Molecules of the Innate Immune System Flashcards
Classes of innate immunity molecules
PRRs Fc receptors Cytokines Defensins Complement Acute phase proteins
What are examples of PRRs?
Toll-like receptors TLR-4, TLR-2 and TLR-3
Mannose receptors
What does TLR-4 do?
On most cells
Recognises Lipopolysaccharides on gram -ve bacteria
What does binding of LPS to TLR-4 result in?
Activation of the cell as binding triggers intracelllular cascades
What does TLR-4 recognise?
LPS on gram -ve bacteria
What does TLR-2 recognise?
Proteoglycans on gram +ve bacteria
Why are Toll-like receptors broadly specific?
Their targets are specific protein sequences, but these are present on many cells so they affect a large range of bacteria.
What does TLR-3 recognise?
Double stranded RNA
What is the difference between TLR-3 and TLR-4/2?
TLR-4/2 are found on CSM
TLR-3 are found intracellularly
What are mannose receptors?
Mannose are found on all cells, but usually they are blocked by other sugars
Bacteria, however have mannose as their surface sufar
Therefore, evolution has told hosts that cells with mannose as their surface sugars are non-self and should be destroyed
What constitutes the complement system?
Zymogens
How many molecules constitute the complement system?
20-30
How are zymogens activated?
By three mechanisms:
Classical - antigen-antibody interactions and C-reactive proteins
Alternative - structures on microbial cell wall
Lectin - receptors recognising sugars
Give an example of a lectin pathway-activating receptor
Mannose-binding lectin
What pathways are usually stimulated during infection?
Normally all the pathways are stimulated
What happens upon activation of the complement pathway?
C3 splits into C3a and C3b
C3b splits C5 into C5a and C5b
What is the role of the comlpement zymogens?
C3d is involved in activation of B cells
C3b and C4b opsonises molecules
C5a and C3a are acute inflammatory proteins that attract neutrophils out of the blood stream and into the tissue by releasing histamines that losen epithelium
C3a, C4a and C5a cause mast cell degranulation and enhanced permeability by the release of cytokines
C5b, C3b and C6/7/8 form MAC?
What is the role of C3d?
B cell regulation
What is the role of C3b and C4d?
Opsonisation.
Phagocytes contain membrane receptors that recognise complement and cause phagocytosis of opsonised molecules
What is the role of C5a and C3a?
Chemotactic molecules
Increase vascular permeability by the release of histamines so the neutrophils can travel from the blood to the tissues
What is the role of C4a, C3a and C5a?
Mast cell degranulation and enhanced permeability by release of cytokines
What complement zymogens form the MAC?
C5b, C3b, C7-9
What is the MAC?
Membrane attack complex
Forms a pore in the bacteria which dysregulates the electroc potential across the membrane and causes cell lysis.
What regulates the complement cascade?
T regulatory cells
What is opsonisation?
Binding of antibodies or complement to the antigen
Increases phagocytosis since there are receptors for the antibody and complement on phagocytes.
How is opsonisation beneficial?
Increases the probability of the antigen being phagocytosed since there are receptors for the antibody and complement on phagocytes.
What molecules are involved in opsonisation?
Antibodies
Complement
What are the receptors for the opsonisation molecules on phagocytes?
Complement receptors
Fc receptors
What are APPs?
Acute phase proteins are produced under the stimulation of cytokines by the liver
Cytokines are released when PRRs recognise molecules
What does APP stand for?
Acute phase proteins
What are examples of APPs?
C3
C-reactive protein
Fibrinogen
What happens to APP concentration in inflammation?
Increases up to 1000 fold
What are the roles of APP?
Promote resolution and repair of inflammatory lesions
Enhance host resistance to infection
Minimize tissue injury
Where are APPs made?
Liver
What triggers the formation of APPs?
Cytokines released once PRRs recognise molecules
What is an inflammatory lesion?
Lesion produced by the inflammatory response
What are defensins?
Defensins small cationic antimicrobial peptides that act on bacteria to destroy them in a similar way to MAC
Where are defensins present?
Everywhere. On every cell
Secreted or transmembrane forms
What do defensins attack?
Bacteria and Fungi
How do defensins eradicate pathogens?
Similarly to MAC
Form pore that dysregulates the membrane potential of the cell leading to cell lysis
What are the two families of defensins?
a-defensins - expressed at all times
b-defensins
What are cytokines?
Small, secreted proteins that act like messengers
Hormonal system of the IS
How big are cytokines?
8-80 kDa
Examples of cytokines
IL-1
IL-6
TNF
Main functions of cytokines?
Masterful multitaskers
Regulate the immune response
Control haematopoiesis
How do cytokines perform their functions?
Once cytokines bind to their receptors, they trigger intracellular singalling cascades within host cells.
What does binding of cytokines onto their receptors cause?
Leads to an increase or decreased expression of genes encoding for
Cell surface molecules
Other cytokines
Cellular activities - activation and proliferation
Important cytokines in the innate IR
TNFa
IL
IFN
CSF
Chemokines
