Session 2: Innate Immunity Flashcards
You have been called to care for a 60-year-old patient in the intensive care unit who was admitted following a car accident. He is currently unconscious and has signs of cerebral oedema. The patient has a tube into his trachea, a central venous line and urinary catheter inserted. He was given a high-dose of corticosteroids to reduce his cerebral oedema and anti-convulsant phenytoin. What causes an increased risk of developing a serious infection here?
Tube in trachea Central venous line Urinary catheter Corticosteroids Phenytoin
Define immune system.
Cells and organs that contribute to immune defences against infectious and non-infectious conditions. (Self vs. non-self)
Define infectious disease.
When the pathogen succeeds in evading and/or overwhelming the host’s immune defences.
What are the four roles of the immune system?
Pathogen recognition (cell surface and soluble receptors) Containing and eliminating the infection (killing and clearing mechanisms) Regulating itself (to minimise damage to host) Remembering pathogens to prevent disease from recurring
How does innate immunity and adaptive immunity change from person to person?
Most of us have the same innate immunity. However our adaptive immunity can be very different.
Complete table
What are the first lines of defence? (barriers)
What’s their function?
Physical barriers
Chemical barriers
Physiological barriers
Biological barriers
To prevent entry** and limit **growth of pathogens.
Give examples of physical barriers.
Skin
Mucous membranes in mouth, resp. tract, GI tract and Urinary tract.
Bronchial cilia
Give examples of physiological barriers.
Diarrhoea in food poisoning
Vomiting (food poisoning, hepatitis, meningitis)
Coughing (pneumonia)
Sneezing (sinusitis)
Give examples of chemical barriers.
Low pH from skin, stomach and vagina.
Antimicrobial molecules
Give examples of antimicrobial molecules.
IgA
Lysozyme
Mucus
Beta-defensins
Gastric acid + pepsin
Give examples of biological barriers.
Normal flora
Beneficial characteristics of normal flora.
Non pathogenic microbes as long as they stay where they are supposed to be. They compete with pathogens for attachment sites and resources which makes it harder for pathogens to adhere.
Produce antimicrobial chemical
Synthesize vitamins like K, B12 and other B vitamins.
Immune maturation
Examples of normal flora organisms found on skin.
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus pyogenes
Candida albicans
Clostridium perfringens
Examples of normal flora organsisms that inhabit nasopharynx.
Streptococcus pneumoniae
Neisseria meningitidis
Haemophilus species
What happens if organisms that inhabit flora in their normal place move to another place?
They can become pathogenic in other places.
If normal flora is displaced from its normal lcoation to sterile location.
Give examples of how normal flora can enter an environment they are not supposed to be in.
Breaching skin integrity.
Skin loss (burns)
Surgery
IV lines
Skin diseases
Injection drug users
Tattooing/body piercing
Where it is common for S. aureus and S. epidermidis to breach into tissue where they are not supposed to be and cause infection.
Fecal-oral route:
Foodborne infection
Fecal-perineal-urethral route
UTIs in women because of poor wipeing technique
Poor dental hygiene/dental work:
Dental extraction
Gingivitis
Brushing/flossing
Displacement of normal flora due to dental hygiene/dental work can cause serious infections in everyone but especially high-risk patients.
What are high-risk patients?
Asplenic or hyposplenic patients
Patients with damaged or prosthetic valves
Patients with previous infective endocarditis
Give examples of when normal flow overgrows and becomes pathogenic when the host is immuno-compromised.
Diabetes
AIDS
Malignant disease
Chemotherapy (mucositis)
Give examples of when normal flora in mucosal surfaces is depltetd by antibiotic therapy.
Intestine -> severe colitis and clostridium difficile
Vagina -> thrush by candida albicans
What are the second lines of defence?
Phagocytes
Chemicals and inflammation
These are factors that will contain and clear the infection once it has invaded.
Explain the role of macrophages.
Present in all organs.
They ingest and destroy microbes by phagocytosis.
They also present microbial antigens to T cells in adaptive immunity.
They also produce cytokines and chemokines.
What are monocytes?
‘Macrophages’ present in blood (5-7%)
They are recruited at infection site and differentiate into macrophages in tissue.
Explain the role of neutrophils.
What bacteria are they effective against?
Present in the blood (60% of blood leucocytes)
They increase in number during infection and recruited by chemokines to the site of infection.
Ingest and destroy pyogenic bacteria like Staphylococcus aureus and Streptococcus pyogenes
Give a few other key cells that are important in innate immunity.
Basophils/mast cells
Eosinophils
Natural killer cells
Dendritic cells
Explain role of basophils/mast cells.
Effective against?
Early actors of inflammation by vasomodulation
Important in allergic responses
Explain of eosinophils in innate immunity.
Effective against?
Defence against multi-cellular parasites (worms)
Explain role of natural killer cells.
Effective against?
Kill all abnormal host cells like virus infected or malignant cells.
Explain the role of dendritic cells.
Present microbial antigens to T cells in acquired immunity.
How does pathogen recognition work?
The important features of pathogen recognition are PAMPs and PRRs.
PAMPs:
These are pathogen associated molecular patterns present on the microbe. Examples such as carbohydrates, lipids, proteins and nucleic acids.
PRRs:
These are pathogen recognition receptor which are present on the phagocytes. They are toll like receptors that recognises PAMPs in order to phagocytose the microbes.
What are opsonins and what are their role?
They are coating proteins that bind to the surface of the microbe in order to enhance attachment of phagocyes to the microbe and clear the microbes easier.
Examples of opsonins.
C3b, C4b which are complement proteins
Antibodies like IgG and IgM.
Acute phase proteins like CRP and MBL
For what types of bacteria is opsonisation very important?
For encaspulated bacteria like Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae b
Explain phagocytosis and killing of pathogens.
A phagocyte recognise a pathogen by the PRR and PAMP interaction as well as by opsonins.
1 - Chemotaxis and ahderence of microbe to phagocyte
2 - Ingestion of microbe by phagocyte
3 - Formation of phagosome inside the phagocyte (a vesicle containing the microbe)
4 - The phagosome now fuses with a lysosome to form a phagolysosome
5 - The lysosome brought with him/her digestive enzymes which digest the ingested microbe.
6 - Formation of residual body containing indigestible material
7 - Discharge of waste materials.
What are the intracellular killing mechanisms of the phagocytes?
Oxygen-dependent pathway which is respiratory burst. Free radicals destroy the microbe.
Oxygen-independent pathways which involve lysozymes, lactoferrin or transferrin, cationic proteins and proteolytic and hydrolytic enzymes.
What is the complement system?
It consist of complement pathways of 20 serum proteins.
The most important serum proteins are C1-C9.
They have to activating pathways (alternative pathway and MBL pathway)
In a few sentences explain the alternative pathway.
Also explain MBL pathway.
Initiated by cell surface microbial constituents like endotoxins on E. coli.
Initiated when MBL binds to mannose containing residues of proteins found on many microbes like Salmonella spp. and Candida albicans
Give examples of actions of C1-C9.
C3a and C5a recruit phagocytes acting as cytokines.
C3b and C4b are opsonins
C5-C9 kills pathogens, have an attack complex and make hole in the membrane of pathogens.
Role of cytokines and chemokinse.
Chemoattraction
Phagocyte activation
Inflammation
Systemic actions of cytokines such as TNFalpha, IL-1 and IL-6.
In the liver as opsonins. CRP and MBL.
Bone marrow for neutrophil mobilisation
Hypothalamus to increase body temperature
Local inflammatory actions of cytokines and chemokines.
Blood vessels get vasodilated. Also increases vascular permeability and expression of adhesion molecules on the endothelium for attraction of and adhesion of neutrophils.
Give causes of reduction of phagocytic activity?
Asplenic and hyposplenic patients
Decrease in neutrophil numbers like in cancer chemotherapy, certain drugs like phenytoin and leukaemia and lymphoma.
Decrease in neutrophil function like in chronic granulomatous disease where respiratory burst doesnt work. In Chediak-Higashi syndrome where phagolysosomes fail to form.
