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MBBS - Y1 > Week 3 - infection and immunity > Flashcards

Week 3 - infection and immunity Flashcards

1
Q

Describe the presentation of fevers. (LO1)

A
  • Rigors.
  • Night sweats.
  • Excessive sweating.
  • Recurrent fever.

Accompanying features:

  • Severe headache and photophobia.
  • Delirium.
  • Myalgia.
  • Shock may accompany severe infections and sepsis.
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2
Q

Describe the history-taking aspect of investigations of fevers. (LO1)

A
  • Presenting complaint.
  • System review.
  • Past medical history.
  • Medication history.
  • Allergy history.
  • Family history.
  • Contact history.
  • Travel history.
  • Occupation.
  • Recreational pursuits.
  • Animal exposures.
  • Dietary history.
  • Sexual history.
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3
Q

Describe the clinical investigations of fevers. (LO1)

A
  • Full blood count (FBC).
  • Urea and electrolytes (U+Es).
  • Liver function tests (LFTs).
  • Blood glucose.
  • Muscle enzymes.
  • Inflammatory markers: ESR, CRP.
  • Test for HIV-1 antibodies.
  • Autoantibodies, including antinuclear antibodies (ANA).
  • Urinalysis and urine culture.
  • Blood culture.
  • Throat swab for culture or PCR.
  • Other speciments as indicated by history - wound swab, sputum culture, stool culture, microscopy, C. diff toxin assay.
  • Specific tests and their priority.
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4
Q

What disease specific tests would be done provided the history indicated it (fever)? (LO1)

A
  • Malaria films on 3 consecutive days or malaria rapid diagnostic test (antigen detection).
  • Test for non-structural protein (NS1) in dengue (antigen detection).
  • Blood cultures for Salmonella typhi.
  • Abdominal ultrasound standard test in many regions of Africa, Asia, Oceania and Central and South America.
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5
Q

Describe the features of factitious fever. (LO1)

A
  • Patient who looks well.
  • Bizarre temperature chart with absence of diurnal variation or temperature-related changes in pulse rate.
  • Temperature >41°C.
  • Absence of sweating during defervescence.
  • Normal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), despite high fever.
  • Evidence of self-injection or self-harm.
  • Normal temperature during supervised (observed) measurement.
  • Infection with multiple commensal organisms (e.g. enteric or mouth flora).
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6
Q

Describe the initial management of fever. (LO1)

A
  • Fever and associated symptoms can be treated with paracetamol.
  • Tepid sponging to cool the skin.
  • Replenishing of salt and water is important in patients with drenching sweats.
  • Further management is focused on underlying cause.
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7
Q

Why is past medical history important when asking about a presenting complaint of fevers? (LO1)

A
  • Defines the ‘host’ and likelihood of infection.
  • Includes surgical and dental procedures involving prosthetic materials.
  • Document previous infections.
  • History of intravenous drug injection or receipt of blood products.
  • Risks for blood-borne viruses, e.g. HIV-1, HBV, and HCV.
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8
Q

Why is medication history important when asking about a presenting complaint of fevers? (LO1)

A
  • Include non-prescription drugs, use of antimicrobials and immunosuppressants.
  • Identify medicines that interact with antimicrobials or that may cause fever.
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9
Q

Why is allergy history important when asking about a presenting complaint of fevers? (LO1)

A
  • Could have an allergy to anti-microbials, noting allergic manifestations (e.g. rash vs. anaphylaxis).
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10
Q

Why is family and contact history important when asking about a presenting complaint of fevers? (LO1)

A
  • Checking for transmissible diseases such as TB, HIV, etc.
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11
Q

Why is travel history important when asking about a presenting complaint of fevers? (LO1)

A
  • Countries visited and whether they were a previous resident.
  • Gives info about relevant exposure and likely vaccination history, e.g. likelihood of BCG vaccination in childhood.
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12
Q

Why is occupation important when asking about a presenting complaint of fevers? (LO1)

A
  • Occupational hazard.
  • e.g. Anthrax in leather tannery workers.
  • Ask about occupation-related vaccines.
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13
Q

Why is recreational pursuit important when asking about a presenting complaint of fevers? (LO1)

A
  • Could be caused by the activity.

- e.g. Leptospirosis in canoeists and windsurfers.

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14
Q

Why is animal exposure important when asking about a presenting complaint of fevers? (LO1)

A
  • Including pets, e.g. dogs.

- Could be hydatid disease.

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15
Q

Why is dietary history important when asking about a presenting complaint of fevers? (LO1)

A
  • Undercooked meats, shellfish, unpasteurised dairy products or well water.
  • Establish who else was exposed, e.g. to food-borne pathogens.
  • Risks for blood-borne viruses, e.g. HIV-1, HBV, and HCV.
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16
Q

Why is sexual history important when asking about a presenting complaint of fevers? (LO1)

A
  • Explore in confidential manner.
  • Most common mode of HIV-1 transmission is heterosexual.
  • Vaccine history and use of prophylactic drugs.
  • In a traveller or infection-predisposed patient, establish adherence to prophylaxis.
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17
Q

List the common differential diagnoses for bacterial infections causing fever. (LO1)

A
  • Osteomyelitis.
  • Pyelonephritis.
  • Abscess.
  • Infective endocarditis.
  • Tuberculosis.
  • Cat scratch disease.
  • Typhoid fever.
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18
Q

List the common differential diagnoses for viral infections causing fever. (LO1)

A
  • Epstein-Barr virus.
  • Cytomegalovirus.
  • Enterovirus.
  • Adenovirus.
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19
Q

List the common differential diagnoses for malignancies causing fever. (LO1)

A
  • Leukaemia.
  • Lymphoma.
  • Neuroblastoma.
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20
Q

List the common differential diagnoses for autoimmune diseases causing fever. (LO1)

A
  • Juveline idiopathic arthritis (JIA).
  • Systemic lupus erythamatous (SLE).
  • Inflammatory bowel disease (IBD).
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21
Q

List the common differential diagnoses for miscellaneous causes of fever. (LO1)

A
  • Kawasaki disease.
  • Drug fever.
  • Periodic fever.
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22
Q

Describe the epidemiology of sepsis. (LO2)

A
  • In 2017, 48.9 million cases and 11 million sepsis-related deaths worldwide, accounting for 20% of all global deaths.
  • 80% of sepsis cases and sepsis-related deaths worldwide occured in low, middle income countries.
  • In 2017, almost half of all global sepsis cases occured among children, 20 million cases and 2.9 million deaths in children <5 years.
  • Increased incidence can be due to: immunosuppression therapy, invasive procedures, transplantation, chemotherapy, newborns, old age, pregnancy, chronic health conditions.
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23
Q

Define sepsis. (LO2)

A

The body’s amplified and dysregulated inflammatory response to infection (involving cytokine storm, e.g. tumour necrosis factor and IL-1). This leads to an imbalance between proinflammatory and anti-inflammatory responses. Also known as, systemic inflammatory response syndrome.

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24
Q

Define septicaemia. (LO2)

A

Bacterial infection in the blood.

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25
Q

Describe the pathophysiology of sepsis. (LO2)

A
  • The inflammatory reaction is mediated by the release of cytokines, including TNF-α, interleukins and prostaglandins from neutrophils and macrophages.
  • The cytokines activate the extrinsic coagulation cascade and inhibit fibrinolysis.
  • Coagulation system activation leads to the consumption of endogenous anticoagulants (e.g. protein C and antithrombin).
  • This leads to the development of microvascular coagulation (thrombosis being a potential factor for organ dysfunction).
  • Toxins from bacteria or thrombi can damage small blood vessels and leak fluid into the surrounding tissues.
  • This affects your heart’s ability to pump blood to your organs which means lower blood pressure (septic shock).
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26
Q

Define severe sepsis and septic shock. (LO2)

A

Sepsis can escalate to severe sepsis. Severe sepsis is the dysfunction of ONE of the major organ systems or unexplained metabolic acidosis.

Septic shock can follow severe sepsis. Septic shock is the severe drop in blood pressure contributing to late-stage multiple-organ failure.

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27
Q

Describe the presentation of initial sepsis. (LO2)

A
  • Easily mistaken for other conditions particularly in post-operative patients, e.g. delirium, primary cardiac dysfunction, pulmonary embolism.

Initially:

  • Fever.
  • Tachycardia.
  • Diaphoresis - excess sweating
  • Tachypnoea.
  • Normal blood pressure.
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28
Q

Describe the presentation of worsening sepsis/septic shock. (LO2)

A
  • Confusion.
  • Decreased alertness (particular in very young or the elderly).
  • Blood pressure decrease.
  • Skin paradoxically warm.
  • Diarrhoea.
  • Nausea.
  • Vomiting.
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29
Q

Describe the presentation of late stage sepsis. (LO2)

A
  • Extremities cool and pale.
  • Peripheral cyanosis and mottling.
  • Hypothermia.
  • Organ dysfunction specific symptoms (e.g. oliguria, dyspnoea - shortness of breath).
  • Leukocytosis (increased leukocytes in blood).
  • Leukopenia (decreased leukocytes in blood).
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30
Q

Describe the investigations for sepsis. (LO2)

A

Abnormal increase in 2 or more of the following:

  • White cell count (>12x10⁹).
  • Body temperature (>38°C)
  • Respiratory rate (>20/min).
  • Heart rate (>90/min).

Lack of evidence of the probable cause of infection can make diagnosis challenging.

Lab tests:

  • FBC.
  • Lactate.
  • C-reactive protein (CRP).
  • Procalcitonin.
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31
Q

Describe the non-immediate management for sepsis. (LO2)

A
  • IV antibiotics within 1 hour of suspecting sepsis.
  • If patient in shock, use combination therapy (2 classes of antibiotics)
  • Patients with hypoperfusion, give 30mL/kg of intravenous crystalloid within 3 hours and reassess frequently.
  • Patients needing vasopressors - target mean arterial pressire is 65mm Hg. Give norepinephrine. Vasopressin or epinephrine can be added. For patients who remain unstable, dobutamine is recommended.
  • Intravenous hydrocortisone for patients who are haemodynamically unstable despite fluids and vasopressors.
  • Blood transfusion reserved for patients with haemoglobin concentration of <7.0g/dL or if haemorrhage or myocardial ischaemia.
  • Platelets given if platelet count is <10,000mm³ or <20,000mm³ with bleeding.
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32
Q

Describe the immediate management of sepsis (within one hour of suspecting). (LO2)

A
  • Oxygen to maintain SpO₂ at >94%.
  • Take blood cultures and consider infective source.
  • Administer intravenous antibiotics.
  • Consider intravenous fluid resuscitation.
  • Check serial lactates.
  • Commence hourly urine output measurement.
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33
Q

Describe the prognosis of sepsis. (LO2)

A
  • Mortality in sepsis is frequent due to organ failure.
  • Risk of mortality increases with number of failing organs.
  • Sepsis with 3 or more failing organs have 70% mortality rate.
  • Sepsis and no organ failure have 15% mortality rate.
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34
Q

Describe the basic process of B cell function. (LO3)

A
  • Pathogen with antigen invades body.
  • Innate immune cells such as phagocytes and antigen presenting cells (APCs) present antigens to T helper cells.
  • T helper cells signal for and recruit B cells and present antigens to B cells.
  • B cells duplicate by a process called clonal expansion and are now called plasma cells.
  • Plasma cells produce antibodies which carry out the adaptive immune response.
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35
Q

Describe the structure of antibodies. (LO3)

A
  • Y-shaped molecule.
  • Constant region with Fc receptors for binding to immune cells.
  • Variable region for binding to antigens.
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36
Q

Describe the function of antibodies. (LO3)

A
  • Antibody produced by B cell binds to a pathogen via the variable region which is complementary to the antigen.
  • By binding the pathogens, antigens can cluster and the exposed Fc receptors signal for other immune cells.
  • The Fc region can trigger the complement cascade which has a membrane attack complex (MAC) which is able to lyse the membranes of pathogens and kill them.
  • Opsonisation: Fc receptors bind macrophages. The antibody bound to the pathogen allows phagocytic cells to recognise pathogens and engulf them. The pathogen lysed by proteases in the lysozyme. Alternatively, phagocytes can produce ROS (reactive oxygen species) which kills pathogens.
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37
Q

Describe the functions of the Fc receptor of antibodies. (LO3)

A
  • The Fc region can trigger the complement cascade which has a membrane attack complex (MAC) which is able to lyse the membranes of pathogens and kill them.
  • Opsonisation: Fc receptors bind macrophages. The antibody bound to the pathogen allows phagocytic cells to recognise pathogens and engulf them. The pathogen lysed by proteases in the lysozyme. Alternatively, phagocytes can produce ROS (reactive oxygen species) which kills pathogens.
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38
Q

List the types of antibodies produced by B cells. (LO3)

A
  • IgA.
  • IgE.
  • IgG.
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39
Q

Describe IgA. (LO3)

A
  • Dimer of 2 IgA molecules bound by joining protein (J protein).
  • Produced in response to mucosal infection.
  • Secreted across epithelial surfaces.
  • IgA tail binds to IgA receptors allowing it to cross epithelial cells in mucosal tissue (lungs/stomach).
  • IgA can bind pathogens which have not yet entered the body.
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40
Q

Describe IgE. (LO3)

A
  • Like IgG but with different Fc domain.
  • Can bind IgE receptors on mast cells and eosinophils.
  • Binding causes degranulation of these cells leading to histamine release which triggers inflammatory response.
  • Mostly defends against parasitses due to binding of eosinophils which can release peroxidase, ribonuclease, deoxyribonuclease, lipase, plasminogen which damage parasites.
  • Also the cause of allergies like hayfever and asthma (atopy). Binding of IgE to mast cells in response to allergens like dust or pollen can prime the immune system which triggers inflammation whenever the allergen is encountered.
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41
Q

Describe IgG. (LO3)

A
  • Carries out main function within the plasma by these mechanisms, e.g. complement cascade, opsonisation.
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42
Q

Explain what is meant by class-switching. (LO3)

A
  • The variable region can be joined to the specific constant regions to create different classes of antibodies which can all bind to the same antigen.
  • Depending on the pathogen and location of immune response, a specific type of antibody is made.
  • VDJ recombination is a genetic mechanism allowing for the creation of a huge range of variable regions to fight off almost all pathogens.
  • Various classes are: IgG, IgE, IgA which are class-switched from the basic class, IgM.
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43
Q

Explain what is meant by differentiation of B cells. (LO3)

A
  • Formation of memory cells or plasma cells.
  • Memory cells circulate through lymphatics and plasma and contain the ability to become plasma cells for antigens from previous infections.
  • Presence of memory cells allows for immunity to certain pathogens.
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44
Q

Describe how a vaccine works to provide immunity. (LO3)

A
  • Antigen in the vaccine is recognised and helps in the production of memory B cells. They produce specific antibodies if a pathogen with that antigen invades the body.
  • Subsequent immune response to the infection is more rapid and disease can be prevented.
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45
Q

Describe the potential life-cycle of a mature B cell. (LO3)

A
  • Initially a mature B cell can become a short-lived plasma cell producing IgM when activated by T helper cells or directly by antigens.
  • Or it can become activated with interacting with T helper cells or antigens, causing proliferation by clonal expansion.
  • B cells can undergo hypermutations which can either increase or decrease affinity for antigens.
  • Those with decreased affinity are apoptosed. Those with increased affinity survive and undergo class-switching.
  • These can further differentiate into memory cells or plasma cells which produce antibodies.
  • Antibodies work by three different mechanisms: neutralisation, opsonisation and the complement cascade.
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46
Q

Describe the three mechanisms of action of antibodies against pathogens. (LO3)

A
  1. Neutralisation - antibodies can directly inhibit toxins produced by pathogens.
  2. Opsonisation - antibodies use their Fc receptor on the constant region to attract phagocytes which lyse pathogens.
  3. Complement cascade - activated complement which forms the membrane attack complex (MAC) which makes holes in the membrane, killing the pathogen.
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47
Q

Describe B cell antigen presentation. (LO3)

A
  • Gene rearrangements hook variable regions to constant regions which are anchored to the cell membrane, forming a B cell receptor.
  • B cell receptor binds the antigen and internalises it (endocytosis).
  • The antigen is prepped for presentation on MHC II to T helper cells via the antigen presenting pathway.
  • Binding of the antigen to T helper cells leads to antigen receptor activation of T cells.
  • T cells release CD40 ligand which binds CD40 surface receptors on B cells.
  • The costimulatory signal leads to T cell mediated cytokine release.
  • B cells proliferate by clonal expansion in response to cytokines.
  • B cells can become plasma cells or memory cells.
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48
Q

List the 3 types of T cells. (LO4)

A
  • T cytotoxic cells - destroy infected cells.
  • T helper cells - recognise antigen presenting cells (APCs) and active B cells.
  • T memory cells - remain in blood stream for secondary response.
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49
Q

Describe the function of T cells. (LO4)

A
  • Antigen presentation lies at the interface between innate and acquired immunity.
  • T cells have T cell receptors that recognise broken down antigens presented by APCs.
  • If the T-cell sees the pieces of virus as ‘foreign’, it will send a signal back to B cells which will make antibodies to the virus.
  • This signal is called T-cell help and is crucial to the production of correct antibodies.
  • The recognition of the antigen by the T cell will also cause T cell proliferation, which in turn, triggers proliferation of B cells (clonal expansion).
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50
Q

Describe the action of T cytotoxic cells. (LO4)

A
  • Recognise infected cell due to antigen presentation.
  • They release perforins which destroy the cell.
  • This leaves the pathogen with nowhere to live - more important for viruses.
  • Can help kill tumour cells.
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51
Q

Describe how T cell diversity occurs. (LO4)

A
  • Allowed by VDJ recombination.
  • Exons of V, D and J region of genes are repeated.
  • A loop forms in D and J cluster - one repeat from each selected for use.
  • The RAG protein removes unused repeats.
  • The same thing happens in the V region after.
  • You end up with a gene that codes for a T cell receptor.
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52
Q

Describe the action of T helper cells. (LO4)

A
  • T cell receptor binds to antigen being presented by B cell.
  • If the B cell has the correct antigen, the T cell expresses CD40 ligand which binds to CD40 on the B cell which sends more signals back to the T cell - COSTIMULATORY SIGNALS.
  • This causes T cell to release cytokines which cause the B cell to duplicate (clonal expansion).
  • Also activates antibody class-switching.
  • B cell released Ig (if differentiated into plasma cell), which helps destroy pathogens.
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53
Q

Explain the important of T cells. (LO4)

A
  • If T cells aren’t made - B cells can’t survive and also can’t produce the correct antibodies.
  • Shown in HIV where T cells are not produced.
  • This vastly weakens the immune system - leaves us susceptible to opportunistic infections.
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54
Q

What are costimulatory signals between T and B cells and why are they important? (LO4)

A
  • When a T cell binds to the antigen presented by B cells, it expresses CD40 ligand if the B cell has the correct antigen.
  • This then binds to CD40 on the B cell which sends more signals back to the T cell.
  • THIS IS COSTIMULATORY SIGNALS.
  • This causes T cells to release cytokines which triggers clonal expansion of B cells.
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55
Q

What is phagocytosis? (LO5)

A
  • The process by which certain living cells called phagocytes ingest or engulf other cells or particles.
  • Phagocytes are derived from the bone marrow - myeloid cells.
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56
Q

List the cells that can engage in phagocytosis. (LO5)

A
  • Macrophages.
  • Monocytes.
  • Neutrophils.
  • Dendritic cells - unlike the others, dendritic cells have the means to “preserve useful information” due to less degradation and the preservation of antigens, allowing better antigen presentation.
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57
Q

What is netosis? (LO5)

A
  • Neutrophil extracellular traps (NET) formation activated by immune receptors that include reactive oxygen species (ROS).
  • NETs can trap and kill pathogens such as viruses, fungi and parasites.
  • If unregulated, NETs can damage healthy tissue and are therefore sometimes associated with autoimmune disorders.
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58
Q

Describe neutrophils in terms of phagocytosis. (LO5)

A
  • Produced daily during homeostasis.
  • Short lived - not more than few hours.
  • During infection, the production increases.
  • After neutrophils kill a pathogen, they die.
  • Dead neutrophils are a major component of pus.
  • Only migrate to inflamed tissue.
  • Can kill pathogens via phagocytosis, via the release of toxic chemicals/enzymes and via NETs.
  • Recruited by chemokines (small proteins that influence the immune system.)
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59
Q

Describe monocytes and macrophages in terms of phagocytosis. (LO5)

A
  • “Macrophages are monocytes that have migrated from the bloodstream into any tissue in the body.”
  • Produced at a steady rate, even during infection.
  • Present in non-inflamed tissue.
  • May survive a long time (possibly years) after phagocytosing a pathogen.
  • Do not produce NETs.
  • Can recruit neutrophils to the site of inflammation.
  • Stimulate the adaptive immune response through antigen presentation.
60
Q

Describe osteoclasts in terms of phagocytosis. (LO5)

A
  • Highly specialised type of macrophage responsible for resorbing bone.
  • Known to be capable of phagocytosis of inert particles.
61
Q

Describe the recruitment of phagocytes. (LO5)

A
  • Monocytes circulate the body and enter healthy tissues.
  • They specialise into macrophages which remain dormant unless stimulated by their receptors.
  • Macrophages at the site of infection will release chemokines which will attract neutrophils.
62
Q

Describe the production of phagocytes. (LO5)

A
  • Neutrophils and monocytes are produced in the bone marrow by stem cell differentiation.
  • They are produced by the same stem cell.
63
Q

Describe the process of phagocytosis. (LO5)

A
  • Triggered by the binding through receptors on phagocytes.
  • Most effective on pathogens which have been opsonised by complement or IgG.
  • Phagocyte releases pseudopodia (temporary arm) that reaches around the pathogen/denatured cell.
  • A phagosome will form after a pathogen is ingested.
  • Lysosomal granules will bind with the phagosome and release lysozymes such as proteases and hydrolases.
  • Other agents are involved and this is called oxidative/respiratory burst and involves toxic superoxides.
64
Q

Define what is meant by pseudopodia. (LO5)

A

The temporary arm released by a phagocyte which reaches around the pathogen/denatured cell and helps the cell ingest it.

65
Q

Explain what is meant by oxidative burst in terms of phagocytosis. (LO5)

A
  • Enzymes and toxic chemicals will be released by macrophages (not neutrophils) to kill the pathogen: hydrogen peroxide, hypochlorous acid, nitric oxide.
  • This occurs inside and outside the phagosome.
66
Q

List the chemicals released in an oxidative burst and their function. (LO5)

A
  • Hypochlorous acid - results in degranulation of microorganisms.
  • Lactoferrin - binds with iron, depriving the pathogen of it.
  • Nitric oxide - acts as a messenger to stimulate T-cells.
67
Q

Describe the receptors involved in phagocytosis and their functions. (LO5)

A
  1. Toll-like receptors - stimulate the release of cytokines, vary a lot, found on different types of APCs.
  2. C-lectin receptors - can stimulate release of cytokines and also bind very strongly to pathogens.
  3. Complement component receptors - phagocytes can bind to pathogens coated in complement components, antigen-antibody complexes and dead cells.
  4. Immunoglobulin receptors - phagocytes can recognise immunoglobulin through Fc receptors and this can trigger phagocytosis.
68
Q

Describe the role of toll-like receptors in phagocytosis. (LO5)

A
  • Stimulate the release of cytokines.
  • Vary a lot.
  • Found on different types of APCs.
69
Q

Describe the role of C-lectin receptors in phagocytosis. (LO5)

A
  • Can stimulate release of cytokines.

- Can also bind very strongly to pathogens.

70
Q

Describe the role of complement component receptors in phagocytosis. (LO5)

A
  • Phagocytes can bind to pathogens coated in complement components, antigen-antibody complexes and dead cells.
71
Q

Describe the role of immunoglobulin receptors in phagocytosis. (LO5)

A
  • Phagocytes can recognise immunoglobulin through Fc receptors and this can trigger phagocytosis.
72
Q

Explain a general difference between macrophage enzymes and neutrophil enzymes. (LO5)

A
  • Macrophage enzymes can regenerate when used up (as they live a long time).
  • Neutrophils cannot produce more enzymes and die when they are all used up.
73
Q

List 2-3 microorganisms which commonly cause infections in primary care. (LO6)

A
  • Influenza viruses.
  • Escherichia coli (E. coli).
  • Salmonella.
74
Q

What are the four types of influenza virus and what species to they affect? (LO6)

A
  • Influenza A (IAV)
  • Influenza B (IBV)
  • Influenza C (ICV)
  • Influenza D (IDV)

A, B and C cause infection in humans to varying degrees.
D primarily affects cows and not believed to have the ability to cause infection in humans.

75
Q

List the typical symptoms of the Influenza A virus. (LO6)

A
  • Fever.
  • Cough.
  • Sore throat.
  • Runny or stuffy nose.
  • Myalgia.
  • Headaches.
  • Fatigue.
76
Q

How is the Influenza A virus classified further? (LO6)

A
  • Broken into different subtypes based on two proteins found on the surface: haemagglutinin (H) and neuraminidase (N).
  • 18 different H subtypes.
  • 11 different N subtypes.
  • 198 possible combinations but we’ve only found 131 to exist.
77
Q

Where is Escherichia coli found and what is its function? (E.coli). (LO6)

A
  • Found in large intestines of humans and animals.
  • Helps break down and digest food.
  • Most forms are harmless but few forms are capable of causing illness if ingested, in addition to UTIs.
78
Q

Which type of E. coli most commonly causes disease in humans? (LO6)

A
  • E. coli O157:H7
  • From contaminated food and water.
  • Healthy adults will recover within a week.
  • Young children and elderly at risk of developing more severe form.
79
Q

List the typical symptoms of an E. coli infection. (LO6)

A
  • Diarrhoea - ranges from mild and watery to severe and blood.
  • Stomach cramps/pain.
  • Nausea, vomiting.
80
Q

Aside from GI infection, what other issue is E. coli capable of causing? (LO6)

A
  • UTIs.
  • Approximately 80-90% of all UTIs are caused by E. coli.
  • Occurs when E. coli enters urethral tract via faecal matter.
  • More common in women due to proximity of urethra to the anus.
81
Q

Where is Salmonella found and how does it cause disease? (LO6)

A
  • Bacterium which causes Salmonellosis.
  • Common disease which affects the gastrointesinal tract.
  • Usually found in intestines of animals and humans.
  • Spread through consumption or exposure of contaminated food.
82
Q

List the typical symptoms of a Salmonella infection and when they appear (LO6)

A
  • Nausea.
  • Vomiting.
  • Abdominal cramps.
  • Diarrhoea.
  • Fever.
  • Chills.
  • Headache.
  • Blood in stool.

Symptoms tend to appear between 6 hours to 6 days after infection and can last up to 7 days.

83
Q

In what instances would antibiotics be prescribed for a Salmonella infection? (LO6)

A
  • Those who have a severe illness.
  • Those with compromised immune system.
  • Anyone >50 years who may have a condition such as heart disease.
  • Children <12 months.
  • Anyone >65 years of age.
84
Q

What are the 4 main signs of a localised infection? (LO7)

A
  • Rubor (redness).
  • Tumor (swelling).
  • Calor (heat).
  • Dolor (pain).
85
Q

What should be ruled out if a patient comes in with a suspected infection? How would you do so? (LO7)

A
  • Rule out sepsis.
  • Use the National Early Warning Score (NEWS), a clinical examination to detect sepsis.
  • If a patient has 2/3 of the “sepsis-3”, they should be diagnosed with sepsis and taken to hospital immediately.
86
Q

List the criteria of “sepsis-3”. (LO7)

A
  • Low systolic blood pressure (≥100mmHg).
  • Increased respiratory rate (≥22 breaths/minute).
  • Altered mental state.

If a patient has 2 out of 3 of these, diagnose them with sepsis and taken to the hospital immediately.

87
Q

Why is it important to know the causative microorganism of infection? (LO7)

A
  • Many different microorganisms can cause a given infection.

- For example, pneumonia can be caused by viruses, bacteria or rarely, fungi.

88
Q

What can be done once a sample of blood, urine, sputum, etc, is taken to identify the causative microorganism in infection? (LO7)

A
  • Stained and examined under a microscope.
  • Cultured.
  • Tested for antibodies.
  • Tested for microorganism’s antigens.
  • Tested for genetic material from the microorganism.

No single test can identify every microorganism. Tests are chosen based on which microorganisms are most likely to cause those symptoms.

89
Q

Why should antibiotics be prescribed before results specify the type of bacteria causing the infection? (LO7)

A

Growth of bacteria can take at least 18 hours, so when an infection is suspected, antibiotics should be given to begin some treatment.

90
Q

Which samples are taken from commensal areas of the body and what is the significance of this regarding the determination of a causative microorganism? (LO7)

A
  • Sputum.
  • Stool.
  • Mucus from the nose, throat or genital area.

These samples contain bacteria that do not cause disease. Doctors need to distinguish between these bacteria and those that could cause the illness.

91
Q

Which samples are taken from sterile areas of the body and what is the significance of this regarding the determination of a causative microorganism? (LO7)

A
  • Urine.
  • Blood.
  • Cerebrospinal fluid.

Finding any bacteria in these samples is abnormal as long as the area from which the sample was taken was cleaned with an antiseptic wipe to prevent contamination.

92
Q

Describe how staining and examination using a microscope can help identify a causative microorganism of infection. (LO7)

A
  • Pathologists can identify microorganisms simply by looking at them under microscopes.
  • Stains are applied to make them stand out.
  • Some microorganisms have a distinctive shape, size and stained colour which allows us to recognise them.
  • Different stains can be used depending on which microorganism is suspected.
93
Q

Describe the limitations of using staining and microscopy to identify a causative microorganism of infection. (LO7)

A
  • Many microorganisms look alike and cannot be distinguished using a microscope.
  • There must be enough of them.
  • They must be large enough to be seen with the microscope - viruses cannot be identified using this.
94
Q

What’s the most common stain used to identify the class of bacteria? (LO7)

A

Gram staining is used to identify whether the causative bacteria is gram positive or negative.
- Gram positive = blue because they retain the violet stain.
- Gram negative = red because they do not retain the violet stain.
Treatments are based on whether bacteria are gram-positive or gram-negative.

95
Q

Identifying bacteria from commensal site can be difficult so it’s important to do a full work-up. What does this include? (LO7)

A
  • C-reactive protein.
  • White blood count.
  • Full blood count.
  • Platelet.
  • MSU, CSU (urine).
  • Wound scab.
  • Pus.
  • Scrapings.
  • PCR swab.
  • PCR full blood.
  • PCR enteric.
  • Serology - antibodies or antigen testing in blood.
  • Rapid antigen tests (legionella, pneumococcus).
  • Rapid POCT (influenza viruses).
96
Q

When and why do we do a urinalysis? (LO8)

A
  • To diagnose a urinary tract and kidney infection.
  • Evaluate cause of kidney failure.
  • Screen for progression of some conditions like Diabetes Mellitus.
  • High blood pressure/hypertension.
97
Q

List some factors to consider before you perform a urinalysis. (LO8)

A
  • Ensure patient doesn’t have sepsis - if suspected, antibiotics and send them straight to hospital.
  • Sex and age matters significantly - test is unreliable on older people and males.
  • Catheters make urinalysis unreliable.
  • Certain diseases can mimic UTIs like STIs.
  • When urinalysis is unreliable, we can only do a urine culture.
  • For women, it may not be worth doing urinalysis.
98
Q

When is is not worth it to perform a urinalysis for women? (LO8)

A

If they have any 2 of:
- Dysuria (burning when urinating).
- Nocturia (wakes up in middle of the night to urinate).
- Cloudy urine.
Skip the urinalysis, do a urine culture and consider antibiotics.

99
Q

What information can be derived from an initial assessment of the urine (simply by looking)? (LO8)

A

Colour:

  • Straw coloured - normal.
  • Darker - more concentrated.
  • Red - contains blood (macroscopic haematuria).
  • Brown - contains bile pigments.

Clarity:

  • Clear - normal/healthy.
  • Cloudy with sediment - UTI, renal stones or high protein count.
  • Frothy - significant proteinuria.

Odour:

  • Offensive - UTI.
  • Sweet - glycosuria.
100
Q

Describe the procedure of a urinalysis. (LO8)

A
  1. Check expiration date of urinalysis dipstick.
  2. Remove dipstick from container without touching any of the squares.
  3. Close container quickly to stop other dipsticks oxidising.
  4. Insert into urine and make sure all squares are fully submerged.
  5. Lay flat on paper towel.
  6. Wait for change in colour.
  7. Wash hands.
101
Q

Explain why findings of bilirubin and urobilinogen are significant in a urinalysis. (LO8)

A

Bilirubin is released when red blood cells die. It is then processed into bile by the liver and moves into the intestines where bilirubin is processed to urobilinogen which is then excreted.

Normal people don’t have this but if bile ducts are clogged or the liver is damaged, the kidneys would filter them out so we’d see them in urine.

102
Q

Explain the significance of finding ketones in a urinalysis. (LO8)

A

We make them when fat is broken down or in diabetes.

103
Q

Explain the significance of finding ascorbic acid in a urinalysis. (LO8)

A

This means vitamin C. If high levels, be cautious with findings.

104
Q

Explain the significance of finding glucose in a urinalysis. (LO8)

A

Sign of diabetes but also present with pregnancy.

105
Q

Explain the significance of finding proteins in a urinalysis. (LO8)

A

When we begin to detect, it’s a sign of kidney disease. Makes urine frothy.

106
Q

Explain the significance of finding erythrocytes in a urinalysis. (LO8)

A

Could be due to a stone, kidney disease, but also due to vigorous exercise.

N.B. Microscopic haematuria is when blood is present in urine but it’s not red.

107
Q

Explain the significance of pH in a urinalysis. (LO8)

A
  • Urine pH ranges from 4.5-8
  • Normal pH is 5.5-6.5
  • Generally it reflects the blood’s pH so acidic urine means acidic blood.
  • If pH is out of the range, start doubting if it’s actually urine.
108
Q

Explain the significance of finding nitrites in a urinalysis. (LO8)

A
  • If there is a gram negative bacterial infection, it can break down nitrates.
  • Means UTI is present.
109
Q

Explain the significance of finding leukocytes in a urinalysis. (LO8)

A
  • Raised leukocytes means UTI.

- 20% of cases of UTI will have negative leukocytes though due to factors like antibiotics or very concentrated urine.

110
Q

Explain the significance of specific gravity in a urinalysis. (LO8)

A
  • Density of urine and kidneys’ ability to dilute or concentrate it.
111
Q

Describe general findings in a urinalysis. (LO8)

A
  • Ketones - we make them when fat is broken down or in diabetes.
  • Ascorbic acid - vitamin C, high means be cautious with findings.
  • Glucose - sign of diabetes but also present with pregnancy.
  • Proteins - at the beginning, sign of kidney disease. Makes pee frothy.
  • Erythrocyte - stone, kidney disease, vigorous exercise.
  • pH - reflects blood pH, if out of wide range, start doubting if its actually urine.
  • Nitrites - gram negative bacteria can break down nitrates, UTI.
  • Leukocytes - raised means UTI, 20% UTI cases negative due to antibiotics or concentrated urine.
  • Specific gravity - density of urine and kidneys’ ability to dilute or concentrate it.
112
Q

List the cells of the innate immune system. (LO9)

A
  • Neutrophils.
  • Macrophages/monocytes.
  • Eosinophils.
  • Basophils.
  • Natural Killer cells (NK)
  • Dendritic cells.
  • Mast cells.
113
Q

Describe the nature and function of neutrophils. (LO9)

A
  • Bactericidal.
  • Phagocytosis.
  • Netosis: ROS releases nuclear elastase (NE) from granules. NE goes to the nucleus, chromatin expands and is released from the cell to capture bacteria.
114
Q

Describe the abundance and function of macrophages/monocytes. (LO9)

A
  • Most abundant white blood cell.
  • Bactericidal.
  • Phagocytosis.
  • Antigen presentation.
115
Q

Describe the abundance and function of eosinophils. (LO9)

A
  • 1% of white blood cells.

- Kills parasites by releasing chemicals on its surface.

116
Q

Describe the abundance and function of basophils. (LO9)

A
  • 1% of white blood cells.
  • Filled with enzymes.
  • Activated in allergic reactions - contain histamine.
117
Q

Describe the function of natural kills (NK) cells. (LO9)

A

Apoptosis of virally/cancer infected cells.

  • Inhibited until activation.
  • Viruses downregulate MHC so NK cells recognise lack of MHC II.
  • Cancer can over-show growth receptors so NK cells recognise the increased receptors.
  • NK cells release enzymes to kill infected cell.
118
Q

Describe the function of dendritic cells. (LO9)

A
  • Antigen-presenting cell.
  • Helps T cells mature by presenting it antigenic material.
  • Messenger between innate and adaptive immune system.
119
Q

Describe the function of mast cells. (LO9)

A
  • Release of histamine and other mediators.

- Histamine causes inflammation - activation of host defence recruitment of immune cells.

120
Q

List the physical barriers against infection. (LO9)

A
  • Epithelial barriers.
  • Flows of fluids/air.
  • Mucus (airways/lungs).
  • Natural acids.
  • Regular flora.
  • Skin.
121
Q

How do epithelial barriers act as physical barriers against infection? (LO9)

A
  • Very tight junctions = hard to penetrate.

- Linings of the mouth, nasal passages, upper airways, lungs and GI tract.

122
Q

How does flow of fluids/air act as a physical barrier against infection? (LO9)

A
  • Longitudinal flow creates flushing actions = prevents adherence of pathogens.
123
Q

How does mucus act as a physical barrier against infection? (LO9)

A
  • Prevents stagnation of secretions from pathogens.
  • Capture and adherence of inhaled droplets and particles.
  • Mucus is moved upwards by cilia towards the pharynx, where it is either swallowed or coughed up.
124
Q

List the natural acids that can act as physical barriers against infection. (LO9)

A
  • Subrin (fatty acids) of skin.
  • Lysozymes in saliva.
  • Hydrochloric acid in the stomach.
  • Acidic environment of the vagina.
125
Q

How does regular flora act as a physical barrier against infection? (LO9)

A
  • Normal bacteria colonising the body so pathogenic bacteria can’t grow.
  • Can produce antimicrobial substances.
  • Vaginal lactobacilli produce lactate, which creates an acidic environment and destroys many potentially infectious organisms.
126
Q

How does the skin act as a physical barrier against infection? (LO9)

A
  • Dead cells get removed by getting ‘wiped’ off.

- Desquamation of skin and epithelial cells also prevents adherence of microorganisms.

127
Q

When are acute phase proteins released? (LO10)

A
  • As a result of the processes of inflammation no matter the cause.
  • Macrophages release IL-1, IL-6, TNF-α which stimulate hepatocytes to produce acute phase proteins in the liver.
  • As production of acute phase proteins increases, albumin levels decrease.
128
Q

What is c-reactive protein (CRP)? (LO10)

A
  • A member of the pentraxin family of proteins.
  • Binds to Fc receptors of monocytes and neutrophils to stimulate production of cytokines.
  • Works as an opsonin.
129
Q

What is C3 protein? (LO10)

A
  • Component of the complement cascade.
  • Being activated by classic and alternative pathways and also by activating the membrane attack complex (MAC) (C5b, C6, C7, C8, C9)
130
Q

What is serum amyloid A (SAA)? (LO10)

A
  • Released during the acute phase of inflammation.

- Involved in recruiting of immune cells to inflammatory sites.

131
Q

What is haptoglobin? (LO10)

A
  • A type of damage-limiting protein.
132
Q

What is fibrinogen? (LO10)

A
  • A type of clotting factor.
  • Inflammatory insults result in substantially increased hepatic expression and increased circulating protein.
  • So the values of fibrinogen in blood increases.
133
Q

List the laboratory features of acute inflammation. (LO10)

A
  • Leucocytosis - reflects the transit of activated neutrophils and monocytes to the site of infection.
  • Platelet count - increased.
  • CRP - increased (most widely used).
  • Fibrinogen, ferritin, complement components - increased.
  • Albumin - reduced.
134
Q

What associated condition is chronic inflammation frequently linked to? (LO10)

A

Normocytic normochromic anaemia.

135
Q

What is ESR? (LO10)

A
  • Erythrocyte sedimentation rate (ESR) is a technique which detects inflammation.
  • Measures the rate of red blood cell sedimentation in one hour.
  • Units: millimeters per hour (mm/h).
136
Q

When does ESR increase? (LO10)

A
  • Pregnancy.
  • Anaemia.
  • Autoimmune disorders.
  • Some kidney diseases.
  • Some cancers (lymphoma and multiple myeloma).
137
Q

When does ESR decrease? (LO10)

A
  • Polycythemia.
  • Hyperviscosity.
  • Sickle cell anaemia.
  • Leukaemia.
  • Low plasma protein.
  • Congestive heart failure.
138
Q

Describe what happens in the resolution of acute inflammation. (LO10)

A
  • Active down-modulation of inflammatory stimuli and repair of bystander damage to local tissues.
  • Extravasated neutrophils undergo apoptosis and phagocytosed by macrophages along with the remains of microorganisms.
  • Macrophages synthesise collagenase and elastase.
  • Collagenase and elastase break down local connective tissue and aid in removal of debris.
  • Reversion of parenchymal cells to a non-inflammatory phenotype.
  • Macrophage-derived cytokines, TGF-β, platelet derived growth factor, stimulate fibroblasts and promote synthesis of new collagen.
  • Angiogenic factors stimulate new vessel formation.
139
Q

Describe the function of macrophages in the resolution of acute inflammation. (LO10)

A
  • Phagocytose extravasated and apoptosed neutrophils.
  • Phagocytose remains of microorganism.
  • Synthesise collagenase and elastase - break down local connective tissue and aid in removal of debris.
  • Release cytokines - transforming growth factor beta (TGF-β) and platelet-derived growth factor - stimulate fibroblasts and promote synthesis of new collagen.
140
Q

How can chronic inflammation come about? (LO10)

A
  • Failure to control the inflammatory stimulus and resolve tissue damage.
  • Results in significant associated bystander damage known as hypersensitivity responses.
  • Persistence of microorganisms can result in ongoing accumulation of neutrophils, macrophages and activated T cells within the lesion.
  • If this is associated with local deposition of fibrous tissue, a granuloma may form which is where the microorganism is protected by a robust cell wall that shields it from killing, despite phagocytosis.
141
Q

What are granulomas? (LO10)

A
  • Characteristic of tuberculosis and leprosy (Hansen’s disease).
  • Where the microorganism is protected by a robust cell wall that shields it from killing, despite phagocytosis.
142
Q

What is antigen presentation? (LO11)

A
  • The gap between innate and adaptive immunity.
  • Will occur when a phagocytic cell engulfs a pathogen in the bloodstream and breaks it down.
  • Once broken down, smaller pieces are presented on major histocompatibility complexes (MHC) on the plasma membrane to T-helper cells.
143
Q

What is extracellular antigen presentation? (LO11)

A

This is the process that takes place to present an antigen of an external peptide of a pathogen, e.g. toxins, or from microbes captured in endosomes.

144
Q

What is intracellular antigen presentation? (LO11)

A
  • The method used to present the peptide antigens that are generated in the cytosolic compartment of the cell.
  • This includes viruses and bacteria that replicate in the cytosol.
  • A target cell is the name for the infected cell that processes intracellular antigens to present on MHC I molecules.
  • The ‘target cell’ could be infected by malignant cells or by a viral protein that has used the cell’s degradative machinery to infect the cell.
145
Q

Describe the process of extracellular antigen presentation. (LO11)

A
  • Pathogen phagocytosed by macrophage or dendritic cell.
  • Endosome containing pathogen is acidified and fused to lysosomes to be fully endocytosed.
  • Pathogen degraded into small proteins and eventually amino acids.
  • MHC II molecule is synthesised in endoplasmic reticulum (ER). An invariant chain blocks the binding site while it travels across the cell to prevent free peptides in the cell from binding.
  • Synthesised MHC II molecules leave the ER through the Golgi apparatus in vesicles which bind to an endosomal vesicle containing degraded peptides from the antigen.
  • Invariant chain is displaced by the antigen due to acidic environment of an endosome initiating proteolytic action.
  • Once MHC II is occupied, the molecules move into the exosomal pathway and fuse with plasma membrane and presented to CD4 T-helper cells.
146
Q

Describe the process of intracellular antigen presentation. (LO11)

A
  • When the cell is infected, pathogenic proteins are being synthesised in the cytosol to attempt to take over the host cell.
  • A proteasome (complex of proteases) is used in cellular degradation by the pathogen.
  • While degradation is taking place, the proteosome has enzymes that catalyse the splitting of the viral protein molecules until they can bind MHC I.
  • Peptides are transported by a transporter associated with antigen presentation (TAP) to the endoplasmic reticulum.
  • The protein enters the ER and binds in empty peptide-binding groove of the MHC I molecules that are still being synthesised.
  • MHC I molecules are unable to fold correctly without the peptides bound to them during synthesis.
  • MHC synthesis is completed in the Golgi apparatus and the molecule exits through the exocytic pathway.
  • MHC I presents antigen on the surface of infected cell where it can bind to CD8 cytotoxic cells.

MBBS - Y1 (14 decks)

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