Innate immunity Flashcards
What is immunity
sucessful resistance to pathogens
What is innate immunity
Or known as natural immuntiy
Non specific, destroys pathogens in general not directed at a specific pathogen
It will not become more efficient after the first
encounter with the pathogen.
What are some barriers that we have for pathogens
Physical- skin, washing hands etc
Chemical- low ph of stomach, fatty acids, secretions
Biological barrier- secretions by microorgansims, competition of normal flora on skin surface
How does mucosal surfaces act as a good external defence (barrier) to pathogens
- Mucous traps pathogens not allow them to adhere to epithelial cells
- tears, saliva, urine wash pathogens away
- airway cilia push mucus with trapped particles to back of throat (mucocilliary clearance)
What is primary cilliary dyskinesia
Autosomnal recessive disorder
Cilia and flagella immotile
Due to gene mutation for motor protein dyenin (for the axoneme)
What are the defences in tissues for pathogens
innate and adaptive (cellular and humoral)
What are some mechanisms invlved in innate immunity
Phagocytes
Complement
inflammation
Interferons
NK
Extracellular killing
How do phagocytes recognise molecule on pathogen
They dont recognise a specific molecule but rather a general carbohydrate profile.
This is done by PATTERN RECOGNITION RECEPTORS
Belong to family of Toll like receptors
The engulf, fuse with lysosome, phagolysosome
After several minutes within phagolysosome, what happens to the microorganism
Inability for microorganism to reproduce
Inhibition of macromolecular synthesis
What are the 2 killing mechanism that phagocytes use
Oxygen dependent pathway- generate oxygen reactive species eg hydrogen peroxide/ superoxide radicals. Reacts with proteins, lipids to kill
Oxygen independent pathway- lysosomal enzymes destroy eg proteases, phospholipases, nucleases and lysozymes.- breaks down cell membrane- less effective than oxy dep.
What are the 2 types of phagocytes
neutrophils-small, segemnted nucleus, short lived
Macrophages-larger, non segment nucleus, long live
What is the mononuclear phagocyte system
After a short while, monocytes will stop circulating and settle in tissues as resident macrophages
They have different names in tissues
Blood=monocytes
Lung=Alveolar macrophages
Liver= Kupffer cells
brain=microglia
bones=osteaclaasts
skin=langerhans cells (dentritic cells)
What is extracellular killing
It is used when the target is too large for phagocytosis. Two cell types are
specialized for it: the eosinophils and the NK cells.
What do eoisinopjhis do in extracellular killing
KILL PARASITES BY DEGRANULATION
- have many granules (lysoomes) and deliver it by exocytosis
- They defend against helminthic attacks
- antibodies and complement proteins stimulate degranulation
What do natural killer cells do in extracellular killing
NK CELLS KILL OUR OWN CELLS BY APOPTOSIS
- type of lymphocyte
- They detect virus-infected cells and some cancer cells
by pattern-recognition receptors. - Extracellular killing of our own cells is called CYTOLYSIS OR CYTOTOXICITY
- Macrophages (dendritic cells) can secret tumour necrosis facotr to stimulate apoptosis (cytolysis)
How does NK cells destroy tumour cells/ virus cells
Granules containing PERFORIN forms pores on membrane
Also secretes a protease called GRANZYME that enters perforin pores and delivers signal for apoptosis
If the target cell refuses to die voluntarily by
apoptosis, it is lysed using more perforin (necrosis).
What are the 2 strategies neutrophils use to kill pathogens (first line defense)
- Engulfment of microbes
- Secretion of antimicrobials
What are neutrophil extracellular traps (NETs)
NETs are networks of extracellular fibers, which bind pathogens.
They are primarily composed of DNA from neutrophils.
NETs allow neutrophils to kill extracellular pathogens while minimizing damage to the host cells.
NET activation and release is known as NETosis.
What are the 2 forms of NETosis
SUICIDAL -the intracellular NET formation is followed by the rupture of the plasma membrane (neutrophil), releasing it into
the extracellular space.
VITAL-blebbing of the nucleus, resulting in a DNA-filled vesicle that is exocytosed and leaves the plasma
membrane intact.
In some cases mitochondrial DNA included in trapping fibres
What is the most important humoral defemse
A set of plasma proteins called COMPLEMENT SYSTEM
What is inflammation
Inflammation is local activation of innate
defenses (both cellular and humoral)
caused by injury or infection.
What 2 cell types responsible for inflammation
mast cells and basophils- both contain granules with histamines
mast cells reside in tissue basophils circulate
How does inflammation develop
- mast cells and basophils undergo degranulation (release content of granules)
- Triggers can be variuos things from pathogen eg C3a or C5a from complement
- Tissue damage tears some mast cells apart, with the same result – mediators of inflammation are
released. - Mediators of inflammation cannot do anything to the pathogen. Instead, they recruit other innate
immune mechanisms to combat it.
Effect of inflammation mediators
*Capillaries dilate, causing redness,
and their walls become more
permeable.
- Swelling occurs as blood plasma floods in
- DIAPEDESIS- cells of capillary move apart (dilate). Hemotaxis causes leukocytes to pass between them
*Temp increaed
*Mediators and swelling cause pain, forcing the host to let the inflamed organ rest.
What do mast cells secrete that causes capillaries to dilate
Histamines
Effects of infkammation.
What do macrophages secrete to cause fatigue, fever, sleepiness etc during inflammation
interluekin 1
what is the main antiviral innate defense
inferons alpha and beta
What do inferons do
They are proteins synthesized and secreted by virus-infected cells as a warning.
Interferons bind to surface receptors of neighbouring cells, triggering “virus alert”.
interferons activate
immune cells in the vicinity and
induces apoptosis in the neighbors
of infected cell.
Due to the interferons, what 2 enzymes are synthesized
Protein kinase- inactivates translation initiation
factor eIF-2
Ribonuclease- degrades mRNAs
This way, the cell stops synthesis of
its proteins in order to prevent
synthesis of viral proteins.
How do complement systems and clotting system similarity
Blood plasma protiens made by liver
Mostlt proteases circulating
Main function is to react to stimulus from injury
Casacde is formed when proteins activate one another
How do you write complemt proteins
With a C
when protein split, bigger with b smaller with a
What are pathways of complenet action
The complement cascade has always the same end but different possible beginnings
It is triggered by polysaccharides in bacterial and fungal cell walls.
The classical activation of the complement requires antibodies;
Whats the most important complement protein
Steps:
C3
- Unstable so splits C3a and C3b
- If C3b is free in blood, it is degraded BUT it is stabilized by binding to microbial cell wall
- Factor B joins C3b and it is cleaved, fragments Bb and Ba
- The complex C3bBb has enzymatic activity. It cleaves
C3 into C3a and C3b, therefore is called C3 convertase. - The C3 convertase cleaves C3 much faster than this happens spontaneously.
- Soon the microbial cell surface around it is covered by C3b fragments.
MEMBRANE ATTACK COMPLEX THEN FILS PATHOGEN WITH WATER CAUSING TO BUFRST
How does C3b facilitate phagocytosis
- phagocytes have receptor for C3b
- easier for them to engulf a target if it is covered
by C3b.
This is called opsonization
Three extracellular complement initiation pathways that make up 1 terminal pathway
*The Classical pathway is activated by
antigen/antibody complexes,
- The Lectin pathway is triggered by
binding of mannose-binding lectin (MBL)
to carbohydrates - The alternative pathway when C3b binds to microbe directly
