Infection - Acute Sepsis and Immune System Flashcards
Define Sepsis
The systemic response to infection
What are common features of sepsis?
Fever Increased Respiratory and Heart Rate Confusion
What is SIRS?
Systemic Inflammatory Response Syndrome
The response to a non-specific injury
If 2 or more results found, we diagnose sepsis
Define values of SIRS
HR >90/minute
Temperature 38
Resp Rate >20
WBCs <4x10^9 or >12x10^9 a litre
What is the difference between Bacteraemia and Septicaemia?
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
Define Severe Sepsis
SIRS and organ dysfunction/hypotension (AKI)
Septic Shock
Severe sepsis with a persistantly low blood pressure despite IV fluids
What are the Sepsis 6?
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
What causes severe sepsis?
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
How do we confirm the diagnosis?
PCR Blood Culture Lumbar Puncture of CSF (if safe)
What are some complications of sepsis?
Organ Failure and Necrosis Hypotension –> Coma –> Death AKI Raised Intracranial Pressure
Define the immune system
The cells and organs that contribute to the immune defences of the body. It can distinguish between self and non self
What is the role of the immune system?
Pathogen recognition Contain and eliminate Self regulation Remembering Pathogens
What is the innate immune system
Initial and fast response. Non specific response and lacks memory. No change in intensity. Aims to prevent entry, limit growth and phagocytose
What are the main barriers of the 1st line of defense?
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
What is the 2nd line of defense in the innate immune system?
Factors that contain and clear the infection.
Describe the process of Phagocytosis
Before this, there is recognition of PAMPs by PRRs on the macrophages
More in the innate system
Opsonins e.g. Complement Proteins
O2 In/Dependent Pathway
Cytokines
Clinical problems with phagocytosis
1) Overreaction- leads to SIRS
2) Reduction- decrease spleen function, neutrophil number and function
Types of Phagocyte:
Macrophages- in all organs
Monocytes- in blood, go to tissues and differentiate into Macrophages
Neutrophils- in the blood
Other Cells of the Innate System (not phagocytes)
Mast Cells
Eosinophils
Natural Killer Cells
Dendritic Cells
Describe the Adaptive Immune System
The adaptive immune response is specific, has memory and can get stronger
Describe Antigen Presenting Cells
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
Describe Major Histocompatability Complexes
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
What clinical problems can be due to MHC molecules?
Transplant Rejection
Autoimmune Disease
Cross reactivity
Describe T Cells
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
Describe B Cells
Function on humeral immunity by secreting antibodies:
IgG
IgA- mucosal
IgM- complement activation
IgE- against helminths, mast cell degranulation
