.
- S phase. DNA is synthesised.
- G2 phase. Cell grows, organelles are replicated.
Mitosis/ M Phase.
Prophase, (Pro)metaphase, Metaphase, Anasphase, Telophase, cytokinesis.
Describe regulation of the cell cycle.
The four checkpoints to be revised in MBChB 1 are:
Restriction Point
G1/S Checkpoint
G2/M Checkpoint
Metaphase Checkpoint
The restriction point:
- Most important apparently.
- A mitogen stimulates a Receptor Tyrosine Kinase, which activated the Ras pathway. (The phosphorylation of Rb, unblocking E2F.)
- Without this, the cell will Diverge to G0 (quiescence).
G1/S and G2/M Checkpoints.
1. Checks for DNA damage. P53 is active where DNA damage is detected. This activates P21, which prevents Cyclin E and A binding CDK 2.
Metaphase Checkpoint.
- Check for spindle attachment to chromatids. If improper attachment is detected, CDK 1 remains phosphorylated.
- If all is well, CDK 1 binds Cyclin B.
*Cyclin B awaits CDK 1 to bind.
Cyclin B is present from G2 in anticipation. CDK1/CYCB is named in some papers as Maturation Promoting Factor (MPF). Allows for destructed of the nuclear envelope, chromatin condensation, spindle formation.
Explain Hydrophobic Cell Signalling and examples of hormones involved.
The signal passes through the plasma membrane, acting on cytosolic receptors. Receptor-signal complex forms the transcription factor. Gene expression is altered, protein is translated and the effect is achieved. Example: testosterone.
Give three reasons why cell signalling should be studied
- It forms the basis of pharmacology.
- Elucidates cellular pathways and processes.
- Allows for the study and understanding on key hallmarks of disease.
Explain the problems hydrophilic signalling molecules face and how this is overcome.
These signal molecules cannot cross the plasma membrane.
Instead they bind cell surface receptors and activate a signal transduction pathway/ cascade. This then leads to an inter-cellular response.
Describe G-Protein Coupled Receptors.
- Serpentine in shape, with 7 transmembrane domains, starting at an extracellular binding site.
- Ligation causes a conformational change at the intracellular domain, where a G-Protein binds.
- GDP is swapped for GTP on the G-Protein.
- The G-Protein splits into alpha and beta subunits.
- Beta affects ion channels, Alpha has three principle targets.
- Adenylyl Cyclase which increases the production of Cyclic AMP from ATP. Binds Protein Kinase A (PKA). PKA moves to phosphorylation L-Type Calcium Channels, CREB and Phosphorylase Kinase.
- Phospholipase C. Acts on IP3 and DAG. IP3 acts on the ER. DAG on Protein Kinase C.
- Other G-Proteins
An example is Adrenaline and Cyclic AMP.
Describe enzyme linked receptors.
Principle steps. Example with Receptor Tyrosine Kinase.
- Ligand binds with two monomers, causing dimerisation.
- The dimer is autophosphorylated.
- Phospho-tyrosine residues in the cytosol act as binding sites for intracellular proteins.
- The signal is transduced.
Example is FGFR3
Describe Ion Channels.
Five principle steps.
- Ligation at one of several binding sites, as the channel is multimeric.
- Conformational change takes place. Classic.
- Central pore is now open.
- Ions passively diffuse.
- Shape is maintained when ligand is bound.
Example is ACH-R.
Name two signalling molecules that bind GPCRs, RTKs and Ion Channels.
- Adrenaline and Glucagon
- PDGF and FGF
- GABA and ACH
Define the term Tumour Suppressor Gene.
A gene which, when transcribed, produces a protein that inhibits tumour growth by suppressing the cell cycle until repair or apoptosis can take place.
Define the term Proto-Oncogene.
A normal functional gene that translates to a protein in normal metabolism, regulating cell cycle and differentiation.
Define the term oncogene
A mutated Proto-oncogene, which is now abberantly expressed. This causes inappropriate expression of a protein and cell behaviour (malignancy).
Describe the term mutation.
A change in genetic mutation.