4. Innate immunity Flashcards
List and describe the factors determining the outcome of the host- pathogen relationship
Infectivity- This is the ability of the microbe to establish itself on the host or within the host
Virulence- This is the capacity of the micorbe to do damage to the host
define the immune system
The cells and organs that contribute to immune defences against infectious and non-infectious conditions (self vs non-self)
define infectious diseases
This is when the pathogen succeeds in evading and/or overwhelming the host’s immune defences
What are the three risk groups more susceptible to infection? (Not caused by disease, other environmental factors or induced)
Children, elderly, pregnant women
What does the spleen do?
It filters bacteria out of the blood, produces phagocytes to fight off foreign invaders.
Give the roles of the immune system
- Pathogen recognition- cell surface and soluble receptors
- Containing/eliminating infections- killing/clearance mechanisms
- Regulating itself- minimum damage to the actual host ie autoimmune - The immune system needs to know when to stop to prevent it from enacting damage against itself.
- Remembering pathogens- prevention of recurring, great in vaccinations
What is innate immunity?
- Nonspecific protection against foreign substances indiscriminantly.
- Fast (within seconds), immediate
- Lack of memory - no antibodies
- No change in intensity
What is adaptive immunity?
- Your immune responses to a specific invader, in which both B and T lymphocytes respond to.
- Slow (takes days), long lasting
- Specific
- Immunologic memory
- Changes in intensity with exposure
List the 4 different innate barriers to infection and their collective function
- Physical barriers
- Physiological barriers
- Chemical barriers
- Biological barriers
Collectively these barriers work to prevent entry and limit growth of pathogens.
Describe the physical barriers involved in innate immunity
- Skin (surface area 1-2 m2)
- Mucous membranes (lines cavities inside the body and prevents an ingress of pathogens)
- Mouth
- Respiratory tract
- GI tract
- Urinary tract - Bronchial cilia
These are present in the lungs and expel out mucus trapped microbes via the cilia
Describe the physiological barriers involved in innate immunity
Expulsion of pathogens from the body
• Diarrhoea- food poisoning
• Vomiting- food poisoning, hepatitis and meningitis
• Coughing- pneumonia
• Sneezing- sinusitus
This however spreads the pathogens to others.
However it’s important to understand that these actions aren’t exclusively associated with infection.
E.g coughing is also associated with asthma.
Describe the chemical barriers involved in innate immunity
Low pH 1. Skin (5.5) 2. Stomach (1-3) 3. Vagina (4.4) Microbes can't survive in these low pHs.
Antimicrobial molecules 1. IgA (Tears, saliva, mucous membrane )- attaches to microbes and prevents it from binding to their host cells 2. Lysozyme (sebum, perspiration, urine) 3. Mucus (Mucous membranes) 4. Beta-defensins (epithelium) 5. Gastric acid + pepsin
Describe the biological barriers involved in innate immunity
Normal flora
• non pathogenic microbes in strategic locations
Where are normal non pathogenic microbes found?
o Nasopharynx o Mouth/Throat o Skin o GI tract o Vagina (lactobacillus spp) • Absent in internal organs/tissues
What are the benefits of normal flora?
- Compete with pathogens for attachment sites and resources
- Produce antimicrobial chemicals
- Synthesize vitamins (K, B12, other B vitamins)
- Immune maturation
Give examples of normal flora that inhabit the skin
- Staphylococcus aureus (week 1, case 1)
- Staphylococcus epidermidis
- Streptococcus pyogenes
- Candida albicans
- Clostridium perfringens
Give examples of normal flora that inhabit the nasopharynx
- Streptococcus pneumoniae (week 3, case 2)
- Neisseria meningitidis (week 3, lecture case)
- Haemophilus species
Where are mucous membranes found?
respiratory tract, gastrointestinal tract, genitourinary tract, mouth
When do normal flora become pathogenic?
When displaced from their normal location to other sites in the body
How can normal flora be displaced from its normal location to sterile locations?
- Skin flora
- Skin loss (burns)
- Surgery
- IV lines
- Skin diseases
- Injection drug users
- Tattooing/ body piercing - Fecal-oral flora
- Foodborne infection - Fecal-perineal-urethral flora
- Urinary tract infection - Oral/ teeth flora
- Dental extraction
- Gingivitis (inflammation of the gums)
- Brushing/ flossing)
There are certain patients that are at a high risk of infections due to specific conditions name them
- Asplenic (and hyposplenic) patients
- Patients with damaged or prosthetic valves
- Patients with previous infective endocarditis
- Patients with diabetes
- AIDS patients
- Patients with malignant diseases
- Patients undergoing chemotherapy(muscositis - inflammation of mucosal membrane which increases surface area for attachment for pathogens to get in)
A lot of these patients(4,5,6,7) are immuno-compromised meaning that their immune system is working below the normal rate
The use of antibiotics can affect the normal flora levels in mucosal surfaces give an example in the intestine
In the intestine you can have severe colitis due to the development of the bacterium Clostridium difficile.
The normal intestinal flora have been dramatically reduced due to the use of antibiotics which reduces competition for pathogens and allows the bacterium to grow.
The use of antibiotics can affect the normal flora levels in mucosal surfaces give an example in the vagina
In the vagina you can have thrush because of the development of the Candida albicans fungi.
The normal vaginal flora have been dramatically reduced due to the use of antibiotics which reduces competition for pathogens and allows the fungi to grow.
principle is that antibiotics deplete the good bacteria, allowing infection to occur
List the second lines of defence in the innate immune response and give their role
- Phagocytes
- Chemicals
- Inflammation
These factors are used if the innate barriers fail - they will contain and clear the infection.
What are the functions of macrophages
- Present in all organs
- Ingest and destroy microbes (Phagocytosis)
- Present microbial antigens to T cells (adaptive immunity)
- Produce cytokines/chemokines
What are the functions of monocytes
- Present in the blood (5-7%)
- Recruited at infection site and differentiate into macrophag
What are the functions of neutrophils
-Present in the blood (60% of blood leukocytes)
-Increased during infection
-Recruited by chemokines to the site of infection
-Ingest and destroy pyogenic bacteria:
Staph. aureus and Strep. pyogenes
What are the functions of basophils/mast cells
- Early actors of inflammation (vasomodulation, regulation of blood flow)
- Important in allergic responses
What are the functions of eosinophils
Defence against multi-cellular parasites (worms)
What are the functions of natural killer cells
Kill all abnormal host cells (virus infected or
malignant)
What are the functions of Dendritic cells
Present microbial antigens to T cells (acquired immunity)
Define pyogenic
pus producing
What does pus contain?
Neutrophils
How do phagocytes recognise pathogens?
- PAMPS and PRRs
* Opsonins
Describe how phagocytes recognise pathogens by PAMPS and PRRs
One way in which pathogens can be recognised is through the use of PAMPS and PRRs.
PAMPS (pathogen associated molecular patterns) are microbial structures found on the surface of the pathogen these can be recognised by phagocytes using PRRs (pathogen recognition receptors).
An example of this would be toll like receptors (TLR) E.G lipopolysaccharide (LPS) and TLR4.
What do cytokines do?
further stimulate Th, B, and Tc cells
What is the PRR used against lipopolysaccharide? In which type of bacteria is this found?
TLR4
Gram negative bacteria
Describe how phagocytes recognise pathogens by opsonins
Another way in which pathogens can be recognised would be through the opsonisation of microbes.
Opsonins are coating proteins that bind to the microbial surfaces and allow enhanced attachment of phagocytes to the microbes to increase the level of clearance. They signal for the engulfment and the degradation of infectious microbes when opsonin receptors on phagocyte bind to the opsonin.
Examples include C3b and IgG.
What are phagocyte microbe interactions
Recognition processes and killing processes
What does the binding of PAMPs and PRRs simulate?
When PRRs bind to PAMPs - simulates release of cytokines/ chemokines for inflammatory response
Give examples of opsonins
Complement proteins • C3b • C4b Antibodies • IgG • IgM Acute phase proteins • C-reactive protein (CRP) • Mannose-binding lectin (MBL)
What is Encapsulated bacteria and why are opsonins important
Bacteria that possess thick carbohydrate coats that protect them from phagocytosis. Encapsulated bacteria cause extracellular infections and can be dealt with by phagocytes only if the bacteria are first coated with antibody and complement.
Opsonins allow this coating and recognisition
What are examples of encapsulated bacteria? Which organ is essential in their clearance?
- Strep pneumoniae
- Haemophilus influenzae B
- Neisseria meningitidis
Spleen
What are acute phase proteins?
- A class of proteins whose plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. They are produced by the liver.
- Enhance the inflammatory response and aid innate immunity
- They include opsonins and complement proteins (but not antibodies as these are produced by B cells not the liver)
What are the two pathwyas of phagocytosis
There are 2 types of pathways in which phagocytes kill pathogens
1. Oxygen dependent (respiratory burst)
Toxic O2 products for the pathogens: Hydrogen peroxide, Hydroxyl radical, Nitric oxide, Singlet oxygen, Hypohalite
2. Oxygen independent
Lysosome, lactoferrin, cationic proteins, proteolytic and hydrolytic enzymes
What is the complement system?
a group of 20 serum proteins that act in a cascade to destroy invading microbes; these function to keep blood pathogen-free
• Most important C1-C9
Give examples of complement proteins. What are their function?
- C3b and C4b - opsonisation of pathogens
- C3a and C5a - recruitment of phagocytes
- C5 - C9 - killing of pathogens, membrane attack complex
What are the two activating pathways of the complement system?
o Alternative pathway
Initiated by cell surface microbial constituents (endotoxins on E. Coli)
o MBL pathway
Initiated when MBL binds to mannose containing residues of proteins found on many microbes (Salmonella spp. Candida albicans)
How are the activities of PAMPS + PRRs different to opsonins?
When PRRs bind to PAMPs - simulates release of cytokines/ chemokines for inflammatory response whereas
When opsonin receptors bind to opsonins - signals killing of microbe
Which immune cells are important for chemoattraction?
Neutrophils, monocytes
Give an overview of phagocytosis
- chemotaxis and adherence of microbe to phagocyte
- ingestion
- phagosome formation
- fusion of phagosome with lysosome
- digestion
- formation of residual body containing indigestible material
- discharge of waste
What are the three main cytokines? What do they do?
TNF alpha, IL-1, IL-6
Systemic actions
• Act on liver to produce acute phase proteins(opsonins):
CRP
MBL (-> complement activation)
• Act on bone marrow to mobilise neutrophils
• Act on hypothalamus to increase body temperature
Local inflammatory actions
• Act on vessels for vasodilation, vascular permeability, expression of adhesion molecules to attract neutrophils
Summary of the innate immune response
Innate barrier breached: entrance and colonization of the pathogens.
The mast cells and the macrophages are the first immune cells present at the site of infection when the innate barriers are breached.
The macrophages immediately starts using their PRRs to see if they recognise any PAMPs.
Once recognised they begin phagocytosis with the help of opsonins.
They also produce cytokines/ chemokines.
Cytokines and chemokines trigger vascular changes (vasodilation/increased vascular permeability).
They also trigger chemoattraction, there’s movement of neutrophils and monocytes from the blood into the site of infection.
There’s also action on the hypothalamus which causes fever preventing pathogen proliferation.
The liver is affected and undergoes an acute phase response e.g CRP proteins are made.
Inflammation at the site occurs resulting in redness, swelling, heat and pain.
What are clinical problems that start when phagocytosis is reduced
- decreased spleen function - asplenic./ hyposplenic
- decreased neutrophil number - chemotherapy, certain drugs e.g. phenytoin, leukaemia and lymphoma
- decreased neutrophil function - chronic granulomatous disease (no respiratory burst), chediak-higashi syndrome (no phagolysosome formation)
