Infection 1+2 Flashcards
1
Q
What is infection?
A
Invasion of a host’s tissue by microorganisms
2
Q
6 microorganism types that can cause infection
A
• Bacteria - • Viruses - e.g. covid • Fungi • Protozoa = e.g. malaria • Helminths (worms) Prions
3
Q
5 ways of infection transmission
A
- Person to person (touch, air droplets, sexually)- Influenza, SARS-CoV-2, EBV, HIV
- Water – Cholera, Hep A
- Food – E.coli, Salmonella
- Insects – Malaria (mosquitos)
- Surface (touching, hand hygiene) – MRSA
4
Q
2 types of transmission
A
Direct
Indirect
5
Q
Direct transmission
A
→ disease caused by direct contact to disease from the resevoir (disease carrier) to host
Eg. Droplet transmission - coughing respiratory droplets
6
Q
Indirect transmission
A
→ diseases caused by transmission through an intermediary source
Eg. Air borne, vehicle (food, water), vectors
7
Q
6 things to ask about in history taking
A
- Details of symptoms
- Time since first exposure
- Contacts (including sexual partners)
- Environment (damp building, air conditioner, overcrowding like Tb)
- Food/drink
- Travel
8
Q
What are markers of infection
A
Generalised signs of infection
- not everyone has the exact same
9
Q
7 markers of infection - patient symptoms
A
- Rise in temperature
- (in some cases temperature may go down)
- General malaise
- (lethargy, body ache, head ache, loss of appetite, eg influenza)
- Pain
- (eg general muscle pain in a number of infections, abdominal pain in Hepatitis, abdomen tender to touch, at site of infection)
- Breathlessness
- (chest infection including pneumoniae)
- Local skin changes
- (eg impetigo –blisters and sores on the skin Cellulitis- redness, heat, pain at the site of infection necrotising faschiitis – deep skin infection)
- Cough
- (dry cough eg whooping cough productive cough - purulent sputum eg tuberculosis)
• Confusion (eg meningitis, sepsis)
10
Q
Virulence factors
A
→ molecules produced by bacteria’ fungi and protozoa that add to their effectiveness
- enable them to achieve colonisation in the host
11
Q
3 things that determine severity of disease
Pathogen level
A
- Virulence factors
- inoculum size (size of pathogen)
- antimicrobial resistance
12
Q
2 things that determine severity of disease
Patient level
A
- Site of infection
- co-morbidities
13
Q
2 general tests for infection
A
- White blood cell count
- c-reactive protein
14
Q
White blood cell count
A
• Generally increase in WBC when someone has infection BUT in some cases cells may decrease for example CD4+ cells in HIV
15
Q
C-reactive protein
A
Increase in C-reactive protein is a marker of infection and inflammation).
• In a study by Wang (2020) CRP levels positively correlated with lung lesions and could reflect disease severity in the early stage of COVID-19 infection)
16
Q
How do doctors know that patients have infection?
A
- History, examination, investigations
- full blood count
- c-reactive protein
- liver kidney function tests
- Imaging
- histopathology
17
Q
5 ways to identify bacteria
A
- Direct microscopy after staining (Gram stain, acid fast stain) - look at shape and size
- Blood culture (growth and identification) let bacteria in blood grow so you can see if it is there
- Swabs (direct staining and microscopy or growth in appropriate medium)
- Nucleic acid amplification/PCR (faster genetic methods)
- Antigen tests
- Antibody tests
18
Q
3 ways to identify viruses
A
- Detection of antigens using Elisa/immunofluorescence - look for antigen and match to virus
- Nucleic acid amplification/PCR
- Antibody tests
19
Q
Features of prokaryotes
A
- Circular dna and plasmids
- no nucleus
- no membrane bound organelles
- cell wall normally made of peptidoglycan
- no carbs in plasma membrane
- 70s ribosomes
20
Q
Features of eukaryotes
A
- chromosomes
- nucleus
- membrane bound organelles
- cell wall only in plant cells
- carbs and sterois in plasma membrane
- ribosomes 80s
21
Q
What are commensals?
A
• Commensals are microorganisms (normally bacteria) that live on the surface of our bodies and in specific areas eg intestinal tract, oral cavity, vagina
- Known as microbiome = all of the commensals together
- Live in harmony with us don’t normally cause disease
22
Q
Antibiotics and commensals
A
• Antibiotics can destroy commensals, e.g. leave to yeast infections and thrush in cavities
23
Q
Naming organisms
A
- Genus + species. (“Surname + first name”) for example: Staphylococcus aureus (Staph aureus, S. aureus)
- Names are sometimes supplemented by adjectives describing growth, typing or antimicrobial susceptibility characteristics, for example E coli 0157, MRSA (methicillin resistant Staph aureus)
24
Q
bacteria cell structure
A
- Plasmids
- Ribosomes
- Cell wall - peptidoglycan
- Food granule
- Plasma membrane
- Chromosome – nucleoid region
- Flagellum
25
4 categories of oxygen tolerance
* Aerobes – can survive in the presence of oxygen
* Obligate aerobes –require oxygen for survival
* Anaerobes – can survive in the absence of oxygen - gas gangrene release gas results in amputation
* Obligate anaerobes –require oxygen-free environment for survival (unless able to form spores)
26
3 bacterial shapes
Coccus = bacteria in circular shape ( clusters or chains)
Spirillus= bacteria in spiral shape
Bacillus - bacteria in a rod shape
27
Arrangement of cocci bacteria
* Clusters = cocci like a bunch of grapes
| * Chains = cocci in a row
28
5 mechanisms of bacterial pathogenesis
Virulence factors --> enable bacteria to establish and cause infection chostentry)
* Evasion of immune system – bacteria escapes immune system(e.g. polysaccharide capsule outside bacteria, so antigens are covered)
* Adherence to host cells (e.g. pili and fimbriae)
* Invasiveness (e.g. enzymes such as collagenase – to breakdown collagen)
* Toxins
29
2 types of toxins
Endotoxins
| Exotoxins
30
Exotoxins
→ toxin secreted by bacteria, released outside the cell
- damages host by destroying cells or disrupting normal cellular metabolism
e.g.diphtheria toxin – produced into environement
31
Endotoxins
→ bacterial toxins consisting of lipids loccited within a cell
Eg. Lipopolysaccharide
32
Endospores
-> almost go to sleep in bad environments and then wake up in suitable environments
• Some bacteria develop endospores to survive lack of nutrients or other adverse environmental factors
• The genetic material is preserved within spores
• spores are Highly resistant form which can withstand chemicals and extremes of temperature
Examples are Clostridium difficile, Bacillus cereus
33
What are gram positive bacteria
• Thick outer layer of peptidoglycan which can retain blue dye (methodine blue) so bacteria appear purple
- lack an outer membrane space
34
What are gram negative bacteria
* Much thinner outer layer of peptidoglycan, methodine blue purple colour is removed as it doesn't stick to the layer
* When counterstaining with pinkish dyes, these counter dyes are retained so bacteria appears pink
- have an extra periplasmic space between peptidoglycan layer and outer membrane
35
Gram positive cocci
- Staph aureus
- coagulase negative staph
- alpha haemolytic strep
- beta haemolytic strep
- strep pyogennes
- strep pneumoniae
36
Gram postive baccili
Bacillus cereus
37
Gram negative cocci
- Neisseria meningitidis
| - neisseria gonorrhea
38
Gram negative bacilli
- E.coli
- salmonellas typhi
- naempphilius influenzas
39
4 things that antibiotics interfere with
– Cell wall synthesis
– Protein synthesis
– Nucleic acid synthesis
– Cell membrane function
40
Properties of viruses
Intracellular obligate parasites – can't exist on their own, need a host cell
• Genetic material is DNA or RNA – never both
• Enveloped or non-enveloped
• Non enveloped – capsid protein surrounds genetic material
• Enveloped – has capsid encasing genome but also an envelope made of lipid bilayer and proteins
• Capsid symmetry can be helical or icosahedral which gives viruses their shape
41
Enveloped virus
→ lipid bilayer envelope and capsid
* enveloped viruses are more sensitive to harsh environments, for example, heat, dryness, compared to non-enveloped viruses
* These are generally transmitted by respiratory, parenteral and sexual routes
42
Non - enveloped virus
→ capsid protein
non enveloped viruses are more stable in adverse environments
These are generally transmitted by the fecal-oral rout
43
Single stranded non - enveloped
Dna viruses
Parovirus 19
44
Double stranded non enveloped
Dna viruses
Adenovirus
Hpv
virus jc
Bk virus
45
Double stranded enveloped
Dna viruses
Herpes
Hepatitis B
Molluscum
Contagiosum
46
Single stranded, positive strand, lcosanedral non c enveloped
Rna viruses
```
Hep A, e
Norovirus
Echovirus
Enterouirus
Coxsackievirus
```
47
Single stranded, positive strand icosanedral or helical enveloped
```
Hiv
Hep C
Rubella
Yellow fever
West nile
```
48
Single stranded, negative strand, helical , enveloped
```
Ebola
Measles
Mumps
Influenza
Parainfluenza
Rsv
```
49
Double stranded. Icoschedral, non - enveloped
Rotavirus
50
Virus growth
Need living cells to replicate (obligate intracellular parasites) = different viruses grow in different types of cells
• Use the living cells to synthesise all the constituents of the virus
• Different viruses grow in different types of cells
• In the laboratory:
– Vero cells
– HeLa cells
– Baby hamster kidney cells (BHK)
51
Viral replication - steps
1. Attachment to the appropriate cells (eg haemagglutinin of influenza virus or glycoprotein GP 120 of HIV to appropriate cell receptor)
2. Penetration of virus into cell (endocytosis or fusion of envelope with host cell membrane)
3. Uncoating viral capsid is removed by viral enzymes or host enzymes leading to release of their genome and other materials such as enzymes into host cell
4. Replication Initiation of transcription or translation of the viral genome resulting in the manufacture of virus components and genome
5. Assembly of components into new virions which a ready for the release
Release of the virions by lysis or budding from the target cells and further infection.
52
Dna virus replication
---> Transcription and replication occurs in the nucleus of the infected cells
• Most DNA viruses assemble in the nucleus
• Early Transcription (Translation of proteins for DNA replication)
• Late Transcription (Translation of structural proteins)
Assembly and release
53
Rna virus replication
----> RNA viruses normally undergo transcription, translation and replication in the cytoplasm.
• Positive sense single stranded RNA can function as mRNA and get translated into proteins by the host ribosomes
• Negative sense RNA has to be changed to positive mRNA using the enzyme RNA dependent RNA polymerase to make a positive strand copy
• which can be read by the ribosomes and result in the manufacture of proteins
54
Latency
---> Latent viral infection – the virus can remain dormant within cells and does not cause symptoms until it is activated by some factor(s)
• Immunosuppression (chemotherapy or infections such as HIV result in reactivation of latent viruses)
55
Examples of latent virus
* Herpes simplex viruses
* Varicella zoster virus (chickenpox and reactivation causes shingles.) - in ganglia
* Cytomegalovirus (in myeloid progenitor cells)
56
Bacteriophage
* DNA is injected into bacteria
* Shape is characteristic like a spaceship
* DNA inside viral head
57
Yeast
* Candida albicans (thrush) = affects immunocomprised people or those on long term antibiotics as it removes cammensals
* Cryptococcus neoformans (usually affects the lungs or the central nervous system)
* Pneumocystis jiroveci (pneumonia) - in younger people and Hiv patient
58
Fungi features t examples
* Produce spores = sometimes spores are infection causing vehicle
* Cell wall (chitin) and cell membrane (ergosterol) different from bacteria and other eukaryotic cells
Yeast -candida albicans
Molds
59
Protozoa
- unicellular eukaryotic organism
• Giardia lamblia – parasitic intestinal disease
• Cryptosporidium parvum – intracellular parasite – epithelial cells of the villi in lower small intestine
• Plasmodium falciparum - malaria (more detail later)
60
Helminths - 3 worms groups t examples
* Cestodes: ribbon-like, segmented intestinal parasites
* Tapeworms (e.g. Taenia saginata – beef tapeworm)
* Nematodes: long non-segmented worms
* Roundworms (e.g. Enterobius vermicularis - pinworm)
* Trematodes: small, flat leaf-like worms that can infect urinary bladder, liver, lungs, blood vessels in the intestine
* Flukes (e.g. Schistosoma mansoni - blood fluke)
61
Prions
Unconventional infectious agents
• Prions are infective proteins with no nucleic acid
• Causative agent of Transmissible Spongiform Encephalopathies
• Accumulation of prion protein in the grey matter and in extracellular amyloid plaques in the brain
– Scrapie in sheep
– Bovine Spongiform Encephalopathy (BSE) in cattle
– Creutzfeldt-Jakob Disease (CJD)
62
Epidemic
Widespread disease within a community e.g. Uk
63
Pandemic
An epidemic which has spread beyond one community eg. All of eu
- an-epidemic that has become widespread
64
What is the infection model?
-> factors that come together that result in infection
How is it managed
How is it treated
Patient outcome
65
Process of the infection model
Infectious agent and patient converge
Patient becomes infected
Accesses medical personnel for treatment
Patient is treated for infection
66
6 parts of the infection model
• The patient (age, immune status, comorbidities)
* The pathogen (bacteria, virus, fungus, parasite)
* What it is, how does it produce infection
* Mechanism of infection
* How is the infection spread from person to person
* Process of infection
* How the organise establishes infection within the host
* Damage host, fight against hosts immune system
* Management of the patient (history, examination, investigations, specific and supportive treatment)
* History to identify infectiona dn organism
• Patient outcome (cure, disability, chronic infection- low lying infection that never goes away, death)
67
Pathogen class
* Bacteriua
* Virus
* Yeast
* Mould
* Protozoa
* Helminth
68
Opportunist pathogens
Enhance function of the body but change and become virulent with a particular environment
69
3 categories of patient factors
Person
Time
Place
70
Patient factors - person
* Age = older and younger people more prone to infection
* Gender = more females have autoimmune disease (immunosuppressant medication = more infection)
* Social factors = housing, mold growth, malnourishment
* Immune status = due to other disorders cancer, HIV that affect immune system
* Co morbidities
71
Patient factors. - time
* Time of year = influenza is a seasonal virus winter,
* Time since exposure to pathogen (incubation time of microorganisms e.g. tb is slow growing symptoms occur a while after infection
72
Patient factors - place
* Current – where are they community, care home, hospital = you can pick up infections in environements
* Travel - from good history
73
Give 8 Mechanisms of infection transmission
* Vertical transmission = mother to baby
* Contiguous = direct spread, coughing and sneezing
* Inoculation = vaccination leading to infections, contaminated needles
* Hematogenous = blood borne infection spread
* Ingestion = worm infection the gut, poor hand hygiene and then touching food
* Inhalation = cold, flu, pneumonia
* Vector = infection being carried by something else – food poisoning, foreign body
* Autoinfection = transferring cheminselles (organisms living on your skin into your body)
74
Pathogen host interaction
Invasion/ attachment ---> how it enters body and causes problems
Damage:
• Pathogen that causes cholera produces toxins causing diarrhea
• Others produce toxins causing host damage, e.g. damaging the skin necrosis
• Inflammatory response of organisms infection
• Interaction with the host defenses (immune system)
= neutrophils can phagocytose or inactivate pathogens
75
4 categories of patient management
Questions
Diagnosis
Treatment
Infection prevention
76
Patient management - questions
* Where is the infection?
| * What is the Infection?
77
Patient management - diagnosis
* History = environment, travel, symptoms
* Examination = of the right organ to see if it is affected
* Investigation = target exact organism
78
Patient management - treatment
* Specific = treatment specific to that organism e.g. specific antibiotic (antivirals, antibiotics)
* Appropriate = something the patient can take e.g. if they are allergic to penicillin
* Supportive = treatment given may not be instant or give instant results, so support them (provide hydration, water or IVF, or pain medications)
79
Patient management - prevention
* How to prevent infection in community education
* How to prevent infection in hospital = infection control mechanisms
- Vaccination
- sterilization
- proper hygiene
80
2 types of investigations
Specific investigations ---> tests to identify the actual infecting agent that causes problems
Supportive investigations --> other investigations that indicate infection
81
Specific investigations - examples
For bacteria:
• Microbiology on specimen for example throat swab, sputum sample, urine sample (uti) or blood culture (if it is systemic) = gram stain
• Detection of antigens or nucleic acid (PCR)
• Blood culture
For viruses
• Antigen detection, viral nucleic acid detection (PCR)
82
Supportive investigations - examples
* Blood tests for example, full blood count (FBC),
* C reactive protein (CRP),
* liver and kidney function tests
* Imaging (X-ray, ultrasound, CT scan, MRI scan
* Blood test look for different components of the blood that are indicators of infection
83
2 types of treatment
* Specific treatment = right medication to get rid of infection (antivirals, antibiotics)
* Supportive treatment = treatment that helps patient, hydration, pain relief etc
84
Specific treatment - examples
* Antimicrobials
* Antivirals
* Antibiotics
* Surgery – in extreme cases e.g. infected replacement
* Drainage of boils
* Debridement – clean of pus and live bacteria
85
Supportive treatment - excemples
* Symptom relief = pain relief , alleviate negative effects
| * Physiological restoration = hydrate them , rehabilitation for patients with paralysis or amputation
86
Outcome -4 paths
* Infection is cured due to right treatment given
* Person is cured of their infection but due to impact of infection they are left with = disability
* Acute infection becomes chronic = not all infection can be removed (e.g. bone infection)
* death
87
Immune system definition
Cells and organs that contribute to immune defences against infectious and non-infectious conditions (self vs non-self)
• T cells be cells, macrophages, neutrophils
88
Infectious disease definition
• When the pathogen succeeds in evading and/or overwhelming the host’s immune defences
89
Immunity definition
interafce of infectious diseases and immune system
90
4 roles of the immune system
* Pathogen recognition (macrophages) = Cell surface and soluble receptors
* Containing/eliminating the infection (neutrophils) = Killing and clearance mechanisms
* Regulating itself = Minimum damage to host(resolution)
* Remembering pathogens (adaptive) = Preventing the disease from recurring
= Immuniological memory protection
91
Properties of innate immune system
```
---> contain and understand intital infection
Fast
• Fast (within seconds)
• Lack of specificity
• Lack of memory
• No change in intensity
```
92
Properties of adaptive immune system
```
--> tailors itself to organism
Very effective
Immunological memory
• Slow (days)
• Specificity
• Immunologic memory
• Changes in intensity
```
93
Innate and adaptive immune system process
* Innate and adaptive immune system happen at the same time
* They can't operate individually to be effective they work together
Innate system – ids pathogen treis to contain it
• Tells adaptive immune system cells what it is to create antibodies
Adaptive immune system produces and releases antibodies - directs innate immune system
94
First line defences
Things present on or within body to limit entry and grow of pathogens
95
4 parts of innate immunity - first line defences
* Physical barriers
* Physiological barriers
* Chemical barriers
* Biological barriers
96
Innate immunity - physical barriers
• Skin
Anything breaking skin barrier = potential cause of infection
* Mucous membranes – capture and expel pathogens from these orifices below
* Mouth
* Respiratory tract – ciliated cells
* GI tract
* Urinary tract
97
Innate immunity - physiological barriers
→ tries to eliminate infection by getting rid of whatever it is infecting
Diarrhoea
• Foodpoisoning
Vomiting
• Foodpoisoning - remove bacteria expel asap
• Hepatitis
• Meningitis
Coughing
• Pneumonia
Sneezing
• Sinusitis
98
Innate immunity - chemical barriers
Low pH → activates enzymes but also damages pathogens that can't survive in acidic conditions
- • Stomach(1-3) • Vagina(4.4)
Antimicrobial molecules
• IgA immunoglobulin that can capture and eliminate mircoorganisms from getting in the eye (Tears, saliva,mucous membrane )
• Lysozyme (sebum, perspiration, • urine)
• Mucus
• Beta-defensins(epithelium)
• Gastric acid + pepsin = within gut
99
Innate immunity - biological barriers
* Normal flora = commensals that take up space where an invading pathogen could exist good protection as they compete with pathogens
* Non pathogenic microbes
* Strategic locations
* Nasopharynx • Mouth/Throat • Skin • GI tract • Vagina (lactobacillus spp)
* Absent in internal organs/tissues
100
Normal flora examples
• Staphylococcus aureus
- upper respiratory tract t skin , can become opportunistic causing skin and respiratory infections
• Candida albicans
Opportunistic pathogenic yeast in gut flora →
• streeptoccus pneumoniae
- in nasopharynx can lead to pneumonia
101
Clinical problems → innate immunity
Normal flora
• occur when Normal flora is displaced from its normal location due to:
- breaches in skin integrity
- fecal oral route
- fecal perineal urethral route
- poor dental hygiene , denial work
102
Clinical problems → innate immunity
High risk patients - examples
* Serious infections in high-riskpatients
* Asplenic (and hyposplenic)patients = patients who have had their spleen removed don't clear infections and filter blood in the same way
* Patients with damaged or prosthetic valves (heart, hip, dental)– natural pooling of blood which leads to bacteria build up
* Patients with previous infective endocarditis - disrupted heart contractions
103
Clinical problems → innate immunity
Immuno-compromised patients
Immuno-compromised patients
* At particular risk of infection
* Even overgrowth of normal flora – this can become pathogenic if it enters body and isn't cleared easily
104
Clinical problems → innate immunity
Antibiotic therapy
Antibitoics
• Can deplete normal flora – give rise for infections to take over place where flora would have been seen
• Intestine -> severe colitis (Clostridiumdifficile)
• Vagina -> thrush (Candida albicans)
105
3 innate immunity - second line defences
* Phagocytes
* Chemicals
* Inflammation
---> factors that will contain and clear infection
106
Microbes - definition
Microroganism , especially bacterium causing disease or fermentation
107
2 types of microbes
Exogenous – from outside environment breach a barrier and enter a system below the barrier
Endogenous → skin hora
108
Innate factors
- Activate phagocytes
Eg. Complement activates phagocytes
109
Role of phagocytes
• Recognition process
• Killing process of infectious microbes
1. Phagocyte is trying to understand organism – first phagocyte = macrophage (tissue resident cells in tissue)
Macrophages eat pathogen to find out what it is and the signal neutrophils to eliminate t kill
110
3 main phagocytes
Macrophages
Neutrophils
Monocytes
111
Macrophages
▪Present in all organs
▪ Ingest and destroy microbes (Phagocytosis)
▪Present microbial antigens to T cells (adaptive immunity)
▪ Produce cytokines/chemokines = to recruit other cells
112
Monocytes
* Precurosor to macrophages
* ▪ Present in the blood (5-7%)
* ▪ Recruited at infection site and differentiate into macrophages at tissues
113
Neutrophils
• Travel all around body
▪Present in the blood (60% of blood leukocytes)
▪Increased during infection
▪Recruited by chemokines to the site of infection
▪Ingest and destroy pyogenic bacteria: Staph. aureus and Strep. pyogenes
114
4 other key cells → innate immunity
Basophils lmast cells
Eoisonophils
Natural killer cells
Dendritic cells
115
Basophils/mast cell - function
▪ Early actors of inflammation(vasomodulation)
▪ Important in allergic responses
Recruit and change conditons of membrane around tissue
116
Eoisonophils - function
▪ Defence against multi-cellular parasites (worms)
117
Natural killer cells- function
▪Kill all abnormal host cells (virus infected or malignant)
| Sit between innate and adaptive immune system
118
Dendritic cells - function
* Present microbial antigens to T cells – like phagocytes
| * Acquired immunity
119
Pathogen recognition
Microbial structures and phagocyes
Microbial structures: - things on pathogen that help us identify it
• Pathogen-associated molecular patterns (PAMPs): Carbohydrates, Lipids, Proteins, Nucleic acids
PAMPS bind to receptors on phagocytes
Phagocytes: - recognise things on pathogens
• Pathogen Recognition Receptors (PRRs): Toll Like Receptors (TLR) = help identify and internalize invading pathogen
120
Examples of pamps and prr inveraction
Lps (lipopolysaccharide) interacts with tlr4 prp
| - lps is found on surface of all gram negative bacteria
121
Pathogen recognition
Opsonisation
---> once pathogen is recognise = oppsonisation of microber = tag maicrobes so other cells can chew them up
• Coating proteins called opsonins that bind to the microbial surfaces land coat them leading to enhanced attachment of phagocytes and clearance of microbes
122
Examples of opsonins
Complement proteins
• C3 - mature adults
• C4
Antibodies
• IgG - mature adults
• IgM
Acute phase proteins – markers
• C-reactive protein (CRP) = elevated CRP in blood test = inflammation = infection
• Mannose-binding lectin (MBL)
123
Clearance of opsonised pathogens
1. neutropjil and invading organsims covered on complements and antibodies
2. Antibody and complement bind to FC receptors on neutrophil
3. Organism is internalsied and neutrophil destroys pathogen
• Phagocytes such as macrophages and neutrophils have Fc receptors on their surface which bind to the Fc region of an antibody which has formed a complex with an antigen.
– This leads to internalisation of the pathogen which has been coated in antibody
– The macrophage produces reactive oxygen species to destroy thepathogen.
124
Roles of phagocytes
Recognition - pamps, opsonins
Englufment
Degredation of infectious microbes
125
Basic phagocytosis
1. Internalized into phagosome
2. Phagosome fuse with lysosome
3. Ros and enzymes in lysosomes destroys bacteria
4. Neutrophil removes digest materials
126
2 phagocyte intracellular kiling mechanisms
Oxygen-dependent pathway (respiratory burst)
Oxygen-independent pathways
127
-Oxygen-dependent pathway (respiratory burst)
* Toxic O2 products for the pathogens:
| * Hydrogen peroxide, Hydroxyl radical, Nitric oxide, Singlet oxygen, Hypohalite
128
Oxygen-independent pathways
```
▪ Lysozyme
▪ Lactoferrin or transferrin
▪ Cationic proteins(cathepsin)
▪ Proteolytic and hydrolytic enzymes
▪ NETs (Neutrophil Extracellular Traps)
```
129
Netosis
---> The process by which neutrophils externally trap pathogens
– Release of decondensed chromatin and granule contents into the extracellular space (neutrophil genetic material) acts as a net for pathgoen
. • Can be used as a mechanism of neutrophil cell death.
• Commonly used to deal with pathogenic insult
130
Second line of defence - 2 chemicals
Complement
| Cytokines , chemokines
131
Complement system
* Activate cells and recruit cells
| * Produce membrane attack complex – complement proteins from pore and punch hole through detsroy organism
132
Complement proteins + roles
* C3a and C5a: Recruitment of phagocytes
* C3b-C4b: Opsonisation of pathogens
* C5-C9: Killing of pathogens Membrane Attack complex
133
Complement system -3 activating pathways
Classical pathway
Alternative Pathway
Mannose Binding Lectin pathway
134
Complement system - classical pathways
nitiated by antibody-antigen
| – reaction (membrane attack complex)
135
Complement system - alternative pathway
Initiated by cell surface microbial – constituents (endotoxins on E. Coli) C3 and C5
136
Complement system -Mannose Binding Lectin pathway
– Initiated when MBL binds to mannose containing residues of proteins found on many microbes (Salmonella spp. – Candida albicans)
137
Actions of cytokines
* Systemic actions
* kickstart liver to produce (opsonins) • CRP • MBL (-> complement activation)
* Bone marrow
* Neutrophil mobilization
* Hypothalamus
* Increased body temperature = fever
* Local inflammatory actions = cytokine storm initiated by macrophages
* Blood vessels
* Vasodilation
* Vascular permeability
* Expression of adhesion molecules -> attraction of neutrophils
138
3 examples of cytokines
Tnf alpha
Il-1
Il-6
139
Summary of innate response
1. Innate barrier breached: entrance and colonization of the pathogens.
2. Complement, mast cells and macrophages activation (PRR) Phagocytosis (opsonins)Cytokine/chemokine production
3. Vascular changes Vasodilation/Vascular permeability Chemoattraction Neutrophils Monocytes (TNF, IL-8)
4. Hypothalamus Fever Liver Acute phase response
5. Redness, heat, swelling andpain: local inflammatio
140
3 clinical problems when phagocytosis is reduced
* Decrease spleen function
* Asplenic patients (No spleen)
* Hyposplenic patients (reduced spleen function)
* Decrease neutrophil number (<1.8x109/l) too low can't mount the repsonse = major effector phagocyte for clearance of infection
* Cancer chemotherapy
* Certain drugs(phenytoin)
* Leukaemia andl ymphoma
• Decrease neutrophil function
• Chronic granulomatous disease (No respiratory burst)
• Chediak-Higashi syndrome (no phagolysosomes formation)
As you get older = neurtophil casues more collateral damage and don't work as well
IL8 = chemoattractant for neutrophils
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How do soap and hand alcohol gel work
Soap - traps fragments of organisms in tiny bubbles that wash away
Alcohol hand gel - actually kills pathogen via denaturation breaking down proteins
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Gram negative bacteria on skin
Enterobacteria
| E-coli
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Gram positive bacteria on skin
- Staphylococcus
- microccus
Corynebacterium
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Examples of cytokines and when they are released
Vasodilatation – Histamine, Serotonin, Prostaglandins, Nitric Oxide
Increased vascular permeability – Histamine, Bradykinins, Leukotrienes, C3a & C5a
Chemotaxis – C5a, LTB4, TNF-alpha, IL-1, Bacterial Peptides
Fever – Prostaglandins, IL-1, TNF-a, IL-6
Pain – Bradykinin, Substance P, Prostaglandins
