Connective tissue Flashcards
What is ground substance?
A basic tissue that provides structural and metabolic support to other tissues and organs.
What does Ground substance add?
Strength and stiffness
What does Ground substance delay?
Delays the spread of infection
Ground substance characteristics
Gel-like extracellular matrix
What does Ground substance contain (x 3) ?
- Water (and salts)
- Glycosaminoglycans (GAGs)
- Proteoglycan molecules
What are glycosaminoglycans?
Polysaccharides, made up of sugar
What do proteoglycan molecules do?
Bind water giving gelatinous property to matrix
What do proteoglycan molecules form?
They form aggregates to make up ground substance.
What is the main component of ground substance?
Glycosaminoglycans
Most common glycosaminoglycans?
- Hyaluronate
- Chondroitin-4-sulphate
- Chondroitin-6-sulphate
- Dermatan sulphate
- Heparin sulphate
- Keratin sulphate
What is the predominant GAG?
Hyaluronic acid
🥲What is hyaluronate so important in GAGs?
Because the viscosity of ground substance depends on the content of it.
How does GAGs stain?
Metachromatically with toluidine blue
🥲What is the ground substance elaborated by?
Endoplasmic reticulum, especially of fibroblast.
🥲What are the most important connective tissue cells?
- Mesenchymal cells
- Fibroblasts
- Adipocytes (fat cells)
- Immune cells
- Macrophages / Monocyte
- Mast cells
- B cell / Plasma cells
- Lymphocyte
What are the most important connective tissue fibres?
- Collagen
- Elastin
Inter-relationship of Connective tissue
- All have one ancestor - mesenchymal stem cell
- All cells have diversity in form and function
- Evidence that interchange is possible
Function of Mesenchymal stem cells (MSCs)
To differentiate into other cells
Function of fibroblasts
Synthesis extracellular matrix; would healing
Function of adipocytes (fat cells)
Store and metabolise fat
Function of macrophages (Histiocytes)
Phagocytic, innate immune cell
Function of mast cells
Histamine reactions; innate immune cell
Function of B cells / Plasma cells
Make antibodies; adaptive immune cell
Function of T cells
Major immune cell; adaptive immune cell
Where are mesenchymal stem cells obtained from?
Bone marrow
What can mesenchymal stem cells do?
Differentiate into all other cells in connective tissue
What type of stem cells are mesenchymal stem cells?
Multipotent
What do mesenchymal stem cells have potential for?
Cell replacement therapy
What is the most abundant cell in connective tissue
Fibroblasts
What do fibroblasts have a role in?
Would healing (secrete collagenous matrix - scar tissue)
Name two cell thats can differentiate into other cells.
Mesenchymal stem cells & fibroblasts
What do fibroblasts synthesise?
Extracellular matrix, i.e secrete components (GAGs, collagen, elastin, ground substance)
What do adipocytes develop from?
Fibroblasts
What do adipocytes do (x 3)?
- Store & metabolise fat (lipids)
- Insulate
- Support and protect organs
Can mature adipocytes divide?
No
Role of white adipose
Energy store - insulation & shock absorption
Role of brown adipose
Stores energy in fat
White adipose percentage of body weight
20% males, 25% females
Where is a macrophage born?
In bone marrow
The birth of macrophage stages
- Stem cell - bone marrow
- Monoblast - bone marrow
- Monocyte - blood
- Macropage - tissue
- Activated macrophage - tissue
What do macrophages present at their surface?
Present pathogen antigens at their cell surface to T cells (elicit an adaptive immune response)
Where are fixed macrophages found at?
Strategic points
What are the roles in disease of macrophages?
- role in atherosclerotic deposits
- destroy influenza infected throat cells
- they release growth factors (tumor cell proliferation)
The replication of what virus occurs in macrophages?
HIV
What historical pathogen was resistant to phagocytosis?
The plague pathogen
Name 3 disorders of macrophages
- Granuloma
- Macrophage Activation Syndrome
- Multicentric reticulohistiocytosis
Name two disease are resistant to lysosomal degradation.
- Leprosy
- Tuberculosis
What do macrophages have for degradation?
Lysosomes
What do macrophages do to foreign materials?
They scavenge foreign materials
What are two types of mast cells?
- Connective tissue type
- Mucosal
5 places mast cells present?
- Skin
- Mucosa of lungs
- Gut
- Mouth
- Nose
What does mast cells stimulate?
Stimulates release of histamine and heparin
What does histamine do?
Dilates venules, activates endothelium, and increases blood vessel permeability
What do mast cells cause (symptoms)?
Causes edema (swelling), warmth, redness, attracts inflammatory cells, activates nerves (itching & pain)
What are mast cells similar to?
Basophils
What do mast cells express
Fc receptor
What do B-cells express?
‘immunoglobulin-receptors’ on surface membrane
What do B-cells bind?
Bind to receptors & induce B-cell differentiation into plasma and memory cells
Are memory cells short or long lived?
Long lived
What do memory cells allow for?
Allow quick attack against same antigen
What do plasma cells produce?
Antibodies
Where are plasma cells usually found?
Tissues – lymph nodes, spleen, intestine
Function of antibodies
- Block entry of viruses by binding viral surface
- Coat antigen on pathogens and facilitate phagocytosis by macrophages
Four types of T-cells
- Helper T cells
- Cytotoxic T cells
- Suppressor T cells
- Memory T cells
Function of Helper T cells
Secrete interleukins to activate B cell, cytotoxic T cell & macrophage
Function of Cytotoxic T cells
Kill virus infected cells & some cancer cells
Function of Suppressor T cells
Suppress response to self antigens
Function of memory T cells
Long lived activated T cells that remain for subsequent activation (i.e. adaptive)
Antigen presenting cells
- Infected macrophage
- B-cell
- Dendritic cell
- Tumour cell
What does T cell expressing T-cell receptor bind?
Binds antigen-MHC complex to become activated
Where is digested foreign material presented?
At the cell surface attached MHC (major histocompatibility complex)
3 types of fibres
- Collagen
- Elastin
- Fibrillin
What are collagen, elastin and fibrillin synthesised by?
Collagen
What type of fibres does collagen make?
Log straight fibres
What is the most common fibre in connective tissue?
Collagen
Where is collagen present?
Found in skin, tendons, ligaments, bone and organs
Collagen weak / strong
Flexible and strong
Fibroblasts (synthesise)→
Collagen proteins (aggregate) →
Collagen proteins (aggregate) →
Tropo-collagen (assemble) →
Tropo-collagen (assemble) →
Collagen microfibrils fibres (form) →
Collagen microfibrils fibres (form) →
Collagen bundles
Fibroblasts (synthesise)→ (full)
Collagen proteins (aggregate) → Tropo-collagen (assemble) → Collagen microfibrils fibres (form) → Collagen bundles
What dictates the type of collagen fibres?
Their structural role in a particular organ
Give 4 examples of collagen fibres
- Gel
- Tight bundles
- Stacked
- Fibres arranged at an angle
Where are gel collagen fibres present?
Extracellular matrix or vitreous humor of eye
Where are tight bundle collagen fibres present?
Tendons
Where are stacked collagen fibres present?
Cornea
Where are collagen fibres arranged at an angle present?
Bones
What are polypeptide chains held together by?
Hydrogen bonds
What are fibril-forming collagen types?
I - III
Where is collagen type I present?
- Found in the supporting elements of high tensile strength.
- Found in bone, skin, tendon, muscles, cornea and walls of blood vessels.
Where is collagen type II present?
- In cartilaginous tissues,
- Inter vertebral disk
- Vitreous body
- Hyaline cartilage.
Where is collagen type III present?
Found in distensible tissues, tissues that can expand due to pressure from within - fetal skin, blood vessels.
What are network-forming collagen types?
IV & VII
Where is collagen type IV found?
Found in the basement membranes and muscles.
Does collagen type IV form fibrils?
No
What is the structure of collagen type IV like?
mesh-like
Where is collagen type VII found?
Beneath stratified squamous epithelia
What does collagen type VII form?
Forms anchoring fibrils that link to the basemen membrane.
What are the fibril-associated collagen types?
IX and XII
Where is collagen type IX found?
In cartilage
Where is collagen type IX localised?
At intersections of cartilage fibres
Where is collagen type XII found?
- Tendons
- Ligaments
Collagen tumors
Fibrosarcoma
Function of fibrosarcoma
Proliferating fibroblast tumor
Systemic disorders (connective fibre related)
Systemic lupus Erythematosus (SLE)
Function of Systemic lupus Erythematosus (SLE)
Autoimmunity against connective tissue
Inherited disorders (connective fibre related) (5)
- Ehlers–Danlos syndrome
- Osteogenesis Imperfecta
- Marfan syndrome
- William’s syndrome
- Cutis laxa
Function of Ehlers–Danlos syndrome
Mutation in gene coding collagen
Function of Osteogenesis Imperfecta
Mutation in collagen synthesis
Function of Marfan syndrome
Mutation in gene coding fibrillin
Function of William’s syndrome
Deletion of gene coding elastin
Function of Cutis laxa
Mutation in gene coding elastin
Dysfunctional collagen synthesis
Keloid Hypertrophy
Function of keloid hypertrophy
Collagen hypergrowth on scars
Fibrosarcoma most common age/gender
Males aged 30-40 years.
What can fibrosarcoma form from?
From fibroblasts in soft tissue
What is fibrosarcoma?
An overgrowth of tissues with an excess deposition of matrix components (i.e. collagen) by proliferating fibroblasts
When does Systemic Lupus erythematosus start
Age 15-50
Survival rate of Systemic Lupus erythematosus
95% (5yr), 90% (10yr) and 78% (20yr)
What happens in Systemic Lupus erythematosus?
Immune system self-attacks connective cells
Systemic Lupus erythematosus gender
More likely in non-European women
Symptoms of Systemic Lupus erythematosus
95% Achy joints (arthralgia) 90% Fever over 38ºC 81% Prolonged or extreme fatigue 90% Arthritis (swollen joints) 74% Skin Rashes 71% Anaemia 50% Kidney Involvement 45% Chest Pain on deep breathing (pleurisy) 30% Sun or light sensitivity (photosensitivity) 27% Hair loss 17% Raynaud's phenomenon (fingers blue) 15% Seizures 12% Mouth or nose ulcers.
Ehlers - Danlos syndrome
- Mutation gene coding collagen
- Hypermobility of joints
- Stretchy skin
Osteogenesis imperfecta is a mutation in..
Collagen synthesis
What does osteogenesis affect?
Skeleton ears and eyes
What is osteogensis also known as?
Brittle bone disease
What is marfan syndrome a mutation in?
In gene coding fibrillin
What does marfan syndrome affect?
- Eysight
- Lungs
- Heart
- Skeleton
How is eyesight affected by marfan syndrome?
- Near-sighted (myopic)
- Ocular lens dislocation
- Retinal detachment
How are lungs affected by marfan syndrome?
Spontaneous lung collapse (pneumothorax)
How is the cardio-vascular system affected by marfan syndrome?
- Aorta widening / dilatation
- Aortic aneurysms
- Mitral and aortic valve proplapse / leakage
How is the skeleton affected by marfan syndrome?
- Scoliosis
- Pectus deformity
- Tall stature
- Loose jointedness
Two syndromes resulting from mutations in elastin
- William’s syndrome
- Cutis Laxa
Cutis Laxa physical effect
Skin hangs loosely in folds
What is cutis laxa a mutation in?
In elastic fibres comprising the dermis
What is deletion elastin associated with?
With connective tissue issues
What are behavioural characteristics of people with William’s syndrome?
Distinctive, cheerful manner & ease with strangers
What is William’s syndrome?
A rare neurodevelopmental disorder
Deletion of William’s syndrome
26 genes on chromosome 7