Infection 1-6 Flashcards

1
Q

What are the 4 steps of the Koch Henle Postulates?

A
  1. Isolate the organism from every case
  2. Propagate in pure culture in vitro
  3. Re-inoculate and produce disease
  4. Re-isolate
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2
Q

What are the key differences between Koch’s postulates and diagnosis?

A

Koch’s - Isolates SAME organism from MANY patients and isolates able to reproduce disease in model

Diagnosis - ONE isolate from ONE patient. Identify if the organism is a recognised pathogen.

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3
Q

How can microbes be classified biologically?

A

Prokaryote
Eukaryote
Viruses

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4
Q

How can microbes be classified medically?

A

Pathogen
Non-pathogen
Opportunistic pathogen

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5
Q

What are the main differences between eukaryotes and prokaryotes?

A

Eukaryotes have membrane bound organeles and multiple chromosomes. Prokaryotes only have one and transcription/translation is coupled (compartmentalised in eu.). Ribosomes - 30+50S=70S pro. 40+60S=80S eu.

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6
Q

How do viruses infect the host?

A

Obligate intracellular parasites that multiply using the host cell’s biosynthetic machinery.

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7
Q

What is a bacteriophage?

A

Virus which infects bacteria

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8
Q

What are the principle characteristics of innate immunity?

A

Rapid response
Invariant
Limited number of specificities
Constant during response

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9
Q

What are the principle characteristics of adaptive immunity?

A

Slow response
Variable
Numerous highly selective specificities
Improve during response

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10
Q

How do neutrophils act?

A

Phagocytosis and killing of microorganisms. Granules contain numerous bactericidal substances.
Phagocytosis particles opsonised by IgG or compliment and functions as effector cell of humoral immunity

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11
Q

How do eosinophils act?

A

Killing of antibody-coated parasites through release of granule contents - highly basic or ‘cationic’ proteins
Bind avidly to IgE-coated particles

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12
Q

Describe the nucleus of a neutrophil (polymorph)

A

multilobed

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13
Q

What type of white blood cells are common at the site of an allergic reaction?

A

Basophils and eosinophils

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14
Q

What is a basophil and how does it work?

A

A leucocyte with large basophilic granules which contain heparin, histamine and other vasoactive amines. Granules released at the site of inflammation and in immediate hypersensitivity (allergic) reactions
Express high affinity receptors for IgE - interaction causes the release of basophil granules

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15
Q

What is a mast cell?

A

A tissue cell which is not bone marrow derived but otherwise similar to its circulating counterpart, the basophil

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16
Q

What is the largest nucleated cell of the blood?

A

Monocyte - 16-20 micrometers.

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17
Q

What is a macrophage?

A

Antigen presenting cell
Mature monocytes
Strongly phagocytic
Receptors for Ig and complement

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18
Q

What are natural killer cells?

A

Type of lymphocyte able to kill virus infected cells and certain types of cancer cells
Large cytoplasmic granules distinguish them microscopically

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19
Q

How do NK cells and cytotoxic T cells act differently?

A

NK act independently of antigen presentation and recognition, which is necessary for the action of T cells

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20
Q

What are dendritic cells?

A

Antigen presenting cells. Possess long processes which interdigitate between lymphoid cells and interdigitate between lymphoid cells and present antigens to them.

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21
Q

What is a B lymphocyte and where is it derived?

A

Precursor of antibody-forming cells. Bone marrow derived

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22
Q

What is a plasma cell?

A

The B lymphocite in its high-rate antibody secreting state. Rarely seen in the blood, but found in spleen, lymph nodes etc whenever antibody is being made.

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23
Q

From where are T lymphocytes derived?

A

Thymus

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24
Q

What are the primary lymphoid organs?

A

Bone marrow where T and B lymphocytes are made. Thymus where T lymphocytes mature/are selected

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25
What are the secondary lymphoid organs?
Eg. Spleen, lymph nodes nad peyers patches. Contain T cells, B cells, antigen presenting cells
26
What cells constitute the bone marrow stroma?
``` Fibroblasts (reticular connective tissue) Macrophages Adipocytes Osteoblasts Osteoclasts Endothelial cells forming the sinusoids ```
27
What are the 3 types of stem cells present in bone marrow?
Haematopoietic - wbc, rbc and platelets Mesenchymal - gatekeeper cells of marrow Endothelial stem cells
28
What is aplastic anaemia?
Bone marrow does not produce sufficient new cells to replenish blood cells. Deficient in all blood cell types. Idiopathic or autoimmune - wbc attack bone marrow
29
Describe the development of T cells.
Precursors arrive at thymus from bone marrow. Cortex and medulla educate thymocytes into mature competent T cells. Mature T cells are released into the peripheral.
30
What are thymocytes?
Precursor lymphocytes from the bone marrow which enter the thymus via blood vessels. Proliferate and mature in the thymus. 1-3% survive the selection process that allows mature T cells to enter the peripheral circulation.
31
Name 2 diseases associated with Thymus disease.
Severe combined Immunodeficiency - SCID | DiGeorge Syndrome - genetic disorder causesd by deletion of a small setion of chromosome 22
32
What type of cells are CD3,4,8,16 and 19?
``` CD3 T cells CD4 Helper T cells CD8 Cytoxic T cells CD16 Macrophages CD 19 B cells ```
33
Describe the path of B cells through lymph nodes.
Travel from the blood stream entering the cortex via high endothelial venules. Leave via efferent lymph.
34
What happens when a B cell encounters an antigen?
Forms primary foci from which proliferating cells migrate to the primary follicle forming a secondary follicle with a germinal centre. A few weeks after it forms, the germinal centre reaction dies down.
35
What may cause lymph nodes to enlarge?
``` Infection Virus Inflammation Cancer Caner of the blood ```
36
What is GALT?
Gut Associated Lymphoid Tissue
37
What is MALT?
Mucosa Associated Lymphoid Tissue
38
What is SALT?
Skin Associated Lymphoid Tissue
39
What are tonsils?
Mass of lymphoid tissue in submucosa of oropharynx. Many lymphoid follicles, mostly with germinal centres
40
What are Peyers patches?
Organised patches of lymphoid follicles int he submucosa of the gut, mainly the ileum
41
What is an infection?
``` Invasion of a host's tissues by microorganisms Disease caused by: - microbial multiplication - toxins - host response ```
42
What is microbiota?
"commensals" Microorganisms carried on skin and mucosal surfaces Normally harmless or even beneficial transfer to other sites can be harmful
43
How may infections be spread?
``` Physical contact Airborne Vector may be necessary Ingestion Inhalation Mother to child - vertical transmission ```
44
What determines the disease caused by an infection?
``` Pathogen: - virulence factors - inoculum size - antimicrobial resistance Patient: - site of infection - co-morbidities ```
45
How do you determine if a patient has an infection?
History - symptoms/exposure Examination Investigations - specific/supportive
46
How do microorganisms cause disease?
Exposure -> adherence -> Invasion -> Multiplication -> Dissemination
47
What are virulence factors?
Factors of viruses that cause disease - exotoxins e.g.. cytolytic, AB toxins, Superantigens, enzymes and endotoxins
48
What are some supportive investigations?
``` Full blood count C reactive protein Blood chemistry Imaging Histopathology ```
49
Name some tests you might use to determine specific infection bacteriology.
Specimen type M, C & S - microscopy, culture and sensitivity (antibiotic susceptibility) Antigen detection Nucleic acid detection
50
Name some tests you might use to determine specific infection virology
Antigen detection Antibody detection Detecting viral nucleic acid
51
What are the 2 semi-independent parts of the lymphatic system?
Lymphatic capillaries and vessels | Lymphoid tissues and organs
52
What is the function of the lymphatic system?
Fluid balance Fat absorption Defence
53
What is the lymphatic system?
A network of vessels that assist in circulating fluids - excess fluid away from interstitial spaces to the blood stream
54
What is the structure of lymphatic capillaries?
Tiny closed end vessels consisting of simple squamous epithelium. More permeable than blood vessels because they lack a basement membrane. Resemble small veins, one way valves
55
How are lymphatic vessels compressed?
Contraction of surrounding smooth muscle Periodic contraction of smooth muscle in lymphatic vessel wall Pressure changes in the chest during breathing
56
Where does the right lymphatic duct converge and empty into?
Upper right limb and right half of head, neck and chest and empties into right subclavian vein
57
Where does the thoracic duct converge and empty into?
Rest of body (compared to right lymphatic duct) and empties into the left subclavian vein
58
What are the lymphoid organs?
Lymph nodes Tonsils Spleen Thymus gland
59
Describe the structure of lymph nodes.
Rounded structures distributed along the lymphatic vessels Outer part - cortex. Follicles with germinal centre (contains dividing lymphocytes) Inner part - medulla. Contains phagocytic macrophages.
60
What are lacteals?
Special lymphatic vessels located in the lining of the small intestine -. fat enters lymphatic vessels and then venous circulation
61
What is chyle?
Lymph that is milky in appearance due to fat.
62
How does the lymphatic system act in the bodies defensive mechanisms?
Removes organisms and foreign substances from the lymph | Associated with activation of the immune system.
63
What is the collective term for lymph node enlargement?
Lymphadenopathy - may be due to lymphadenitis (painful and responding to foreign antigen) or metastatic cancer (usually painless and firm)
64
What is the function of tonsils?
Trap and remove bacteria and other foreign materials
65
How is tonsillitis caused?
Congestion of bacteria.
66
What is the spleen?
The largest lymphatic organ containing sinuses filled with blood. 2 tissue types - red and white pulp.
67
What is red pulp?
Receives arterial blood which passes into venous sinuses. Lined by macrophages - removes old red cells and recycles iron
68
What is white pulp?
T and B cell compartments with macrophages and other immune cells.
69
What is the function of white pulp?
Recognise pathogens, remove pathogens and activate T cells and B cells
70
How does age affect the thymus?
Largest at infancy and during puberty, small in an adult and replaced by fat and connective tissue in the elderly.
71
What is the function of the thymus?
Site of T lymphocyte production | Secretes protein hormones called thymosins
72
What are the main types of fungi?
Yeast | Mould
73
What are the 2 most common types of pathogenic parasites in humans?
``` Protozoa Helminth (worm) ```
74
How does age affect immunity?
Different antibodies at different ages - inter-uterine from mother etc
75
How does gender affect immunity?
Hormones | Anatomy - UTI
76
How do social factors affect immunity?
What you are exposed to.
77
How does time affect disease?
Calendar time - weather, temperature etc | Relative time - time since being somewhere (?)
78
How does where a patient has been affect their chances of disease?
Some diseases are more common in different countries/places and people who have visited are less likely to have immunity than those that live there. Therefore, where they currently live and have recently visited can affect their health
79
Name some mechanisms of infection
``` Contiguous spread Inoculation Haematogenous Ingestion Inhalation Vector Vertical transmission ```
80
What 3 things is a diagnosis based on?
History Examination Investigation
81
What specific treatments might be given for an infection?
Antimicrobials | Surgery - drainage, debridement, dead space removal
82
What supportive treatment might be given for an infection?
Symptom relief | Physiological restoration
83
What is a purpuric rash?
The appearance of red or purple discolouration on the skin that does not blanch on applying pressure. Looks like bleeding under the skin. 3-10 mm diameter of spots
84
What are the clinical features of sepsis?
``` Systemic inflammatory response syndrome A response to a non-specific insult Two or more of: - Temperature 38 - Heart rate >90 - Resp. rate >20/min WBC 12x10^9/L ```
85
What is bacteraemia?
Presence of bacteria in the blood
86
What is septicaemia?
Clinical term meaning generalised sepsis
87
What is sepsis?
The systemic response to infection - SIRS + documented/presumed infection
88
Define severe sepsis.
SIRS + organ dysfunction/hypoperfusion (hypotension, decreased urine output)
89
Define septic shock.
Severe sepsis + persistently low blood pressure despite administration of intravenous fluids
90
What is the common bacterial pathogen to cause meningococcal meningitis in a teenager and how is it spread?
Neisseria meningitidis. Spread by direct contact with respiratory secretions. Most people are harmlessly colonised but in the unlucky few, rapidly progressive.
91
How is low blood pressure caused in a septic patient despite the high pulse rate?
Endotoxins that the bacteria release cause vasodilation, decreasing total peripheral resistance. Mean arterial blood pressure = Total peripheral resistance + Cardiac output
92
What is the role of a pilus on a bacterial cell?
Enhances attachment to other cells
93
What does the polysaccharide capsule on a bacterial cell do?
Promotes adherence | Prevents phagocytosis
94
In the inflammatory cascade, what are the local effects of cytokines?
Stimulate inflammatory response to promote wound repair and recruit RE system
95
In the inflammatory cascade, what are the systemic effects of cytokines?
Stimulating growth factor, macrophages and platelets. Goal is homeostasis. Lead to activation of humoral cascade and RE system
96
How can the release of cytokines cause organ ischaemia, dysfunction and failure?
Cytokines initiate the production of thrombin and also inhibit fibrinolysis Coagulation cascade leads to microvascular thrombosis... Microvascular injury is the major cause of shock and multiorgan failure
97
What urgent investigations would you order on someone with sepsis?
``` Full blood count, urea and electrolytes EDTA bottle for PCR Blood sugar Liver function test C-reactive protein Clotting studies Blood gases ```
98
What are the sepsis 6 and when must they be delivered?
Within 1 hr: Deliver high flow oxygen Take blood cultures and other cultures and consider source Administer empirical IV antibiotics Measure serum lactate Start IV fluid resuscitation Commence accurate urine output measurement
99
What are the requirements for an antibiotic for meningitis?
Active against the pathogen that penetrates the CSF | Empiric choice is ceftriaxone
100
What are some life threatening complications of sepsis?
``` Irreversible hypotension Respiratory failure Acute kidney injury Raised intracranial pressure Ischaemic necrosis of digits/hands/feet ```
101
How is a diagnosis of sepsis confirmed?
Blood culture PCR of blood Lumbar puncture (if safe) - culture of CSF and PCR
102
What is the cerebrospinal fluid examined for in sepsis?
Appearance - turbidity and colour Microscopy - WBCs and RBCs Gram stain Referral for PCR
103
Describe Neisseria meningitidis.
Gram-negative diplococcus Numerous serogroups based on polysaccharide capsular antigen - evades immune response by preventing phagocytosis Outer membrane acts as an endotoxin
104
What % of adults may be carriers of meningococcal disease?
25%
105
How is meningococcal disease spread?
aerosols and nasopharyngeal secretions. Acquired by clearance, carriage or invasion
106
What is the most common group of meningococcal disease?
In England, 1000 cases/yr mainly group B, fatality rate approx 10% but elsewhere, group A predominates. 'Meningitis belt' across Africa.
107
Describe some preventions of meningitis.
Meningococcal C conjugate vaccine ACWY vaccines available for immunocompromised patients and travel protection People in close contact to patients can be given antibiotic prophylaxis and considered for vaccinations
108
Why is there no vaccine in routine use for meningococcal group B?
B capsule poorly immunogenic and similar to neural tissue. | Vaccine developed after screening candidate proteins from genome
109
Define the immune system.
Cells and organs that contribute to immune defences against infectious and non-infectious substances
110
Define infectious disease.
When the pathogen succeeds in evading and/or overwhelming the host's immune defences.
111
What are the roles of the immune system?
Pathogen recognition Containing/eliminating the infection Regulating itself Remembering pathogens
112
What type of barriers can the innate immune system form?
``` Physical barriers Physiological barriers Chemical barriers Biological barriers (limit entry and growth of pathogens) ```
113
What physical barriers does the innate immune system provide?
Skin Mucous membranes Bronchial cilia
114
What physiological barriers does the innate immune system provide?
Diarrhoea Vomiting Coughing Sneezing
115
What are the chemical barriers of the innate immune system?
Low pH - skin, stoomac, vagina | Antimicrobial molecules - IgA, lysozyme, mucous, beta-defensins, gastric acid and pepsin
116
What are some biological barriers of the innate immune system?
Normal flora - non pathogenic microbesin strategic locations eg nasopharynx, mouth, skin, GI tract, vagina etc. Absent from internal organs
117
What are the benefits of normal flora?
Compete with pathogens for attachment site and resources Produce antimicrobial chemicals Synthesize vitamins
118
What are some examples of normal flora that inhabit the skin?
``` Staphylococcus aureus Staphylococcus epidermidis Streptococcus pyogenes Candida albicans Clostridium perfingens ```
119
What are some examples of normal flora that inhabit the nasopharynx?
Streptococcus pneumoniae Neisseria meningitidis Haemophius species
120
How might normal flora be displaced from its normal location to a sterile location?
Breaching the skin integrity - skin loss, surgery, injection drug users, IV line Fecal-oral route - food borne infection Fecal-perineal-urethral route - urinary tract infection (women) Poor dental hygiene/dental work (most common) - dental extraction, gingivitis, flossing
121
Who are considered to be high risk patients for infection?
Asplenic (and hyposplenic) Patients with damaged or prosthetic valves Patients with previous infective endocarditis Would be given antibiotic prophylaxis
122
When might normal flora overgrow and become pathogenic?
When host is immune-compromised - diabetic, AIDS, malignant disease, chemotherapy
123
When might normal flora be depleted by antibiotics?
Intestine -> severe colitis (Clostridium difficile) | Vagina -> thrush (Candida albicans)
124
What is the second line of defence in innate immunity?
Phagocytes and chemicals -> inflammation (factors that will contain and clear the infection)
125
How are pathogens recognised?
Microbial structures: Pathogen-associated molecular patterns (PAMPs): carbohydrates, lipids, proteins, nucleic acids recognised by: Phagocytes: Pathogen Recognition Receptors (PRRs): Toll like receptors Opsonins might bind to the microbial surfaces leading to an enhanced attachment of phagocytes and clearance of microbes
126
What are some examples of PAMPs and PRRs for gram negative bacteria?
Lipopolysaccharide (LPS) -> TLR4 Lipoprotein and lipopeptides -> TLR2 Porins
127
What are some examples of PAMPs and PRRs for gram positive bacteria?
Peptidoglycan -> TLR2 | Lipoteichoic acids -> TLR4
128
What are some examples of PAMPs and PRRs for all mycobacteria?
Lipoarabinomannan -> TLR2 | Mannose-rich glycans
129
What is an example of a PAMP and PRR for Bacterial flagella?
Flagellin -> TLR5
130
Give some examples of opsonins.
Complement proteins eg C3b and C4b Antibodies - IgG, IgM Acute phase proteins - C-reactive protein (CRP), manose-binding lectin (MBL) Theses are essential in clearing encapsulated bacteria
131
How do phagocytes act?
Recognise PAMPs/opsonins, engulf and degrade infectious microbes
132
What are the 2 pathways by which phagocytes might kill pathogens?
Oxygen-dependent pathway (respiratory burst) | Oxygen-independent pathways
133
How does the oxygen dependent pathway by which phagocytes may kill pathogens work?
Produces toxic O2 products for teh pathogens: Hydrogen peroxide, hydroxyl radical, nitric oxide, singlet oxygen, hypohalite
134
What are the oxygen independent pathways by which a phagocyte might destroy a pathogen?
Lysozyme Lactoferrin or transferrin Cationic proteins Proteolytic and hydrolytic enzymes
135
What are the 2 activating pathways of the complement system?
Alternative pathway - initiated by cell surface microbial constituents MBL pathway - Initiated when MBL binds to mannose containing residues of proteins found on Salmonella app. Candida albicans
136
What do serum proteins C3a and C5a do?
Recruit phagocytes
137
What do serum proteins C3b -C4b do?
Opsonisation of pathogens
138
What do serum pathogens C5-C9 do?
Kill pathogen's membrane and attack complex
139
What do cytokines/chemokines do?
chemoattraction phagocyte activation inflammation
140
What are the anti-microbial actions of macrophage-derived TNF/IL-1/IL-6?
Liver (opsins) - CRP and MBL (-> complement activation) Bone marrow - Neutrophil mobilisation Inflammatory actions - Vasodilation Vascular permeability Adhesion molecules -> attraction of neutrophils Hypthalamus - increased body temperature
141
How does an infection cause sepsis and multi-organ failure?
Infection activates microbial toxins (LPS) which can cause overreaction of TLR4 receptor and complements. This can cause an excessive inflammatory response which leads to sepsis and multi-organ failure.
142
How does an excessive inflammatory response lead to decreased tissue/organ perfusion?
cytokine shower coagulopathy vasodilation capillary leak
143
Why might phagocytosis be reduced?
Decrease spleen function (asplenic/hyposplenic) Decrease neutrophil number (cancer chemo, certain drugs, leukaemia and lymphoma) Decrease neutrophil function (chronic granulomatous disease (no reps burst), Chediak-Higashi syndrome (no phagolysosome formation))
144
What are the 5 stages of innate immunity?
1. Innate barriers 2. Compliment, mast cells and macrophages activation (PRR) 3. Vascular changes and chemoattraction 4. Hypothalamus and liver are involved 5. Redness, heat, swelling and pain - local inflammation
145
What is the mechanism of action of the first line of defence in innate immunity?
Limit entry and growth of pathogens at portals of entry
146
What is the mechanism of action of the second line of defence in innate immunity?
Contain and eliminate the infection
147
What are healthcare infections?
Infections arising as a consequence of providing healthcare. In hospital patients neither present nor incubating at time of admission. For practical purposes, this means onset is at least 48 hrs. Also includes infections in hospital visitors and healthcare workers
148
Why are healthcare infections important?
Frequent - prevalence = 8% of in-patients Impact on health Impact on healthcare organisations Preventable Av of 1 day extra in hospital (not everyone gets them but can stay in hospital for 10 days...)
149
What type of HCAI is most common(roughly)?
GI - 21% UTI - 20% Varies across hospitals and departments
150
How might you prevent infection?
Prevent pathogen entering Prevent the mechanism of infection Prevent infection occurring
151
What are some common healthcare infection viral pathogens?
Blood borne (Hep. B/C, HIV) Nonovirus Influenza Chicken pox
152
What are some common healthcare infection bacterial pathogens?
Staph aureus inc. MRSA (MSSA more common than MRSA) Clostridium difficile Escherichia coli, Klebsiella pneumoniae Pseudomonas aeruginosa Mycobacterium tuberculosis - histopathologists
153
What are some common healthcare infection fungi pathogens?
Candida albicans | Aspergillus species
154
What are some common healthcare infection parasites?
Malaria
155
What risk factors are common in patients that make them more susceptible to infection?
``` Extremes of age Obesity/malnourished diabetes cancer immunosuppression smoker surgical patient emergency admission ```
156
What are the 4 Ps of infection, prevention and control?
Patient - risks/interactions with other people Pathogen - virulence/ecological factors Practice (of the hospital and staff) Place - fixed and variable features (beds in a bay, patients:toilets
157
How can we prevent patients becoming infected?
``` General: optimise patient's condition Antimicrobial prophylaxis Skin prep Hand hygiene ``` Specific: MRSA screens Mupirocin nasal ointment Disinfectant body wash
158
How might we halt patient to patient transmission of HCAI?
Physical barriers: Isolation of infected patients Protection of susceptible patients
159
How can HCAI be prevented from transferring from healthcare professionals to patients?
Healthcare workers should be disease free and vaccinated Good practice: Good clinical techniques (eg. sterile non-touch) Hand hygiene PPE - personal protective equipment Antimicrobial prescribing
160
What are some environmental features that may contribute to HCAI?
``` -Built environment: space/layout Toilets Wash hand basins - Furniture and furnishings - Cleaning: - Medical devices - Appropriate kitchen and ward food facilities -must have good food hygiene practice - Theatres/patient rooms - positive/negative pressure rooms. ```
161
How must the hospital be cleaned?
Disinfectants Steam cleaning Hydrogen peroxide vapour - v toxic to vapour and humans - whole, empty room.
162
How must medical devices be cleaned to prevent HCAI?
Single use equipment Sterilisation Decontamination
163
Why is travel history important?
Imported disease Different strains of pathogen - antigenically different, impacts on protection and detection, antibiotic resistance Infection prevention - on the ward and in the lab
164
What are the key aspects of the travel history?
``` Where When How (direct or via) Accommodation How long Specific risks (including sexual contacts) Preventive measures ```
165
What are the 4 main species of malaria?
Plasmodium falciparum, vivax, ovals and malariae
166
How many deaths does malaria cause each year?
1 million (250 million cases)
167
How is malaria spread?
Vector - female Anopheles mosquito (contained in salivary gland) No case-to-case spread but cryptic and iatrogenic cases rarely reported
168
What is the incubation period of malaria?
1-3 weeks after bite
169
What will the presenting history of a patient with malaria be?
Starts non-specific - headache, cough, fatigue, malaise, athralgia, myalgia Fever chills and sweats which eventually cycled every 3rd or 4th day
170
What would you expect to see on examination of a patient with malaria?
Other than fever often few signs (+/- splenomegaly) Cerebral features - coma Respiratory distress - metabolic acidosis, pulmonary oedema
171
What investigations would be done to confirm malaria?
Blood smear to detect parasite FBC, U&Es , LFT, glucose Head CT if CNS symptoms
172
What treatment would be given to a patient with malaria?
Dependent on species: P. falciparum ('maignant') - quinine or artemisinin P. ovale, vivax malariae ('benign') - chloroquine +/- primaquine ( for exo-erythrocytic phase)
173
Hw can malaria be prevented?
Assess risk Bite prevention Chemoprophylaxis
174
What is the mechanism of infection of typhoid?
Faecal-oral from contaminated food/water source is cases or carrier. Widely distributed in some countries due to poor sanitation
175
Who is typhoid most common in?
Children
176
What organisms might cause Typhoid?
Salmonella enterica serovar Typhi/paratyphi A, B or C Entericobacteriaceae, aerobic gram - rod Non-lactose fermenter
177
What is the virulence of salmonella?
Gram - endotoxin, VI antigen Invasion which allows intracellular growth Fimbriae adhere to epithelium over ileal lymphoid tissue (Peyers patches) -> RE system
178
What are the 2 phases of malaria?
Exo-erythrocytic (liver - asymptomatic) and erythrocytic (RBCs - fever etc)
179
What are the signs and symptoms of enteric fever (typhoid)?
``` Systemic disease with fever and headache Incubation period 7 - 24days Abdominal discomfort Constipation Dry cough Hepatosplenomegaly Occasionally rash Relative bradycardia Complications include intestinal haemorrhage and perforation Paratyphoid is generally milder ```
180
What would be seen on investigation of an enteric fever?
Moderate anaemia Relative lympopenia Raised LFTs (transaminase and bilirubin) Culture of blood and faeces taken Serology (antibody detection) no longer used
181
What treatment would be given to someone with enteric fever?
Antibiotics - usually ceftriaxone or azithromycin for 7 - 14 days
182
How might enteric fever be prevented?
Food and water hygiene precautions Typhoid vaccine to high risk travellers and lab personnel - Vi capsular polysaccharide antigen or live attenuated vaccine Protective effect - 50 - 75%
183
Other than typhoid, what else might a salmonella infection cause?
'Food-poisoning' eg. Salmonella typhimurium or Enteritidis Widespread distribution Diarrhoea, fever, vomiting, abdominal pain Generally self limiting but bacteraemia and deep-seated infections may occur
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What type of organism is Brucellosis?
A zoonosis - primary animal pathogen eg B. abortus (cattle), B. melitensis (goats and sheep) Gram negative coccobacillus
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How is Brucellosis transmitted?
Through skin breaks/GI tract
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What are the signs and symptoms, how is a diagnosis made and what is the treatment of Brucellosis?
Non-specific febrile illness - undulant fever Bone/joint involvement, epidydimitis Diagnosis from blood culture Treat with doxycycline and rifampicin
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What is the virion of a virus?
Genome (nucleic acid) + capsid (protein surrounding genome)
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What are the stages of replication of a virus?
``` Adsorption Entry Uncoating Transcription Virion synthesis Assembly Release ```
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How might you detect an infection (what do you look for)?
Antibodies Antigen By PCR
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How are blood borne viruses transmitted?
Blood Sex Therefore if they have one, may have another so must check for all
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How does silent transmission of BBVs occur?
Asymptomatic period so may transfer then
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Describe the pathogen of HIV.
Retrovirus Single stranded RNA HIV-1 from chimpanzee HIV-2 from sooty mangabey
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How do HIV affect the host cell?
``` Attach to CD4 cell Reverse transcriptase makes DNA from teh RNA Integration into host nucleus Reproduction of viral components Assembly of new HIV viruses Released ```
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What are the symptoms of primary HIV illness?
``` Fever Rash Flu-like Weight loss Pharyngitis Generalised lymphadenopathy Immune system deteriorates so other disease present ```
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What is classified as AIDs?
CD4 count less than 200
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What tests would you do for HIV?
``` Standard - CVS, resp, abdomen, neurology... MOuth Eye Skin Genitals Lymphs ```
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How is HIV diagnosed?
``` HIV 1&2 comined ab/ag test (window period) 2 week Immunoblot HIV viral load Resistance profile CD4 ```
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What investigations are ordered for a patient with known HIV?
General organ systems Status of HIV/immune system Infections - other BBV, opportunistic infections, past history Underlying co-morbidities
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What can you do for a person with HIV? How can you iproce their life?
``` Prevent related disease - undetected viral load, increase CD4 Reduce co-morbidity and mortality Improve quality of life Prevent resistance Prevent transmission ```
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How do you treat HIV?
3 drugs acting in defferent parts of the lifecycle HAART patient must be compliant
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How can you prevent HIV?
``` No sex Use condoms Know who you are having sex with No IVDU Use clean needles if you are Screened negative blood for transfusions ```
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How can you reduce the risk of HIV transmission?
Don't breast feed if safer - if not, only 6 months Circumcision Pre exposure drugs Post exposure drugs - antiretroviral drugs Vaccination not yet established
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Describe the Hepatitis virus.
Hepadnaviridae double stranded DNA virus Genotype A-D
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What is the difference between acute and chronic Hep B?
Acute - fever, surface antigen, antibody produced -> cured Chronic - body doesn't heal itself - liver cirrhosis Both can also cause liver failure
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What signs will a patient with Hep B present with?
Jaundice | Signs of chronic liver disease
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What is practice-staging of Hep B?
Combination of different specific antigens/antibody tests - acute - chronic - past - vaccinated
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WHat investigations will be done on a patient with suspected hep B?
``` General state Liver function Other BBV/STI Cancer screening Other causes of liver disease Image liver - biopsy/ultrasound endoscopy for oesophageal viruses Any complications from liver damage ```
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What should be done for a patient with hep B?
Monitor viral load, liver function and complications Decide when to give antivirals Monitor antiviral side effects Prevent other liver disease
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What is given for Hep B?
Usually single drugs - supression rather than cure | Follow NICE 2013 guidelines - interferon, tenofovir
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How can the transmission of hep B be prevented?
``` Vaccination - generalised/targeted Safe sex Mother to child interventions Screening blood/products Post exposure prophylaxis - needlestick injury ```
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Describe the pathogen of Hep C.
Single stranded RNA Flavivirus 6 genotyeps
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How is hep C mostly transmitted?
Injecting drug use most common | Also through sexual transmission but less common (more common for B and HIV)
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How can Hep C be fatal?
Cause liver cancer
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What type of Hepatitis is curable?
Hep C
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Where are antigen presenting cells present?
``` Skin (SALT) Mucu membrane (GALT, NALT, BALT) Lymphoid organs (lymph node, spleen) Blood circulation (plasmacytoid and myeloid DCs) ```
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How are pathogens captured?
Phagocytosis (whole microbe) | Micropinocytosis (soluble particles)
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How do pathogen sensors differ?
``` Extracellular pathogens (bacteria) -present to CD4+ T cells - humoral immunity Intracellular pathogens (viruses) - present to CD8+ T cell - cell dependent immunity ```
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Where do interdigitating dendritic cells exist?
Lymph nodes - present to T and B cells
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Where are langerhans' cells present?
Skin - present to T cells
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What class of molecules are found on all nucleated cells?
Class I
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Where are class II molecules found?
Dendritic cells Macrophages B cells
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What are the key features of MHC class I and class II molecules?
Co-dominant expression - Both parental genes are expressed -> increase number of different MHC molecules Polymorphic genes - different alleles among different individuals -> increase presentation of different antigens/microbe
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What ain the main function of MHC class I molecules?
Present viral peptides
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What is the main function of MHC class II molecules?
Present bacterial peptides
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What is the structure of MHC class I and class II molecules?
``` Peptide binding cleft - variable region with highly polymorphic residues Broad specificity - Many peptides presented by the same MHC molecule Responsive T cells - MHC class I: CD8+ T cells, class II: CD4+ T cells ```
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What are Elite Suppressors?
Long term nonprogressors (LTNP) can control viral replication. Dependent on MHC molecule presen - HLA-B27, B51, B57 present key peptides for teh survival of the virus causing an effecting T cell response Rapid progressors have HLA-B35 and are homozygotes in HLA-1 alleles. This icauses a mutation in the less critical peptides presented by MHC I causing weak T cell response
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What molecule is mismatched in a rejected transplant organ?
HLA molecule. Graft-versus-host reaction
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How is HLA associated with autoimmune disease?
Ankylosing spondylitis - HLA-B27 in 90% of patients | Insulin-Dependent Diabetes Mellitus - HLADQ2 -> 50-75% of patients
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What is a common problem with MHC molecules? Give examples.
Cross reactivity between microbial and host antigens Rheumatic heart disease - Streptocoocus progenies and antigen in cardiac muscle Guillain-Barre syndrome - Campylobacter jejuni and Myelin-associated gangliosides Type 1 diabetes - Coxsakieviruses (A2, A5 and A9) and pancreatic islet cells
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What type of T cells are there?
CD3+, CD4+ (TH1 and TH2 cells) | CD3+, CD8+ (cytotoxic T cells or TC)
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What is the function of CD8+ T cells?
Protect against intracellular pathogens
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What is the function of CD4+ T cells?
Provide help for antibody production and regulate immune response
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What cytokines are produced by CD4+ cells?
TH1 cells: TNFalpha, IFNgamma | TH2 cells: IL-4, IL-5, IL-10
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How are naive CD4 T cells activated?
``` Professional antigen presenting cells engulf foreign material and bring to lymph nodes. Here they begin to present antigens which are bound to MHC class II allowing CD4+ cells that express the specific TCR cells against the peptide/MHC complex to activate. Verification that it is a foreign cell and not self, must then come from CD28 on the T cell and B7 on the APC (co-stimulatory molecules). ```
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What happens to a CD4+ T cell that is not verified?
It becomes anergic - will not respond to any foreign cells in the future. Eventually apoptose
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How are naive CD8 cells activated?
Same as CD4+ BUT MHC I instead of MHC II are presented by APC
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What are the functions of CD4+ TH1 cells?
Cell-mediated immunity against intracellular microbes Killing of infected cells - cytotoxic T cells, natural killer cells Phagocytosis - macrophages (IFNgamma) Antibody production (B cells) - IgG1-3
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What do CD8+ cells produce that kill infected cells?
Perforins | Granzymes
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What are the functions of TH2 CD4+ T cells?
Humoral immunity against extracellular microbes Killing of parasites - eosinophils (IL-5) Antibody production - B cells (IgG4) Mast cell activation - IgE Mucosal protection - IgA
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How are naive B cells activated?
By CD4+ T helper cells through immunological synapse. T cell independent - Type 1 - B cell binds to antigen and receives secondary activation by toll-like receptors. Then limited to IgM antibodies that are specific TLR-binding antigen Type 2 - Antigens that are expressed on the surface of pathogens with an organised and repetitive form can activate B cells by cross-linking of antigen receptors in a multi-valent fashion. Many bacteria have repeating carbohydrate epitopes that stimulate B cells, cross linking their IgM antigen receptors, leading to IgM synthesis in the absence of T cell stimulation.
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What are some characteristics of the humoral response?
``` Fast Strong Long duration High affinity Isotype switch ```
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What are the functions of IgG antibodies?
Fc-dependent phagocytosis Complement activation Neonatal Immunity Toxin/virus neutralisation
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What is the function of IgA antibodies?
Mucosal immunity
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What are the functions of IgE antibodies?
Immunity against helmiths | Mast cell degranulation (allergies)
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What is the function of IgM antibodies?
Complement activation
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What medical achievements have been derived from study of the adaptive immune system?
``` Disease prevention - vaccination/active immunisation Immunoglobulin therapies - immune deficiencies Immediate protection - passive immunity (antibody transfer) Diagnostic tests (antibody based) - infectious diseases, autoimmune diseases, blood type and HLA types ```