Innate / Cytokines Flashcards
Name the 3 professional phagocytes
Neutrophils
Monocytes
Macrophages
Whats the normal amount of neutrophils in the blood
7.5 x 10^9 /l
Whats the half life of neutrophils
7 hours
Where do monocytes do their phagocytosis?
Bloodstream
What do monocytes form when they enter tissue?
Macrophages
What is macrophages toxic mediator?
nitric oxide
What contains more organelles… macrophages or monocytes?
Macrophages
Name a non professional phagocyte
Whats its main role?
Dentritic cells
Antigen presentation
What produces NETS
Neutrophils
How do NETS work?
Release of DNA /Protein from neutrophil
Binds /kill pathogens
What are the two types of NETS
Suicadal NETS
Vital NETosis
Name the 3 phagocyte stages
Quiescent
Primed
Activated
During the quiescent stage of a phagocyte, how do they react and what damage is there to vasculature ?
React weakly
Minimal damage
How is a phagocyte Primed?
How long does it take?
Subthreshold of cytokine
Primed for phagocytosis
Over minutes to hours
What happens when a phagocyte is activated?
What type of response is activated?
Full effective response
Granule response
ROS
What are the 3 components used in the identification of a PAMP (LPS) on macrophages
TLR-4
CD14
LBP
Name 3 opsonin proteins
CRP
Complement (C3b)
Antibody (IgM)
Opsonisation can increase phagocytosis by how much?
4000x
During respiratory burst, what enzyme adds electron electron to produce free radicals?
NADPH oxidase
Super oxide—> H202 —> Hydroxyl radicals + ?
Hypochlorite ions
What can evade ROS
Salmonella
What term is given to someone with decreased neutrophil production?
Neutropenia
How much neutrophils are present in Neutropenia?
< 0.2 x 10^9 /l
Name an injection which can boost neutrophil count
GCSF
LAD
Leukocyte adhesion deficiency
CGD (genetic Q)
Inherited and X linked
What is there a defect in CGD
Phox protein on NADPH
What can escape the ROS system if you have CGD
Staph.aureus
Aspergillus
Name a diagnostic test used in CGD
NBT
Lack of blue colour indicates low neutrophil count
Name 3 systems of CGD
Lymphadenitis
Granulomas in liver
Osteomyelitis
Name 3 treatments of CGD
Prophylactic antibiotics
IFN-y (boosts no oxidase dep. killing)
Bone marrow transplant (BMT)
What is the size of cytokines
25kDa
Whats the affinity of a cytokine to its specific receptor
10^-12 Kdis
Pleiotropy cytokine
1 cytokine
Multiple effects
Redundancy
Many cytokines
One function
Antagonism example
MCRA
Aldosterone antagonist
Where are cytokines released from?
And example?
Inflammasomes
NLRP3
What activates caspase 1?
What does Caspase 1 activate?
PAMP /DAMP
Inflammasomes
Where are inflammasomes found?
Macrophages
Neutrophils
Name an example of a chemokine
What releases it?
IL-8
Neutrophils
What do chemokines bind to?
What does this cause?
Endothelial surface
Causes selectins to migrate to endothelial surface
Whats the role of prostaglandins?
Increase Vascular Permeability
increase Vascular Dilation
Induce Neutrophil chemotaxis
Give an example of a PG and the cell which produces it
Monocytes (PGE2)
Neutrophils (PGE2)
Mast Cell (PGD2)
Name 3 roles of leukotrines
Chemoattractant neutrophils (LTB4)
Induce smooth muscle contraction
Causes stasis
What 3 cells produces LT?
Macrophages
Monocytes
Neutrophils
What do Selectins bind to on leukocytes?
Give example
Mucin like CAM
LSelectin —> GlyCAM-1
Whats the step that selectins cause
Rolling Adhesion Step
Integrity are found where?
What do they bind to?
Example
Leukocytes
Ig CAM
a4b7 —> IgCAM-1
What chemokine causes the recruitment of Ig CAM / selectins to the endothelial surface
IL-8
What triggers MC to release PG /LT?
PAMPs + TLR-4
IgE
Name 3 cytokines released from activated macrophages for local effects
Il-1b
TNF-a
Il-6
What is Il-b
Mitogen
Encourages a cell to divide (lymphocytes)
What organ produces Acute Phase Proteins
Liver
Where are SP-A/D found?
What do they bind to?
Whats its two roles
Macrophages in alveolar fluid in lung
Bind to pathogens via globular lectin domain
Opsonisation
Phagocytosis
Name a respiratory pathogen where SPA-D prevent it from spreading by promoting phagocytosis
Pneumocystis jirovecii fungus
Name 5 acute phase proteins
SPA/D
CRP
MBL
Fibrinogen
Name 2 cytokines which inhibits inflammation
What do they do?
Il-10
TGF-b
Deactivates macrophages and their antigen presentation
Name two hormones which inhibit macrophages and decrease fever
Where are they produced?
MSH
CSH
Pituitary gland
Name a drug treatment against altered inflammatory response /(sepsis)
Corticosteroids
Define chronic inflammation
Inflammatory agent persists due to resistance or deficient immunity
What do macrophages form in CI?
M1 —> M2 (epitheliod)
Granuloma
What are the two stages of sepsis
Warm
Cold
During warm stage, what 3 symptoms are present
> 38*
Tachycardia
> 12x10^3 mm^-3 WBC count
During cold stage, what 3 symptoms are present?
Cold <36*
Hypotension <90mmHg
Purpura (skin lesions)
Sepsis 6
High oxygen
Blood cultures
IV antibiotics
IV fluids
Lactate check
Monitor urine output
Name two tests for sepsis
CBC test
Bowel/urine culture
Name an anti inflammatory drug
How does it work?
Whats a danger with it?
APC
Inhibits thrombin formation
Inhibits WBC adhesion
Severe bleeding