Innate Immunity Flashcards
Define infectious disease
When the pathogen succeeds in evading and/or overwhelming the host’s immune defences
What is the immune system?
Cells and organs that contribute to immune defences against infectious and non-infectious conditions
Four roles of the immune system?
Pathogen recognition
Containing/eliminating the infection
Regulating itself
Remembering pathogens
Give features of innate immunity that make it different from adaptive
Fast
Recognises group pathogens by shared structures
Lack of memory
No change in intensity
What are the first lines of defence in the innate immune system?
Physical barriers eg skin, mucous membranes, bronchial cilia
Physiological barriers eg diarrhoea, vomiting, coughing, sneezing
Chemical barriers eg low pH, antimicrobials molecules
Biological barriers eg normal flora
In the first line of defence, where can antimicrobials molecules be found and give examples
Tears and saliva have IgA
Sebum, sweat and urine have lysozyme
Mucus
β-defensins in epithelia
How do normal flora prevent infection?
Compete with pathogens for attachment sites and resources
Produce antimicrobial chemicals
Synthesise vitamins K and B
Name some flora that inhabit the skin
Staph aureus Staph epidermis Streptococcus pyogenes Candida albicans Clostridium perfringens
Name some flora that inhabit the nasopharynx
Streptococcus pneumoniae
Neisseria meningitidis
Haemophilus species
How can normal flora be displaced from normal location?
Breaching skin integrity Fecal-oral route Fecal-perineal-urethral route Poor dental hygiene/dental work Can over grow and become pathogenic in immunocompromised Can be depleted by antibiotics
Give examples of natural flora that can become depleted with antibiotic use
Intestine - get severe colitis caused by C. difficile
Vagina - get thrush when lactobacillus is depleted and Candida albicans can grow more
Give the overall mechanisms of second lines of defence in innate immunity
Phagocytes
Complement system
Cytokines/chemokines
Give examples of phagocytes and where they are found
Macrophages Monocytes Neutrophils Basophils/mast cells Eosinophils Natural killer cells Dendritic cells
Where are macrophages found and what do they do?
Present in all organs
Phagocytosis
Present microbial agents to T cells
Produce cytokines/chemokines
Where are monocytes found and what do they do?
Present in blood
Recruited to infection site
Differentiate into macrophages
Where are neutrophils found and what do they do?
Present in blood
Increased during infection
Recruited by chemokines to the site of infection
Phagocytose pyogenic bacteria eg staph aureus and strep pyogenes
When are basophils/mast cells seen?
Early actors in inflammation
Allergic response
Phagocytosis
What do eosinophils do?
Defence against multicellular parasites
What do natural killer cells do?
Kill all abnormal host cells (virus infected or malignant)
What do dendritic cells do?
Present microbial antigens to T cells
How do phagocytes recognise pathogens?
Microbe have pathogen-associated molecular patterns (PAMPs)
Phagocytes recognise these using their pathogen recognition receptors (PRRs)
What can PAMPs be made up of?
Carbohydrates
Lipids
Proteins
Nucleic acids
What do opsonins do?
Bind to microbial surfaces
Cause enhanced attachment of phagocytes and clearance of microbes
Give some examples of opsonins
Complement proteins - C3b, C4b
Antibodies - IgG, IgM
Acute phase proteins - CRP, mannose-binding lectin
What type of bacteria are opsonins essential for clearing? Give examples
Encapsulated bacteria
Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae B
What are the mechanisms for phagocyte intracellular killing?
Oxygen dependent
Oxygen independent
What does the oxygen-dependent pathway involve?
A respiratory burst of hydrogen peroxide, hydroxyl radical, nitric oxide, singlet oxygen, hydrohalite
What does oxygen independent pathway involve?
Lysozyme
Lactoferrine/transferring
Cationic proteins
Proteolytic and hydrolytic enzymes
How can the complement system be activated?
Alternative pathway - initiated by cell surface microbial constituents on pathogens
MBL pathway - initiated when mannose-binding lectin binds to mannose containing residues of proteins found on Salmonella spp and Candida albicans
How do the two pathways activate the complement system?
Cleave proteins which activates them
What are the proteins involved in the complement system (overall)?
C1-C9
What do C3a and C5a do?
Recruit phagocytes
What do C3b and C4b do?
Opsonisation
What do proteins C5-C9 do?
Kill pathogens - bind to membrane of the microbe to produce attack complex, puts holes in the membrane
What do cytokines and chemokines do in innate immunity?
Cytokines - activate phagocytes
Chemokines - chemoattraction
What cytokines/chemokines do macrophages release?
TNF-α
IL-1
IL-6
When cytokines/chemokines are released, what effect to the have in the liver?
Cause release of CRP and MBL -> complement activation
When cytokines/chemokines are released, what effect to the have in the bone marrow?
Cause neutrophil mobilisation
When cytokines/chemokines are released, what effect to the have in the hypothalamus?
Increased body temperature
What inflammatory actions do cytokines have?
Vasodilation
Increased vascular permeability
Release of adhesion molecules which attract neutrophils
What can happen when microbial toxins cause overreaction of TLR4 receptor on neutrophils, endothelium and monocytes?
Get an excessive inflammatory response
Sepsis and multi-organ failure caused by cytokine shower, coagulopathy, vasodilation, capillary leak
What can reduce phagocytosis?
Decreased spleen function (asplenic/hyposplenic)
Decreased neutrophils from chemo, dugs, leukaemia, lymphoma
Decreased neutrophil function
- chronic granulomatous disease (no respiratory burst)
- Chediak-Higashi syndrome (no phagolysosome formation)
What does the PRR TLR5 recognise?
Flagellin on bacterial flagella
What does the PRR TLR2 recognise?
Peptidoglycan on Gram positive bacteria
Lipoprotein and lipopeptides on Gram negative bacteria
Mycobacteria
What does the PRR TLR4 recognise?
Lipopolysaccharide (LPS) on Gram negative
Lipoteichoic acids on Gram positive
