The innate immune system

What are the roles of the immune system?

• pathogenic recognition

• Containing/eliminating the infection

• Regulating itself by minimising damage to host

• Remembering pathogens to prevent diseases from recurring

What is difference between innate and adaptive immunity?

Innate:

• immediate protection(fast) At the location of in the infection

• Lack of specificity and memory

Adaptive:

• Slow Long lasting protection

• Specific to the pathogen

• Immunological memory

Name the factors that prevent entry and limit growth of pathogens

• physical barriers

• Physiological barriers

• Chemical barriers

• Biological barriers

What are the roles of commensals (skin flora)

• compete with positions for attachment sites and resources

• Synthesise vitamins, e.g. vit K, B12

• Produce antimicrobial chemicals

Name some of the physical barriers of the innate immune system

• skin

• Mucous membranes

• Cillia

Name the physiological barriers of the innate immune system

Diarrhoea (food poisoning)

Vomiting ( food poisoning / …)

Coughing (pneumonia)

Sneezing (influenza)

Name the chemical barriers of the innate immune system

Low pH eg. Skin, stomach, Vagina

Antimicrobial molecules: IgA (tears, saliva, mucous membranes), lysozymes (sebum,urine), mucus, beta-defensins (epithelium), gastric acid and pepsin

Name the biological barriers of the innate immune system

Normal flora(commensals) in the Gi tract, vagina, nasopharynx, mouth/thorat

** absent in internal organs/ tissues

What are some commensals found on the skin?

Staphylococcus aureus

Staphylococcus epidermis

Streptococcus pyogens

Candida albicans

What are some commensals found In the nasopharynx?

Streptococcus pneumoniae

Neisseria meningitis

Haemophilus species

How can flora be displaced from its normal location?

Breaching the skin eg. Surgery, IV lines, skin loss, tattoo, injections

Fecal-oral route: foodbourne diseases

Fecal-perineal-urethral route: UTI

Poor dental hygiene/dental work: dental extractions, gingivitis, nrushi

What patients are high risk for serious infections from dental problems?

Patients with damaged/prosthetic valves

Patients with previous infective endocarditis

When can the normal flora overgrow and what happens if it does?

When the host is immunocompromised eg. Diabetes, AIDS, chemo

OR

When antibiotics deplete normal microflora eg. In the intestine: c.diff → colitis, vagina: Candida albicans → thrush

It becomes pathogenic

What happens in the second line of defence (to clear the infection)?

1. Macrophages have PPR on their surface that recognise PAMPs on the pathogen and phagocytose them

2. Macrophages release cytokines that recruit other cells eg. Monocytes, neutrophils to the site of infection

3. Cytokines also cause inflammation → vasodilation, change in vascular permeability and mast cell degranulation

What are PAMPs made up of?

Pathogen associated molecular patterns

Carbs, lipids, proteins, nucleic acids

Where are PPR s found?

Pattern recognition receptors

Bound to a host (eg. Macrophage, B cell, dendritic cell, neutrophil) or soluble

What does IL-1 do ?

stimulates the hypothalamus to increase body temp

What does IL-6 do ?

Stimulates the liver to:

• release CRP → acts as an opsonin + marker of infection

• Make MBL → activate complements

What does IL-8 do ?

Stimulates blood vessels to recruit neutrophils to site of infection

What do dendritic cells do?

Phagocytose the pathogen and travel in the blood/lymphatic system to resent antigen to a T cell to activate the adaptive immune system

What is the classical pathway of the complement system?

Antibody recognises antigen and form an antibody- antigen complex → membrane attack complex which forms pores in the cell membrane to kill pathogens via osmolysis

** C5-C9

What is the alternative pathway of the complement system?

Initiates by the surface microbial constituents eg. Endotoxins on E-coil

What is the Mannose binding lectin pathway of the complement system?

Initiated when MBL binds to the mannose-containing residues of proteins found on microbes eg. Salmonella, Candida albicans

What does C3a and C5a do?

Recruit phagocytes

What does C3b - C4b do?

Opsonisation of pathogens

What does C5 - C9 do?

Kill pathogens by the membrane attack complex

What is the function of macrophages and where are they found ?

Present in all organs (tissues)

• Phagocytosis

• Present antigens to T cells (adaptive immunity)

• Produce cytokines/chemokines

What is the function of monocytes and where are they found ?

Present in the blood

Recruited at infection site and differentiate into macrophages

What is the function of neutrophils and where are they found ?

Present in the blood Recruited

Recruited by chemokines to site of infection to inject and destroy pyogenic bacteria

What is the function of basophils/mast cells?

Involved in inflammation (vasomodation) and allergic responses

What is the function of eosinophils?

Defence against parasites/ worms

What is the function of natural killer cells?

Kill abdominal host cells (virus infected/ malignant)

Name some opsonins

• C3, C4 (complement proteins)

• IgG, IgM

• CRP, MBL (acute phase proteins)

Why are opsonins important?

Ended to clear encapsulated bacteria as PAMPs might be masked by polysaccharide coating So PPR may not be able to attach

Eg. Nesseria meningitis, strep pneumoniae, heaemophilus influenza b

How does the macrophage bind to a pathogen that has been opsonised?

They have a Fc receptor that bind to the Fc reaction of the antibody → R.O.S destroy the pathogen

What is the process of NETosis?

neutrophils externally trap pathogens by releasing decondesnsed chromatin and granule contents into the extracellular space

What factors affect phagocytosis?

• having no spleen/ reduced spleen function

• Decreased neutrophil number: chemotherapy, leukaemia/ lymphoma, drugs

• Decreased neutrophil function: chronic granulomatous disease (no respitory burst), chediak-higashi syndrome( no phagolysosome formation)