2. Innate Immune Response Flashcards
What is the second barrier to infection after the external skin/mucosal barriers are damaged?
Innate immune response
How quickly will pathogens usually be removed if a small scratch occurs?
0-4 hours
What are the effector mechanisms?
Cells and molecules which kill foreign organisms
How does the cells of the innate response recognise pathogens? How is the pathogen then killed?
Pattern recognition receptors (PRRs) on innate cells recognise the pattern associated molecular patterns on the pathogens (PAMPs), lytic molecules generated to damage organism
What are macrophages derived from?
Monocytes (produced in bone marrow)
What is present on macrophages to allow them to recognise different types of organisms and effect cells differently?
Pattern recognition receptors (PRRs)
How do dendritic cells link the innate and adaptive immune systems?
Internalise pathogenic antigens, break them up and present the antigens on their cellular surface in association with MHC, adaptive particles recognise these and are activated
What are sentinel cells?
Antigen presenting cells e.g. macrophages, dendritic cells
What are the three types of polymorphonuclear (multi-lobed nuclei) leukocytes (white blood cell)?
Neutrophils (phagocytic), eosinophils (weakly phagocytic), basophils (histamine)
How do neutrophils and eosinophils antagonise larger organisms?
By releasing lytic granules onto the surface of the pathogen (e.g. worms)
What is the role of the Mast cells?
Allergic response, stimulate adaptive TH2 response
What is the role of NK cells?
Kill intracellular organisms and virus/parasite infected cells
What are the two types of dendritic cell?
- Dendritic
2. Follicular Dendritic
What are the difference between dendritic and follicular dendritic cells?
- D: widespread location. FD: germinal centres of secondary lymphoid tissue
- D: contains MHCII. FD: doesn’t
- D: contains CD80 & CD86. FD: doesn’t
- D: phagocytoses. FD: doesn’t
- D: presents processed antigen to T cells FD: presents native antigen to B cells
How do dendritic cells present antigen to T cells and active adaptive immune response?
Take in foreign organism and degrade, couple peptides of antigen fragments to MHCII and present to T cell, CD86/CD80 ligate then bind to T cell receptor CD28, co-stimulation causes powerful T helper cell activation which then releases interferon gamma which activates B cells and macrophages
What is the secondary lymphoid tissue?
Spleen and lymph nodes
How do follicular dendritic cells present antigen and activate B cells?
Just present whole native antigen to B cells, B cells recognise Ag-Ab complex and bring them to centre of 2nd lymphoid tissue, Fc receptor on FD cell recognises Fc region of immune complex w/ complement receptor, activates B cell
How do NK cells protect against viruses/cancer? Give an example of a virus and cancer
Roam around, if any cells are found without MHCI/with many activators then NK kills it.
e. g. Tumour cells do not show MHCI - so NK binds and kills
e. g. Cytomegalovirus changes shape of MHCI so recognised as ‘self’ BUT host cell becomes stressed so overproduces activator receptor - NK kills
What are the 5 types of molecules of innate immunity?
PRRs, complement, Acute phase proteins, Defensins, Cytokines
Describe Pattern recognition receptors. Give 3 examples of PRRs.
Found on all innate immune cells, recognise broad range of microorganisms (broadly specific), Toll-like, scavenger and mannose receptors are all PRRs
What is complement produced by? What does it consist of? How does it kill pathogens? What else does it carry out?
- Produced by macrophages in liver during infection
- Collection of 9 lytic proteins (C1-9)
- When microorganism recognised, lytic pathway set up which terminates with production of membrane attack complex (MAC) which sticks onto outer membrane of pathogen and lyses the cell
- Opsonisation - coats pathogen/microorganism to make it more available to phagocytes (enhance phagocytosis)
What are acute phase proteins produced by? How is it activated? What do APPs consist of?
- Produced by liver
- Activated by molecules entering liver
- Produces C-reactive protein, amyloid proteins - these antagonise microorganisms
What are defensins?
Killer molecules - cationic (+ve charge?) proteins which exist intra and extracellularly and kill microorganissm
What are cytokines? What are the two types of cytokine? What unwanted effect may these cause?
- Signalling molecules
- Inflammatory and anti-inflammatory
- Allergies, but inflammatory response may be regulated by anti-inflammatory cytokines (e.g. interferon gamma, interleukin 10/4)
What is the acute phase response?
- Activated by inflammatory cytokines after skin puncture
- Chemotactic gradient generated by chemokine
- Attracts phagocytic cells
- coagulation cascade activate, seals skin
- phagocytes engulf and destroy organisms - neutrophils first eat up organisms, macrophages eat up neutrophils
What are the two types of defensin?
Alpha - constitutively expressed
Beta - some constitutively expressed, others require activation by bacterial lipopolysaccharide
Describe defensins and their method of microorganism penetration
Natures antibiotics (cationic molecules, amphipathic), hydrophobic head pierces membrane of microorganisms and causes pore formation which causes cell to burst, allowing other cytokines into cell
How does the immune system distinguish between self and non-self tissues?
Using PRRs, especially important in the gut due to commensal bacteria -
What do PRRs recognise?
PAMPs - pathogen associated molecular pattern
DAMPs - host danger associated molecular patterns (e.g. heat shock proteins)
What are the four different types of receptors for antigen recognition?
Pattern recognition receptors, major histocompatibility complex, T-cell receptor, Antibody
What is the role of MHCI?
Present antigens of virus/parasite infected cells, activating cytotoxic T cells which ligate and destroy cell
What is the location, recognition, protein diversity and genes of the PRR, MHC, TCR and BCR?
- PRR: cell surface, recognises PAMPs and DAMPs, 10s-100s of diff. versions in an individual, each protein individually encoded, low polymorphism
- MHC: cell surface, each MHC binds many diff. peptide sequences, 12 diff. versions in an individual, each protein individually encoded, v polymorphic
- TCR: cell surface, highly peptide-MHC specific, millions of diff. versions, genetic recomb. creates diversity
- cell surface/secreted, highly antigen specific, millions of diff. versions, genetic recomb. creates diversity
What is the toll-like receptor?
First found in drosophila, present on surface of cells and intracellularly, activates NfkB/IRF transcription factors which enter nucleus and trigger generation of inflammatory cytokines
What are TLR2, TLR4, TLR5 and TLR3/7/8/9 responsible for?
2: recognises lipopeptides/lipoproteins/glycolipids of a range of microorganisms
4: recognises glycolipids from trypanosomes
5: recognises flagellin
7,8,9: internalised, recognise RNA from viruses, CPG unmethylated DNA from bacteria and CPG units from parasitic cells
What are the five types of phagocytic cell?
monocytes, macrophages, dendritic cells, neutrophils, eosinophils
What is chemotaxis and where is it produced?
movement of a cell in response to a chemical stimulus
gradient produced from infection site to lining of blood vessels
How do endothelial cells attract phagocytes to a site of infection?
Releasing cytokines cause attraction of phagocytes, neutrophils can then engulf and destroy organism (if antibodies around then opsonisation occurs),
What do activated T cells produce?
Inflammatory cytokines, activating macrophages
What are fixed tissue macrophages? Give some examples
Macrophages that protect against infection in certain parts of the body. e.g. Microglia in brain, Kupffer cells in liver
What are the 8 steps in phagocytosis?
- Chemotaxis - draws phagocytic cell toward pathogen
- Adherence to pathogen via PAMP recognition
- cell activation via Pathogen recognition receptor
- initiation of phagocytosis
- phagosome formation
- phagolysosome formation
- bacterial killing and digestion
- release of degradation products
How do antibody and complement help phagocytosis?
Microbes can be coated by either antibody or complement - Y shape of antibodies enhances phagocytosis and complement causes opsonisation (antibodies can also cause this though)
What are the two types of microbial mechanism of phagocytic cell?
Oxygen dependent and oxygen independent - these are present in macrophages and neutrophils
What is the oxygen dependent pathway for generation of hydroxy free radicals/HOCl chloramines in phagocytic cells?
NADPH reduced to NADP, O2–>O, O–> H2O2, H2O2–> hydroxy free radical/HOCl chloramines
Nitric oxide also can be produced
What is the oxygen independent pathway for generation of proteolytic enzymes?
Cathepsin G, lysozymes, lactoferrin, proteolytic enzymes
