Lecture 6A - Immunity and Response to Infection Flashcards
What are many new drugs and vaccines aimed at?
either diminishing or enhancing the immune response
What are the two types of immunity?
specific and non specific
Within the two types of immunity, what are the subdivision?
external and internal
What are the gut and interior of the lungs classed as?
external as they are lined with epithelial tissues in contact with the outside world
What is non specific immunity?
designed to oppose the entry and spread of all pathogens
What is specific immunity?
targeted against particular agents causing illness, usually proteins but can be other small molecules as well
External non specific barriers against disease?
society
behaviour
social distancing
wearing face covering/masks
safety glasses
How is society an external barrier?
clean water and sewage treatment is the single most important factor for increased life span during the last 2 centuries, hygienic food preparation and preservation have also helped
How is behaviour an external barrier?
the concept of germs as a transmissible agent of disease has lead to adoption of methods of hygiene such as washing hands, use of condoms, deep cleaning in hospitals
External defences?
skin and the mucous membranes of nose, mouth, ears, eyes, gut and urogenital tract are all points of vulnerability through which transmission of disease can occur
What is the skin an example of?
an inherent, non-specific physical defence agains disease
Ears?
we produce wax
Respiratory tract?
mucus, surfactant (contains anti-viral lipoproteins)
alveolar macrophages which resident outside the body
Intestine as defence?
pH of 1 in the stomach
pH of urogenital tract?
4.5, fights against disease and keeps tract healthy
How do eyes produce defence?
through tears
maternal foetal defence?
transmission of antibodies across the placenta and through mothers milk
What is our microbiome?
a biofilm of healthy bacteria in the gut can help reduce the changes of pathogenic bacteria invading the mucosal epithelium and expanding in number
What does the skin secrete?
sebum
What do secretions such as mucus do?
traps invaders and is continuously wafted out of the lungs by thousands of cilia
How infections spread?
acquisition during foetal life or at birth
contact (usually onto hands)
coughing
faecal
sexual
blood and blood products
insect or animal bites
food/water borne
injury
What can happen if a benign bacterium penetrates the body wall?
it can cause severe infection
e.g. appendicitis
Internal non-specific immunity?
the second line of defence
phagocytic cells
pyrogens
chemical mediators
complement proteins
What are phagocytic cells?
omnivorous scavengers that detect foreign cells, proteins and particles and engulf and phagocytose them
What are pyrogens?
peptides secreted by leukocytes and other cells
they act on the hypothalamus to raise body temperature and cause symptoms of fever
What might raised temp do?
inhibit iron uptake by the bacteria, which can slow bacterial growth
What are chemical mediators of inflammation?
e.g. interferons
interfere with viral replication and are used in multiple sclerosis and have also been tried in COVID-19
What are complement proteins?
recognise foreign proteins and cells and trigger their destruction (also part of specific immunity)
What do foreign objects usually have?
a set of signals/peptides or proteins which are obviously not part of the body
What does the non-specific response begin with?
ingestion and digestion of foreign particles and toxins by amoeboid like cells (phagocytosis)
What are neutrophils?
the first to arrive at the site of infection and destroy bacteria
found in blood and tissue
What are ‘roaming’ mononuclear phagocytes?
‘monocytes’ in the blood stream differentiate into macrophages in tissues
can move out of the blood stream and into tissue where there is damage and differentiate into phagocytes to help fight infection
What are ‘fixed’ organ specific phagocytes?
reticular endothelial system - fixed phagocytic cells associated with particular organs (e.g. Kuffper cells in the liver)
these will ingest and destroy any foreign particles and old red/white blood cells they come across
What are dendritic cells?
share the same cell lineage as monocytes in the bone marrow and can differentiate from them
often found in tissues in contact with the external environment, but some reside in lymph also derived from monocytes
What do dendritic cells play a major role in?
antigen presentation
What are dendritic cells important for?
major part of the early warning system for the onset of disease, they constantly sample the environment for abnormal proteins, taking them up and digesting them
they present peptide fragments of the digested proteins to immune cells
Where do dendritic cells travel through?
the lymph nodes to present antigens to other cells
Neutrophils locations?
blood and all tissues
Monocytes locations?
blood and all tissues
Tissue macrophages locations?
all tissues (including spleen (histiocytes), lymph nodes, bone marrow)
Kuffper cells locations?
liver
Alveolar macrophages locations?
lungs
Microglia locations?
central nervous systems
Dendritic cells locations?
blood, lymph and tissues
What does the hepatic portal vein branch out to?
numerous tubular channels called sinusoids
similar structure is found in the spleen
What are the fixed endothelial cells of the liver?
phagocytic and will ingest and destroy any foreign particles and old red or white blood cells
What are the phagocytes of the liver?
Kuffper cells
What is the collective name for the tissue specific phagocytes?
the reticular endothelial system
What are the liver and spleen particularly effective at?
cleansing blood
What are examples of other fixed cells?
alveolar macrophages, microglia in the CNS and osteoclasts in bone
How do phagocytic cells get to the site of injury?
some are already there but when injury occurs we need additional phagocytic cells out of the bloodstream and into the injured tissue
What attracts additional neutrophils and monocytes from the bloodstream?
chemical attractants from invading bacteria and tissue leukocytes
Where is histamine released from?
mast cells and basophils
What does histamine do?
makes the gaps in the endothelial wall of the blood vessel more leaky, allowing the cells to squeeze through
(diapedesis)
What is chemotaxis?
the leukocytes (WBC) are attracted down a concentration gradient of chemical attractants produced by the invading bacteria and by the leukocytes immediately on hand
What is chemotaxis triggered by?
chemicals recognised as foreign potentially leaking from the pathogen and these track along the chemotactic gradient towards the invading bacteria and engulf it and destroy it
WBC can also move from the blood stream through gaps in the endothelial cells into tissue
What is diapedesis?
squeezing out of the blood stream through the wall of the blood vessel into surrounding tissue
What happens once phagocytic cell arrives at site?
it engulfs the foreign particle and digests it
Where can lysozymes escape to?
interstitial fluid, which adds to inflammation in the region and can harm healthy tissue
When is diapedesis good?
when it only attacks the bacteria
What is an important step for macrophage to be activated?
recognise the chemicals released by the unwanted organism or present on its surface as being a foreign particle or sugar
What can macrophages also release?
chemical mediators such as tumour necrosis factor and nitric oxide
What can the chemical mediators do?
trigger programmed cell death from outside (such as cancer cells)
What else can macrophages release?
chemicals to attract and activate additional phagocytic cells to assist in the neutralisation of any infectious or harmful agent
What do macrophages do when they sense a foreign cell?
ingest the harmful agent and destroy it
What are dendritic cells as a response?
specialist macrophages and early warning cells
Where are dendritic cells derived from?
circulating monocytes in the blood
Where are dendritic cells often found?
in tissues in contact with the external environment, but some reside in lymph and also derived from monocytes
What do dendritic cells do?
constantly sample their milieu for the presence of foreign chemical signatures
What do dendritic cells to do antigens?
the digest trapped antigens, present them to other cells in the immune system, triggering a specific response
