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Medicine Year 1 > Case 7 SBA > Flashcards

Case 7 SBA Flashcards

1
Q

Define immunity

A

The ability of an organism to resist infection. Can be natural, artificial, active, or passive

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2
Q

Define immune response

A

The reaction of the cells and molecules of the immune system to the presence of a substance not recognised as self

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3
Q

Define immune system

A

The cells, molecules, and organs that provide us with specific (adaptive) and non-specific (innate) protection against foreign bodies

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4
Q

What are the four functions of the immune system?

A

Recognition, reaction, regulation, and retention

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5
Q

Describe active immunity

A

Requires the engagement of the innate adaptive immune response.
Activation of B cells that differentiate into plasma cells to produce antibodies
Has immunological memory so provides long term protection.

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6
Q

Describe passive immunity

A

No immunological memory.
Antibodies are transferred rather than actively generated.
Provides short term protection.

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7
Q

Example of natural passive immunity

A

Mother passing on antibodies to baby via placenta or breast milk

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8
Q

Example of artificial passive immunity

A

Giving antibodies from an immune individual directly to a non-immune individual

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9
Q

Define immunogen

A

Any molecule that can induce an immune response

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10
Q

Define antigen

A

Any foreign molecule that generates antibodies

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11
Q

Define epitope

A

The specific part of the antigen that binds to the antibody or T cell receptor

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12
Q

Describe the mechanism of B cells

A

Antigen presented to helper T cells on MHCII which triggers B cells to differentiate into plasma cells that can secrete antibodies

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13
Q

What are the functions of the antibodies secreted by plasma cells?

A

Opsonisation: neutralisation, agglutination, chemoattraction, natural killer cell activation, and classical complement cascade activation.

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14
Q

Describe how precursory T cells mature

A

They migrate to the thymus and become thymocytes. The thymocytes are trained to discriminate between self and non-self using MHCI complexes. Thymocytes then become either CD4 or CD8 T cells.

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15
Q

Describe CD4 T cells

A

Regulatory T cells, helper T cells, and memory cells. Recognise foreign antigens on MHCII complexes

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16
Q

Describe CD8 T cells

A

Cytotoxic T cells and memory cells. Recognise self antigens on MHCI complexes

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17
Q

Describe T cells

A

Antigen specific but can’t secrete their own antibodies. Can only recognise processed antigens presented on MHC complexes.

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18
Q

Describe helper T cells

A

Make cytokines, help maturation of B cells, and help activate cytotoxic T cells and macrophages.

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19
Q

Describe regulatory T cells

A

Actively supress activation of the immune system

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20
Q

Describe memory T cells

A

T lymphocytes that have previously encountered and responded to a specific antigen. Long lived and can expand to large numbers upon re-exposure to the same antigen

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21
Q

Describe the action of cytotoxic T cells

A

MHCI complex binds to antigens. If self, CD8 cytotoxic cells recognise and leave alone. If viral proteins are there instead, it is recognised as not self and a response is triggered - apoptosis is mediated by perforin and granzymes.

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22
Q

What are the lymphoid lineage cells?

A

B cells, plasma cells, memory B cells, T cells, and natural killer cells

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23
Q

What are the adaptive lymphocytes?

A

B and T cells

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24
Q

Are natural killer cells part of the innate or adaptive response?

A

Innate

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25
Q

What are the polymorphonuclear leukocytes/granulocytes and where to they come from?

A

Neutrophil, eosinophil, basophil, and mast cells. Come from the myeloid lineage.

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26
Q

What type of response do the granulocytes give?

A

Innate

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27
Q

Describe the function of basophils

A

Non-phagocytic, instead undergo degranulation – release molecules from the granulocytes to combat pathogen. Found in the blood. Stain blue/purple. Have two lobes in the nucleus.

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28
Q

Describe dendritic cells

A

Immature dendritic cells are mainly phagocytic, they constantly sample lymph to check for new pathogens. Mature when they encounter a new pathogen then does antigen presenting. Takes phagocytosed antigen to adaptive immune cells and stimulates their response (foreign pathogen on MHCII complex).

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29
Q

Describe the function of eosinophils

A

Are phagocytic, deal primarily with parasites. Very abundant in allergic and hypersensitivity diseases. Found in the blood. Stain pink/orange with a c-shaped nucleus.

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30
Q

Describe the function of mast cells

A

Sentinel cell found living in tissues. Non-phagocytic, instead release granules containing histamine and active agents. Major role in allergic response.

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31
Q

Describe monocytes

A

Differentiate into macrophages and dendritic cells. Only found in the blood. Agranulocyte/professional antigen presenting cell. Phagocytic and cytokine release. Large nucleus because of need to differentiate. Antigen presentation from blood.

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32
Q

Describe macrophages

A

Phagocytic (first response) and cytokine release. Antigen presentation. Found in lymph and tissue. Can either be fixed or roaming. Have pattern recognition receptors (PRR) on surface that recognise general pathogen cell surfaces that are either phagocytic or signalling

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33
Q

Describe the mechanism of macrophage phagocytosis

A

PRR looks for pathogen associated molecular patterns (PAMP). PAMP binds with PRR and induces cytoskeletal rearrangement to engulf the pathogen –> internalised phagosome binds with lysosome to form phagolysosome which releases reactive oxygen species to destroy it

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34
Q

Describe macrophage signalling

A

If pathogen level too high, signalling PRR activated which releases cytokines – PAMP binds to toll-like receptors which induces signalling cascade and activates transcription factors NFκB and IRF3/7 which make cytokines and cause inflammation

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35
Q

Describe natural killer cells

A

Free roaming cells found in all compartments. Check MHCI levels and kill abnormal cells – MHCI is downregulated in infection so lower levels detected by NK receptors trigger a response

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36
Q

Describe the natural killer cell antibody dependent cell cytotoxicity mechanism

A

NK cells are activated to degranulate when they bind to antibodies bound to the surface of targeted cells –> crosslinking of CD16 triggers the release of perforins and other proteins and target cell killing occurs through a process of apoptosis.

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37
Q

Describe neutrophils

A

Main function is phagocytosis but also activate bactericidal mechanism. Make up pus. Undergoes oxidative burst that destroys the cell as well as the pathogen. Found in blood. Stain purple and have a nucleus with three lobes.

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38
Q

What are the three major differences between B and T cells?

A

B cells directly recognise native antigens whereas T cells only recognise processed antigens (partly degraded and displayed as peptides on the surface of antigen presenting cells).

B cells differentiate to plasma cells to secrete antibodies whereas differentiated T cells do not produce antibodies.

B cells produce relative low amounts of cytokines and require specific differentiation and activation conditions whereas activated T cells produce large amounts of cytokines.

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39
Q

Describe the role of primary lymphoid organs in the immune system

A

Bone marrow created the cells and thymus trains T cells to differentiate between self and not self.

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40
Q

Describe the role of secondary lymphoid organs in the immune system

A

Spleen and lymph nodes filtrate harmful substances out of blood and lymph fluid, respectively. Immune response occurs within the secondary lymphoid organs.

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41
Q

Describe the origin of cells involved in the immune system

A

Bone marrow is the origin for all white cell types. Haematopoietic stem cells differentiate into common lymphoid progenitor cells and common myeloid progenitor cells that then further break down into specific cell types.

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42
Q

Describe the function of the innate immune system

A

The first line of defence against foreign invaders. It can distinguish between invaders and the self but not between different types of invader. Recruits the adaptive immune system by releasing cytokines.

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43
Q

Describe the response of the innate immune system

A

The same, non-specific response to every invader. Gives a fever response within minutes or hours.

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44
Q

What are the four components of the innate immune system?

A

Physical barriers, sentinel cellular barriers, complement cascade, and cellular induced innate responses.

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45
Q

Describe chemokines and give an example

A

A type of cytokine that stimulates migration and activation of cells, the ‘air traffic controllers’ of the cytokine world. Example CXCL-8 which is responsible for the recruitment of leukocytes to the site of infection.

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46
Q

Describe cytokines

A

Small proteins that alter the behaviour of other cells, particularly immune cells

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47
Q

Examples of cytokines

A

IL-1β, TNF-α, IL-6, and IL-12

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48
Q

TNF-α action

A

Lymphocyte activation, increases vascular permeability, activates natural killer cells, eases access of effector cells, causes fever
PRIME MEDIATOR IN SEPSIS

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49
Q

IL-1β action

A

Lymphocyte activation, improves access of effector cells at site of infection, causes fever

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50
Q

IL-6 action

A

Lymphocyte activation, causes fever

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51
Q

IL-12 action

A

Activates natural killer cells

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52
Q

Describe 1st generation antihistamines

A

H1 receptor blockers. Tend to be drowsy from anticholinergic effects, can cross the blood brain barrier. Examples are chlorphenamine, diphenhydramine, and doxylamine.

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53
Q

Describe 2nd generation antihistamines

A

H1 receptor blockers. Less drowsy as can’t cross the blood brain barrier. Examples are cetirizine/Zyrtec and loratadine/Claritin.

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54
Q

What are the mechanisms of antihistamines?

A

Neutral receptor antagonists or inverse agonists (induce the opposite effect to the endogenous agonist)

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55
Q

What are the uses of antihistamines?

A

Treating allergy, insomnia, motion sickness, and anxiety

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56
Q

Describe some pharmacokinetic characteristics of antihistamines

A

Oral route, 1-2 hours until peak effect, last for 3-6 hours or 8-12 if long-acting, wide distribution, metabolised by liver, excreted in urine

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57
Q

Major side effects of antihistamines

A

CNS: drowsiness, dizziness, tinnitus, fatigue
Peripheral antimuscarinic effects: dry mouth, blurred vision, constipation, urine retention
GI disturbances and allergic dermatitis can also occur

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58
Q

Describe muscarinic antagonists

A

Act as bronchodilators as inhibit ACh from reaching receptors. Mainly used in COPD. Reduce mucus secretion and may increase mucociliary clearance

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59
Q

SAMA

A

Ipratroprium bromide. Bronchodilation onset relatively slow and usually maximal 30-60 minutes after inhalation. May persist for 6-8 hours. Take 3 or 4 times daily

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60
Q

LAMA

A

Tiotropium bromide, glycopyrronium bromide, umeclidinium bromide, aclidinium bromide. Take all once daily except for aclidinium which is twice daily.

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61
Q

Side effects of antimuscarinic drugs

A

Dry mouth, GI motility problems, tachycardia, nausea

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62
Q

Side effects of inhaled corticosteroids

A

Oropharyngeal candidiasis may occur; adrenal suppression and reduced bone mineral density when taken long-term.

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63
Q

Side effects of oral corticosteroids

A

Suppression of immune response to infection, Cushing’s, osteoporosis, hyperglycaemia, muscle wasting, and growth inhibition - all from long-term use.

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64
Q

Describe the mechanism of action of corticosteroids

A

Interact with glucocorticoid receptors –> moves to nucleus –> inhibits NFκB –> inhibits histone acetyltransferase and recruits histone deacetylase 2 –> HDAC2 deacetylates and modulates gene transcription in target tissues

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65
Q

Describe the action of beclomethasone and budesonide

A

Takes weeks for full effect. Reduces inflammation: reduce activation of eosinophils –> reduce production of IgE –> reduces production of leukotrienes and platelet activating factor –> inhibits induction of cyclo-oxygenase pathway –> fewer inflammatory cytokines.
May also upregulate β2 receptor expression

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66
Q

Mechanism of action of β2 adrenoreceptor agonists

A

Cause relaxation of airway smooth muscle by increasing cyclic AMP through Gs.

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67
Q

Describe short acting β2 agonists

A

Examples are salbutamol and terbutaline. Use as needed for acute episodes. Take via inhalation and gives relief within 5-10 minutes. Maximal effect reached within 30 minutes and has a duration of 3-5 hours.

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68
Q

Describe longer-acting β2 agonists

A

Examples are salmeterol and formoterol. Given regularly twice daily. Slow onset so not appropriate for an acute episode. Roughly 12 hour duration - lipophilic structures aid duration. Used alongside corticosteroids

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69
Q

β2 agonist side effects

A

Muscle tremor at high doses, tachycardia, cardiac dysrhythmias, and risk of paradoxical bronchospasm.

70
Q

What minimises the side effects of β2 agonists?

A

Delivery via inhalation rather than systemic route

71
Q

Describe the mechanism of methylxanthines

A

Cause an increase in levels of cyclic AMP through non-competitive inhibition of the phosphodiesterase enzyme (PDE) which leads to bronchodilation.

72
Q

Describe the mechanism of theophylline

A

Is a methylxanthine. Competitive non-selective antagonist of adenosine A1 and A2 receptors. Antagonism of A2b receptors inhibits release of histamine and leukotrienes

73
Q

Pharmacokinetics of theophylline

A

Administered IV for severe acute asthma, orally as a second line drug in addition to steroids in patients who respond poorly to β2 agonists, metabolised by CYP450, narrow therapeutic window

74
Q

Side effects of theophylline

A

Dysrhythmias, seizures, tremor, positive inotropic/chronotropic, insomnia. Caused by antagonism of A1 receptors

75
Q

What are leukotrienes?

A

Inflammatory molecules released by mast cells in an asthma attack and are also responsible for drawing eosinophils to the bronchioles in chronic asthma which causes general bronchial hyperreactivity

76
Q

Leukotriene receptor antagonist mechanism and what it works for

A

Block the cysteinyl LT1 receptor on respiratory mucosa and block infiltrating inflammatory cells. Reduces response to exercise-induced asthma, early and late responses to inhaled allergen, and acute response to aspirin in sensitive patients

77
Q

Pharmacokinetics of leukotriene receptor antagonists

A

Montelukast and zafirlukast. Given orally as tablets 1-2 times daily, extensively metabolised and undergoes biliary excretion. Used in combination with steroids if patient not responding to β2 agonists

78
Q

Leukotriene receptor antagonist side effects

A

Abdominal pain, thirst, and headache

79
Q

Describe the effects of histamine in the inflammatory process

A

Itchiness, contraction of respiratory airways, blood vessel dilation, and gastric acid secretion. Also has high chemoattractant ability meaning it enhances secretion of pro-inflammatory cytokines

80
Q

Why does allergy occur?

A

Failure of immune tolerance

81
Q

What is immune tolerance?

A

The system that generates suppression of cellular or humoral immune responses - a hypo responsiveness

82
Q

Define allergic reaction

A

A hypersensitivity reaction initiated by immunological mechanisms

83
Q

Define allergen

A

An antigen that triggers an allergic reaction

84
Q

Define atopy

A

The tendency to develop allergic. Associated with allergic asthma, eczema, and allergic rhinitis. Occurs in 20-30% of population

85
Q

Define anaphylaxis

A

A severe, life-threatening, generalised or systemic hypersensitivity reaction. Characterised by rapidly developing ABC changes

86
Q

Mechanism of anaphylaxis

A

Release of histamine leads to bronchoconstriction, mucus secretion, reduced cardiac contractility, increased vascular permeability, coronary and peripheral artery vasoconstriction, and venodilation

87
Q

Mechanism of type I hypersensitivity

A

Antigen presented by APC to TH2 –> TH2 releases IL-4 and IL-12 which activate B cells –> B cells proliferate and differentiate into plasma cells –> Plasma cells synthesise and secrete IgE –> IgE binds to FC portion of mast cells –> on re-exposure, mast cells with IgE bind to antigen and degranulate –> degranulation activates eosinophils via IL-5 releasing further cytokines for more delayed effects

88
Q

Symptoms of type I hypersensitivity

A

expulsion of GI tract contents, congestion and blockage of airways (coughing, wheezing, phlegm), swelling and mucus secretion in nasal passages, increased blood flow and vessel permeability, oedema, hypotension

89
Q

Examples of type I hypersensitivity

A

Hayfever, hives/urticaria, asthma (localised), anaphylaxis (systemic), and angiodema

90
Q

Mechanism of type II hypersensitivity reactions

A

Takes hours to a day. IgG or IgM binds to the cells of a particular tissue –> Ab/Ag complexes formed –> classical complement cascade activated –> cells eliminated through cytotoxic action and complement-mediated cell lysis

91
Q

What are the two types of type II hypersensitivity reactions?

A

Intrinsic - failure in immune tolerance with normal self antigens
Extrinsic - with a foreign antigen that resembles host cells

92
Q

Examples of type II hypersensitivity reactions

A

Drug-induced thrombocytopenia, autoimmune haemolytic anaemia, Grave’s disease, Goodpasture syndrome, and mismatched blood types

93
Q

Describe the mismatched blood type transfusion reaction

A

Foreign RBCs destroyed by complement mediated lysis triggered by IgG which produces fever, clots, lower back pain and Hgb in urine. The Hgb is either passed to the kidneys leading to haemoglobinuria or is broken down into bilirubin which can be toxic

94
Q

Mechanism of type III hypersensitivity reactions

A

IgG or IgM binds to antigen in the circulation and forms immune complexes that are deposited in various tissues. These bind to FC receptors on leukocytes and mast cells leading to inflammatory response

95
Q

Examples of type III hypersensitivity reactions

A

Post-streptococcal glomerulonephritis, reactive or rheumatoid arthritis, SLE, Henoch-Schonlein Purpura (IgA vasculitis)

96
Q

Mechanism of type IV hypersensitivity reactions

A

TH1 cells cross-present other molecules rather than bacterial antigen to B cells. On re-exposure, TH1 produces inflammatory cytokines which causes macrophage activation leading to oxygen radicals and nitric oxide production

97
Q

Examples of type IV hypersensitivity reactions

A

Mantoux test (tuberculin skin test) and contact dermatitis

98
Q

Causes of anaphylaxis

A

Foods (milk and peanuts), insect stings/bites, pollen, medications (antibiotics and anaesthetics), and 20% idiopathic

99
Q

Describe the differences between allergy and intolerance

A

Allergies are an adverse, immune-mediated response that can either IgE or non-IgE. Intolerances are non-immune mediated responses to food. Can be enzyme deficiencies, pharmacological, or an undefined intolerance

100
Q

Describe the techniques used in investigating allergic disease

A

Allergy focused history (symptoms, exposure to trigger, timing of reaction, atopy) and examination (skin, nose, eyes, chest, and growth parameters for children). Skin prick test, specific IgE measurement, component test, and food challenge

101
Q

Describe the treatment options in allergic disease

A

Awareness, avoidance, management of comorbidities, re-introduction to allergens for non-IgE allergies, EpiPens, immunotherapy (if avoidance is not possible), and anti-IgE monoclonal antibody treatment (mostly asthma and urticaria), antihistamines when necessary

102
Q

Describe interferons

A

A group of signalling proteins made and released by mast cells in the presence of a virus. They cause nearby cells to increase levels of MHCI. Interfere with viral replication, activate immune cells, and increase host cell defences

103
Q

Describe acute phase protein action

A

Plasma concentration increases in response to inflammation - liver responds to cytotoxins in the bloodstream by producing as many as possible to restore homeostasis

104
Q

Examples of acute phase proteins

A

Complement factors, CRP, mannose binding lectin, and fibrinogen

105
Q

Why can viruses cause epidemics and pandemics?

A

Genetic variability that gives rise to antigenic changes that evade previous immunity

106
Q

Define antigenic drift

A

Minor changes in H and N proteins by random mutations/substitutions. Drift variants escape immunity from the parent virus and cause disease. Occurs roughly every 4 years. Results in flu A and B epidemics/pandemics

107
Q

Define antigenic shift

A

Occurs when two different viruses infect the same cell and genetic re-assortment occurs - results in flu A acquiring new H and usually new N proteins. New viruses can go on to cause flu A pandemics. Occurs every 10-20 years

108
Q

Define endemic

A

A disease that is always present in a certain population or region

109
Q

Define epidemic

A

An outbreak of a contagious disease that spreads rapidly and widely

110
Q

Define pandemic

A

Epidemic over a wide geographic area and affecting a large proportion of the population

111
Q

What are the four systemic effects of inflammation?

A

Fever, acute phase proteins, leukocytosis, sepsis

112
Q

Describe the fever mechanism

A

A pyrogen e.g. lipopolysaccharide on gram negative bacteria acts as a PAMP and binds with PRR –> inflammatory cytokines secreted into the bloodstream –> cytokines go to brain and bind to receptors on brain endothelial cells –> activates PGE2 synthesis –> goes to hypothalamus –> body temperature raised

113
Q

What is the purpose of the fever mechanism?

A

Helps stop pathogen replication and induces hyperactivation of phagocytic leukocytes

114
Q

Action of CRP

A

Promotes opsonisation and the classical complement cascade. Important inflammatory marker

115
Q

Action of fibrinogen

A

Helps with blood clotting and is useful for establishing the effects of chronic inflammation over time

116
Q

Leukocytosis mechanism

A

PRR/PAMP interaction –> more cytokines produced –> haematopoietic stem cells activated –> increased numbers of leukocytes –> leukocytes released into circulation –> increased white cell count

117
Q

Describe serous inflammation

A

Exudation of fluid into spaces created by cell injury or body cavities. Fluid not infected and does not contain large numbers of leukocytes - effusion. E.g. skin blister from burn or infection

118
Q

Describe fibrinous inflammation

A

Fibrinogen passes out of blood and fibrin gets deposited into extracellular space after increases in vascular permeability or procoagulant stimuli e.g. cancer cells. Characteristic in lining of body cavities. Appears as eosinophilic meshwork or amorphous coagulum

119
Q

Describe purulent inflammation

A

Production of pus consisting of neutrophils, cellular debris, and oedema fluid. Commonly occurs due to infection by bacteria that causes liquefactive necrosis e.g. staphylococcus

120
Q

Describe abscesses

A

Localised collection of purulent inflammatory tissue with central mass of necrotic leukocytes and tissue cells surrounded by preserved neutrophils - enclosed by surrounding tissues

121
Q

Describe ulcers

A

Local excavation of surface of organ or tissue produced by sloughing of inflamed necrotic tissue. Can only occur when inflammation and necrosis is on or near the surface of the tissue.

122
Q

Where do ulcers commonly occur?

A

Mucosa of mouth, GI tract, genitourinary tract, and skin. Also occurs in subcutaneous tissue of lower extremities in older people with circulatory disturbances that predispose them to extensive ischaemic necrosis

123
Q

Presentation of acute inflammation

A

Rapid onset, short duration, mainly neutrophils, prominent characteristic response.

124
Q

Cardinal symptoms of acute inflammation

A

Redness, heat, swelling, pain, loss of function

125
Q

What are the three changes caused by acute inflammation

A

Vasodilation, increase in vascular permeability, and leukocyte recruitment

126
Q

Describe inflammatory vasodilation

A

Leads to heat and redness. Blood flow gets slowed down, giving leukocytes time to exit circulation. Histamine is the main driver of vasodilation.

127
Q

Describe increase in vascular permeability from inflammation

A

Leads to swelling and pain. Endothelial cells retract creating gaps that allow leukocytes to get through and leave circulation. Direct endothelial injury and leukocyte-endothelial injury also have the same effect

128
Q

Describe the process of leukocyte recruitment

A

Margination – leukocytes move from centre to peripheral parts of blood vessel, directly engaging with the endothelial cells 🡪 Rolling – leukocytes roll along the surface of the endothelial layer, slowed down by selectin/glycoprotein and integrin/integrin ligand interactions which are fragile and easily break 🡪 Stable adhesions – cytokines released from the site of injury increase integrin/integrin binding which stops the leukocyte at the site of injury 🡪 Emigration/transmigration/diapedesis – leukocyte extends its pseudopodia downwards and squeezes through endothelial gap junctions, mediated by protein PCAM1 🡪 Chemotaxis – leukocytes follow a chemokine gradient to find and locate pathogens. Complement C3a and C5a are potent chemokines. Quick response of neutrophils which are replaced by macrophages at roughly the 24-hour mark.

129
Q

Define inflammation

A

Protective response of vascularised tissues to infections and damaged tissues that brings cells and molecules of host defence from the circulation to the sites where they are needed, in order to eliminate the offending agents e.g. release of cytokines and chemokines recruiting neutrophils and monocytes from the bloodstream

130
Q

Histamine in chronic inflammation

A

Vasodilation, increased permeability, leukocyte recruitment

131
Q

What do plasma proteins cause in chronic inflammation?

A

Vasodilation, increased permeability, leukocyte recruitment

132
Q

Cytokines in chronic inflammation

A

Vasodilation, increased permeability, leukocyte recruitment

133
Q

Prostaglandins in chronic inflammation

A

Vasodilation, increased permeability

134
Q

Leukotrienes in chronic inflammation

A

Increased permeability, leukocyte recruitment

135
Q

Describe bradykinin and its actions

A

Made from kininogens, plasma proteins produced in the liver. Increases vascular permeability by gap junction dissociation, increases histamine release from mast cells, and increases local endothelial eicosanoid production (eicosanoids are prostaglandins and leukotrienes).

136
Q

What do NSAIDs inhibit?

A

COX1 and 2 stopping prostaglandin production

137
Q

What do glucocorticoids inhibit in inflammation ?

A

Phospholipase A2 stopping leukotriene production

138
Q

Which cells propagate chronic inflammation?

A

Macrophages that do phagocytosis: initiate tissue repair by making growth factors, secrete chemokines and cytokines, and lymphocyte activation through antigen presentation on MHCII
Lymphocytes (T and B cells): secrete antibodies, chemokines, and cytokines that propagate chronic inflammation.

139
Q

How does infection affect wound healing?

A

Prevents the resolution of inflammation and causes additional tissue damage – prevent the deposition of collagen because of ongoing infective response.

140
Q

How does nutritional status affect wound healing?

A

Protein and vitamin deficiencies can inhibit collagen production which impedes the ability of the tissue to be repaired e.g. vitamin C deficiency prevents fibroblasts from synthesizing new collagen

141
Q

How does glucocorticoid treatment affect wound healing?

A

Weaken scar formation as they inhibit TGF-β, the main growth factor for stimulating fibroblasts to secrete collagen. Also activate MMPs which are responsible for the degradation of extracellular matrix components – promotes degradation of collagen that is already in place (helpful in eye wounds as the tissue needs to remain transparent).

142
Q

How does diabetes affect wound healing?

A

Particularly in lower limbs. Increased blood glucose narrows the arteries as a consequence of impaired nitric oxide signalling (also increases blood pressure). This reduces blood flow to the lower extremities, preventing the efficient recruitment of leukocytes. Increased blood glucose also prevents activation of leukocytes

143
Q

Causes of chronic inflammation

A

Persistent infection, hypersensitivity disease, and prolonged exposure to potential toxic agents

144
Q

What are the three major components of chronic inflammation?

A

Infiltration with mononuclear cells (macrophages and lymphocytes), tissue destruction (macrophages releasing cytokines), and attempts at healing (connective collagen deposition – fibrosis).

145
Q

Describe granulomatous inflammation

A

A cellular attempt to contain an offending agent that is difficult to eradicate. A circle of necrosis is surrounded by a ring of macrophages that differentiate into specialised epithelioid cells that keep the pathogen inside. Two types – foreign body granulomas from non-degrading surgical sutures and immune granulomas e.g. TB.

146
Q

Describe fibrosis

A

Secretion of cytokines (TNF, IL-1, and IL-4) and growth factors (TGF-β and FGF) cause fibroblast proliferation, recruitment of bone marrow fibroblasts, and inhibition of matrix metallopeptidase. This leads to excess deposition of extracellular matrix proteins (collagen) that provides tensile strength where tissue has been destroyed, causing fibrosis

147
Q

What are the two types of tissue repair?

A

Regeneration and scar formation

148
Q

What determines the ability of a tissue to repair itself?

A

Its intrinsic proliferative capacity

149
Q

Describe labile tissues

A

Continuously dividing, regenerate rapidly after an injury e.g. mucus membranes, lymphoid cells, haematopoietic cells

150
Q

Describe stable tissues

A

Long lifespan, capable of rapid division following injury. Are put back into the cell cycle from G0 e.g. smooth muscle, epithelial liver, kidney, and lung, fibroblasts, and endothelial cells

151
Q

Describe permanent tissues

A

Very limited regenerative ability - may regenerate portions of the cell e.g. neurons, cardiac muscle, lens epithelium

152
Q

Describe regeneration

A

Growth factors and development of mature cells from stem cells lead to cell proliferation.

153
Q

What are the steps of scar formation?

A

Inflammation –> angiogenesis –> formation of granulation tissue –> remodelling of connective tissue

154
Q

Purpose of inflammation in scar formation?

A

Remove injurious agent, limit tissue damage, and prepare the wound environment for repair (growth factor/cytokine production drives cellular recruitment and proliferation)

155
Q

Describe angiogenesis

A

Formation of small vessels, can give oedema - leaky as new cells, VEGF made by fibroblasts

156
Q

Describe formation of granulation tissue

A

Fibroblast activation, deposition of loose connective tissue, TGF-β, tissue is pink, soft, and fragile

157
Q

Describe remodelling of connective tissue

A

Maturation and reorganisation of connective tissue, matrix metalloproteinase used, scar formation, departure of leukocytes, fibroblast inactivation

158
Q

What dictates whether tissue undergoes regeneration or scar formation?

A

Whether or not the basement membrane is damaged

159
Q

What are the three roles of inflammation?

A

Delivery of effector cells and molecules to site of infection, promotion of blood clotting at infection site, promotion of tissue repair

160
Q

Describe asthma

A

A disease characterised by recurrent attacks of breathlessness and wheezing which vary in severity and frequency from person to person. It is also characterised by paroxysmal and reversible obstruction of the airways. An inflammatory condition combined with bronchial hyper-responsiveness and hypersensitivity. In an attack, the lining of the passages swell causes the airways to narrow and reducing airflow

161
Q

Main symptoms of asthma

A

Wheeze, shortness of breath, and night or early morning cough.

162
Q

What causes wheeze?

A

Occurs when the small airways are narrowed – from bronchospasm, swelling of the airway passages, increased airway secretions, inhaled objects, or abnormal growth in the airways.

163
Q

Aggravating factors of asthma?

A

URTIs, cold air, exercise, irritants, allergens, time of day, work related factors e.g. dust and paint fumes, damp/mouldy housing conditions, and strong emotions.

164
Q

What is the pathophysiological response to asthma triggers?

A

Reversible airway obstruction, bronchial hyperreactivity, and inflammation of airways.

165
Q

Describe the airway changes in chronic asthma

A

Infiltration of walls with pro-inflammatory lymphocytes and mast cells that release cytokines and eosinophils, smooth muscle hypertrophy, thickened basement membrane, leaking of fluid from dilated blood vessels, damaged epithelia, increased mucus production, bronchospasm, and reduced airway lumen

166
Q

Describe intrinsic asthma

A

No known causative agents, but may be triggered by exposure to chemical agents/drugs, exercise, respiratory infections, or stress

167
Q

Describe extrinsic asthma

A

Often in atopic individuals and is associated with common allergens like pollen, dust, animals, and nuts. More common in childhood where it is associated with eczema.

168
Q

Describe the classical complement cascade

A

C1 protein has 6 Q subunits that bind to the FCP portion of an antibody when it is bound to an antigen. When two or more units bind, the complex undergoes a conformational change and twists, exposing C1s and C1r. C1r cleaves C1s, activating the C1. Activated C1 cleaves C2 and C4 🡪 C2b joins C4b on the surface of the pathogen 🡪 C3 convertase is formed (C4b2b). C3 convertase converts C3 into C3a and C3b – over 1000 per second. C3b is also known as opsonin which helps phagocytes to grip bacteria – it coats the bacteria to counteract antiphagocytic capsule. Some C3b joins to form the C4b2b3b complex (C5 convertase) which cleaves C5. C5b binds to C6, C7, and C8 – this complex penetrates though the pathogen cell membrane with the assistance of small groups of C9 that help form a channel through the membrane. C9C5bC6C7C8 = membrane attack complex that destroys gram negative bacteria.

169
Q

Describe the lectin binding complement cascade

A

Uses mannose binding lectin protein which can cleave C4 and C2 then is the same as the classical cascade.

170
Q

Describe the alternative complement cascade

A

There are always small amounts of C3b. Factor B binds to C3b and pathogen surface, allowing factor B to be cleaved by factor D. Bb stays with C3b and cleaves C3 – this is an amplification step.

171
Q

What are the actions of C3a and C5a?

A

Chemotaxins – they recruit neutrophils, eosinophils, monocytes, and macrophages to the site of inflammation. They also act as anaphylatoxins – cause the release of proinflammatory molecules from neutrophils and basophils.

Medicine Year 1 (23 decks)

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