Download Lect 03 - Connective Tissue

Lect 03 - Connective Tissue - General
8 Types of Surface Epithelium
Structure & Function
Lect # 3
Type
General Connective Tissue & Muscle
Feature
Example
3 Simple Types
Prof Kumlesh K. Dev
Department of Physiology
1. Squamous
Diffusion
Blood vessels
2. Cuboidal
Synthesis of hormones
Thyroid gland
3. Columnar
Digestion, absorption, lubrication
Small intestine
4. Squamous (+/- Keratin)
Protection
Skin
5 Cuboidal
5.
Saliva
Salivary gland
6. Columnar
Saliva
Salivary duct
7. Pseudostratified columnar
Airways
Trachea
8. Transitional epithelium
Distention
Bladder
3 Stratified Types
SKELETAL
CARTILAGE
GENERAL
BONE
CELLS
FLUID
BLOOD
FIBRES
LYMPH
GROUND SUBSTANCE
Cell Memb. Specialisations of Epithelium
Type
2 Special Types
Skeletal Muscle: summary
Functions
Basal Surface
1. Basement membrane
anchors epithelial cells to underlying tissue
Free surface
1. Keratin
protective
2. Cilia
increase surface area & particle movement
3. Microvilli
increase surface area & particle movement
Intercellular junctions
1. Tight junction
cell-cell contacts (virtually impermeable to fluid)
2. Adherent junction
cell-cell contacts
3. Gap junction
permit passage of ions & molecules between cells
4. Desmosome
cell-cell contacts
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Lect 03 - Connective Tissue - General
Comparing Synapses
Nerve - Nerve Synapse
Neuromuscular Junction
¾ nerve-nerve synapse smaller
than
h
a NMJ with
i h a narrower
synaptic cleft
¾ NMJ is larger than a nervenerve synapse with
i h a wider
id
synaptic cleft
¾ smooth postsynaptic
membrane gives small
surface area
¾ folds of postsynaptic
membrane gives larger
surface area
¾ may be excitatory or
inhibitory
¾ the NMJ is always
excitatory
¾ numerous transmitter
substances
¾ only one transmitter –
Acetylcholine
¾ potential is lower - always
subthreshold
¾ potential is higher - always
suprathreshold
¾ summation needed
¾ no summation needed
Four Tissue Types
1. Epithelial tissue
–
–
2. Muscle (excitable) tissue
–
–
–
General Properties
Components (cells and fibres in a matrix)
─ Cells
─ Matrix
─ Fibres
─ Classification
─ Specialised Connective Tissues
─ Cartilage
─ Bone
─ Blood
Skeletal (striated) muscle
Smooth muscle
Cardiac muscle
3. Nervous (excitable) tissue
–
–
Brain
Spinal cord
4. Connective tissue (cells, fibres, matrix)
–
–
–
–
Outline
─
─
Lining/barrier of secretory
Skin and mucous membranes
Loose connective tissue
Dense fibrous tissue (Capsule, Ligament, Tendon)
Cartilage & Bone
Blood (originate from bone marrow)
Functions of Connective Tissue
─
structural framework
─
transports fluids and dissolved
materials
─
stores lipids
─
protects organs
─
defends body from pathogens
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Lect 03 - Connective Tissue - General
Specialised Connective Tissue
Lect 4
SKELETAL
Lect 3
GENERAL
Lect 5
Connective Tissue Components
FLUID
‘cells and fibres in a matrix’
CARTILAGE
BONE
CELLS
Mesenchymal cells
Fibroblasts
Adipocytes (fat cells)
Immune cells
- Macrophages
- Mast cells
- Plasma cells
- Lymphocyte
- Monocyte
BLOOD
FIBRES
CELLS
LYMPH
Mesenchymal cells
Collagen
Fibroblasts
Elastin
Adipocytes (fat cells)
Immune cells
- Macrophages/Monocyte
- Mast cells
- B cells/Plasma cells
- Lymphocyte
GROUND SUBSTANCE
Collagen
Elastin
Inter-relationship of Connective Tissue Cells
─ one ancestor
(mesenchymal stem cell)
─ diversity of form/function
─ interchange possible
FIBRES
7 Cells of Connective Tissue
Type
Function
1. Mesenchymal stem cells (MSCs)
differentiate into other cells
2. Fibroblasts
synthesis extracellular matrix; wound healing
3. Adipocytes (fat cells)
store and metabolise fat
4. Macrophages (Histiocytes)
phagocytic, innate immune cell
5. Mast Cells
histamine reactions; innate immune cell
6. B cells/Plasma Cells
make antibodies; adaptive immune cell
7. T Cells
major immune cell; adaptive immune cell
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Lect 03 - Connective Tissue - General
1. Mesenchymal stem cells (MSCs)
Mesenchymal cells
Fibroblasts
Adipocytes (fat cells)
Immune cells
- Macrophage/Monocyte
- Mast
M
cells
ll
- B cells/Plasma cells
- Lymphocyte
─ originate in mesoderm germ
layer in embryo
─ unattached to each other,
allowing them to migrate
─ are multipotent
─ can differentiate into all other
cells in connective tissue
─ synthesise extracellular matrix
i.e. secrete components (GAGs,
collagen, elastin, ground
substance)
─ transform into myofibroblasts to
provide contraction of wound
3. Adipocytes (fat cells)
─ insulate (slow heat loss)
─ can differentiate into other cells
Mesenchymal cells
Fibroblasts
Adipocytes (fat cells)
Immune cells
- Macrophage/Monocyte
- Mast
M
cells
ll
- B cells/Plasma cells
- Lymphocyte
─ role in wound healing i.e. secrete
collagenous matrix (scar tissue)
─ potential for cell replacement
therapy
─ store & metabolise fat (lipid)
─ most abundant cell in connective
tissue
─ structural framework of many
tissues
─ obtained from bone marrow
─ develop from fibroblasts
2. Fibroblasts
4. Macrophages/Monocytes (Histiocytes)
Mesenchymal cells
Fibroblasts
Adipocytes (fat cells)
Immune cells
- Macrophage/Monocyte
- Mast
M
cells
ll
- B cells/Plasma cells
- Lymphocyte
─ support and protect organs
─ contain large lipid droplets (TAG)
─ these lipid droplets push
cytoplasm to edge of cell
─ clustered in adipose tissue or
single cells in areolar tissue
─ mature adipocytes cannot divide
white adipose
Macrophages (innate immune system)
─ about 21 microns in diameter
─ activated macrophages fuse: multinucleate giant cells
─ phagocytic
─ scavenge foreign materials (bacteria, debris…)
RBC
─ have lysosomes for degradation
bacteria
─ last months, digest 100’s bacteria before they die
─ present pathogen antigens at their cell surface to T cells
(elicit an adaptive immune response)
─ fixed macrophages found at strategic points
Role in disease
─ role in atherosclerotic deposits
─ destroy influenza infected throat cells
─ HIV virus replication occurs in macrophages
─ they release growth factors (tumor cell proliferation)
─ the plague pathogen was resistant to phagocytosis
─ leprosy & tuberculosis resistant to lysosomal degradation
─ Disorders: Granuloma; Macrophage Activation Syndrome;
Multicentric reticulohistiocytosis
Mesenchymal cells
Fibroblasts
Adipocytes (fat cells)
Immune cells
- Macrophage/Monocyte
- Mast
M
cells
ll
- B cells/Plasma cells
- Lymphocyte
Fixed Macrophages
1. Dust/Alveolar type (lungs)
2. Histiocytes (connective tissue)
3. Kupffer cells (liver)
4. Microglial cells (nervous)
5. Osteoclasts (bone)
6. Sinusoidal lining cells (spleen)
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Lect 03 - Connective Tissue - General
5. Mast Cells
6. B cells/Plasma Cells
Mast cells (innate immune system)
─ similar to basophils
─ 2 types: connective tissue & mucosal mast cells
─ present in skin,
skin mucosa of lungs
lungs, gut
gut, mouth
mouth, nose
─ express Fc receptor, binds IgE (made by B-cells),
which bind allergens
─ stimulates release of histamine and heparin
─ histamine dilates venules, activates endothelium,
and increases blood vessel permeability
─ causes edema (swelling), warmth, redness, attracts
Fc receptor
inflammatory cells, activates nerves (itching & pain) expressed on
Role in disease
─ Asthma, eczema, itch, rhinitis allergies
─ Antihistamines block histamine receptors on nerves
─ Also have inhibitors of histamine release
Anaphylaxis - allergens (nuts, stings) cause body-wide
degranulation, vasodilation and shock
mast cells
Mesenchymal cells
Fibroblasts
Adipocytes (fat cells)
Immune cells
- Macrophage/Monocyte
- Mast
M
cells
ll
- B cells/Plasma cells
- Lymphocyte
Pathogen
enters tissue
IgE production
by B-cells
B cells
Mesenchymal cells
Fibroblasts
Adipocytes (fat cells)
Immune cells
- Macrophage/Monocyte
- Mast
M
cells
ll
- B cells/Plasma cells
- Lymphocyte
B-cells (adaptive immune system)
Activation of B-cells
─ 1. B cells produce ‘immunoglobulin-receptors’
that are inserted on surface membrane
─ 2. antigens bind to receptors & induce B-cell
differentiation into plasma and memory cells
─ 3. memory cells are long lived and allow quick
attack against same antigen (explains
vaccination principle) – (ie adaptive)
Plasma cells produce antibodies
─ plasma cells produce antibodies specific for
antigens
─ plasma cells not usually found in blood but in
tissues – lymph nodes, spleen, intestine, etc.
Function of antibodies
Histamine release
Arthritis, multiple sclerosis - autoimmune diseases
─ block entry of viruses by binding viral surface
─ coat antigen on pathogens and facilitate
phagocytosis by macrophages
PLASMA CELL IN BONE
MARROW
with large granular nucleus
Specialised Connective Tissue
7. T cells (Lymphocytes)
- 6-9µm diameter, makes up 20-50% of WBCs
Lect 4
Four types of T-cells
- Helper T cells (Th) – secrete interleukins to
activate B cell, cytotoxic T cell & macrophage
- Cytotoxic T cells (Tc) – kill virus infected cells &
some cancer cells
- Suppressor T cells (Ts) – suppress response to
self antigens
- Memory T cells – long lived activated T cells that
remain for subsequent activation (i.e. adaptive)
CARTILAGE
T-cell moving toward a chemical gradient
Activation of T-cells
• Antigen presenting cells (APC)
• infected macrophage
• B-cell
• dendritic cell
• tumor cell
• digested foreign material is presented at the cell
surface attached MHC (major histocompatibility complex) ‘immune synapse’
• T cell expressing T-cell receptor (TCR) binds
antigen-MHC complex to become activated
SKELETAL
(cells talk via
receptors)
Lect 3
GENERAL
BONE
CELLS
Mesenchymal cells
Fibroblasts
Adipocytes (fat cells)
Immune cells
- Macrophages
- Mast cells
- Plasma cells
- Lymphocyte
- Monocyte
Lect 5
FLUID
BLOOD
FIBRES
LYMPH
GROUND SUBSTANCE
Collagen
Elastin
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Lect 03 - Connective Tissue - General
Fibres and Matrix
Collagen
─ makes long straight fibres
─ flexible and strong
─ 3 types
yp ((chemically
y similar))
─ Collagen
─ Elastic
─ Reticular
─ most common fibre in
connective tissue
─ found in skin, tendons,
ligaments, bone and organs
Fibroblasts
─ All synthesised by fibroblasts
─ also synthesise matrix (glycoproteins
and water content variable)
synthesise
collagen
g p
proteins
aggregate
EM of type I collagen
tropo-collagen
assemble
collagen microfibrils fibres
form
collagen bundles
Elastin and Fibrillin
Nine Connective Fibre Related Diseases
Type
Function
Collagen tumors
1. Fibosarcoma
─ formed by fibroblasts
proliferating fibroblast tumor
Systematic disorders
─ branched and wavy
2. Systemic lupus Erythematosus (SLE) autoimmunity against connective tissue
─ can stretch and recoil
Inherited disorders
─ found in skin, lungs and
3. Ehlers–Danlos syndrome
4. Osteogenesis Imperfecta
5 M
5.
Marfan
f syndrome
d
6. William’s syndrome
7. Cutis laxa
blood vessels
mutation in gene coding collagen
mutation in collagen synthesis
mutation
t ti in
i gene coding
di fib
fibrillin
illi
deletion of gene coding elastin
mutation in gene coding elastin
Dysfunctional collagen synthesis
9. Keloid Hypertrophy
collagen hypergrowth on scars
elastin
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Lect 03 - Connective Tissue - General
Fibrosarcoma (tumor)
SLE (Lupus) auto-immune CT disease
─ immune system self-attacks connective cells in heart, joints,
skin, lungs, blood vessels, liver, kidneys, and nervous system
─ excess deposition of martix
components (i.e. collagen) by
proliferating fibroblasts
─ more likely in women than in men and in non-Europeans
─ overgrowth of tissues
─ good survival rate 95% (5yr), 90% (10yr) and 78% (20yr)
─ starts between ages of 15 – 50
─ malignant tumors and some
diseases (pulmonary fibrosis,
liver cirrhosis, cardiovascular
fibrosis) can lead to organ
failure and death
Fibroblast surrounded by
collagen matrix.
Inherited disorders (collagen)
EHLERS-DANLOS
SYNDROME
OSTEOGENESIS
IMPERFECTA
─ mutation gene coding collagen
─ mutation in collagen synthesis
─ hypermobility of joints
─ affects skeleton ears & eyes
95%
90%
81%
90%
74%
71%
50%
45%
30%
27%
17%
15%
12%
Achy joints (arthralgia)
Fever over 38ºC
Prolonged or extreme fatigue
Arthritis (swollen joints)
Skin Rashes
Anaemia
Kidney Involvement
Chest Pain on deep breathing (pleurisy)
Sun or light sensitivity (photosensitivity)
Hair loss
Raynaud's phenomenon (fingers blue)
Seizures
Mouth or nose ulcers.
Marfan Syndrome (fibrillin)
─ mutation in gene coding fibrillin
─ affects eyesight, lungs, heart and skeleton
─ ‘brittle bone disease’
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Lect 03 - Connective Tissue - General
Mutations in elastin
WILLIAM’S
SYNDROME
Synthesis abnormalities (collagen)
KELOID
HYPERTROPHY
CUTIS LAXA
─ rare neurodevelopmental disorder
─ mutation in elastic fibers
─ distinctive, cheerful manner & ease
comprising the dermis
with strangers
─ skin hangs loosely in folds
─ deletion ~26 genes on chromosome 7
─ deletion elastin associated with
connective-tissue issues
─ overgrowth of collagen at site of
healed skin injury
Specialised Connective Tissue
Lect 4
SKELETAL
CARTILAGE
Lect 3
GENERAL
BONE
CELLS
Mesenchymal cells
Fibroblasts
Adipocytes (fat cells)
Immune cells
- Macrophages
- Mast cells
- Plasma cells
- Lymphocyte
- Monocyte
Lect 5
FLUID
BLOOD
FIBRES
Collagen
Elastin
LYMPH
GROUND SUBSTANCE
Ground Substance
─
─
─
─
gel-like extracellular matrix
adds strength and stiffness
fills spaces between cells and fibers
delays spread of infection
Ground Substance Contains:
1. Water (and salts)
2. Glycosaminoglycans (GAGs)
─ polysaccharides, made of sugars
─ many types: chondroitin sulphate; hyaluran…
3. Proteoglycan molecules
─ heavily glycosylated ‘glycoprotein’
─ consist of core protein with covalently bound GAGs
─ form aggregates to make up ground substance
─ proteoglycans contain carboxyl and sulphate groups
that bind water giving gelatinous property to matrix
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Lect 03 - Connective Tissue - General
Classification of Connective Tissues
─ Function: to withstand longitudinal stress
─ Location: between muscle and bone
─ Structure: bundles of collagen fibres
fibres.
─ Proportion of fibres
─ Low — Loose (dermis, white fat, brown fat)
─ High — Dense (also many fibroblasts and collagen)
─ Arrangement
g
of fibres
─ Regular (parallel fibers): Tendons and Ligaments
─ Ligaments: collagenous bands that stabilise joints
─ Tendons: provide connections between muscles & bones
─ Irregular (random meshwork of fibres): Capsule
Loose Connective Tissue: Dermis
Dermis (Areolar Tissue)
─ Loosely irregular organised cells
and fibres
─ Separates skin from deeper
structures (‘Areolar’, clear)
Functions
─ Protects body organs
─ Holds organs in place
─ Water, salt, nutrition reservoir
─ Extensive blood supply
─ Nutrition
─ Differentiation e.g. Epidermal
Loose Connective Tissue: Fat
White Adipose (energy store)
─ One droplet of fat (unilocular)
─ Distribution: general,
general esp
esp.
subcutaneous, e.g. buttocks,
breasts, abdomen
─ Role: Insulation, shock absorption
Brown Adipose (body heat)
─ Manyy droplets
p
– multilocular
─ Distribution: pericardial, peri-renal,
interscapular
─ Role: in hibernators, stores energy
in fat
Skin — lamina propria
Learning Outcomes – (Lesson 7)
To be able to:
1.
2
2.
3.
4.
5.
state the general functions of CT
state the names and properties of the principal CT fibres and cells
outline the role of the matrix in conferring properties of CT
explain the morphological classification of CT
relate structure to function of the different types of CT
6.
7.
8.
9.
10.
11.
12.
13.
explain the inter-relatedness of all CT cells.
describe morphological/functional classification of types of connective tissue
list components of CT (cell types, fibres, matrix) and their functions
outline the role of the matrix in conferring differing properties of CT
recognise the inter-relatedness of all CT cells (incl. Blood)
define types and appearance of adipose tissue in sections (BAT, WAT)
define 3 types of cartilage and mechanisms of cartilage growth
explain effect of vitamin C deficiency and lupus in terms of CT lesions.
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