Immunology 3 Flashcards
Two major mechanisms of communication in immune system?
Direct contact - RECEPTOR : LIGAND interactions
Indirect contact - production and secretion of CYTOKINES
Mechanism of direct contact?
Recteptor : ligand:
Receptor on immune cell recognises ligand on the surface of a pathogen/tissue cell/another immune cell
Example of direct contact?
Between TLR4 and LPS
Toll-Like Receptor 4 detects lipopolysaccharide on gram -ve bacteria and activates innate immune system
Mechanism of indirect contact?
Injured tissue cells and activated immune cells (both innate and adaptive) can produce and secrete CYTOKINES
How do the cytokines in indirect contact function?
Will signal cells at local and distant sites
Can act on cells that produced them in autocrine signalling to cause changes
Examples of cytokines?
IL-2, IL-10, IL-1, IL-6 (Interleukin)
IFNγ (Interferon γ)
TNFα (Tumour Necrosis Factor α)
How do pathogens activate the innate immune system?
Innate immune cells must recognise and respond to pathogens
Macrophages, Mast cells, NK cells, Neutrophils
What are the steps in activating the innate immune system?
Recognition phase
Activation phase
Effector phase
Mechanism of recognition phase?
Pathogens express “signature” molecules not found on human cells: Pathogen Associated Molecular Patterns (PAMPs) - common to many different pathogens
Innate immune cells express specific receptors for PAMPS: Pattern Recognition Receptors (PRRs) - found intra and extracellularly thus, detect intra and extracellular pathogens
Examples of PRRs on immune cells and the corresponding PAMPS on pathogens
Toll-like receptor 4 (TLR4) detects LPS on Gram -ve bacteria
Dectin 1 detects β-glucans of fungi
NOD2 detects Muramyl dipeptide of M. tuberculosis
TLR7 detects ssRNA in viruses
What do the activation and effector phases cause?
Acute inflammation and pathogen killing
How is tissue homeostasis regulated in the skin?
Induction of apoptosis
Specific recognition and removal of dying cells by phagocytes, like macrophages
How are apoptotic cells cleared by tissue-resident macrophages?
Apoptotic cells release CYTOKINE-LIKE signals to attract and activate macrophages
Macrophages recognise specific signals expressed on surface of apoptotic cells
Phagocytosis occurs
Macrophages secrete anti-inflammatory cytokines (like IL-10)
How does phagocytosis occur?
Receptor bind to ligands on apoptotic cells, forming phagocytic cup
Cup extends around target and pinches off, forming phagolysosome
Lysomesome fuses to form phagolysosome - contents degraded
Debris released into ECF
What happens when physical barriers are breached by pathogens?
Wounded/infection skin tissue
PAMPs on pathogens are recognised by macrophages, mast cells and NK cells
What do macrophages do as part of the early innate immune response?
Kill pathogens
Produce pro-inflammatory mediators
What is the innate immune response of macrophages?
Phagocytosis
Production of toxic reactive oxygen and nitrogen species (oxygen dependent killing)
How is the killing ability of macrophages enhanced?
By cytokines, like IFNγ - produced by NK cells and some T cells
Act on macrophages to:
Increase production of toxic O2 and N species
Increase microbicidal activity - destroys microbes
Boost antigen presentation capability
What do mast cells do as part of the early innate immune response?
Produce pro-inflammatory mediatiors
What is the innate immune response of mast cells?
Reside in tissue and protect mucosal surfaces, to protect against parasites
Degranulation - release of pre-formed pro-inflammatory mediators
Gene expression - produce new pro-inflammatory mediators
What do NK cells do as part of the early innate immune response?
Kill infected tissue cells
Produce pro-inflammatory mediators
What is the function of NK cells?
Specifically kill virally infected cell ad abnormal cancer cells
Produce pro-inflammatory mediators
What are the systemic effects of cytokine release?
Neutrophil production
Acute Phase Response
Fever
Function of acute phase response?
Change in plasma conc. of specific proteins in response to inflammation
How does acute phase response occur?
Driven by cytokines produced during localised inflammatory responses
Changes are due to altered protein synthesis in liver (due to action of cytokines)
Some Acute Phase Proteins (APPs) increase; others decrease
Time course of all acute phase proteins are not the same
Major functions of some acute phase proteins?
CRP (C reactive protein), SAP (serum amyloid protein) and complement proteins - prevent infection spread and act as diagnostic markers
Fibrinogen - would healing and coagulation
CRP, proteinase inhibitors - prevent systemic inflammation
Function of C reactive protein?
Major acute phase protein in humans; acts as marker for inflammation (below 10mg/l is normal; inflammation increases in severity as value increase above 10)
Enhances phagocytosis - it OPSONIZES bacteria making phagocytes more able to recognise them
Complement system activation
Structure of C reactive protein?
Pentraxin - 5 identical sub-units
