Week 2 Flashcards
Innate immune response
- tissue resident white blood cells (leukocytes) at site of infection
• recognise invading pathogen
• release chemical messenger proteins (chemokines recruit more WBC; cytokines activate more WBC -
phagocytic cells engulf invading pathogens and destroy them in large numbers
• Tissue resident macrophages – first responders
• Recruited neutrophils – professional killers
Phagocytes and pattern recognition
Phagocytes recognise microbes through pattern recognition
- Shared structures unique to subsets of microbes =
Pathogen Associated Molecular Patterns (PAMPs) eg:
• LPS of Gram-negative bacteria
• flagellin of bacteria
• Viral RNA or viral DNA
- Toll-like receptors (TLRs) are Pattern Recognition Receptors (PRRs)
- Recognition sends danger signal
- Stimulates production and secretion of cytokines
Inflammation
• Cytokines induce inflammation
• Series of events in reaction to tissue damage – injury and/or infection
• Site becomes swollen, red, hot and painful – part of normal healing process
• Underlying mechanisms explain the symptoms
- Vasodilation – increase in blood vessel diameter and permeability
- Brings more WBCs to site of infection
Fever
• Cytokines, interleukin-1 (IL-1) induces fever
• Phagocytic cells more efficient at elevated body temperature
• Some pathogens unable to reproduce at higher temperatures, e.g. influenza virus
• If fever gets too high – dangerous and life threatening
Interferons
Cytokines that interfere with viral replication and spread
• IFNs made by infected cell in response to viral replication
• Act on neighbour to induce an antiviral state
• Cell in antiviral state do not allow viral replication
• Contribute to flu-like symptoms of aches, headache, chill
Antigen presenting cells (APCs)
• Macrophages and dendritic cells are antigen presenting cells (APCs)
• At sites of infection, APCs use TLRs to recognise a pathogen and then send signals for immune activation
• They ingest and digest pathogens
• Initiate adaptive immune response
Dendritic cells
• DCs that have picked up antigen at the site of infection migrate to nearby (local, draining) lymph nodes
• Activate adaptive immune cells responsible for microbial clearance – T and B cells
• Strategically located where they concentrate
components for adaptive immune responses
- Lymphatic system = network of vessels returning fluid that has leaked out of blood back to circulation
- Lymph = fluid
• Blood is filtered through the spleen
• Like a lymph node for blood-borne pathogens
• Other specialised lymphatic structures exists in areas of high pathogen exposure e.g. gut and respiratory tract
Lymphocytes
• WBCs of adaptive immune response
• T cells and B cells
• Initially formed in bone marrow
• Circulate through blood
• Can leave blood and enter lymph nodes looking for antigen presented by DCs
• If they find DCs presenting foreign antigen that they are specific for, they will become activated
• If they don’t, they keep moving
• Activated lymphocytes undergo rapid proliferation and lymph nodes swell
T cells
• T cells migrate from bone marrow to the thymus
• Complete development and maturation in thymus
• MATURE (but NAÏVE) T cells that have not seen foreign antigen before leave the thymus and begin to circulate
• Upon activation by DC + antigen, they become EFFECTOR T cells:
• Helper CD4+ T cells (Th) coordinate entire adaptive response – activate CTLs and B cells
• Cytotoxic/killer CD8+ T cells (Tc cells or CTLs) are professional killing cells – viruses and tumours
• During activation, some Th cells and Tc cells develop into relatively inactive = long-lived MEMORY T cells
T cell receptors
• **TCRs* recognise foreign antigen presented MHCs by APCs
• Each naïve CD4+ T cell has lots of identical TCRs (same specificity)
- Different CD4+ T cells have different TCRs and antigen specificities
• APC (DCS) release cytokines that attract and activate **naïve CD4+ T **
antigen presented on
• Naïve CD4+ T cells specific for presented activated and begins to divide antigen (C in this case) is activated and begins to divide
• Results in activated effector CD4+ T helper (Th) cells, all bearing TCRs specific for the activating antigen
• Process takes several days to complete = clonal expansion (lymph node swelling)
Microbial clearance
•DCS present antigen to CD4+ and CD8+ T cells activating them > effector Th cells and Tc cells
• Th cell specific for the same antigen secrete cytokines that further stimulate/help Tc cells
• Tc cells can then go looking for host cells infected with virus, displaying viral antigen on MHC
• Tc cells proliferate and leave lymph node in search of infected host cells
• Tc cells recognises infected cell displaying same foreign antigen bound to MHC on surface that was used to activate them from naive cells
• Releases toxic chemicals to cause infected cell to die = targeted cell killing; uninfected cells not displaying antigen are not affected
Antibody functions
a) Coat surface of viral particles preventing them from
attaching to host cell receptors = neutralisation
b) Each antibody has two antigen binding sites - large agglutinated clumps of antigen and antibody may form. Complexes are readily available to phagocytic cells = agglutination
c) Enhances phagocytosis by acting as opsonin for phagocytic cells which have receptors for antibody tail = opsonisation
Vaccines
Vaccines induce immune memory without causing disease
• Ability to mount ever stronger immune response with each antigen exposure is basis of vaccination
• Primary immune response stimulated by exposure to dead / inactivated, weakened / attenuated, or component of pathogen
• Subsequent exposure to live pathogen immediately triggers secondary adaptive response
Nosocomial infection
Defined as a hospital acquired infection
- “hot beds” for infection
• sick people - damaged barriers, weakened immunity
• Medical staff movement
- Preventable with basic control measures
• Hand washing
• Instrument sterilisation
- Antimicrobial resistance (AMR)
• Once curable infection no longer respond
Physical control: Manipulation of environment
- Microbes have optimal growth temperature (range)
- Direct and inexpensive
-
Heat is effective means of killing = ”cidal”
• can penetrate an object and kill organisms throughout
• denatures proteins (not suitable for all substances) -
Cold generally doesn’t kill, it inhibits growth = ”static”
• inhibits microbial replication -
Heat to sterilise = complete elimination of all organisms
• Dry heat (flame or hot oven) - requires considerable time and higher temps
• Moist heat (for autoclaves add pressure) - penetrates more quickly at lower temps - Pasteurisation = temporary heating of liquids/ foods sensitive to prolonged heat (lose flavour)
- Liquids that can’t tolerate high temps may be filtered through membrane with pores of size to exclude microbes
- Radiation can be used to kill microorganisms in some situations
-
UV rarely sterilises, but can significantly reduce numbers on surfaces
• Inhibits microbial DNA replication - Gamma radiation used for some food products
-
Drying is an “age-old” way of preserving fish and meat products
• Coupled with water removal by salt/sugar
Chemical control on living and non-living materials
- For non-living materials = disinfectants
• Bleach (chlorine) – forms an acid when added to water
• Alcohol – kills by denaturing proteins and disrupting microbial cell membranes - For living tissue = antiseptics
• Iodine – binds enzymes to inhibit activity, also affects microbial cell membranes
• Alcohol – good for skin, but not open wounds
• Soaps, detergents disrupt microbial adherence, can kill through disruption of microbial cell membrane