Strand 5- Cells and Tissues

What is an organelle

a membrane bound or non-membrane bound subcellular structure with one of more specific functions

Light microscopy

• cheap, fast, readily available

• allows magnification of 400x

• tissue cut thin and allows light through and stained w haematoxylin and eosin

• uses a set of lenses to magnify an image using light

electron microscopy

• slow expensive and only in specialist centres

• allow magnification of 1,000,000+

• tissue embedded in very hard resin and cut ultra thin

• uses beams of electrons instead of light

nucleus

• membrane bound organelle

• Most cells have one

• holds most of cells genetic material

• structural support for genetic material provided by nuclear lamina (lamin proteins)

nuclear envelope

• bilayer of 2x phospolipid bilayer

• inner membrane connected to lamin proteins of nucleus

• outer membrane connected to endoplasmic reticulum

• contains many pores to regulate passage of molecules in and out of nucleus

nucleoulus

• located inside nucleus

• made of proteins and rDNA

• site of ribosome production

Ribosomes

• site of protein synthesis

• two subunits:

  • 50s (binds to tRNA)

  • 30s (binds to mRNA)

location of ribosomes

• free: make proteins for use in cell

• bound: make proteins for export or for membrane surface

RER

• continuous with nuclear membrane and SER

• main functions are protein synthesis and protein modification

SER

• originates form and stays continuous w RER

• no ribosomes

• synthesise lipids, cholesterol, steroid hormones, phospholipids

golgi apparatus

• helps sort and package proteins and lipids made by endoplasmic reticulum

• once package they can be trafficked to correct location

secretory vesicles

• release contents onto cell surfaces via exocytosis

• vary in size e.g. antibodies in plasma cells vs goblet cells in intestinal epithelium

lysosomes

• membrane bound spheres full of digestive enzymes

• have low pH

• recycling centre of cells

  • recycle old organelles

  • apoptosis

  • destroy micro organisms, lots of macrophages

peroxisomes

• another membrane bound cell organelle full of enzymes inc. oxidases

• originate from ER

• main functions:

  • Scavenge free radicals

  • lipid metabolism

Microtubules (tubulin)

• biggest fibre 25nm

• main roles:

  • moving organelles

  • movement of cilia/flagella

  • chromosome separation in cell division

intermediate filaments

• 8-12 nm

• main roles:

  • anchors organelles into place

  • makes up nuclear lamina

Actin microfilaments

• 7nm

• main roles:

  • muscle contraction

  • pseudopodia formation in phagocytosis

  • cleavage furrow formation in cell division

mitochondria

• involved in aerobic respiration

• folded membrane to increase SA

• own DNA

Diseases from mitochondrial DNA

• occurs when mutation inherited in mitochondrial DNA

• Rare and severe

• only inherited from mother

types of respiration

• aerobic:

  • getting energy from fuel using oxygen

  • cell cytoplasm and mitochondria

  • Glycolysis, link reaction, Krebs cycle, oxidative phosphorylation

  • forms Water, CO₂, 36 ATP

• anaerobic:

  • getting energy without oxygen

  • cell cytoplasm

  • glycolysis, NAD regeneration

  • Forms lactic acid and 2 ATP

cytosol

• semi-fluid substance filling interior of cell and embedding the other organelles

• space is enclosed by cell membrane and membranes of different organelles thus making up a separate cellular compartment

cytoplasm

Cytosol+ all organelles- nucleus

nucleoplasm

Fluid within nucleus

protoplasm

cytosol+ all organelles including nucleus

the cell cycle

• describes sequence that leads to cell proliferation

• crucial to regenerate cells and tissues

• interphase (95%) and mitosis

phases of cell cycle

• G0- Resting Phase:

  • cells perform functions without actively preparing to divide

  • may re-enter G1

• G1- cell growth:

  • cells increase in size and produce organelles

• S-DNA replication

• G2-Cell growth:

  • cell growth continues and proteins are synthesised in preparation for mitosis

regulation of cell cycle

• checkpoints:

  • G₀ will be signalled by growth factors to enter G₁

  • after restriction point, cell has committed to cell growth

  • G₁/S checkpoint checks for DNA damage

  • G₂/M checkpoint checks for damaged or unduplicated DNA

Checkpoints in cell cycle

• G1:

  • check for DNA damage before commttting to DNA replication

• G2:

  • ensure DNA replication is complete and undamamged before mitsoisi

  • ensures genome only replicated once per cycle

• M:

  • Arrests mitsosis if daughter chromosomes are misaligned on mitotic spindle

Cyclins

• regulate cell cycles and associated enzymes called cyclin-dependent kinases (CDKs)

• Cyclin-CDK complexes permit the protein phosphorylation and signal transduction that allows progression through the cell cycle

• specific cyclin-CDK complexes are active throughout diff. phases of cell cycle

CDK inhibitors

enforce cell cycle checkpoints by modulation activity of cyclin-CDK complexes

how does dysregulation of cell cycle lead to cancer

• oncogene:

  • mutated overactive positive regulator of cell cycle

  • e.g. growth factor receptors, protein kinases, transcription factors

HER 2 (ERBB2)

• proto oncogene located on long arm of chromosome 17

• growth factor receptor

• activates intracellular signalling pathways in response to extracellular signals→ promotes cell proliferation

• mutation can cause it to become oncogene→ overexpression in mammary epithelial cells of some breast cancers

tumour surpressor genes

Act to inhibit cell proliferation and survival:

• cell cycle regulators e.g. RB1, CDN2A

• DNA damage repair e.g. BRCA1/2, MLH1

• Apoptosis inducers e.g. TP53

• Growth signal inhibitors e.g. PTEN, NF1

• Adhesion and invasion suppressors e.g. CDH1

p16 as a tumour suppressor gene

• (P16-INK4A)

• CDK inhibitor

• Encoded by CDKN2A tumour suppressor gene on 9p21

• inhibits Cyclin D-CDK4/6 complexes→ prevents phosphorylation of Rb→ E2F remains inactive→ cells stay in G1

• upregulated in cellular stress, DNA damage and oncogene activation e.g. oncogenic infection

• Germline alterations in CDKN2A most frequently associated with predisposition to melanoma and pancreatic cancer

steps in mitosis

• Prophase:

  • chromosomes condense and become visible

  • mitotic spindle starts to form

  • nucleolus disappears

• Prometaphase:

  • nuclear membrane disappears

  • chromosomes begin to attach to mitotic spindle via kinetochore microtubules

• Metaphase;

  • chromosoems align in plate around centre of mitotic spindle

  • mitotic spindle checkpoint

• Anaphase:

  • spindle fibres contract towards opposite poles, separating sister chromatids

• Telophase:

  • kinetochore microtubules disappear

  • nucelar envelope forms around each group of daughter chromosomes

• cytokinesis

mitosis

separation of chromosomes and physical division of cell into two daughter cells following G2

meisosis

DNA replication is followed by two rounds of cell leading to formation of haploid cells

steps in meiosis

1. prophase I

   • DNA condenses into chromosomes- consists of 2 sister chromatids joined by centromere

   • chromosomes arranged side by side in homologous pairs- bivalents

   • centrioles migrate to poles to form spindle

   • nuclear envelope breaks down and nucleolus disintegrates

2. Metaphase I

   • bivalents line up along equator of the spindle

   • maternal and paternal chromosomes position themselves independently of the others- independent assortment

3. Anaphase I

   • homologous pairs are separated as microtubules pull whole chromosomes to opposite ends of the spindle

4. Telophase I

   • chromosomes arrive at opposite poles

   • spindle fibres break down

   • nuclear envelopes form around two groups of chromosomes and nucleoli reform

5. Cytokinesis

   • cytoplasm divides- organelles distributed and cell surface membrane pinches inwards

6. Prophase II

   • nuclear envelope breaks down and chromosomes condense

   • spindle forms perpendicular to old one

7. Metaphase II

   • chromosomes line up in a single file along the equator

8. Anaphase II

   • centromeres divide and individual chromatids are pulled to opposite poles

     • four groups of chromosomes with half the number of chromosomes as original

9. Telophase II

   • nuclear membranes form around each group of chromosomes

10. Cytokinesis

    • cytoplasm divides to create 4 haploid cells

differences in gametogenesis in males and females

• male gametogenesis starts at puberty and continues throughout life

• female gametogenesis starts at foetal life

• meiosis is arrested at two points:

  • prophase of Meiosis I before birth

  • arrested at metaphase of Meiosis II during puberty

  • and is only completed upon fertilisation of secondary oocyte

necrosis

• pathological cell deatg in response to irreversible injury e.g. ischaemia, toxins, chemicals

• loss of membrane integrity, enzyme digestion of cells and host inflammatory repsonse

  • - patterns of necrosis:

  • coagulative

  • liquefactive

  • caseous

  • fat 

  • fibrinoid

coagulative necrosis

• caused by ischaemia→ all tissues except vbrain

• protein denaturation predominates

• architecture of tissue is preserved for at least a few days

fibrinoid necrosis

• vasucular damage caise dby immune-complex deposition in artery walls

• bright pink amorphus ‘fibrioid’ appearance in vessel walls

• SLE, polyarteritis nodosa, rheumatoid, ANCA-associated vasculitis

liquefactive necrosis

• enzymatic digestion of tissue into a viscous liquid

• bacterial infections (abscesses)

• ischaemia of the brain

caseous necrosis

• cheese like, granulomatous

• TB, some fungal infections

fat necrosis

• focal areas of fat destruction

• liapse activation releases fatty acids from triglycerides which complex with calcium- fat saponification

• pancreatitis, trauma, surgery

apoptosis

• programmed cell death that is tightly regulated

• selective elimination of unwanted cells

• apoptotic cells fragment and alter their surface components to become a target for ohagocytosis

• dead cells cleared before contents leak→ no inflammatory reaction

causes of apoptosis

• physiological apoptosis

• pathological apoptosis

physiological apoptosis

• involution of primordial structures during foetal development

• hormone-dependant involution in adult life

• cell turnover and homeostasis in proliferating cell populations

• deletions of delf-reactive lymphocytes

• death of cells that have served their purpose

pathological apoptosis

• DNA damage (e.g. due to hypoxia, radiation, cytotoxic drugs)

• accumulation of misfolded proteisn

• cell death in ciral infection

• atrophy of parenchymal organs after duct obstruction e.g. pancreas, kidney

mechanisms of necrosis

• cellular injury causes cellular and organelle swelling, plasma membrane by blebbing and fatty change

• irreversible injury leads to death by necrosis:

  • denaturation of cellular proteins

  • enzymatic digestion of dead cell

  • leakage of cellular contents through damaged membranes

  • local inflammatory response

mechanisms of apoptosis

• results in activation of caspases

• initiation phase:

  • activation of caspases in a cascade

• Execution phase:

  • terminal caspases trigger cellular fragmentation

• Two distinct pathways that result in caspase activation:

  • mitochondrial/intrinsic

  • death receptor/ extrinsic

mitochondria (intrinsic) pathway

• BCL-2 family of proteins controls integrity of mitochondrial membrane

• lack of survival signals, cellular stress/damage→ inactivation f anti-apoptotic proteins

• net result= increased permeability of mitochondrial membrane and leakage of cytochrome C

• activates initiator caspases (9)→ activation cascade→ executor caspases (3,6) trigger apoptosis

death receptor (extrinsic) pathway

• death receptors are members of the TNF receptor family

• contain a cytoplasmic domain that is essential for delivering apoptotic signals

• e.g. Fas receptor and Fas L on activated T cells

• death domain binds to an adaptor protein that activates initiator caspases (8,10)→ activation cascade→ execution caspases (3,6) trigger apoptosis

cell

functional unit of all living organisms

tissue

• cells of similar morphology and function along with extracellular matrix from tissues

• relatively homogeneous in structure e.g. bone, muscle, cartilage

organ

anatomically discrete collections of tissues that perform certain specific functions e.g. eye, liver, kidney

tissues and organs

• together may constitute integrated functional systems forming anatomical entities e.g. CNS, GIT, GUT

• functionally specialised cells often grouped ‘parenchyma’

• less specialised supportive tissue, ‘stroma’

tissue types

• supportive/connective tissue

• epithelial tissues

• muscle

• nervous tissue

supportive/connective tissue

• term applied to tissues which provide structure, strength and physical/ metabolic support generally

• 3 core properties:

  • tensile strength- collagen

  • elasticity- elastin fibrils

  • volume- glycoproteins, complex carbohydrates

features of epithelial tissue

• cellular composition

• structure

• function

• regeneration

types of epithelial tissue

• squamous

• cuboidal

• columnar

• transitional

• simple

• stratified

• pseudostratified

squamous epithelium

• flattened, irregularly shaped cells

• form continuous surface

• delicate, supported by basement membrane

• can line surfaces involved in passive transport e.g. of gas, lungs

cuboidal epithelia

• simple cuboidal epithelium- intermediate form between simple squamous and simple columnar

• perpendicular section, cells appear square

• nucleus is round and central to cell

columnar epithelium

• simple columnar similar to simple cuboidal, except cells are taller and appear columnar in perpendicular sections

• height depends on activity and function

• nuclei elongated and often basal- ‘polarity’

• ciliated

• mainly found in female reproductive tract

transitional epithelium

• also know as urothelium

• stratified, found in urinary tract only

• specialised→ in contact with toxins in urine

• transitional→ has some features intermediation between stratified cuboidal and stratified squamous epithelia

• non-distended and stretched states look slightly different

simple epithelia

• single layer of cells

• interfaces involved in selective diffusion

• little protection

stratified epithelium

• two or more layers of cells

• protective function

• poorly suited for absorption and secretion

pseudostratified epithelium

• conveys erroneous impression that there is more than one layer of cells

• e.g. almost exclusively confined to airways of respiratory system- pseudostratified columnar ciliated epithelium

skin

• keratinising stratified squamous epithelium

• variable number of cell layers

• maturation from cuboidal base layer to flattened surface layer

• basal cells adherent to underlying basement membrane

• accumulate keratin

• intermediate filaments crosslink with proteins

epithelium found in nasal cavity and mucosa

• pseudostratified ciliated columnar epithelium

epithelium in nasopharynx

• pseudostratified ciliated columnar epithelium

• numerous mucin secreting goblet cells

epithelium in larynx

columnar ciliated respiratory-type epithelium

epithelium in trachea

• respiratory epithelium, similar to rest of bronchial tree

• tall pseudostratified columnar cells with goblet cells

• serous cells

• basal stem cells→ can divide and replace cells

epithelium in primary bronchus

• respiratory epithelium

• less tall, contains fewer goblet cells

• submucosa contains fewer seromucinous glands

epithelium in tertiary segmental bronchus

• tall columnar epithelium with little pseudo stratification

• goblet cell numbers greatly diminished

epithelium in bronchiole

• no cartilage or submucosal glands in the wall

• epithelium composed of ciliated columnar cells and few goblet cells

epithelium in alveoli

• surface epithelium

• supporting tissue

• most of alveolar surface area is covered by large squamous cells called type I pneumocytes

epithelium in oral cavity, pharynx and oesophagus

• stratified squamous type

• not keratinised in oral cavity

epithelium in stomach

• gastric type secretory mucosa

• only occurs in stomach

• long, closely packed tubular glands that are simple or branched depending on the region of the stomach

epithelium in small intestine

• intestinal type absorptive mucosa

• mucosa arranged into finger-like projections called villi which serve to increase surface area

• intervening short glands→ crypts

• duodenum-. some crypts extend through muscularis mucosae to form submucosal glands→ Brunner’s glands

epithelium in large intestine

• colorectal type absorptive/protective mucosa

• mucosa arranged into closely packed, straight tubular glands consisting of cells specialised for water absorption

• mucus secreting goblet cells to lubricate passage of faeces

genitourinary epithelium

• transitional epithelium/urothelium

• stratified→ 3-6 layers thick

• cells of basal layer are compact and cuboidal

• umbrella cells

coeliac disease

• show flattening or loss of normal intestinal villi

• marked increased in number of lymphocytes and plasma cells in lamina propria

• maintain integrity of mucosal surface→ increased proliferation of steam cells at bases of crypts

bullous pemphigoid

• any disease that damages dermo-epidermal junction can lead to separation of epidermis and dermis

• initially space fills with fluids→ vesicles/bullae

• antibodies react against antigens in hemidesmosomes or lamina lucida

  • reaction continues, triggering damage to membrane and further separation of dermis and epidermis plus blistering