Session 3 ILOs - Adaptive immunity (part 1) and Sepsis

Question 1

Describe the features of acute sepsis

Answer 1

• Increased heart rate
• Increased respiratory rate
• Decreased urine output
• Decreased blood pressure

Use NEWS to help identify possible sepsis
Use ‘Red Flag Sepsis’ to diagnose sepsis (QSOFA less common way)

Question 2

Understand the mechanism by which micro-organisms trigger the inflammatory cascade

Answer 2

Infection is triggered when a pathogen breaches the body’s barriers - leading to the generation of an immune response which causes inflammation
Sepsis occurs when the inflammatory process becomes overwhelming and occurs systemically (rather than locally)

• Vasodilation
• Capillary leakage
• Amplification fo the immune system

Question 3

Understand the principles of supportive and specific treatment for acute sepsis

Answer 3

Supportive treatment:

• Fluids
• Oxygen (if appropriate) or breathing support
• Renal dialysis if kidneys are damaged

Specific treatment:
- Antibiotics (specific)

Question 4

Describe the Sepsis Six Bundle

Answer 4

Give 3, take 3:

Give:

• Antibiotics
• Fluids
• Oxygen (if appropriate)

Take:

• Cultures
• Urine output
• Lactate and Hb

Question 5

Describe features of Antigen Presenting Cells (where are they located etc.)

Answer 5

Strategic location:

• Mucosal membranes
• Skin
• Blood
• Lymph nodes
• Spleen

Diversity in pathogen sensors (PRRs looking for PAMPs)

• Extracellular pathogens (e.g. bacteria)
• Intracellular pathogens (viruses)

Diversity in pathogen capture mechanisms:

• Phagocytosis (for whole microbe)
• Macropinocytosis (for solute particles)

Question 6

Describe MHC molecules in relation to microbe presentation

Answer 6

Antigen presenting cells have Major Histocompatability Complex (MHC) molecules - also known as Human Leukocyte Antigens (HLA)

There are 6 types of MHC molecules in 2 classes:
Class 1: 
HLA A, HLA B and HLA C
- Expressed on all nucleated cells
- Present intracellular microbes

Class 2:
HLA DP, HLA DQ, HLA DR
- Expressed on antigen presenting cells
- Present extracellular microbes

Question 7

Describe the processing and presentation of microbial antigens to T lymphocytes

Answer 7

Endogenous pathway (e.g. viruses):

• Marked for description by proteasome and it’s cut up
• Viral peptide transported to ER by TAP proteins
• Formation of peptide-MHC complex (class 1) if right match
• This is then presented to CD8+ T cell

Exogenous pathway (e.g. bacteria):

• Microbe is captured by phagocytosis or micropinocytosis
• Degraded into small peptides
• Small peptides fuse with a vesicle containing the class 2 MHC molecules
• Formation of peptide-MHC complex (class 2) if right match
• This is then presented to CD4+ T cell

Question 8

Describe T cells (2 types) and their role with regard to infections

Describe how antigen presenting cells activate the right adaptive immune response

Answer 8

Naive T cells:

• T cells that have not previously encountered the antigen
• Examples: dendritic and Langerhan cells

Effector T cells:

• T cells that have previously encountered the antigen and are capable of performing effector functions during an immune response
• Examples: macrophages and B cells

Each of the different Antigen presenting cells has a different function:

Dendritic cells: T cell response against most pathogens
Langerhan cells: T cell response against most pathogens
Macrophages: Phagocytic activities
B cells: Antibody response (humeral response)