MCB Lecture 42 Innate Immune System Flashcards
What are the two types of molecules that can be detected on microbes?
PAMPs: molecules conserved in microorganisms. Not unique, but rather found in many taxonomical groups eg. LSP
Antigens: molecules on a microorganism that are particular to that particular species. Eg. Haemoglutinin and Neurominadase on influenza virus
Why have an immune system?
To protect the individual against invading microorganisms
Which receptor recognises PAMPs?
PAMP recognition receptor
PRR
Which receptor recognises antigens?
Antigen receptor
Antibody
What are the requirements of the innate immune system? (4)
- Rapid
- Present at birth
- Appropriate for pathogen
- Distinguish self from non self
What are opportunistic infections?
These are microorganisms that only cause harm when given the opportunity; opportunistic invaders
Describe how and when the immune system evolved
It enveloped due to pressure from microorgansism a that were invading and causing harm
The innate immune system evolved first
The adaptive immune system evolved when some pathogens escaped the innate immune system
What are the characteristics of the innate immune system? (5)
- Fast response
- The magnitude is constant
- First line of defence
- Non specific
- Interacts and educated the adaptive response
What are the components of the innate immune system?
Barriers, secretions, cells
Describe how epithelium is part of the immune system
These form a physical barrier to prevent microorganisms getting into the host Eg. Epithelium of trachea and lungs Skin epithelium Gut epithelium Nasal epithelium
Describe how secretions form part of the immune system
These are secreted by epithelium, and prevent microorganisms from getting in, or killing them
Eg.
Mucous secreted by trachea epithelium
Lysosyme and Phospholipase A in the mouth and tears
Gastric juice: acidic to kill the pathogen
Bile salts
Where is lysosyme found?
In the mouth and in tears
Where is Phospholipase A found?
What does it do?
In the mouth and in tears
It disrupts the cell membrane of bacteria and other pathogens
Describe how normal flora protect us in the immune response
Commensals are found on many outer surfaces of the body
They take up space so that other bacteria which are harmful cannot take up residence
They prime out innate immune system
Eg. On skin In throat In the gut Vagina
What are plasma factors ? (3)
- C reactive proteins
- Mannose binding lectin
- Complement proteins
Describe the function of C reactive protein
These coat microbes and trigger phagocytosis and the complement cascade
What is mannose binding lectin?
It is a protein that binds to mannose on the surface of a bacterium.
It triggers the complement cascade
What is a lectin?
It is a protein that binds to a sugar
Give a brief description of the complement system
Activated via one of three pathways
Critical step: C3 is cleaved
Outcomes: microbe is phagocytosed, lysed and phagocytes and inflammatory cells are attracted
How can the complement system be activated?
- Classical pathway: antibody binds. C1 -> C2 -> C4
- Lectin pathway: lectin binds to mannam.
- Alternate pathway: binding to molecules on the surface of the pathogen
What is the critical step in the complement system?
Cleavage of the C3 protein
What does proteolysis of the complement proteins bring about?
It brings about the evolution of other cleavage products
These bind to the surface of pathogens and bring about the outcomes
What are the outcomes of the complement system?
- Opsonisation : C3b coats a pathogen, and phagocytosis is induced
- Lysis: C5,6,7,8,9 come together to form a pore in the cell wall of the microbe. The cell lyses and dies
- Chemotaxis: C3,4,5a attract phagocytes and inflammatory cells
Describe the process of opsonisation
How is it activated?
C3b coats a microbe, and phagocytosis is induced
It is activated by the cleavage of C3, ie the complement system
Describe the process of chemotaxis
How is it activated?
Cleavage products from c,savage of C3 attract phagocytes and inflammatory cells to the area
It is activated by the complement system
Describe the process of microbial lysis
How is it activated?
C5,6,7,8,9 come together to form a pore in the microbial cell wall
The cell lyses and dies
What are the three different types of cell in the innate immune system?
Phagocytic
Cytotoxic
Inflammatory
What is a neutrophil?
It is also known as a granulocyte
It is a phagocytic cell
What is a Monocyte?
It is a precursor to a macrophage
It has phagocytic capabilities
What is a phagocyte?
It is a cell that engulfs and kills a bacterium
What is a dendritic cell?
It’s a phagocytic cell
What is a Eosinophil?
It is a cytotoxic cell
It releases toxic granules that kill microbes
What is a NK cell?
It is a cytotoxic cell
It releases toxic granules that kill microbes
What is a basophils?
These are inflammatory cells
They release inflammatory substances
What are the two lineages of cell production?
Where does this occur?
Myeloid: neutrophil, Monocyte, macrophage, Eosinophil, basophils
Lymphoid: NK cell, b lymphocyte, t lymphocyte
What is the role of receptors in the innate immune system?
These bind to the PAMP and a signal transduction pathway is initiated
Normally, gene transcription will be altered: production of defensins etc
What are some receptors in the innate immune system?
Toll like receptor (TLR)
NOD
RIG
Describe the function of toll like receptors
- Ligand (PAMP) binds
PAMP can be: element of the flagellum, CgP DNA, LPS - Signal transduction pathway ensues
- Gene transcription is altered: anti-infection factors, defensins
What are the outcomes of PRR-PAMP?
Phagocytosis
Expression of certain cell surface receptors
Production of chemokines, cytokines, defensins
What are cytokines?
These are molecules that are released by an infected cell that tell neighbouring cells (with the correct receptor) that it is infected
What are chemokines?
These are molecules released by infected cells that attract cells with the appropriate receptor to the area
What stimulates the production of cytokines and chemokines?
PRR binding to a PAMP
Which receptors detect chemokines?
What is special about these receptors?
CCR
CXCR
They both have two cyteines
What a the two types of phagocytes?
Polymorphonuclear neutrophils
Mononuclear phagocytes
What are the functions of phagocytes?
They engulf and kill pathogens
They produce and release cytokines and chemokines
Describe the process of phagocytosis
- Extension of Filopodia
- Formation of a phagosome
- Formation of phagolysosome
- Lysis and killing of the bacterium
What molecules bring about degredation and killing of microbes in the lysosome?
Hydrolytic enzymes Low pH Reactive oxygen species Reactive nitrogen species Defensins
What are the two options in the outcome of the innate immune system?
The pathogen is removed
The pathogen avoids removal, and the adaptive immune system must play a role
What are the four types of cytokines?
Inflammatory
Antiviral
Stimulatory
Suppressive
What is the role of IL-1?
This is an inflammatory cytokine released by activated macrophages
What is the role of IL-6?
This is an inflammatory cytokine released by activated macrophages
What is the role of IL-12?
This is a stimulatory cytokine released by activated macrophages
What is the role of IL-10?
This is a suppressive cytokine released by activated macrophages
What is the role of GM-CSF?
This is a stimulatory cytokine released by activated macrophages
What is the role of TNF-alpha?
This is an inflammatory cytokine released by activated macrophages
What is the role of TGF-beta in the innate immune system?
This is a suppressive cytokine released by activated macrophages
What is the role of IFN-alpha?
This is an antiviral cytokine released by activated macrophages
Which are the inflammatory cytokines released by activated macrophages?
IL-1
IL-6
TNF-alpha
Which are the stimulatory cytokines released by macrophages?
GM-CSF
IL-12
Which are the antiviral cytokines released by activated macrophages?
IFN-alpha
Which are the suppressive cytokines released by activated macrophages?
IL-10
TGF-beta
Which chemokine is released by activated macrophages?
CXCL8, aka IL-8
What are defensins?
These are molecules produced by macrophages that bind to and kill bacteria that have been phagocytosed by putting holes in the bacterial cell membrane. The bacteria experiences efflux of nutrients and ions, and dies
Which chemicals are present in tears that protect from microbes?
Lysozyme
Phospholipase A
Which chemicals are present in the mouth that protect from microbes?
Lysozyme
Phospholipase A
Histatins
Which chemicals are present in the stomach and gut that protect from microbes?
Low pH
Bile salts
A-defensins
Lysopeptide
Which chemicals are present on the skin that protect from microbes?
Fatty acids Lysozyme Low pH RNA-ases DNA-ases
Which chemicals are present on the vagina that protect from microbes?
Low pH
Which chemicals are present in the respiratory tract that protect from microbes?
Beta-defensins
