RECOGNITION OF PATHOGENS BY THE INNATE IMMUNE SYSTEM

what are the immune system’s 3 levels of defense?

• barriers (mechanical, chemical and biologic)

• innate immune system

• adaptive immune system (most severe)

what are the 2 components of the innate immune system?

• humoral components (plasma proteins)

• cellular components

what is the main granulocyte in the blood?

neutrophils

features of granulocytes

• have large nuclei

• have granules

what type of cell is an NK cell?

large granular lymphocyte

how are PAMPs (pathogen-associated molecular patterns) detected?

by PRRs (pattern recognition receptors)

what type of cells express the highest numbers of PRRs on their surface?

• macrophages

• dendritic cells

• mast cells

what specific receptors are PAMPs recognised by?

TLRs (toll-like receptors) - detect coat proteins, flagellin etc.

what type of cells are TLRs expressed on?

macrophages, neutrophilic and dendritic cells

what happens when a virus is internalised?

nucleic acids are exposed = more replication of virus and is recognised by endosomes (intracellular TLR)

what receptor detects sugars (mannose, fructose and beta-glucan)?

CLRs (c-type lectin receptors)

what type of cells are CLRs expressed on?

macrophages and dendritic cells

how do immune cells respond when their receptors bind to PAMPs?

cell is activated which mediates inflammation which produces interferons to activate adaptive immunity = pathogen clearance

how does acute inflammation occur when a microbe binds to a TLR?

1. cell is activated which activates NFk-betas, then pro-inflammatory cytokines (IL1 and IL6) are produced to spread message

2. vasodilation and increased vascular permeability cause redness, heat and swelling

3. inflammatory cells migrate into tissue, releasing inflammatory mediators = pain + phagocytosis

how is virus replication inhibited when a microbe binds to a TLR?

IRFs are released which can either cause ribonuclease to degrade mRNA or protein kinase to inhibit protein synthesis which both inhibit replication

what are the symptoms of an infection?

• pain

• redness

• swelling

• heat

• infection associated inflammation caused by PAMP activation of PRRs

features of blisters

• sterile inflammation

• no infection

• swelling, pain

• inflammatory response elicited by physical damage to tissue cells = cell lysis

what do blisters release?

DAMPs (damage associated molecular patterns) - usually nuclear or cytosolic cell components released to the extracellular environment

examples of DAMPs

• DNA

• ATP

• histones, nucleic acids released from nucleus

how does TLR signalling work?

1. DAMP binds to TLRs

2. ligand-induced dimerisation of TLRs occurs = activation of signalling pathways = release of pro-inflammatory cytokines = inflammation

what are abscesses made of?

necrotic nutrients and dead and live bacteria

how is pus (abscess) formed?

enzymes released by necrotic neutrophils cause cell liquefaction - DAMPs and PAMPs promote inflammation

features of NK cells

• recognise and kill virus-infected and transformed cells

• have natural immunity against cancer

• large nucleus

how are NK cells kept inactive to not kill normal cells?

binding of MHC class 1 to inhibitory receptor

what happens during cancer or an infection?

MHC class 1 expression decreases (gets internalised) = no NK cell inhibition so the NK cell is triggered by signals from activating receptors. activated NK cell releases granule contents = apoptosis in target cell

how does PRR signalling promote an adaptive immune response?

1. pathogen binds to cell and is broken down

2. pathogen fargements are expressed on MHC-2 on cell surface

3. presented antigens migrate to lymph nodes where the antigen is presented to T and B cells = antibody production and proliferation = adaptive immunity

what is the complement system?

part of the innate immune system

what happens when a complement protein (a pro-enzyme) is activated?

1. small fragment is released (Ca)- mediator of inflammation which attracts immune cells into tissue

2. large fragment released (Cb) - enzyme that activates the next proenzyme in the cascade and binds to the microbes surface

what are the 3 pathways of complement activation?

• lectin pathway - activated by MBL and binds to sugar PAMP

• classical pathway - activated by CRP (can also be mediated by antibodies and binds to antibody)

• alternative pathway - activated by C3b and binds to foreign surface

all in the presence of a microbe

how do bacteria become opsonised?

C3b/C5b bind directly to bacteria surface coating on bacteria’s cell wall = opsonised which allows immune cells to bind to bacteria due to presence of complement receptors, then phagocytosis occurs

how do bacteria become lysed?

many pores are formed in the lipid bilayer of the bacteria

how does complement mediated inflammation occur?

C3a/C5a -

• activate tissue mast cells

• activate endothelial cells which then become leaky

• attract innate immune cells from blood into infection site

what are the functions of the complement system?

• destruction of pathogen

• phagocytosis enhancement

• inflammation

• chemotaxis - attracting macrophages and neutrophils

What is a key feature of innate immunity?

Always present = rapid response