Innate Immune System Flashcards
What is the immune system?
Cells and organs that contribute to immune defences against infectious and non-infectious conditions
What is an infectious disease?
When the pathogen succeds in evading and/or overwhelming the host’s immune defences
What are the roles of the immune response?
Pathogen recognition
Containing/eliminating the infection
Regulating itself
Remembering pathogens
What is required for the immune response to recognise pathogens?
Cell surface and soluble receptors
What is the purpose of pathogen recognition?
Distinguish between infectious and noninfectious diseases
How does the immune system contain/eliminate infection?
Killing and clearance mechanisms
Why is it important that the immune system regulates itself?
To produce minimum damage to the host, leading to resolution
Why does the immune system remember pathogens?
Prevents the disease for reoccurring
What are the features of the innate immune system?
Fast
Lack of specificity
Lack of memory
No change in intensity of response to primary or secondary encounters
How fast does the innate immune system act?
Within seconds
How specific is the innate immune system?
At best it can recognise groups of bacteria
What does the first line of immune defence consist of?
Barriers that limit entry and growth of pathogens at portals of entry
What are the barriers in the first line immune defence?
Physical barriers
Physiological barriers
Chemical barriers
Normal flora
What are the physical barriers in the innate immune system?
Skin
Mucous membranes
Bronchial cilia
What is the surface area of the skin?
1-2m squared
What do mucous membranes line?
Cavities exposed to air; Mouth Respiratory tract GI tract Urinary tract
What is the purpose of bronchial cilia?
Waft trapped microbes to the pharynx for swallowing
What are the physiological barriers in the innate immune system?
Diarrhoea
Vomiting
Coughing
Sneezing
When is diarrhoea a physiological barrier?
In food poisioning
When is vomiting a physiological barrier?
Food poisioning
Hepatitis
Meningitis
When is coughing a physiological barrier?
Pneumonia
When is sneezing a physiological barrier?
Sinusitis
What are the chemical barriers to infection?
Low pH
Antimicrobial molecules
Where has low pH to resist infection?
Skin
Stomach
Vagina
What pH is the skin?
5.5
What pH is the stomach?
1-3
What pH is the vagina?
4.4
What causes the low pH of the vagina?
Lactobacillus commensal bacteria
What antimicrobials molecules consist the innate immune system?
IgA Lysozyme Mucus Beta-defensins Gastric acid and pepsin
Where is IgA found?
Tears
Saliva
Mucous membranes
Where is lysozyme found?
Sebum
Respiration
Urine
Where is mucus found?
Mucous membrane
What secretes beta-defensins?
Mucous membrane epithelia
What is the normal flora?
Non pathogenic microbes that are found in strategic locations
Where are the normal flora found?
Nasopharynx Mouth/throat Skin GI tract Vagina
Where is normal flora absent?
Internal organs/tissues
What are the benefits of the normal flora?
Compete with pathogens for attachment sites and resources
Produce antimicrobial chemicals
Synthesise vitamins
What vitamins are synthesised by the normal flora?
K
B12
Other B vitamins
What organisms are found in the normal flora of the skin?
Staphylococcus aureus Staphylococcus epidermidis Streptococcus pyogenes Candida albicans Clostridium perfringens
What organisms are found in the normal flora of the nasopharynx?
Streptococcus pneumoniae
Neisseria meningitidis
Haemophilus species
When can problems occur with the normal flora?
When normal flora is displaced from its normal location to a sterile location
How can normal flora be displaced from its normal location to a sterile location?
Breaching the skin integrity
Poor dental hygiene/dental work
Fecal-oral route
Fecal-perineal-urethral route
How can the skin integrity be breached?
Skin loss (burns)
Surgery
Injection drug uses
IV lines
What can poor dental hygiene and dental work lead to?
Bacteraemia
Give three examples of poor dental hygiene or dental work that can lead to bacteraemia
Dental extraction
Gingivitis
Brushing/flossing
What patients are at particular risk of dental related bacteraemia?
Asplenic/hyposplenic
Damaged or prosthetic heart valves
Previous infective endocarditis
When is the fecal-oral route likely?
In foodbourne infection
When is the fecal-perineal-urethral route likely?
Urinary tract infections in women
When may the normal flora become overgrown and pathogenic?
When the host becomes immunocompromised
When normal flora is depleted by antibiotics
What may cause a patient to be immunocompromised?
Diabetes
AIDS
Malignant disease
Chemotherapy
What can happen in the intestines when the normal flora is depleted by antibiotics?
Severe colitis resulting from clostridium difficile
What can happen in the vagina when the normal flora is depleted by antibiotics?
Thrush resulting from candida albicans
What is the second line of defence of the innate immune system?
Phagocytes and chemicals that cause inflammation to contain and clear the infection
What cells are involved in innate immunity?
Macrophages Monocytes Neutrophils Basophils / mast cells Eosinophils Natural Killer cells Dendritic cells
What kind of cells are macrophages, monocytes, and neutrophils?
Macrophages
What organs are macrophages present in?
All organs
What do macrophages do?
Ingest and destroy microbes in phagocytosis
Ingest microbial antigens to T cells in adaptive immunity
Produce cytokines/chemokines
Where are monocytes present?
Blood
What % of the blood are monocytes?
5-7%
What do monocytes do?
Recruited to infection site and differentiated into macrophages
Where are neutrophils present?
In the blood
What % of blood leukocytes are neutrophils?
60%
What happens to neutrophil numbers during infection?
Increased
What recruits neutrophils to the site of infection?
Chemokines
What do neutrophils do?
Ingest and destroy pyogenic bacteria
Give two examples of pyogenic bacteria
S. aureus
Strep. pyogenes
What is the role of basophils/mast cells?
Early actors of inflammation (vasomodulation)
Where are basophils/mast cells important?
In allergic responses
When are eosinophils important?
Defence against multi-cellular parasites (worms)
What do NK cells do?
Kill all abnormal host cells (virus infected or malignant)
What do dendritic cells do?
Present microbial antigens to T cells in acquired immunity
How does pathogen recognition occur?
Through interactions between pathogen-associated molecular patterns (PAMPs) on the microbe and pathogen recognition receptors (PRRs) known as toll like receptors
What are the PAMPS for gram negative bacteria?
Lipopolysaccharides (LPS)
Lipoproteins and lipopeptides
Porin
What is the PRR for lipopolysaccharides?
TLR4
What is the PRR for lipoproteins and lipopeptides?
TLR2
What is the PRR for porins?
TLR2
What are the PAMPs for gram +ve bacteria?
Peptidoglycan
Lipoteichoic acids
What is the PRR for peptidoglycan?
TLR2
What is the PRR for lipoteichonic acids?
TLR4
What are the PAMPs for all mycobacteria?
Lipoarabinomannan
Mannose-rich glycans
What is the PRR for lipoarabinomannan?
TLR2
What is the PRR for mannose-rich glycans?
TLR2
What is the PAMP for bacterial flagella?
Flagellin
What is the PRR for flagellin?
TLR5
What are opsonins?
Coating proteins
What do opsonins do?
Bind to microbial surfaces
What does the binding of opsonins lead to?
Enhanced attachment of phagocytes and clearance of phagocytes
What are the classes of opsonins?
Complement proteins
Antibodies
Acute phase proteins
Give 2 complement proteins that can act as opsonins
C3b
C4b
Give two antibodies that can act as opsonins
IgG
IgM
Give two acute phase proteins that can act as opsonins
C-reactive protein (CRP)
Mannose-binding lectin (MBL)
What is opsonisation essential for?
Clearing encapsulated bacteria
Give an example of an encapsulated bacteria
Neisseria meningitidis
What do opsonins and PRRs work together to do?
Initiate phagocytosis
What happens once a microbe has been recognised by receptors on the surface of the phagocyte?
The microbe is engulfed and destroyed
What happens in the process of phagocytosis?
- Chemotaxis and adherence of microbe to phagocyte
- Ingestion of microbe by phagocyte
- Formation of a phagosome
- Fusion of the phagosome with a lysosome to form a phagolysosome
- Digestion of ingested microbe by enzymes
- Formation of a residual body containing indigestible material
- Discharge of waste material
How do phagocytes kill pathogens?
Using different intracellular killing mechanisms
What intracellular killing mechanisms are used by phagocytes?
Oxygen-dependant pathway (respiratory burst)
Oxygen independent pathways
What happens in the oxygen-dependant pathway of phagocytic killing?
Releases toxic O2 products to kill the pathogens
What toxic O2 products are released in the respiratory burst?
Hydrogen peroxide Hydroxyl radical Nitric oxide Singlet oxygen Hypophalite
What are the oxygen-independent pathways of phagocytic killing?
Lysozyme
Lactoferrin or transferrin
Cationic proteins
Proteolytic and hydrolytic enzymes
Give an example of a cationic protein
Cathepsin
What does the complement system consist of?
20 serum proteins
What are the most important serum proteins in the complement system?
C1-9
What does C3a and C5a do?
Recruit phagocytes
What does C3b-C4b do?
Opsonise pathogens
What does C5-C9 do?
Kill pathogens by membrane attack complex
What are the activating pathways of the complement system?
Alternative pathway
MBL pathway
What happens in the alternative pathway of complement activation?
Complement initiated by cell surface microbial constituents
What happens in the MBL pathway of complement activation?
Complement initiated when MBL binds to mannose containing residues of proteins found on many microbes
Give a microbe that will induce the alternative pathway of complement activation
Endotoxins on E. Coli
Give two microbes that will induce the MBL pathway of complement activation
Salmonella spp.
Candida albicans
What to cytokine/chemokines cause?
Chemoattraction
Phagocyte activation
Inflammation
Give three chemokines
TNF-alpha
IL-1
IL-6
Where do TNF-alpha, IL-1, and IL-6 have effects?
Liver
Bone marrow
Hypothalamus
Also have inflammatory actions
What is the effect of chemokines in the liver?
Release CRP
Release MBL, leading to complement activation
What is the effect of chemokines in the bone marrow?
Neutrophil mobilisation
What is the inflammatory effect of chemokines?
Vasodilation
Vascular permeability
Adhesion molecules lead to attraction of neutrophils
What is the effect of chemokines in the hypothalamus?
Increased body temperature
When do clinical problems start with the innate immune system?
When there is decreased phagocytosis
When may someone have decreased phagocytosis?
Decrease in spleen function
Decreased neutrophil number
Decreased neutrophil function
When may someone have decreased spleen function?
Asplenic/hyposplenic patients
When may someone have decreased neutrophil numbers?
Cancer chemotherapy
Certain drugs
Leukaemia and lymphoma
Give a drug that could lead to decreased neutrophil numbers
Phenytoin
When may someone have decreased neutrophil function?
Chronic granulomatous disease
Chediak-Higashi syndrome
Why does chronic granulomatous disease cause a decrease in neutrophil function?
No respiratory burst
Why does Chediak-Higashi syndrome lead to reduced neutrophil function?
No phagolysosome formation