L19- Innate defences against infection

what are the innate defense mechanisms

• barriers

• cellular defences

• molecular defences

give examples of physical and chemical barriers to infection

• Skin (fatty acids, commensals)

• Mucus membranes (cilia, commensals, low pH)

• Lysozyme in tears

• acid in stomach

what does AMP stand for

antimicrobial peptide

what does PPR stand for

pattern recognition receptor

where are PRRs (patten recognition receptors) located

host cells

• macrophages

• neutrophils

• dendritic cells

what is the purpose of PPRs (pattern recognition receptors)

• to allow identification of pathogens

• to recognise simple molecules and regular patterns

  • e/g/ lock and key mechanism

what does TLR stand for

toll-like receptor

describe Toll-like receptors (TLRs) on the membrane surface

• evolutionary conserved

• 10 in humans

• each has its own repertoire of pathogen-associated molecular patterns (PAMPs)

what does PAMP stand for

pathogen-associated molecular pattern

describe the function of PAMPs

a part of the pathogen that gets recognised by the host

give 3 examples of PRRs (pattern recognition receptors)

• toll-like receptors (TLRs)

• NOD-like receptors

• RIG-I-like helicases

describe NOD-like receptors

• intracellular

• nucleotide-binding oligomerisation domain

what do PAMPs contain

• mannose-rich oligosaccharides

• peptidoglycans

• lipopolysaccharides

• unmethylated CpG DNA

define haematopoiesis

formation of blood cells

where are leucocytes (white blood cells) produced

pluripotent haematopoietic stem cells in bone marrow

what do leucocytes include

• B,T and NK lymphocytes

• monocytes (tissue macrophages)

• granulocytes

• tissue mast cells

define NK lymphocytes

natural killer cells

• has granules with enzymes that can kill tumor cells or cells infected with a virus

what are the 3 granulocytes that are included in leucocytes

• neutrophils

• eosinophils

• basophils

what is the role of dendritic cells in the immune response

forms the bridge between innate and adaptive immune responses

what is the function of a macrophage

• phagocytosis

• antigen presentation

what is the function of a dendritic cell

• antigen uptake in its peripheral sites

• antigen presentation

what is the function of a neutrophil

• phagocytosis

• activation of bactericidal mechanisms

what is the function of a eosinophil

killing of antibody-coated parasites

what is the function of a basophil

• promotion of allergic responses

• augmentation of anti-parasitic immunity

what is the function of a mast cell

release of granules containing histamine and active agents

what happens if we have a problem with phagocytosis

• bacterial infections

• fungal infections

• recurrent infections

• discovered early in life

what is an example of a fungal infection from phagocyte malfunction

chronic granulomatous disease (CGD)

explain the neutrophil as a phagocytic cell

• short lived

• multi-lobed nucleus (PMN)

• abundant in sites of acute inflammation

• most common wbc in circulation

explain mononuclear phagocytes

• blood monocytes, Kuppfer cells, alveolar macrophages etc

• Monocytes when in blood

• macrophage when in tissue

• longer lived cells (months)

• monocyte → macrophage

what are there recognition (binding of microbe) receptors for

• common bacterial components (mannose, LPS)

• complement (C3b)

• antibody (Fc)

define internalisation (endocytosis)

enclosing microbe in a membrane bound vacuole (phagosome)

define fusion in phagocytosis

a phagasome fuses with the lysosome to form a phagolysosome

what is acidification as a phagocytic killing mechanism

pH 3.5-4 bacteriostatic or bacteriocidal

what are the toxic oxygen products used in a phagocytic killing mechanism

• superoxide

• hydrogen peroxide

• singlet oxygen

• hydroxyl radical

• hypohalite

what is the toxic nitrogen oxide used in a phagocytic killing mechanism

Nitric oxide (NO)

what are antimicrobial peptides used in a phagocytic killing mechanism

defensins, cationic proteins

what the enzymes used in a phagocytic killing mechanism

• lysozyme

• acid hydrolases

what are the competitors used in a phagocytic killing mechanism

• lactoferrin (binds iron)

• vitamin B12 binding protein

describe oxygen dependent killing

• hexose monophosphate shunt generates NADPH

• NADPH oxidase generates reactive oxygen intermediates

• CGD problem with NADPH pathway

• reactive oxygen intermediates are bacteriostatic or bactericidal

• H2O2 + myeloperoxidase + halide → halogenation and killing

what are the additional functions of macrophages

• can be activated by bacterial products or cytokines

• secrete soluble factors (cytokines)

• present antigen to lymphocytes

what is extracellular killing active against

• infected cells

• organisms too large for phagocytosis

what is the function of an eosinophil

killing of antibody-coated parasites

how do eosinophils carry out a specific-adaptive immune response

• granules contain cationic (+) protein and basic protein

• bind to helminths, granules release → damage membrane

what do innate cells lack

antigen specific receptors

what are the roles of natural killer cells

• active against viral infected cells

• attack some tumour cells

what are NK cells activated by

• IFNalpha, IFNbeta (type 1)

• IL12 (interferon and interleukin- cytokines)

what can NK cells produce

IFN gamma

what does IFN gamma do

helps to control infections

what does a deficiency in NK cells cause

an increased risk of herpes

what do sub-groups of cytokines include

• lymphokines

• interferons

• interleukins

• chemokines

what is the molecular weight of cytokines

• low (5-25kDa)

what are cytokines secreted by

cells that stimulate or inhibit the activity, proliferation or differentiations of other cells