L4: Innate Immunity Flashcards
What factors determine the outcome of host-pathogen relationship?
Infection require patient and pathogen
Pathogen- infectivity –> ability of microbe to establish on or within the host
Patient- host immune response–> Essential in determining outcome of pathogen invasion
Mechanism of action- virulence –> capacity of microbe to do damage to the host
Which groups are most at risk of infection?
Elderly
Children
Pregnant women
Define immune system?
Cells and organs that contribute to the immune defences against infectious and non-infectious conditions (self vs non-self)
Define infectious disease?
When a pathogen suceeds in evading and/or overwhelming the host’s immune defences
What are the key roles of the immune system? How does it do this?
Pathogen recognition–> cell surface and soluble receptors
Containing/ eliminating the infection–> killing and clearance mechanisms
Regulating itself–> minimise damage to host
Remembering pathogens–> prevent disease from recurring
What are the two methods of response in the immune system?
Innate--> Immediate --> prevent microorganisms getting in --> fast (within seconds) --> non specific --> no memory --> no change in sensitivity Adaptive --> long lasting --> Slow (days) --> Specific --> Immunological memory --> Changes in sensitivity
What are the main first lines of defence?
Physical barriers Physiological barriers Chemical barriers Biological barriers --> prevent entry and limit growth
What are the physical barriers?
Skin –> water tight, 1-2m surface area
Mucous membrane–> mouth, respiratory tract, GI tract and urinary tract–> traps pathogens
Bronchial cilia–> trap bacteria in mucous, mucocillary escalator up to mouth
What are the physiological barriers?
Symptoms that the patient presents with
- Diarrhoea
- Vomiting
- Coughing
- Sneezing
In response to pathogen to eliminate pathogen from body
What are the chemical barriers?
Low pH --> point of entry -Skin pH 5.5 -Stomach pH 1-3 -Vagina pH 4.4 Antimicrobial factors
What are the antimicrobial factors?
- IgA (tears, saliva, mucous
- Lysosomes (sebum, perspiration, urine)
- Mucus (mucous membrane)
- Beta-defensins (epithelium)
- Gastric acid + pepsin
What are the biological barriers?
Normal flora
- -> absent from internal organs/tissues
- Compete with pathogens for attachment sites and resources
- Produce antimicrobials and chemicals
- Synthesis vitamins (K, B12 and other B vitamins)
- Immune maturation –> stops immune system producing wrong response
What is the normal flora?
–> non pathological (unless they enter a new environment in the body)
–> strategic locations (nasopharynx, mouth/throat, skin, GI tract, vagina)
Helps normal body functions
What are the normal flora that inhabit the skin?
Staphylococcus aureus Staphylococcus epidermis Streptoccoccus pyogenes Candiba albicans Clostridium perfringens
What are the normal flora that inhabit the nasopharnyx?
Streptococcus pneumoniae
Neisseria meningitidis
Haemophilus species
How does the normal flora lead to infection?
If it become displaced and enters a new body compartment –> infection
e.g. breaching the skin (burns, cuts, tattoos, injections, surgery), fecal-oral route (foodborne infection), Fecal-perineal-urethral route, poor dental hygiene (gets in through gums)
Which patients are at highest risk of serious infection?
Patients
- without a spleen (asplenic or hyposplenic)
- damaged or prosthetic valves
- previous ineffective endocarditis
What else can causes normal flora to become pathogenic?
Overgrowth and host becomes immuno-compromised (diabetes, AIDS, malignant diseases, chemotherapy)
or
Flora is depleted in mucosal surfaces by antibiotic therapy –> intestine (severe colitis), vagina (thursh)
What is the second line of defence after the barriers have been breached?
Phagocytes and chemicals
–> contain and clear infection
What are the names of the main phagocytes?
Macrophages Monocytes Neutrophils Basophils Eosinophils Natural killer cells Dendritic cells
What are the key features about macrophages?
Present in all organs
Ingest and destroy microbes (phagocytosis)
Present microbial antigens to T cells (adaptive immunity)
Produce cytokines/chemokines
What are monocytes? What is there function?
Precursor to macrophages
Present in blood (5-7%)
Recruited at infection site and differentiate into macrophages
What is the main function of neutrophils?
Present in blood (60% of leukocytes)
Increased during infection
Recruited by chemokines to infection
Ingest and destroy progenitor bacteria (Staph aureus and Strep progenies)
What are the functions of basophil/ mast cells?
Inflammation (vasomodulation)
Allergic response
What are eosinophils used for?
Defence—> multicellular parasites(worms)
What is the function of natural killer cells?
Kill abnormal host cells
What do dendritic cells do?
Present microbial antigens to T cells (acquired immunity)
How are pathogens (microbes) recognised?
Pathogen Associated Molecular pattern (PAMPs)
- Carbs, lipids, proteins, nuclei acids on surface
- 100 PAMPs (shared)
- Not in host
Phagocytes - Pathogen recognition receptors (PRRs)
- Best = Toll like receptor
What is significant about PRRs?
Can recognised more than one PAMP
E.g. TLR4 (toll like receptor 4) —> lipopolysaccharide (LPS) Gram -ve bacteria and lipoteichoic acids gram +ve bacteria
What other molecule helps with pathogen recognition?
Opsonins
Increase recognition ability
Opsonins receptor on phagocyte bind —> kill microbe
Give some examples of the classes of opsonins? Give a few examples of each?
Complement proteins
- C3b , C4b
Antibodies
- IgG, IgM
Acute phase proteins
- C reactive proteins
- Mannose binding proteins
What microbes is opsonisation essential for?
Encapsulated bacteria
Why is the spleen so important for clearing infection?
Blood borne pathogens recognised and removed
Specialised macrophages attack encapsulated bacteria
Describe the process of phagocytosis?
Chemotaxis and adherence of microbe to phagocyte
Microbe ingested
Forms phagosome
Phagosome fuses with lysosome —> phagolysosome
Digestion by enzyme
Residual body—> indigestible material
Discharge of waste material
What are the two mechanisms for killing a microbe? Which one is the major pathway?
Oxygen dependent pathway - major pathway - respiratory burst - Toxic o2 products for pathogens —> H2O2, OH•, NO, O•, hypohalite Oxygen independent pathway - lysosomes - lactoferrin or transferrin - Cationic proteins (cathepsin) - Proteolytic and hydrologic enzymes
What is the final stage of the innate immune response?
Inflammation
- factors that will contain and clear the infection
What are the complement pathways?
Contains 20 serum proteins
Activated by enzymatic cascade
Produces–> C1-C9 –> antimicrobial action
What are the two activating pathways?
less important
2 activating pathways for the complement system
- Alternative pathway
(—> initiated by cell surface microbial constituents- endotoxins)
- MBL pathways
(—> initiated when MBL binds to mannose containing residues of proteins found on many microbes)
What are the main products of the complement pathways?
C3a and C5a—> recruitment of phagocytes
C3b- C4b: opsonisation of pathogens
C5-C9: Killing of pathogens, membrane attack complex
What cytokines are produced by macrophages?
TNFalpha
IL-1
IL-6
What are the systemic effects of the cytokines?
Liver (opsonins) --> CRP --> MBL (--> complement actvation) Bone marrow --> neutorphil mobilization Hypothalamus --> ↑ body tempterature
What are the local inflammatory actions?
Blood vessel–> vasodilation, vascular permeability and expression of adhesion molecules –> attraction of neutrophils
Why do the vascular changes occur?
Allow other cells to enter BV - monocytes -neutrophils Increase blood flow to infection site Allow more immune cells into tissue
Give a brief summary of the innate immune system response?
- Innate barriers breached
- Complement, mast cells and macrophages activation (PRR)
- Vascular changes –> vasodilation/ ↑vascaular permeability, chemoattraction (neutrophils, monocytes (TNF, IL-8))
- Hypothalamus ↑thermostat= fever, Liver–> acute phase response
- Redness, heat, swelling and pain –> local inflammation
What can cause decreased spleen function?
Asplenic patients
Hyposplenic patients
What can cause the neutrophil number to reduce?
Cancer chemotherapy
Certain drugs (phenytoin)
Leukaemia and lymphoma
What causes the neutrophil function to decrease?
Chronic granulomatous disease (No respiratory burst)
Chediak-Higashi syndrome (no phagolysosomes formation)
Define the function of first lines of defence? and second lines of defence?
First line–> various barriers –> limit entry and growth of pathogens at portal of entry
Second line –> phagocytes/chemicals –> contain and eliminate the infection
