Immunity - Host Defence Flashcards
What are non-immune mechanisms?
Airflow, cough, cilia
Causes of Resp admissions?
Infections = half e.g.influenza and pneumonia, acute lower resp infections and acute upper resp infections
Inflammation= half e.g, chronic obstructive lung disease, asthma etc
What is acute inflammation?
Hot red swollen and sore because: Vasodilation leads to exudation of plasma incl antibodies
Inflammation - Inflammation is our defence against infection and a hostile environment
BUT
Many of us will die of diseases caused by inflammatory processes
What occurs in acute inflammation?
Activation of biochemical cascades, e.g. complement and coagulation cascades (to target bacteria as it triggers the pain receptors)
Migration of blood leukocytes into the tissues, mainly neutrophils but also some monocytes (protects against infection) - increase blood flow and permeability of vessels
What causes COPD?
COPD: Alveolar units destroyed and walls broken down by repeated inflammation and delivery of neutophil proteases that break down protein in the lung - lined with mucus and inflammatory cells = damaged lungs
What is ARDS?
Acute respiratory distress syndrome
Pathophysiology:
- Endothelial leak – leading to extravasation of protein and fluid
- Lungs – reduced compliance, increased shunting
- Heart – pulmonary hypertension, reduced cardiac output
- Hypoxia
Where des inflammation occur in?
Chronic respiratory pulmonary disease
Acute respiratory distress syndrome
Bronchiectasis
Interstitial lung disease
Asthma
Where is acute inflammation occurring?
Initiated in the tissues, by epithelial production of hydrogen peroxide and release of cellular contents.
Macrophages
What are macrophages?
Macrophages: role to control and coordinate signalling of what’s coming in to ensure you don’t get an influx of neutrophils when you don’t need.
Amplified by specialist macrophages including:
Kupffer cells (Liver)
Alveolar macrophages (lung)
Histiocytes (skin,bone)
Dendritic cells
How do macrophages react to pathogens or tissue injury?
by recognising:
PAMPS pathogen associated molecular patterns
DAMPS damage associated molecular patterns
Essentially recognise pathogens and damage
What is the difference between innate and adaptive immune response?
innate has to recognise pathogens we’ve never seen before.
Does this by having pattern recognition systems (PRR- pathogen recognition receptors)
What are the two types of PRR?
- signalling - TLRs - toll like receptors - vulnerable to fungal infections
Mice resistant to endotoxin shock
Recognise conserved molecular patterns to pathogens
Also recognises/activated by endogenous mediators of inflammation (things released by other cells)
NLRs - nod lie receptors
- Endocytic - recognise common things on microorganisms and engage between host cell and pathogen and allow phagocytosis to kill them
What are some endocytic receptors?
Mannose receptors
Glucagon receptors
Scavenger receptors
Where are cells in the immune system made?
In the bone marrow by process of matopoesis
What are alveolar macrophages?
How are alveolar macrophages different?
Different to circulating macrophages and macrophages in other tissues because cells sitting in the lung must protect it (open to the environment) and don’t allow over active inflammation (impacts gas exchange)
Produced during forestall life and colonise the lung
Feral wave and mature wave from foetal monocytes.
What is macrophage plasticity?
What are the most common WBCs?
Neutrophils - called granulates as they contain granules
Primary - myeloperoxidase converts reactive oxygen species into very toxic hypogloxyacid?, elastase, cathepsins which are proteases that cut proteins in the bacteria or fungus but also damages tissues when released but also allow neutrophils to penetrate to areas to clear bacteria where they otherwise could not access, defensins
Secondary - receptors, lysozymes, collagenase
How do neutrophils work?
Encounters tissue damage
Stick to endothelium and start to roll
Then it will firmly adhere
Starts to transmigrate between endothelial cells into the tissue
Accompanied by the Adema? (Classic sign of inflammation)
Neutrophils are now the predominant phagocytise cells which take up bacteria and digest and kill them within the,
Can also release granule contents which damage tissues so must be safely removed at the end - by the death of neutrophil by apoptosis (genetically programmed form of cell death where the key effected proteins are cut up by proteases in the cell and recognised as apoptopic
Eventually tissues are restored to normal state
What are neutrophils functions?
Identify threat as receptors
Activation
Adhesion
Migration/chemotaxis
Phagocytosis
Bacterial killing
Apoptosis - programmed cell death
What can neutrophils recognise?
bacterial structures
Host mediators cytokines, complement, lipids
Host opsonisesc FcR immunoglobulin, CR3 complement
Host adhesion molecules
What is stimulus response coupling?
Stimulus response coupling: signal transduction pathways involving calcium, protein, kinases, phospholipases, G proteins
What does adhesion involves?
Adhesion: integrins
Margin action: selection
Require changes in endothelium and neutrophils e.g. CD18 beta-2(needed for adhesion) integrity deficiency no transendothelial migration, delayed separation of umbilical cord, recurrent severe cutaneous and deep infections
What is chemotaxis?
Migration/ chemotaxis: Ability to detect a conc gradient and move along it by moving receptors to the leading edge
What is phagocytosis?
Phagocytosis: membrane invagination and pinching phagosome, fusion with granules phagolysosome
What does bacterial killing involve?
ROS generated by a membrane enzyme compels - the NADPH oxidase assembles of phagosome membrane able to use ATP to generate reactive oxygen species e.g.
Cytochrome B 91kD (X-linked) - P47 cytosolic factor (Aut Rec)
Severe recurrent infection, staph and fungi
Interferon restores P47 activity
Usually dead in their 20s
What is apoptosis?
How does neutrophil recognition by macrophages work?
What are the functions of lungs?
Respiration:
•Ventilation and gas exchange: O2, CO2, pH, warming and humidifying
Non-respiratory functions:
•Synthesis, activation and inactivation of vasoactive substances, hormones, neuropeptides
•Lung defence: complement activation, leucocyte recruitment, host defence proteins, cytokines and growth factors
•Speech, vomiting, defecation.
How much air do we inhale?
10,000 litres
What are the diff host defence?
Intrinsic: Always present: Physical and chemical. Apoptosis, autophagy, RNA silencing, antiviral proteins
Innate defence: Induced by infection (Interferon, cytokines, macrophages, NK cells
Adaptive immunity: Tailored to a pathogen (T cell, B cells)
How does Resp epithelium work as a barrier?
Muscociliary escalator
What are the chemical epithelial barriers?
antiproteinases
•anti-fungal peptides
•anti-microbial peptides
•Antiviral proteins
•Opsins
Produced by most (all?) epithelial cells
How does mucus protect the airway?
Mucus protects the epithelium from foreign material and from fluid loss
•Mucus is transported from the lower respiratory tract into the pharynx by air flow and mucociliary clearance.
What is mucus?
Airway mucus is a viscoelastic gel containing water, carbohydrates, proteins, and lipids.
•It is the secretory product of the mucous cells (the goblet cells of the airway surface epithelium and the submucosal glands).
What is the final step of the mucosciliary escalator?
Cilia beat in directional waves to move the mucus up the airways
What are causes of cough?
- Irritants - smokes, fumes, dust etc
- Diseased conditions like COPD, tumours
- Infections like influenze
How is cough initiated?
Voluntarily or reflexively
Both afferent and efferent pathways
Afferent: sensory of trigeminal,glossopharyngeal, SLN and Vagus
Efferent: RLN and spinal nerves
What is a sneeze?
Involuntary expulsion of air containing irritants from nose
What are causes of a sneeze?
- Irritation of nasal mucosa
- Excess fluid in airway
How does a sneeze come about?
- Receptor
- Sensory neurone
- Association neurone - Integration centre -brian stem
- Motor neuron
- Effector - nose
What occurs if functional plasticity in airway epithelium affect a complete repair and go wrong?
Results in pulmonary disease
What underpins many obstructive lung diseases?
Abnormal epithelial responses to injury/insult underpin many obstructive lung diseases
An example of goblet cell metaplasia* in the airway of a heavy smoker
What is associated with severe disease?
Mucus plugs/inflammation is associated with severe disease
Mucus and inflammatory cells blocking the airways. Hence the term obstructive lung disease is sometimes used
Mucus plugs can completely obstruct the airways and can be fatal
