Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MP324 > L1 - L7 > Flashcards

L1 - L7 Flashcards

1
Q

Immune System
- Innate

A

early phase host response (minutes to hours)

  • does not increase with repeated exposure
  • discriminates between groups of pathogens
  • activates adaptive immune response

involves early responders: neutrophils, macrophages, eosinophils & dendritic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Immune System
- Adaptive

A

generated by specific lymphocytes

  • discriminates between pathogens
  • involves T & B cells
  • takes 1-4 days
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Inflammation Mediators

  • chemokines, cytokines
A

Short Term Mediators
- prostaglandins, leukotrienes, bradykinin

Chemokines
- small molecules that attract WBC to site of infection

Cytokines
- Large proteins that activate immune cells which drive transcription of immune proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Innate Immune System
- Pathogen Recognition by macrophages, neutrophils etc.

A

PRR’s on immune cells respond to pathogen fragments
- called PAMPs (pathogen associated molecular patterns)

  • Biggest PRR’s is TLR’s
  • sense gram -/+ , viruses, & flagella proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

TLR’s in Innate Immune Response

  • TLR6:TLR2 - gram+
  • TLR1:TLR2 - gram-
A

TLR6:TLR2 - sense gram + bacteria
- recognise diacyl lipopeptides

TLR1:TLR2 - sense gram-
- recognise triacyl lipopeptides

  1. activating TLR’s will trigger tissue inflammation
  2. releases cytokines to make blood vessels more permeable
  3. increases blood flow + increases chemokine release to attract WBC to infection site (Diapedisis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Dendritic Cell Role - T-Cell Activation

  • CD4+ activates T-helper
  • CD8+ activates cytotoxic
A
  1. dendritic cell presents antigen to naive CD4+ via MHCII to activate T-helper cell
  2. dendritic cell presents antigen to naive CD8+ via MHC-I to activate cytotoxic T killer cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Dendritic Cell Further Functions

  • Adaptive immunity
A
  1. dendritic cells release CYTOKINES which guides naive CD4+ cells down specific lineage
    - based on PAMP’s
  • bacteria directed down TH1 pathway
  • worm infections are directed TH2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

T-Cell Lineages

  • TH1 - by dendritic IL-17
  • TH2 - releases IL4
A

T-helper 1 (TH1)
- TH1 release Cytokines to activate IFNy, TNF-a macrophages, neutrophils

T-Helper 2 (TH2)
- IL4 stimulates IgE which activates mast cells
- histamine recruits eosinophils causing inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

TH2 Allergic Asthma Phases

  • Sensitisation
A
  1. pollen engulfed by dendritic cell which then presents its antigen to CD4+ via MHC-II
  2. normally T-cell would not respond but it does
    - T-cell gets activated & differentiates into TH2 with help of IL4
  3. TH2 lineage release IL4, causing B-cells to release IgE antibody - which is sensitised to pollen)
  4. IgE binds to mast cell receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

TH2 Allergic Asthma
- Effector Phase

A
  1. when pollen comes for the second time it binds to IgE receptor on mast cells causing mediator release
  2. this causes histamine release and other inflammatory modulators to cause inflammatory response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

TH2 Allergic Asthma
- Second Phase

A
  1. TH2 cells release IL-5 & IL-13 to recruit eosinophils in bone marrow
  2. Eosinophils release contractile mediators (histamine & leukotrienes)
  3. this causes airway smooth muscle contraction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

TH2 Asthma Effector Cells
- mast cells

A

activated by IgE
- this causes bronchial hyperresponsiveness

antihistamines dont work in asthma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

TH2 Asthma Effector Cells

  • Eosinophils
    -IL-5
A
  • IL-5 supports oesinophil development & recruits them
  • Eosinophils release cytokines and mediators which cause inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Asthma Response Initiation

A
  • TH2 mediated most of the time due to TH2 releasing IL4 which interacts with mast cells and eosinophil to cause inflammation
  • sometimes inflammatory environment leads CD4+ T-cells down TH1 pathway
  • this makes the effector cells that damage the airways different than normal TH2 lineage asthma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

TH1 Lineage Allergic Asthma
- induced by IL-12 cytokine

A
  • Dendritic cell releases IL-12 causes TH1 to release INFy + TNFa
  • they stimulate neutrophils & macrophages (damaging effector cells)
  • TH1 protects from respiratory virus like influenza, TB & kleb
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

TH1 Asthma Effector Cells
- Neutrophils

A
  • neutrophil inflammation pathway in asthma usually more severe , causing airway remodel
  • neutrophils engulf pathogens tagged for destruction (opsonisation)
  • activated by TNF-a
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Asthma Stimuli
- non-specific & specific

A

non-specific
- exercise, cold air, hyperventilation, chemicals

specific
- allergens
- aspirin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Characteristics of Asthma

  • pathology: recurrent breathlessness and wheezing
A

1 - Inflammatory response: eosinophils, mast cells and neutrophils

2 - Hyper-responsiveness of smooth muscle to substances that cause contraction such as acetylcholine, histamine

3 - Hypo-responsiveness of the smooth muscle to substances that relax smooth muscle, such as adrenaline.

4 - Neuronal imbalance

5 - Hyperplasia and hypertrophy

19
Q

Asthma Structural Remodelling

A

epithelial damage, basement membrane thickening, increased muscle leads to more contraction

20
Q

Neuronal Imbalances in Asthma Patients

  • Afferent nerves (C-fibres) respond to histamine, bradykinin, PG causing reflex bronchoconstriction
A

Reduced B Adrenoceptors in bronchial smooth muscle
- making it less responsive to adrenaline
- this reduces the relaxation of airways

Increased Cholinergic drive
- consequence of inflammatory mediators in airway
- activates C-fibre sensory cells in the airway
- results in release of ACh bronchoconstrictor

21
Q

B2 Adrenoceptor Agonists

  • Mechanism of Action
  • treats asthma
A

LABAs have lipophilic groups which allow them to react with receptor for longer than SABAS’s

  • Beta Agonists activate GS protein which activated adenyl cyclase which activates PKA
  • PKA phosphorylates beneficial processes like SMC calcium efflux
  • also inhibits MPK pathway by Raf-1 Kinase
22
Q

Actions of Beta Agonists in Asthma

A
  • decreases cholinergic ACh release
  • decreases inflammatory mediator release (& histamine)
  • decr vascular permeability & inc. mucocilliary clearance

Desensitisation
- Phosphorylation of occupied receptor by GRK. enables binding of beta-arrestin

23
Q

Asthma Steroid Drugs (ICS)

  • inhaled (beclomethasone)
  • oral (prednisolone)
  • IV (hydrocortisone)
A

Glucocorticoids dampen many aspects on inflammation in asthma

  • work by inhibiting pro-inflammatory genes & decreasing pro-inflammatory mediators
  • inhibits cytokines: TNFa, IL-1 etc
  • also decr inflammatory release from WBC & inc B-adrenoceptor activity
24
Q

Leukotriene Inhibitors
- Montelukast

A
  • S/E - eosinophilia , churgg strass
25
Q

Xanthines & MoA

A

Adenosine Receptor Antagonist
- These drugs block inhibitory action of adenosine on adenylyl cyclase , allowing intracellular cAMP to accumulate and promote relaxation

Phosphodiesterase (PDE) Inhibitor
- blocks reduction in intracellular cyclic AMP & relaxes smooth muscle

26
Q

Theophylline Xanthine

  • Phosphodiesterase Inhibitor + adenosine antagonist
A

PDE inhibition - PDE3 inhibition causes smooth muscle relaxation, PDE4 inhibition stops mediator release

Adenosine Antagonist - Adenosine prevents adenyl cyclase allowing intracellular cAMP build up

Oral S/E
- anorexia, vomiting, risk of seizures from toxic dose

IV S/E
- increased arrythmias, palpitations

27
Q

Aims Of Asthma Treatment

  • normal lung function >80% predicted PEFR
A
  • if 6 months or more. consider reduce ICS therapy
  • no daytime symptoms
  • no night-time awakening
  • no need for rescue medication
  • no asthma attacks
  • no limitations on activity or exercise
28
Q

Asthma Management - Adults

Stage 4: refer to specialist

Fluticasone - most potent ICS

A

suspected : SABA while monitoring

Stage 1: SABA + low dose ICS (budesonide)

Stage 2: SABA + low dose ICS + LABA (salmeterol)
- use combined ICS/LABA inhaler (fostair)

Stage 3: SABA +increase ICS and/or add Montelukast (phosphodiesterase inhibitor to inhibit leukotrienes)
- continue with LABA unless having no effect

29
Q

Asthma Management Children

  • stage 4 specialist care
A

suspected : SABA

Stage 1: SABA + very low ICS (or Montelukast if >5)

Stage 2 : SABA + very low ICS
- if >5 add LABA , , if <5 add montelukast

Stage 3 : SABA + increased ICS
- if >5 add LABA , , if <5 add montelukast

30
Q

COPD Characterisation

A

Epithelial Cells activated by irritants and release inflammatory mediators (innate + adaptive)
- 5-10x macrophage increase in airways

  • more T cells (especially CD8+ cytotoxic cells)
  • impaired macrophage ability to phagocytose pathogen
  • decreased mucocillary clearance
  • increased protease activity
  • a1-AT reduction (protease inhibitor)
31
Q

FEV1 & FVC

  • FEV1 <0.8 means COPD
  • FEV1/FVC <0.7means COPD
A

FEV1 - forced exhalation of breath in 1 second

FEV1/VC Ratio - FEV1 divided by max amount of breath that CAN be exhaled in one breath

  • stage 1: FEV1 50 - 79%
  • stage 2: FEV1 33 - 50%
  • stage 3: FEV1 <33%
32
Q

Genetic COPD Susceptibility

  • a1-AT protease inhibitor
A
  1. alpha 1 anti-trypsin (a1-AT) is a protease inhibitor
    - balances elastin activity & other destructive proteases
  2. pathogenic mutations cause a1-AT to self associate into polymer chains, stopping its anti-protease activity
  3. tissue destruction happens from increased proteases
33
Q

COPD Chronic Bronchitis

  • includes: bronchospasm, dyspnoea, wheezing
A
  • hypoxia & elevated CO2
  • diagnosed with persistent productive cough for at least 3months consecutively in 2 consecutive years
  • mucus hypersecretion - traps inhaled toxins which can cause inflammation in airways when infected
34
Q

COPD Emphysema

  • permanent enlargement of alveoli and destruction
A
  • patients inhale/exhale larger volumes to try and reach the enlarged cell walls of alveolar cells for gas exchange
  • progressively larger lungs, limiting ventilation
  • hypoxemia, elevated CO2
35
Q

COPD Inflammation

  • Epithelial cell activation
A
  1. epithelial cells activated by inhaled irritants to produce inflammatory mediators including TNFa, IL-1B , IL-6 , IL8
  2. causes 5-10x inc. in macrophages in airways, alveolar fluid and sputum
36
Q

COPD vs Asthma

A

COPD
- not reversible with bronchodilator
- occurs in older patients mostly
- neutrophil & macrophage mediated
- less responsive to ICS treatment

Asthma
- Reversible with SABAs
- usually starts in childhood
- mast cell and eosinophil mediated

37
Q

COPD Management
- Bronchodilators

A
  • given to reduce dyspnoea (major COPD symptom)
  • dyspnoea caused by increased alveolar volume
  • short term relief
38
Q

COPD Management

  • Beta Agonists MoA
A
  1. bind to B2 receptors & stimulates cAMP
  2. cAMP activates PKA which inhibits MLCK in lungs
  3. fall in MLCK promotes calcium efflux which reduces contraction
  4. also inhibits MPK pathway by phosphorylating Raf1-kinase causing bronchodilation
39
Q

Beta Agonists - SABA & LABA

S/E - tachycardia, tremors, hypokalaemia

A

SABA
- used in acute and chronic COPD
- onset within 3min & duration 4-6hrs

LABA
- given when patient is symptomatic despite SABA
- long duration of action because of lipophilic group

40
Q

COPD Management

  • Muscarinic Antagonists
    M1 receptors - peribranchial ganglia
    M3 receptors - bronchial smooth muscle
A

parasympathetic innervation causes bronchial smooth muscle contraction
- best innervation by blocking M1 & M3

SAMA’s : ipratropium bromide
- blocks all muscarinic receptors non-selectively
- onset minutes , peak 1-2hr , duration 4hr

LAMA’s : Tiotropium
- binds to M1 & M3, dissociates rapidly from M2
- onset 30min , peak 3hr , duration >24hr

41
Q

COPD Management

  • Methylxanthines e.g. theophylline
A

PDE inhibitor
- inhibiting PDE4 on inflammatory cells reduces cytokine & chemokine release.
-decreases inflammatory cell transcription

S/E - anorexia , anxiety , arrythmia/seizure

42
Q

COPD Management

  • ICS
A

COPD inflammation dominated by neutrophilic infiltration

  • neutrophilic infiltration not as responsive to ICS as eosinophils in asthma
43
Q

COPD Management

  • Combo Therapy
A

LABA/ICS Therapy

  • ICS regulates coupling of B receptors to G-proteins & enhance cAMP activation
  • chronic SABA/LABA use leads to reduced B-receptor expression
  • ICS reverses this, increasing B-receptor transcription and synthesis
44
Q

COPD Management

  • PDE-4 Inhibitors
A

reduce inflammation in airways :
- by inhibiting cAMP breakdown

  • roflumilast once daily
    reduces moderate/severe exacerbations & severe COPD
    S/E - diarrhoea, nausea, weight loss, headache

MP324 (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions