Infection - Acute Sepsis and Immune System

Question 1

Define Sepsis

Answer 1

The systemic response to infection

Question 2

What are common features of sepsis?

Answer 2

Fever Increased Respiratory and Heart Rate Confusion

Question 3

What is SIRS?

Answer 3

Systemic Inflammatory Response Syndrome

The response to a non-specific injury

If 2 or more results found, we diagnose sepsis

Question 4

Define values of SIRS

Answer 4

HR >90/minute

Temperature 38

Resp Rate >20

WBCs <4x10^9 or >12x10^9 a litre

Question 5

What is the difference between Bacteraemia and Septicaemia?

Answer 5

Bacteraemia is the presence of bacteria in the blood, can be cleared naturally, can be with/out clinical features

Septicaemia is the clinical term for generalised sepsis

Question 6

Define Severe Sepsis

Answer 6

SIRS and organ dysfunction/hypotension (AKI)

Question 7

Septic Shock

Answer 7

Severe sepsis with a persistantly low blood pressure despite IV fluids

Question 8

What are the Sepsis 6?

Answer 8

The 6 interventions we do in Sepsis 1) High Flow Oxygen 2) IV Fluids 3) General Empiric IV Antibiotics (needs to penetrate CSF) 4) Take Blood Culture 5) Measure FBC and Serum Lactate 6) Measure Urine Output

Question 9

What causes severe sepsis?

Answer 9

Bacteria release endotoxins which bind to Macrophages. This stimulates the release of cytokines. In SIRS this is overplayed so… Cytokines promote coagulation which can lead to thrombosis, ischaemia –> organ failure. This can cause necrosis

Question 10

How do we confirm the diagnosis?

Answer 10

PCR Blood Culture Lumbar Puncture of CSF (if safe)

Question 11

What are some complications of sepsis?

Answer 11

Organ Failure and Necrosis Hypotension –> Coma –> Death AKI Raised Intracranial Pressure

Question 12

Define the immune system

Answer 12

The cells and organs that contribute to the immune defences of the body. It can distinguish between self and non self

Question 13

What is the role of the immune system?

Answer 13

Pathogen recognition Contain and eliminate Self regulation Remembering Pathogens

Question 14

What is the innate immune system

Answer 14

Initial and fast response. Non specific response and lacks memory. No change in intensity. Aims to prevent entry, limit growth and phagocytose

Question 15

What are the main barriers of the 1st line of defense?

Answer 15

Physical- Skin, Membranes, Cilia Physiological- Coughing, Sneezing, Vomiting, Diarrhoea Chemical- Low pH (vagina, skin, stomach) Antimicrobials- IgA, lysozyme, mucus, gastric acid… Biological- flora, compete with pathogens

Question 16

What is the 2nd line of defense in the innate immune system?

Answer 16

Factors that contain and clear the infection.

Question 17

Describe the process of Phagocytosis

Answer 17

Before this, there is recognition of PAMPs by PRRs on the macrophages

Question 18

More in the innate system

Answer 18

Opsonins e.g. Complement Proteins

O2 In/Dependent Pathway

Cytokines

Question 19

Clinical problems with phagocytosis

Answer 19

1) Overreaction- leads to SIRS
2) Reduction- decrease spleen function, neutrophil number and function

Question 20

Types of Phagocyte:

Answer 20

Macrophages- in all organs

Monocytes- in blood, go to tissues and differentiate into Macrophages

Neutrophils- in the blood

Question 21

Other Cells of the Innate System (not phagocytes)

Answer 21

Mast Cells

Eosinophils
Natural Killer Cells

Dendritic Cells

Question 22

Describe the Adaptive Immune System

Answer 22

The adaptive immune response is specific, has memory and can get stronger

Question 23

Describe Antigen Presenting Cells

Answer 23

Present Antigens to T cells

They capture pathogens (PAMP and PRRs- extra/intracellular)

Types: Macrophages, Dendritic, Langerhans, B Cells

Have the Major Histocompatability Complex (Human Leukocyte Antigen) which present antigens to regulate immunity

Question 24

Describe Major Histocompatability Complexes

Answer 24

Set of cell surface molecules which regulate the immune system

2 Classes:

Class I - Found on all cells, for Intracellular Microbes (Virus)

Class II - Found on Dendritc, Macrophages, B cells, for Extracellular Microbes

They have co-dominant expression and polymorphic genes

Question 25

What clinical problems can be due to MHC molecules?

Answer 25

Transplant Rejection

Autoimmune Disease

Cross reactivity

Question 26

Describe T Cells

Answer 26

Produced in Bone Marrow, develop in the Thymus

CD8 recognise class I (also known as Cytotoxic T Cells)

CD4 recognise class II (also known as T Helper Cells)

Produce Cytokines, which further stimulate the immune response

Question 27

Describe B Cells

Answer 27

Function on humeral immunity by secreting antibodies:

IgG

IgA- mucosal

IgM- complement activation

IgE- against helminths, mast cell degranulation