Blood Immunity and innate immunity Flashcards
How do staph infections occur?
caused by staforius/staphylococcus bacteria, types of germs commonly found on the skin or in the nose of even healthy individuals. They get in the body through skin breaks.
How do lysozyme in tears and saliva protect the body
the enzyme disrupts the surface of bacteria - physiological barrier
What is innate immunity
Is the bodies response that is not learnt or adapt (is fixed) and relies on distinction between self and non-self (first line response)
What type of cells provide your cellular innate immune defence
myeloid cells
Two components of immunity
Cellular and humoral
What does your myeloid lineage give rise to
all the white blood cells in innate immunity
Most abundant white blood cell in immunity
neutrophils
What are macrophages
activated form on monocytes
What do myeloid cells do?
detect microorganisms while in capillaries and migrate to find infection
What is the humoral component of immunity?
are the soluble proteins in blood that opsise microorganisms
What is the cellular component of immunity?
Cellular immunity consists of either myeloid cells (innate) or lymphoid cells (adaptive)
Why is complement in the humoral component of immunity?
because complement is soluble
What do lectin binding proteins do
they activate complement and recognize unique carbohydrates on the surface of bacteria
What is the purpose of terminal Sialic acid
We have terminal sialic acid to distinguish our self cells from other cells
What do Antimicrobial peptides do
produce peptides that attach to the surface of bacteria that cause they to lyse
Where are Antimicrobial peptides found
found in places like saliva
What is an auto-immune response?
is when immune system destroys own cells (e.g. type 1 diabetes)
What is the first line response to pathogen invasion?
Innate immunity
What cell arrives first when you injure yourself
neutrophils will arrive to engulf infection
Did innate immunity occur before or after adaptive immunity
before
Is innate immunity present in prokaryotes and eukaryotes
yes
3 stages of innate immunity in mammals
Complement (C’)
Myeloid cells and phagocytosis (neutrophils and macrophages)
Pattern Recognition Receptors (PRR)
Does innate immunity have memory
no
3 main types of pathogens
viruses
Bacteria, yeast and fungi
Protozoa and parasite
What are viruses
are intracellular pathogens that use host cell machinery for replication. Need a means of detecting infected cells and destroying them while leaving normal host cells alone
What type of defence against viruses does the body rely on
cellular immunity - need to be able to distinguish infected from normal cells.
How long does viral illness take before being cured (generally)
24-48 hours
What occurs to immune system in HIV
it is destroyed so people die from opportunistic infections
What are Bacteria, yeast and fungi
Are (mostly) extracellular pathogens that are engulfed and destruction by phagocytic cells
What type defence of defence against Bacteria, yeast and fungi does the body rely on
Defence is primarily mediated by innate mechanisms and phagocytosis
What can distinguish between the different types of bacteria?
a gram stain
What are gram positive bacteria
bacteria that have a thick peptidoglycan cell wall as a defence and are resistant to direct complement MAC lysis
Does gram positive bacteria light up on a gram stain
yes
What can destroy gram positive bacteria
phagocytosis (not killed directly by complement)
Examples of gram positive bacteria
S. aureus, S. pyogenes
What are gram negative bacteria
bacteria with thinner peptidoglycan layer and an outer membrane and are often more sensitive to complement MAC lysis
Does gram negative bacteria light up on a gram stain
no
What can destroy gram negative bacteria
These bacteria can often be lysed directly by complement. (Membrane Attack Complex)
Examples of gram negative bacteria
E. coli, H. influenza
What do β-lactam antibiotics do
block peptidoglycan/cell wall synthesis (cell cannot divide effectively)
Example of β-lactam antibiotics
penicillin
What are Protozoa and parasite
Complex organisms are often multicellular and highly developed (helminths - worms)
Where are Protozoa and parasite found
Can live inside (malaria – plasmodium falciparum lives inside the red blood cell) or outside cells.
How are Protozoa and parasite killed
Require direct killing by chemical mediators released by specialist myeloid cells (Basophils, mast cells, and eosinophils) because they are too big to be killed by phagocytic cells
What are the granules in specialist myeloid cells that kill Protozoa and parasites
granules are filled with cytotoxic chemicals. Degranulation releases these toxic inflammatory chemicals such as histamine
5 steps of recruiting a neutrophil
Activation, tethering, adhesion, diapedesis, chemotaxis
What is activation in recruiting a neutrophil
Chemokines from tissue injury or inflammation activate the local endothelial cells lining an adjacent capillary wall.
What is tethering in recruiting a neutrophil
Neutrophil tethers to the inside capillary wall. Mediated by selectins on endothelial cells and sialyl Lewis X (sLex), a carbohydrate antigen, on neutrophils. This causes weak binding and the neutrophil to roll
What is adhesion in recruiting a neutrophil
strong binding between neutrophil integrins and ICAM-1 on the endothelium. Neutrophil immobilises and flattens
What is diapedesis in recruiting a neutrophil
neutrophil finds junction and squeezes between endothelial cells and out of the capillary into the tissue (interstitial space)
What is chemotaxis in recruiting a neutrophil
Neutrophil migrates along a chemokine gradient to the site of infection
What makes neutrophils find bacteria
serum
How do neutrophils migrate up the chemoattractant gradient
they polymerize actin filaments at their leading edge and depolymerize those filaments at their trailing edge.
What are the complement receptors
CR1, CR2, CR3, CR4 (Complement receptor 1-4)
What is opsonisation
This is the process of coating microbes with complement proteins to form complex complement convertases ready for phagocytosis
What do myeloid cell receptors bind to on bacteria
activated complement components deposited on bacteria
What is the main neutrophil receptor
CR1
What does CR1 bind to
C3b on bacteria (Complement convertase covering bacteria)
What initiates phagocytosis
Cross-linking of the surface CRs and complex on bacteria
What is FcR
the Fc receptor (FCR) is a group of surface membrane molecules that specifically recognize and bind immunoglobulin
What binds to bacterial antigens in FcR (antibody) mediated phagocytosis
Antibody (IgM and IgG) and C1
What does neutrophil FcR bind to
the antibody Fc region
What does the binding of the FcR and Fc region do
Activates phagocytosis (cell captures and engulfs bacteria)
What is a phagosome
phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis
What is a phagolysosome
is a cytoplasmic body formed by the fusion of a phagosome with a lysosome in a process that occurs during phagocytosis
What happens inside a phagolysosome
it acidifies and superoxides kill bacteria
What is phagocytosis
engulfment of the microbe by phagocytes (neutrophils and macrophages) that destroys the organism
5 steps of phagocytosis
- Ingestion
- Fusion
- Acidification
- Digestion
- Exocytosis
What is ingestion in phagocytosis
The bacterium is captured by receptors, membrane invaginates into a phagosome
What is fusion in phagocytosis
The phagosome and lysosome fuse to form a phagolysosome.
What is acidification in phagocytosis
the phagolysosome acidified with H+ pumped in
What is digestion in phagocytosis
Acidification activates protease and stimulates the production of superoxides such as H2O2 (peroxide) and HOCl (hypochlorous acid) which kill bacteria.
What is exocytosis in phagocytosis
expulsion of the digested microbe
What are pattern recognition receptors (PRR)
Are receptors found on many myeloid cells that recognise complex microbial molecular patterns
What are PRR’s essential for
recognising the unique pathogen patterns on the surface of microbacteria (tells adaptive immune response to make antibodies)
What are Toll-Like Receptors (TLR)
TLR are Leucine Rich Repeat (LRR) receptors that look like a “slinky”. There are 9 TLR molecules
How many TLR receptors are there
9
What does activation through TLR do?
stimulates a strong innate response through an important inflammation pathway
What are Pathogen Associated Molecular Patterns (PAMPs)
unique molecules that are
produced by microbes. Structurally complex & evolutionarily stable which are recognised by PRR
What is LPS
(lipopolysaccharide), a type of PAMP
Are PAMPS evolutionarily stable?
yes - don’t change too much with time
What do PAMPS stimulate
They stimulate the ‘power’ switch for the adaptive response
What is the TLR receptor for LPS
TLR4
What type of bacteria is LPS from
Gram negative bacteria
What does LPS cause in the body
a fever
What is septic shock
Release of LPS by Gram negative bacterial infections, an uncontrolled Gram negative infection in the blood
