11) Infection And Inflammation Flashcards

(90 cards)

1
Q

Functions of the skin

A

Protection from external damage- UV light, chemical, thermal and mechanical injury and resistance to sheer stress

Barrier: waterproof and bacteria

Sensation : touch, pressure, pain and temperature

Metabolic: synthesises vit D3, subcutaneous fat is a major energy store

Thermoregulation: insulation, heat loss by sweat evaporation and vasodilation

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2
Q

3 layers of skin

A

1) epidermis (epithelium)
2) dermis (connective tissue)
3) hypodermis / subcutis (fascia)

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3
Q

Structure of 3 skin layers

A

Epidermis: stratified squamous epithelium (keratinised):keratinocytes

Dermis: dense irregular connective tissue: fibroblasts, collagen I, elastin, blood, nerves and receptors. Divided into papillary and reticular dermis

Hypodermis / subcutis: adipose tissue and main blood supply

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4
Q

What are the 5 strata (layers) of keratinocytes in the epidermis / epithelium

A

1) stratum basale (bottom)
2) stratum spinosum
3) stratum granulosum
4) stratum lucidum
5) stratum corneum (top)

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5
Q

How do the keratinocytes form a barrier

A
  • tight junctions (prevent paracellular diffusion)
  • desmosomes and hemidesmosomes (mechanical and sheer)
  • keratin (microorganisms)
  • phospholipid (waterproof)
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6
Q

2 different types of keratinocytes cancer

A
  • basal cell carcinoma (approx 80%) from basal layer
  • squamous cell carcinoma (approx 20%) from upper epidermal layers

Both are curable, linked to total cumulative sun exposure, common on head, neck and hands

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7
Q

4 skin cell types in epidermis

A

Keratinocytes: 95% of cells, produce keratin, stratified squamous keratinising epithelial cells

Melanocytes: pigment synthesising cells responsible for skin and hair colour, neural crest derived cells lying in stratum basale, melanosomes in cytoplasm contain melanin and are passed to keratinocytes

Langerhans cells: all layers and upper dermis-prominent in spinosum. Bone marrow derived. Dendritic, antigen-presenting cells migrate to regional lymph nodes and communicate with immune system

Merkel cells: clear cells in stratum basale. Plentiful in touch areas. Connected to keratinocytes and afferent nerves. Neuroendocrine function

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8
Q

What determines skin pigmentation

A

Varied skin colour is due to increased melanocytes activity (not number) - focal activity is a freckle

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9
Q

What happens with increased number of melanocytes

A

Disordered pigmentation
- lentigo maligna

  • albinism: lack of melanin due to lack of enzyme required to make melanin tyrosinase

Vitiligo: Macules of de-pigmented skin enlarging over time. Cause unknown

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10
Q

What is a mole / nevi

A
  • congenital / acquired benign tumours
  • pigmented / non-pigmented, flat/elevated , hairy / not
  • more abundant on sun exposed skin
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11
Q

What is a malignant melanoma

A

Rapidly progressive, metastatic

  • arise from pre-existing or new nevi
  • uneven surface, irregular borders, slightly raised, black/ brown colour
  • most common on areas exposed intermittently (back / legs) and in indoor workers
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12
Q

ABCD method for recognising melanoma

A

A- asymmetry
B- borders - distinct, smooth, regular border
C- colour- uneven colour
D- diameter- large

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13
Q

How does skin stay on

A
  • interdigitation between epidermis and dermis increases SA
  • hemidesmosomes adhere the epidermis to the dermis
  • basement membrane sits between epidermis and dermis :
    Sheets of matrix at interface of parenchyma and support tissue
  • composed mainly of type IV collagen, glycoproteins and GAGs
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14
Q

What is epidermolysis bullosa

A

Group of rare, inherited contains causing separation of the epidermis from the dermis with minimal shearing forces: no inflammatory cell infiltrate

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15
Q

What are the 3 types of epidermolysis bullosa

A
  • EB simplex: defective cytoskeleton
  • junction also EB: defective hemidesmosomes
  • dystrophic EB: defective BM collagen
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16
Q

Structure of dermis

A

Dense connective tissue
Collagen 70%
Papillary: conical papillae, richly vascularised, lymph and nerve
Reticular: horizontal collagen and elastin fibres
Contains hair and gland structures

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17
Q

Where are different types of skin found

A

Thin- most locations, less well defined rete ridges, thinner keratin later, lots of eccrine glands

Thick: fingertips and feet soles: thick epidermis, thick keratin later, well developed rete ridges, lots of eccrine glands

Hairy skin- scalp, axilla, groin: thin epidermis, lots of hair follicles and subaceous glands

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18
Q

Skin specialisations

A

Hair follicles- produce hair shafts (keratin) for thermoregulation and display. Erector pili muscle

Sweat glands: eccrine - dermal subcut junction of all skin, produce sweat. Ducts open onto skin surface (thermoregulation)
Apocrine: localised scent production. Open into hair follicles above sebaceous duct. Functional at puberty

Sebaceous glands: majority associated with hair follicles, secrete lipid mixture: sebum into hair follicle

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19
Q

Sensory (afferent) nerve endings of the skin

A
  • Pacinian corpuscle (modified Schwann cells): subcutis, deep pressure and vibration
  • meissners corpuscle: papillary dermis, rapidly adapting mechanoreceptors
  • Ruffini corpuscle: mechanoreceptors, stretching of skin
  • free nerve endings (pain, itch, temp) papillary dermis
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20
Q

Efferent nerve endings of the skin

A

Vessel diameter and blood flow

Information to sweat glands and erector pili muscles

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21
Q

4 types of bacterial infection of the skin.

A
  • impetigo : strep /. Staph
    Subcorneal blisters +/- pus
    Burst and spread: yellow crusting
    Highly contagious (children)
  • cellulitis
    Superficial dermis
    Can lead to necrotising fasciitis
    Limbs- penetrating injury / bite

Boil: infection in a hair follicle

Acne: infected follicle blocked with keratin plug

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22
Q

Describe the cellular adaptive mechanism: homeostasis

A

Cells operate within a restricted internal physiological range to maintain an acceptable internal millieu: homeostasis.

They are constantly adapting to changes in their environment to maintain this. This is a reversible process and results from both normal and pathologic stimuli. Failure of cells to adapt = cell death

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23
Q

What is hypertrophy

A

Increase in the size of cells
Can be physiologic / pathologic
No new cells just bigger
Examples: exercise, hypertension

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24
Q

What is hyperplasia

A

Increase in number of cells eg breast development at puberty or liver regeneration after resection / wound healing

Eg psoriasis leads to thickened skin

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25
What is an example of hypertrophy and hyperplasia occurring together
Uterine enlargement during pregnancy is a consequence of smooth muscle hypertrophy and hyperplasia
26
What is atrophy
Shrinkage in cell size due to loss of cell substance Functionally diminished but alive eg immobilised or aging limb muscle
27
What is involution
Reduction in number of functioning cells due to reduction in functional demand (myometrium of uterus postpartum) - usually by programmed cell death (apoptosis)
28
What is metaplasia
Change in type of cell - reprogramming of stem cells Survival mechanism in response to injury ef smoking - specialised function is lost. Can predispose to neoplasia
29
Purpose of acute inflammation
Protective mechanism that functions to: 1) eradicate cause of injury 2) remove damaged cellular material 3) initiates repair process
30
What 3 steps do cells go through in acute inflammation
1) vasodilation - slowing local blood flow to the area - allowing time for plasma containing mediators to leave and for neutrophils to come into contact with the vessel wall - enabling cells to contact the capillary endothelium - generating heat and redness 2) increased vascular permeability - allowing plasma carrying mediators out - causing swelling (oedema / tumour/ turgor) 3) cellular activation and migration - neutrophils are activated to migrate from the vessels. They have great capacity for phagocytosis - short lived so need to be replaced
31
What happens after acute inflammation
1) resolution - rare 2) repair (fibrosis / scarring) 3) chronic inflammation - lasts as long as stimulus lasts 4) abscess formation - neutrophils doing a lot of phagocytosis, they die and produce pus so body produces collagen- heals by fibrosis
32
Describe the process of resolution (post acute inflammation)
Restitution of normal tissue structure and function -fluid is reabsorbed. Neutrophils and macrophages clear damaged tissue Growth factors and cytokines are released into damaged area to help regenerate
33
What is cell turnover
Cells divide to replace themselves and to expand and differentiate into mature tissue Skin epithelium is generated by the basal layer undergoing cell division to give rise to the laters above. These become progressively more differentiated and eventually die and are shed (this is called turnover)
34
What is the meanings of the words labile, stable and permanent in the sense of cell regeneration.
Labile- replicates throughout life Stable- non dividing in normal circumstances but capable of regeneration Permanent - non dividing cells
35
What factors affect the outcome ie repair or resolution after acute inflammation
*Severity of tissue damage: parenchyma (functional cells) or parenchyma and stroma (support cells / connective tissue) Labile- can resolve Stable- capable of regeneration so can resolve or scar Permanent - non dividing cells; always scarring * type of agent which has caused damage eg TB, virus) * complete resolution is uncommon
36
How does healing by fibrosis after acute inflammation happen ( 3 stages)
1) granulation tissue - macrophages, fibroblasts and new blood vessels 2) fibrosis and scar formation - fibroblasts lay down matrix - scar is formed as amount of collagen laid down is increased to strengthen the tissue 3) remodelling - over time the number of vessels is reduces and a pale scar remains
37
Describe the proliferative phase of wound healing
- granulation tissue - building tissue to fill the wound - fibroblasts secrete: matrix components, growth factors to stimulate angiogenesis - epithelial cells re grow over the wound
38
Describe the wound contraction and remodelling phase
- remodelling / organisation of the matrix to develop appropriate tissue architecture for the function of the tissue. Due to the action of fibroblasts laying down collagen and collagenases breaking down collagen to orientate for maximal tensile strength - wound contraction - decreased vascularity
39
Summary of resolution vs repair
Resolution: - arises from damage to parenchyma in labile / stable tissues - remove damaging stimulus, inflammatory cells, mediators and exudate - replace injured cells by regeneration - restore normal function - Minimal / absent evidence of damage Repair: - arises from damage to parenchyma and stroma - replace damaged tissue with connective tissue - formation of granulation tissue - formation of scar tissue - remodel for strength - lacks functional capabilities of damaged tissue
40
What are the mediators of repair (growth factors)
Growth factors are hormone like molecules that stimulate proliferation, differentiation and maturation of cells. In healing they attract endothelial cells and fibroblasts and therefore have a role in angiogenesis and production of the extracellular matrix
41
What are the anti-viral effects of antibodies
- antibody: blocks binding and entry to cells, activates intra-cellular degradation via TRIM21 - antibody + complement : damage to enveloped viruses, opsonisation for phagocytosis - antibody bound to infected cells: antibody-dependent cellular cytotoxicity
42
Describe the formation of the enveloped RNA viruses
Glycoproteins are synthesised by mRNA and inserted into the the host plasma membrane - matrix proteins synthesised by viral mRNA will form part of the envelope. - modified region of host plasma membrane extends out from cell surface - modified region is pinched off from host cell, enclosing viral matrix protein and RNA within capsid; modified membrane and matrix from viral envelope
43
What are 2 strategies of defence against extra-cellular viruses
1) antibodies to virus surface antigens may block the binding of viruses to cell surface receptors, neutralising the viruses. 2) antibodies can activate complement that may damage the lipid membranes of enveloped viruses 3) antibodies and complement proteins may also act as opsonins to promote phagocytosis of viruses 4) some viruses have evolved evasion mechanisms to protect themselves from the immune system eg influenza mutates the structure of its surface proteins
44
What is antigenic drift and antigenic shift
Antigenic drift is gradual changes in the virus due to accumulation of point mutations. Antigenic shift is the dramatic changes due to recombination between different strains of the virus
45
Strategies of defence directed at intra-cellular viruses
1) early innate response by interferons and natural killer cells limits the growth and spread of infection 2) adaptive response by Tc cells takes longer to activate but has higher efficiency 3) infected cells produce and secrete type 1 interferons. These bind to receptors on neighbouring cells and trigger an anti-viral state in which these cells are resistant to virus replication 4) type 1 interferons enhance expression of HLA class I making cells better targets for Tc cells and activate natural killer cells 5) NK cells sense changes in the infected cells’ surface constituents that are indicative of the cells being abnormal
46
Properties of viruses (size)
- small (20-50nm) - too small to see down light microscope (can be seen down electron microscope) - filterable agents
47
Properties of viruses (structure)
Simple | Contain nucleic acids surrounded by proteins and there is an outer membrane of lipid
48
Properties of viruses (metabolism)
Metabolically inert - rely on host cell - obligate intracellular parasites
49
Properties of viruses (replication)
Independent synthesis of component parts - may be in separate parts of the cell under separate control - subsequent assembly into new particles
50
Viral components: nucleic acid
DNA: - double stranded or single stranded - circular (covalently closed) or linear - 3kb-200kb (kilo bases)- 1 protein is about 1000 ``` RNA: - ds or ss - ss may be +ve or -ve polarity - linear or segmented (influenza- 8 strands of -ve mRNA) 5kb-10kb ```
51
Viral components: proteins
Capsid formation : - symmetry -icosahedral (sphere) or helical Attachment: - specific interaction between viral ligand and cellular receptor - determines viral tropism Enzymes: - mostly concerned with macromolecular synthesis Interference with cell function - to stop apoptosis, to avoid immune recognition
52
Viral components: lipid envelope
Derived from host cell membranes Must contain external attachment proteins Stripping of envelope leads to loss of infect II the (lots of things strip lipid: alcohol, aldehyde) - enveloped viruses generally more fragile (easy to strip lipid and disinfect)
53
Steps of viral replication
1) attachment : viral ligand / cellular receptor 2) entry : - endocytosis - fusion : viruses that have a lipid envelope - fuses with cell surface lipid 3) uncoating : 4) macromolecular synthesis : - multiple copies of viral genome - multiple copies of viral proteins (requires production of +ve ss RNA ie mRNA 5) assembly 6) release : - budding (yields enveloped virus) - cell lysis.
54
A DNA virus can form a double stranded DNA intermediate. Why is this an evolutionary advantage?
Because it can then be integrated into the host cells chromosomes using DNA integrase
55
Define genome
Total genetic material of an organism, comprising the genes contained in its chromosomes
56
What is nodular hyperplasia
Hyperplasia that occurs in a non-uniform pattern in an organ or tissue includes hyperplasia of the prostate gland and breast
57
Define atrophy
Reduction in the volume of a tissue (reduction in volume or cell number) - cell loss is commonly replaced by adipose tissue or fibrous tissue
58
Common causes of atrophy
``` Denervation Immobilisation Reduced endocrine stimulation Ischaemia Ageing ```
59
What is physiological atrophy (involution)
Most instances of involution are the result of withdrawal of an endocrine stimulus Eg - breast after cessation of lactation - uterus after parturition - thymus after puberty
60
What is hypoplasia and agenesis
Hypoplasia: incomplete growth of an organ Agenesis: complete failure of development of an organ in embryogenesis
61
Examples of metaplasia
Oesophagus in response to reflux - squamous epithelium to columnar Lungs in response to smoking - columnar epithelium to squamous Bladder in response to stones - transitional epithelium to squamous
62
Sublethal cell damage
Cells exposed to pathological stimuli may become damaged - molecular responses aim to repair damage and may manifest in structural changed - these changes are called cellular degenerations - these degenerations are potentially recoverable
63
Vacuolation in cell damage
In a damaged cell, mechanisms which maintain ion pumps fail. Water is retained by the cell Membrane systems become dilated with fluid (forms sac like structures- vacuoles) Cell becomes vacuolated and (histologically) pale stained
64
Define vacuolation
A large space within a cell filled with a substance eg mucin or glycogen - a cell is said to show vacuolation when it has developed vacuoles.
65
Hydronic change
A cell which is severely vacuolated as a result of pathological fluid accumulation is said to have undergone hydropic degeneration
66
How is sublethal cell damage recoverable
- if a damaging stimulus abates, a cell may recover - damaged organelles are removed by autophagy - damaged proteins are removed by ubiquitin-mediated proteolysis - residual materials may remain as inclusion bodies - stigmata of damage
67
What is lethal damage
If cellular damage is severe or maintained it may lead to cell death - may occur in the form of tissue necrosis - may also occur as apoptosis in which it is programmed and managed
68
Coagulation necrosis
Some stimuli to cells cause instant protein coagulation - cells die immediately - stimuli: extreme heat, extreme pH change, sudden anoxia
69
Liquefactive necrosis
If cell damage is above a level that is capable of recovery the cell dies - cell death is followed by a series of structural changes called necrosis - liquefactive necrosis is the most common form of necrosis - cell death is accompanied by spillage of cellular contents into the environment
70
Consequences of necrosis
Necrosis liberates cell proteins into tissue fluids This stimulates a tissue response to injury The tissue response to injury recruits neutrophils and other cells in a process called inflammation
71
What are opportunistic pathogens
Pathogens that only cause serious disease when host defences are impaired
72
What are primary pathogens
Capable of causing disease in absence of immune or physiological defect
73
What are virulence determinants
Contribute to the ability of both groups of bacteria to cause disease. Rarely is possession of a single virulence determinant sufficient to make a bacterium pathogenic
74
Bacterial disease processes
1) colonisation- establishing the disease in the tissues (adhesion and nutrient acquisition) 2) invasion of tissues - move from initial site of infection deeper into tissues or from site to site 3) avoidance of host defences 4) tissue damage 5) transmission- from one host to another
75
What is colonisation (stage 1 of disease processes) in detail
Establishment of a stable population of bacteria in the host Source of bacteria is in the environment, infected individuals or our own normal flora Frequently the first interaction occurs on a mucosal surface eg respiratory tract, GI tract or urogenital tract
76
How do bacteria utilise mucosal surfaces
Mucus forms a protective barrier and these sites are also subject to normal physiological flushing mechanisms eg saliva in the mouth and peristalsis in the gut. To overcome these flushing mechanisms and persist, bacteria must adhere to mucosal surfaces
77
Outline process of bacteria adherence
1st stage- association- involves non specific forces eg charge and hydrophobicity - weak and reversible 2nd stage- adhesion- involves specific binding between bacterial adhesins and host receptors (strong interactions and non-reversible) Subsequent stages may result in aggregation to produce a biofilm on a surface
78
Examples of bacterial adhesins
Fimbriae/ pili- rod like protein adhesins eg E. coli Polysaccharide adhesins eg oral streptococci
79
How to bacteria undergo nutrient acquisition
Iron is essential for bacterial growth In tissues, free iron levels are below that required to support bacterial growth To acquire enough iron to grow, bacteria express high affinity iron uptake systems 2 main systems: 1) siderophores 2) direct binding of iron transport proteins
80
What are the ways the immune system eliminates non-pathogenic bacteria
Complement alone kills many gram-negative bacteria Complement and antibodies oposonize bacteria, promoting phagocytosis and killing by polymorphonuclear leukocytes and macrophages Cytokines modulate both antibody and phagocytic responses
81
How do bacteria avoid complement
Gram negative bacteria causing sepsis are complement resistant so can survive and grow in bloodstream. Their resistance is due to lipopolysaccharide on bacterial surface. Polysaccharide side chains of LPS sterically hinder access of activated complement components to the bacterial membrane Capsules may also interfere with complement binding Surface proteins inhibit binding of complement to the bacterial surface Staphyloccous aureus produces factors that interfere with complement activation
82
How do bacteria avoid phagocytes
Some bacteria produce toxins which kill phagocytes or inhibit their migration to sites of infection Inherent physical properties of some bacterial capsules inhibit phagocytosis Some bacteria inhibit the pathways involved in intracellular killing within phagocytes
83
Systemic action of cytokines in response to injury / infection
- acts centrally to elicit pyrogenic response. Evidence for specific cytokines receptors in hypothalamus - elevates corticosteroids as part of ‘stress response’ which promotes inflammatory in the short term Increases hepatic protein (heat shock or acute phase proteins eg lipopolysaccharide binding protein) This stimulates bone marrow to release leukocytes
84
What does proliferation of many cells lead to
Granulation of the tissue - dense population of macrophages, fibroblasts and neovascularisation in a loose matrix of collagen - fibroblast produce collagen for structural purposes - proliferation of blood vessels ensures supply of nutrients and oxygen - various metalloproteinases stimulate cell movement in wound area
85
What does failure to stop the proliferative phase lead to
Granulomatous condition eg rheumatoid arthritis or scleroderma
86
Define angiogenesis
The formation of new blood vessels which occurs during wound healing and is promoted by growth factors This process is also seen in many malignant tumours and has become a target for anti-cancer therapy
87
Why is there increased incidence of venous ulceration in the elderly, men and post-menopausal women
Both don’t produce much oestrogen and testosterone and DHEA levels decline with age
88
Why do men have slower healing rate of wounds
High oestrogen = faster wound healing | High testosterone = slower wound healing
89
What is the maturation phase of wound healing
Cessation of proliferative phase leads to maturation phase and remodelling of the tissue. 1) reduced vascularisation : lessens demand for nutrients as metabolic activity of tissue declines 2) remodelling of collagen and reinnervation of nerves - increases strength of tissues and the return of ‘sensation’ but lack of elastin causes scar tissue
90
Effect of glucocorticoid treatment (long term)
Long term treatment inhibits inflammation at several steps in the process by reducing, among others: 1) prostanoid and leukotriene production and therefore inflammatory synergy between humoral and cellular factors 2) expression of cell adhesion molecules 3) chemotaxis of neutrophils 4) cytokines production 5) potentiates vasoconstrictors