S3: sepsis, adaptive immunity & applying the infection model

Question 1

Where are microorganisms that cause pneumonia mainly found? How do they cause pneumonia?

Answer 1

Found in the normal flora of the upper respiratory tract

Pneumonia: infection of the terminal air sacs (alveoli) and tissue of the lung

Question 2

Describe the pathogenesis of pneumococcal lobar pneumonia

Answer 2

Cause: streptococcus pneumoniae (diplococci)
Pneumococci multiply rapidly in alveolar spaces and induce extensive oedema
Incite an acute inflammatory response in which neutrophils are prominent -> macrophages replace the neutrophils and ingest debris
Process usually resolves

Question 3

Describe the role of the innate immune system and microbiota relating to infections of the lower respiratory tract

Answer 3

Lower respiratory tract is virtually sterile (a variety of host mechanisms exist to maintain this sterile environment)
Physical barriers: cough reflux, mucociliary escalator (cigarette smoking, narcotics, alcohol consumption reduces the efficiency of this)
Non-specific cellular & humoral factors produced in the lung = IgA, complement, neutrophils, macrophages

Question 4

Describe the clinical features of pneumonia

Answer 4

Fever, malaise, tachypnea, tachycardia, cough (can be productive but doesn’t have to be)
Most important consequence: impairment of respiratory function & patient needs to be assessed urgently by checking respiratory rate & oxygen saturation
Diagnosis made by chest x-ray

Question 5

Define and describe the main features of community-acquired pneumonia

Answer 5

Defined as pneumonia which develops outside the hospital

May be a primary disease or it may be secondary to a predisposing factor such as chronic lung disease, diabetes mellitus

Question 6

Describe the main microbiological features of Streptococcus pneumoniae

Answer 6

Gram positive coccus
Alpha haemolysis – ability to oxidise iron in Hb molecules (characteristic green colour that surrounds them when cultured on a blood agar plate)
Most common cause of pneumonia in all age groups except < 2-year-olds (respiratory syncytial virus in this age group)

Question 7

Describe adenovirus as a cause of upper respiratory tract infections

Answer 7

Nonenveloped, icosahedral viruses containing double-stranded linear DNA
Most common manifestation of infection in infants/young children (causes 4 groups of infection: respiratory tract, ocular, GI and urinary)
Identified by direct test of stool specimens by ELISA to detect viral antigens

Question 8

Define sepsis and describe the features of acute sepsis. What is septic shock?

Answer 8

Sepsis = characterised by a life-threatening organ dysfunction due to a dysregulated host response to infection
Diagnostic tools such as QSOFA and red flag sepsis are used
Physiological features of sepsis: tachypnoea, low BP, confusion (reduced blood perfusion to the brain), reduction in urine output, pyrexia
Septic shock = subset of sepsis where particularly profound circulatory, cellular and metabolic abnormalities substantially increase mortality

Question 9

How do micro-organisms trigger the inflammatory cascade?

Answer 9

• gain entry into the host
• adherence to host cells eg. via cell surface adhesion molecules
• invasive into host cells/mucosal surfaces
• results in inflammation

Question 10

Who is at increased risk from sepsis?

Answer 10

Very young
Elderly
Pregnant, post-partum
Patients with impaired immune system due to illness or drugs

Question 11

Describe the principles of supportive and specific treatment for acute sepsis

Answer 11

Sepsis 6 within the first hour

Other non-emergency treatments: vaccination, prophylaxis for close contacts

Question 12

Describe the Sepsis Six Bundle

Answer 12

3 in, 3 out!
IN: oxygen, antibiotics, fluids (only if appropriate)
OUT: blood cultures, lactate & Hb, urine output

Question 13

Describe features of Antigen Presenting Cells

Answer 13

4 types – dendritic, Langerhans cells, macrophages, B cells
If APC = macrophage, effector T-cell will then phagocytose the pathogen
If APC = B-cell, effector T-cells respond by stimulating the production of antibodies (humoral response)
Diversity in the type of pathogen sensed and methods in which these APCs capture the pathogens

Question 14

Describe MHC molecules in relation to microbe presentation

Answer 14

MHC II expressed on dendritic cells, B cells and macrophages -> present microbial peptides from extracellular microbes
MHC I complexes exist in all nucleated cells -> present microbial peptides from intracellular microbes

Question 15

Describe the endogenous pathway

Answer 15

MHC class I

1) Virus enters the cytosol
2) Detected by a proteosome
3) Broken down into viral peptides
4) Transported into ER via TAP proteins
5) Leaves the cytoplasm to present to a CD8+ T cell

Question 16

Describe the exogenous pathway

Answer 16

MHC class II

1) Bacteria enters cell via phagocytosis/micropinocytosis
2) Broken down in endosomes
3) Endosomes fuse with large vesicle containing MHC class II complex
4) Presented to a CD4+ T cell by APCs only

Question 17

Describe T cells and their role with regard to infections

Answer 17

T cells are either naïve or effector
Naïve = have not seen the antigen before
Effector = have seen the antigen before and respond in particular ways depending on the APC

Question 18

Name 4 common organisms that cause community acquired pneumonia

Answer 18

Streptococcus pneumoniae
Haemophilus influenzae
Staphylococcus aureus
Moraxella catarrhalis