Genes & Embryo Development PDF
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University of Plymouth
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Summary
This document provides an overview of genetics, inheritance, mutations, and innate immunity. It discusses the structure of chromosomes, patterns of inheritance (monogenic and polygenic), mutations (inherited and somatic), and epigenetic effects. Further, the document covers innate immunity components, infection-induced inflammation, and the process of embryonic development from fertilization to gastrulation, along with defects like Down's and Turner syndromes.
Full Transcript
2.1 Genes 1: Structure of the chromosome and patterns of inheritance ** Revise and revisit core issues in genetics covered at a pre-university level; nucleotide bases\>codons\>genes\>DNA\>RNA** Bases/nucleotides: adenine, guanine (purines), cytosine, thyamine, uracil (pyrimidines) A-T (U in RNA)...
2.1 Genes 1: Structure of the chromosome and patterns of inheritance ** Revise and revisit core issues in genetics covered at a pre-university level; nucleotide bases\>codons\>genes\>DNA\>RNA** Bases/nucleotides: adenine, guanine (purines), cytosine, thyamine, uracil (pyrimidines) A-T (U in RNA) G-C \^hydrogen bonds DNA -- double helix, strands run in opp directions, wrapped around histones 5'-\>3' (main use) 3'\ 5^th^ carbon in carbon chain 3' -\> 3^rd^ carbon in carbon chain Transcription -\> copy of DNA by enzyme RNA polymerase (U instead of T) into RNA Translation of RNA at riboome to create proteins - Read in codon: 3 bases coding single amino acid Genome: whole set of DNA, stored in chromosomes in nuclei RBC do not have genome Different genes express in different cells for cell function -\> makes diff proteins ** Revise and revisit core Mendelian genetics, autosomal/x-linked, dominant/recessive patterns of inheritance covered at a pre-university level** Monogenic inheritance: trait determined by one set of alleles/specific gene (mendelian) Polygenic inheritance: trait determined by more than one gene (non-mendelian) e.g. skin colour )continuous variation Multifactorial/complex traits: influenced by more than one gene + environmental factors (height) Genotype: describes genetic info (HH or Hh or hh) Phenotype: physical characteristic of phenotype (colour/height) Allele: diff form of gene found at same place on chromosome (H or h) Homozygous: same alleles (HH/hh) Heterozygous: diff alleles (Hh) ** Introduce the theme of complex patterns of inheritance** Monogenic: - Autosomal traits are carried out on any chromosomes other than X and Y - Dominant or recessive - Autosomal dom/rec - x-linked are carried out on x chromosomes (colour blindness, haemophilia A) Polygenic: - Show continuous variation - Genetic risk factors (e.g. cancers and type 2 diabetes) ** Define mutation and explain the terms inherited and somatic mutations** - Change in DNA sequence - Allows for evolution and diseases - Germ line mutation passed through gamates - Somatic mutations in somatic cell cannot be passed on - Substitution mutation: genetic mutation effect varies based on resulting protein from mutation -\> point mutation -\> silent, nonsense, missense ![](media/image2.png) Deletion & insertion mutation: amino acids are inserted/deleted -\> causes frameshift Translocation mutation: section of chromosome moves -\> changes chromosomes or location on chromosome -\> chops genes in half/inactivate them/change expression ![](media/image4.png) ** Introduce the concept of genetic vs epigenetic effects and their significance** Epigenetics: research explaining stable, heritable traits not explained by gene sequence Gene modifying to change gene expression e.g. methylation -\> adding methyl group to DNA base Epigenetic changes can be caused by environmental factors (e.g. mice exposed to particular smell and painful stimulus have offspring that are likely to have aversion to same smell) Reversible and do not change DNA sequence -\> activate DNA sequence more/less INTRO TO INNATE IMMUNITY Summarise the components of the innate immune system - 1^st^ line of defence - Phylogenetically older than adaptive - Mechanisms exist before microbial encounter - Components: barriers, cytokines (signalling cells -\> pro-inflam, proliferation apoptosis, differentiation, growth), circulator effector cells, circulating effector proteins (compliment system -\> group together for effect) Barriers:![](media/image6.png) ![](media/image8.png) Circulating effector cells: ![](media/image10.png) Neutrophils, dendritic cells + macrophages: - first cells at site of infection - Detect infection -\> signal infection -\> clear debris from infected tissue Phagocytosis: - MHC II -- extracellular antigen presenting cell - MCH 1 - intracellular Natural killer cells:![](media/image12.png) - Circulated w inhibitory receptor (doesnt do shit), sees infected cell w/o inhibitor, NK cell activates and signals other NK cells to kill infected cell. Needs 2 signals for it to activate - Kind of lymphocyte - No class I MHC = kill bc CD8 cant recognise it - 5-10% of lymph in blood and spleen - Effector functions: perforin (creates opening) + granzyme (goes in and causes apoptosis) - Macrophage (MΦ) interaction controls intracellular infection until adaptive immune system takes over -\> controls inflammation - Macrophage infected -\> releases IL-12 -\> activates NK cell -\> NK cell releases IFN-ϒ -\> affects MΦ activation and differentiation and kills phagocytosed bacteria - IL-12 increases NK cell population -- inflams place Secrete IFN-ϒ Innate lymphoid cells: ![](media/image14.png) - group of cytokine producing lymph that don\'t express T-cell receptor - Respond to cytokines instead of antigens - 3^rd^ largest lymph population - Defined by transcription Mast cells, eosinophils and basophils: Mast cells - release histamine - Increase vascular permeability + smooth muscle contraction - Allergies - Tissue resident Basophils - Release histamine - Circulating - Important in parasite infection Eosinophils - Release inflam molecules - Also respond to parasites ** Explain how infection leads to inflammation** Inflam - Protective mechanism - Recruitment of leukocytes and extravasation of plasma proteins onto site of infection - Activate leukocyte to eliminate infection - If not managed can dmg host tissue -\> pathology Extravasation 1.Secretion of cytokines and chemokines at site of infection 2.Selectin mediated rolling of leukocytes 3.Increase in integrin affinity 4.Integrin mediated attachment to endothelium 5.Transmigration through endothelium 6.Migration to site of infection Compliment system - X Interpret the features of innate immune recognition - Recognition of microbial pathogens and not somatic cells - 4 major classes - TLR -- bacteria and virus - CLR -- fungi - NLR -- bacteria and cell dmg - RLR -- viruses ![](media/image16.png) Define the key effector mechanisms of the innate immunity Describe how the innate immune response orchestrates the adaptive immunity Discuss the components of the innate immune system present in the oral cavity EMBRYO To consider the earliest stages of embryonic development from fertilisation to gastrulation Germ cell formation and fertilisation: - Somatic cell has 46 chromosomes - 22 homologous sets one sex each frm mother and father - Female XX - Male XY Fertilisation -- fusion of male and female germ cells Spermatoza -- sperm cell Ova -- egg cell Fertilisation leads to a zygote Diploid -- complete number of chromosomes in somatic cells Haploid -- half the number of chromosomes in gamete cells Miosis -- cell division of somatic cells -\> identical daughter cells Meiosis -- cell division in reproductive cells -\> half number of chromosomes from somatic cells Cell division: (mitosis) - DNA replicates during synthetic phase - DNA doubles -\> tetraploid - Divides equally btw new daughter cells - Prenatal development: ![](media/image18.png) +-----------------------+-----------------------+-----------------------+ | **Stage 1 (0-4 | **Stage 2** | **Stage 3** | | weeks)** | | | +=======================+=======================+=======================+ | Cellular | Morphogenesis | Growth and maturation | | proliferation | | | +-----------------------+-----------------------+-----------------------+ | Cellular migration | Many intricate | | | | | | | | embryologic processes | | +-----------------------+-----------------------+-----------------------+ | Some degree of | | | | cellular | | | | differentiation | | | +-----------------------+-----------------------+-----------------------+ Induction, competence and differentiation: - Patterning important in development from initial axial (head to tail) specification of embryo in segmentation - Spatial and temporal event -\> starts induction, competence and differentiation - Can be used for teeth development and supporting tissues - Induction: process that initiates differentiation. Incudcer -\> agent that provides cells w signal to enter this process - Homeobox genes, growth factors and retinoic acids crucial to development ** To explore the events taking place in human development weeks 1-3 gametogenesis, blastocyst formation and gastrulation (formation of the trilaminar embryo)** Week 1: ![](media/image20.png) - Fertilised egg -\> rapid divisions -\> ball of cells called morula - Fluid build up in morula and cell realignment -\> blastocyst (blastula) Week 2: - Day 8 -\> cells of embryoblast differentiate into 2-layered disc -\> bilaminar disc - Ectodermal layer (dorsal) are columnar -\> reorganise to form amniotic cavity - Secondary yolk sac (ventral) aka, endothermal layer form roof of the second cavity) ![](media/image22.png) WEEK 3: - Conversion of **bilaminar embryo disc (ectoderm + endoderm) -\> trilaminar embryo disc** - Begins w formation of **primitive streak** - Changes in cell shapes, rearrangement, movement and alterations in adhesive properties ![](media/image24.png) Gastrulation: - Blastula -\> gastrula - Slight enlargement of ectodermal and endodermal cells - After **2 weeks**, axis of embryo is established - Plate (cranial)/prochordal end aka head end (rostral) - Tail (caudal) end is cecal plate - Cells go thru streak -\> change shape and divert from streak (lateral and cephalic directions) - Cells if epiblast break off and travel -\> primitive pit -\> epiblast layer -\> form 3 layers; endoderm, mesoderm + ectoderm Endoderm -- formed by epiblast cells migrated from primitive pit -\> displace hypoblast Mesoderm -- lie btw endo and ectoderm (intra and extraembryonic mesoderm Ectoderm -- remaining epiblast cells in place @ primitive pit ↑ these cells responsible for forming diff tissues of fetus Ectoderm: liver, pancreas, lining of urethra + bladder + reproductive system, epithelial lining of digestive+ respiratory tracts Mesoderm: notochord, MSK, muscle layer of stomach + intestines, circulatory system, respiratory system, outer lining of gut Endoderm: epidermis of skin, cornea + lens of eye, nervous system **To site the discussion in the context of well-known defects in embryological development such as Down's syndrome, Turner syndrome etc.** Defects include meiosis malfunction -\> abnormal number of chromosomes → congenital abnormalities → head and neck region including teeth Trisomy 21: - 24 chromosome gamete fusing w normal gamete resulting in zygote containing 47 chromosomes -\> extra chromosome - 21^st^ chromosome pair has 3 chromosomes → trisomic - Facial clefts, shortened palate, protruding + fissured tongue, delayed eruption of teeth Turner Syndrome: - Most common chromosomal disorders in femaes - Partial/complete missing X chromosome - Monosomy - Dysmorphic stigmata, short, sexual infantilism, renal + cardiac + skeletal + endocrine + metabolic abnormalities \~10% of mutations are caused by single gene malfunction - Autosomal dom: achondroplasia, cleidocranial dysostosis, osteogenesis imperfecta + dentinogenesis imperfect - Autosomal recessive: chondroecto dysplasia, cystic fibrosis ** To introduce the term 'epigenetic' and briefly discuss how genetic and epigenetic processes are important in regulating development even at this early stage** DNA methylation - Methyl group addition to cytosines via covalent modification - CpG region -\> clusters in promoter regions of target genes - Hypermethylation ↓ gene transcription - Hypomethylation ↑ gene transcription Histone modification: - Positively charged nuclear proteins that DNA wraps around - Modify these → transcription factors reg activity of promoters Non-coding RNA: - Cluster of RNA that doesn't encode func proteins - Can regulate expression of gene and chromosome to control cell diff Genetics -\> inheritance -\> traits and disorders Epigenetics -\> what genes are activated -\> chem modifications to DNA and proteins -\> when and where genes are active PREGNANCY - **Describe the physiological changes to the body during pregnancy** - Basal metabolic rate - Cardiac output - Blood volume - Oxygen utilisation - Ventilation - Renal tubule reabsorption - GFR - Lumbar lordosis - Symphysis pubis diastasis + back pain Weight gain by mother: - Average foetus - +embryonic fluid - Uterus - Breasts - Body fluid - Fat accumulation ↑ chance of developing abnormalities is foetus 1^st^ trimester symptoms - 80% of miscarriage occur in 1^st^ trimester (10-15% of pregnancy) - Morning sickness \- nausea (50-70%) \- vomiting (40-50%) \- sensitive/sore breasts \- frequent urination \- constipation \- changing emotions \- hyperemesis gravidarum 2^nd^ trimester symptoms - Some nausea + vomiting - Frequent urination - Insomnia - Indigestion + muscle cramping - Feel foetal movements (18-20 weeks) (kicking?) - Pain w stretched uterus - Leukorrhea -\> vaginal discharge 3^rd^ trimester symptoms - Breathlessness -\> pressure on diaphragm - oedema -\> swollen ankles and toes -\> caused by vena cave -\> restricts blood flow - frequent urination - itchy skin - Braxton hicks -\> contractions + nesting instincts - Water breaks Endocrine changes: Hormone changes - hCG (human chorionic gonadotropin) -\> supports corpus luteum -\> temp organ in ovary in early pregnancy -\> what preg tests detects -\> peak 7-12 weeks -\> placenta stakes over - progesterone -\> establishes placenta -\> blood vessel formation for womb + strengthens pelvic wall muscles for labour, ↓ lactation - oestrogen -\> ↑ uterus growth, maintains lining, foetal organ development (lungs + liver), regulates hormone, ↑ breast growth + milk duct dev w progesterone -\> ↓ FSH + LH (no ovulation) -\> - prolactin -\> hormone ↑ breast milk, ↑ mammary gland size - relaxin -\> ↓ uterus contraction to stop premature birth, relaxes blood vessels ↑ blood to placenta + kidneys, relaxes pelvic joints and softens + lengthens cervix during birth - oxytocin -\> ↑ at start of labour, stims contractions of uterine muscle, ↑ production of prostaglandins which also ↑ contractions, can be given to induce labour ![A chart of pregnancy Description automatically generated](media/image26.png) Digestive system: - nausea + vomiting -\> maybe from hCG, made worse by low blood sugar - hyperemesis gravidarum (morning sickness) -\> vom \>3x a day, severe dehydration, lose weight - pyrosis -\> gastric reflux/heartburn - progesterone ↓ motilin (hormone that moves through food through DS) -\> delayed gastric emptying - growing foetus displaces stomach ↑ gastric pressure Urinary system - polyurea - downward pressure of enlarging foetus on bladder - hypotonia -\> ↓ decreased muscle tone from progesterone CVS - ↑ blood volume -\> 20-100% - RBC ↑ 110% - WBC ↑ 150% - Varicose veins + haemorrhoids by placenta stopping venous return - Uterus growth can compress vena cava in supine position -\> tilt patient on the side - ↓ blood pressure - ↑ CO (↑ HR and SV) - ↓ vascular resistance (vasodilation) Respiratory system - Diaphragm moves up 4-5cm -\> ↓ functional residual capacity -\> breathlessness - ↑ skin elasticity -\> stretch marks if too fast - ↑ pigmentation of skin from ↑ melanocyte stim hormone (MSH) -\> UV protection - ↑ areola - Lineaniagra -- line on abdomen MSK - Relaxin -\> ligament laxity + softening of connective tissue -\> pelvic floor, ligaments in hips - Changes in weight - Realignment of spinal curvature - Back pain common Immune System - ↑ sepsis - Placenta forms immunological barrier btw mum and foetus -\> foetus isn't rejected - **Describe the changes to the oral cavity during pregnancy** - Dental tissues: teeth, oral mucosa, salivary tissues - Gum hypertrophy - Incidence gingivitis - Tissue perfusion -\> bleeding risk Tooth morph -- primary + mixed dentition - **Compare the root and crown anatomy of the primary and** **permanent teeth.** - smaller than permanent teeth - crown appears more bulbous w pronounced labial/buccal cingulae - cervical margins ↑ - cusps more pointed - softer enamel (wears easier) + more opaque -\> whiter - thinner enamel → consistent depth (0.5-1mm) - larger relative pulp chamber - primary teeth calcify before birth -\> neonatal lines - only perm molars calcify before birth -\> neonatal lines - shorter + more delicate roots - prim incisors and canines = longer roots relative to crown height - roots of prim molars divergent -\> extend beyond dimensions of crown - irregular pulp canals - neonatal lines form from pressures from growing -\> calcify before birth - primary molar occlusal fossa dentine thickness ↑ (A) - thicker dentine (B) - pulpal horns higher in primary molar → esp mesial horn (C) - ↑ cervical ridges esp on buccal of primary molars (D) - Enamel rods @ cervix slope occlusally instead of gingivally (E) - Constricted neck compared perm molar (F) - Prim teeth roots longer + slender (G) - Roots of prim teeth flare out more (H) ** Describe exfoliation dates of the primary dentition and** **subsequent eruption dates of the permanent dentition.** Dental age: - Which teeth have erupted - Amount of resorption of prim teeth roots - Development of perm teeth Gen observations: - Prim -\> mixed starts at 6yo - Perm teeth erupt in groups - Teeth norm emerge when 75% of roots are completed - 2-3 years for root completion after teeth eruption 6yo: - Mandib central incisor - Mandib 1^st^ perm molar - Max 1^st^ perm molar ↑ erupt \~ same time but hard to determine bc of biological variation - Prim incisors smaller than perm -\> spacing prior to perm eruption is normal - Reassure parents abt this ![](media/image28.png) 7yo: Max central incisors Mandib lat incisors - Root form of max lat incisors - Canines + premolars still getting ready - Diastema (gap btw teeth) can occur btw max central incisors - Close as lat incisors erupt - Larger space can require ortho intervention 8yo: Max lat incisors - After this, delay 2-3y before more upper teeth appear 9yo: - Prim canines + first & second molars still there - \~1/3 root of mandib canines and 1^st^ premolars complete - Root development of 2^nd^ premolar is starting - Root development of max 1^st^ premolar starts + 2^nd^ premolar is about to start 10yo: Root development of max canine + 2^nd^ premolar & mandib 2^nd^ premolar - ↑ root resorption in prim canines - \~1/2 of roots of mandib canine and 1^st^ premolar complete - \~1/2 of the root of max 1^st^ premolar complete Dent age of 10 signs: - Roots of mandib incisors complete - Max lat incisors root almost done 11yo: - Root of all perm incisors + 1^st^ perm molar should be complete - Only prim teeth left: max canine + second molar, mandib 2^nd^ molar Mandib arch: - Mandib canine + 1^st^ premolar and max 1^st^ premolar erupt sameish time - Mostly mandib canine 1^st^ Max arch: - 1^st^ premolar erupts before canine 12yo: - Max canine + 2^nd^ premolar and mandib 2^nd^ premolar erupt - Radiograph 3^rd^ molar formation 13-15: - Completion of roots of perm teeth - Eruption of 2^nd^ premolars - 3^rd^ molars more apparent on radiographs 18-21: - 3^rd^ molar erupts ** Describe the development of permanent teeth between 7-21 years, including calcification and root formation.** A chart with numbers and symbols Description automatically generated with medium confidence ![A table with numbers and letters Description automatically generated](media/image30.png) ** Describe the mixed dentition with relevance appropriate** **restoration.** Normal variation: - 2^nd^ molar eruption before premolars in mandib arch -\> decreases space available for premolar -\> crowding - Canine eruption before premolars on max arch -\> canine forced labially out of arch - Asymmetries btw R and L sides -\> should erupt within 6 months of each other -\> if not, further investigate Restoration: - Caries progression faster bc thinner enamel and dentine - Restore ASAP - Pulp higher - Flat contact point - More vulnerable to cariogenic acid Preventative considerations: - Behaviours - Good oral hygiene - ↑ chance of caries on perm teeth w caries during mixed dentition - Erupting teeth difficult to clean - Tender gums contribute to not cleaning - Might have to do SSC (stainless steel crown) if proximal surface involved - Conical ant roots = easy removal - Flared molar roots -\> careful as premolar buds located close Prob w premature loss: - Crowding absent; little -- no effect on perm dentition - Crowding present; space loss upper arch always greater than lower, loss of 2^nd^ prim molar = greater loss than 1^st^ prim molar, 2^nd^ prim molar loss before 1^st^ molar eruption = loss of 2^nd^ premolar space, extractions after 10yo = little space loss - Early loss causes mesial drift -\> crowding/occlusial irregularities - Distal drift of ant teeth ** Chart the mixed dentition appropriately.** **ORAL HIST** - **Be able to identify oral tissues and cell types in a histological image** Dentosphere : World of Dentistry: MCQs on Oral Histology - Development and Growth of Teeth ![6: Structure and Physiology of the Periodontium \| Pocket Dentistry](media/image32.jpeg) image ![Dental Pulp Functions of the Dental Pulp Nutrition](media/image34.jpeg) **↑DENTAL PULP ↑** - Loose connective tissue - Capillaries + nerves - ECM -\> collagen I + II proteoglycans - Fibroblast - Odontoblast - Stem/undifferentiated mesenchymal cells - Lymphocyte - Plasma - Macrophage A close-up of a microscopic view of a human body Description automatically generated **↑PDL↑** - Connective tissue anchoring tooth to alveolar bone - Principle + sharpy fibres -\> collagen I + III - Blood vessel + nerves Cells: - Fibroblasts - Osteoblast + osteoclast - Cementoblast + cementoclast - Epithelial rests of malassez - Macrophage - Stem cells ![A close-up of a microscope Description automatically generated](media/image36.png) A diagram of the human body Description automatically generated - **Be able to describe how structure relates to function** - Stratified squamous epithelium - Buccal/labial lining - Masticatory surface; hard palate, attached gingiva, dorsum of tongue) - Specialist cells -\> taste buds - Varying amounts of keratin 1. Parotid 2. Submandib 3. subligual - **Recognise and describe changes that occur in oral disease** ![Histopathology of Caries in Enamel and Dentine - dentalnotebook](media/image42.jpeg) Caries↑ A close-up of a microscope Description automatically generated Perio↑ ![Squamous Cell Carcinoma of the Tongue After Bone Marrow Transplant and Graft-Versus-Host Disease: A Case Report and Review of the Literature - Journal of Oral and Maxillofacial Surgery](media/image44.jpeg) Oral cancer ↑ Big pink circle is keratin pearls (also not at apical surface) -\> cells differentiating in wrong places of tissue -\> no distinguished layers - **Revise your knowledge of key oral tissues, their development & function** A close-up of a microscope Description automatically generated A: stratified squamous epithelium B: basal layer C: connective tissue (lamina propria) -\> mainly collagen + fibroblast D: lumen of blood vessel E: salivary gland ![](media/image46.png) A: enamel rod B: enamel lamella C: striae of retzius D: dentinoenamel juction E: dentine tubules image O: oral mucosa V: vermillion border -- transition to oral mucosa S: skin -\> cutaneous skin M: muscle G: gland -\> minor salivary gland ![A close-up of a pink and white background Description automatically generated](media/image49.png) A: PDL B: Dentine C: cementum D: bone E: epithelial rests A microscope view of a cell Description automatically generated A: outer enamel epithelium B: stellate reticulum C: dental papilla D: dental lamina E: Inner enamel epithelium **ADAPTIVE IMMUNITY** - **Describe the cellular and soluble components of the adaptive immune system** Mechanical barrier: - Epithelial layer; prevent microbial entry - Enzymes/pH; breakdown microbial structures - Commensal microbes; outcompete pathogens Circulator effector proteins + functions: - Cytokines: messenger molecules that regulate immune cells + molecules - Complement: opsonisation, neutralisation, coagulation, MAC formation Inflam cytokines + functions: - [TNFα]: Key inflammatory mediator, potent stimulator of inflammation, multiple roles incl. neutrophil and endothelial cell activation, apoptosis - [IL-1β]: Key inflammatory mediator, multiple roles incl. activates endothelial cells, induces coagulation, pyrogenic -\> raise temp to kill off pathogens + denature proteins - [IFNγ]: Anti-viral response; activates MΦs, NK cells. Also important in anti-tumour responses - [IL-8]: Chemotactic for neutrophils Effector cells: - Macrophage -\> phagocytosis, antigen presentation, inflam reg, cytokine production - Neutrophil -\> phagocytosis, early inflam - Dendritic cell -\> antigen presentation, cytokine production - NK cels -\> kill infected cells, recognise tumour cells - Eosinophils + basophils -\> granulocytes release membrane dmg granules -\> anti-parasite - Mast cells -\> release potent inflame mediator -\> histamine - **Discuss the key functions of the adaptive immune system** - B lymph -\> antibodies - T lymph -\> effector T cells ![](media/image53.png) ↑cholesterol differentiation -\> CD8+ Specificity -\> ensures distinct antigens react only to target antigens Diversity -\> creates lots of diff antigens Memory -\> allows rapid and enhances responses to same antigen Clonal expansion -\> makes lots of pathogen specific lymphocytes Specialisation -\> makes responses optima for defence against diff types of organisms, switches off when done - **Distinguish between humoral and cell mediated immunity** Humoral produces antigen specific antibodies and cell mediated does not. Relies more on B cells and cell mediated relies on T cells, macrophages and cytokine release. Cell mediated: - Lechen planus -\> t cell targeted to host cell - Sjogren's syndrome Humoral: - Pemphigus/pemphigoid; antibodies targeted to host cell - Sjogrens syndrome Sjogren's syndrome: - Autoimmune tissue destruction of exocrine glands -\> salivary gland - Humoral response -\> autoantibodies to MMP + muscarinic receptors - Cell mediated destruction of acinar + ductal cells Lichen planus: - Chronic inflam affecting skin + mucous membranes - Rash/white patches in mouth -\> blister formation - Idiopathic (dunno what triggers it) - Can be from dental materials - Remove material Pemphigous: - Autoimmune disease that attacks top layer of skin + mucous membranes - **Compare and contrast innate and adaptive immunity** **EMBRYO -- FACE** - **Understand Neural Crest formation and their final fate** 1. Nervous system development starts by ectoderm thickening at rostral (head) end -\> neural plate 2. Margins of plate raise -\> neural fold. Folds also make groove 3. Folds merge -\> neural tube 4. Thickens again and separates -\> forms floor of amniotic cavity A close-up of a cross-section of a human body Description automatically generated ![A close-up of a cross section of a human body Description automatically generated](media/image56.png) - Ant portion of neural tube expands -\> forms fore-, mid-, and hindbrain - Part associated w hindbrain develops 8 bulges -\> rhombomeres - Somitomeres contributes w head muscles SOMITES: Each somite has 3 parts: - Sclerotome: becomes 2 adjacent vertebrae + articulating discs - Myotome: origin to muscles - Dermatome: becomes connective tissue of skin RHOMBOMERES: - Midbrain + rhombomeres 1 & 2 make face and first branchial arch - NCC from rhombomeres 3 onwards make pharyngeal structures NEURAL CREST: - Group of cells @ dorsal margin of closing neural folds - Become separate from neuroectoderm - Receive inductive signals to undergo epithelial-mesenchymal transformation - Exhibit exceptional capacity of stem + progenitor cells - 3-4 week of embryo development NEURAL CREST CELL: - Signalling molecules (Wnt + FGF) are secreted by surrounding nonneural ectoderm - Induces neural crest cell cascade - Competence determined by expression of members of "Snail zinc-finger transcription factor family" -\> repress expression of cell adhesion molecule E-cadherin - Origin of most of connective tissue of head - Embryo connective tissue from ectomesenchyme - Proper migration essential for craniofacial skeleton + teeth - All tissues of tooth (EXCEPT ENAMEL + SOME CEMENTUM) from neural crest cells 1. Growth 2. Morphogenesis 3. Ceff diff 4. Pattern formation - **Explore branchial arches formation and developmental processes** A list of medical information Description automatically generated with medium confidence![A purple and white text on a purple background Description automatically generated](media/image58.tiff) - **Examine development of the face and related structures** - Week 4-10 - Interaction btw neural crest mesenchyme + sensory facial ectodermal placodes - Epithelial-mesenchymal interactions - Sequential activation of specific genes + signalling molecules A close-up of a human body Description automatically generated Week 4 ↑ ![A close-up of a baby\'s body Description automatically generated](media/image60.png) Week 5↑ Week 6: - 2 mandib processes fuse to form lower jaw - Max processes grow below lat nasal processes towards med nasal processes - Forms naso-optic furrows -\> nasolacrimal groove - Ectodermal rod of cells sink below surface -\> canalises to form nasolacrimal duct A close-up of a baby\'s head Description automatically generated - **Reveal development of the tongue and muscular structures** SECONDARY PLATE: - Distinction btw oral and nasal cavity after secondary plate formation - Happens btw week 7 and 8 - Done after \~3 months ![A diagram of a human body Description automatically generated](media/image62.png) A diagram of a human body Description automatically generated![A diagram of the human body Description automatically generated](media/image64.png) Head position is important in tongue development -\> at 9 weeks head is raised to allow tongue room to move forward TONGUE FORMATION: - Begins at 4 weeks of gestation - Lingual swellings + tuberculum impar (from first arch) form ant 2/3 of tongue - Hypobranchial eminence overgrows second arch - Pharyngeal arches meet in midline below primitive mouth - Develops alongside nerve of first arch - 7 week -\> intramembranous ossification -\> forms bone from existing cartilage - Bone formation spreads rapidly ant towards midline + post towards bifurcation of mandib nerve to lingual + inf alveolar nerve branches - Midline, medial + lateral alveolar plates of bone develop -\> forming tooth germs that subdivide through bone - Ramus develops by spread of post ossification into mesenchyme of first arch, turning away from Meckel's cartilage -\> divergence marked by lingula - Finishes by week 10 -\> Meckel's cartilage degenerates to make place for new bone - Further growth from 3 secondary cartilages: condylar (most important), coronoid, symphyseal cartilage CONDYLAR CARTILAGE: - Appears @ 12 weeks - Cone/carrot shaped mass in ramus - @ 20 weeks is thin on condylar head - Stays until late 20's MAXILLA DEVELOPMENT: - Centre of ossification alongside nasal capsule cartilage - Appears @ angle btw division of anterosuperior dental nerve + inf orbital nerve - Ossification spreads post towards developing zygoma + ant towards incisor region + sup to form frontal process - Zygomatic/malar cart appears in developing zygomatic process which is major to zygomatic dev - Max sinus dev at 16 weeks as shadow groove on nasal aspect TMJ DEVELOPMENT: - Initially formed from membranous centres of ossification - Broad band of undiff mesenchyme btw dev ramus of mandible + squamous tympanic bone -\> dense strip of mesenchyme as condylar cartilage forms - Adjacent mesenchyme forms joint cavity - Strip -\> articular disk - **Discuss clinical considerations and anomalies in facial development** Holoprosencephaly: - Forebrain fails to divide ito 2 separate hemispheres and ventricles - 1:10,000 - Unknown cause -\> chromosomal abnormality, gene mutation, maternal diabetes, infection, drugs? - Facial anomalies - Cyclops - Multifactorial aetiology -\> genetic + environmental disturbances - Disturbance btw week 6 +7 - Diff forms; median, bilateral, oblique, lateral, median mandib - ![](media/image67.png)Can be btw lip and palate -\> normal, cleft lip + alveolus, cleft palate 1^st^ arch syndromes: - Most congenital abnormalities of craniofacial region involve change in pharyngeal arch - Not enough migration of neural crest cells into 1^st^ pharyngeal arch in week 4 - Might be -\> decreased cell proliferation or increased cell death - Pierre Robin's sequence + Treacher Collins' syndrome Pierre Robin's: - Hetero birth defect - 1:8500 - Equal in male and female - Autosomal recessive hereditary -\> maybe X linked - Micrognathia, glossoptosis, ear defect, speech defects A close-up of a baby\'s face Description automatically generated Treacher Collins': - 1:10000 - Autosomal dom - Negative canthal tilt, micrognathia, absent/malformed ears, lip + palate clefts - Mutation of Tcof1 gene - Disrupts protein sysnthesis -\> treacle Environ factors for congenital defects: - Infection -\> rubella virus, treponema pallidum - X-ray - Cortisone - Hormones - Nutritional deficiency - Alcohol abuse Fetal Alcohol disorder: - Caused by drinking more than 4 units alcohol/day - 33% of kids w FAS have alcoholic mums - Dependent and related to time where foetus is exposed