Innate immunity 2 Flashcards
What are the possible effector responses of innate immune cells?
phagocytosis, degranulation, antigen presentation, mediator release
What are mediators?
Soluble proteins or chemicals produced by immune cells in an immune response
Where do immune cells in the oral mucosa come from?
Some are tissue resident even in health (release chemokines during infection), others arrive from circulation in response to signalling molecules
Which is the main type of immune cell that is an early responder to infection?
Neutrophils
What is neutrophil chemotaxis?
Neutrophils moving towards an increasing concentration of chemokines
Which cytokine/chemokine is important for recruitment of immune cells?
CXCL8 (IL-8) - a type of chemokine and cytokine
Diapedesis definition?
The migration of immune cells out of circulation into blood vessel walls (cellular migration)
Which word is extravasation the old term for?
Diapedesis
How does diapedesis occur?
Receptors and ligands on neutrophils and endothelial cells interact to enable neutrophils to move towards an increasing chemokine (CXCL8) concentration in the surrounding tissues.
Which receptors are involved in diapedesis?
Selectins (e.g. E-selectins), Integrins (e.g. LFA-I), Immunoglobulin superfamily
What is LFA-I?
Lymphocyte Function-associated Antigen 1 (an integrin receptor involved in diapedesis)
What are granules?
Vesicles containing soluble mediators
What mediators do granules contain?
Proteinases, Antimicrobials (e.g. AMPs, lactoferrin), Chemical mediators (e.g. histamine)
Which immune cells undergo degranulation?
eosinophils, basophils, neutrophils, NK cells, mast cells (granulocytes, innate immune cells)
Where is histamine released from?
Mast cells and Basophils when they degranulate
What are the wide spread effects of histamine?
Vasodilation and increased vascular permeability (more leaky so more diapedesis), smooth muscle contraction, bronchoconstriction, neurotransmission (itching sensation in allergies)
What process do neutrophils undergo?
NETosis which traps pathogens (as well as degranulation and phagocytosis)
What is NETosis?
The release of proteins and chromatin (DNA) from neutrophils during degranulation to form extra-cellular fibril matrix (Neutrophil Extracellular Traps)
Function of natural killer cells
recognise and kill abnormal cells (and invading microbes)
Examples of abnormal cells killed by natural killer cells
cancer cells, host cells infected by virus
What is ADCC?
Antibody-Dependent Cellular Cytotoxicity - B cells produce antibodies that bind to abnormal cells / microorganisms and tag them for apoptosis by NK cells and eosinophils
How do NK cells cause apoptosis of abnormal cells?
NK cells release perforin (creates pores in abnormal cells) and granzymes (lyse cell)
What is apoptosis?
Programmed cell death
Function of eosinophils
Undergoes ADCC for destruction of microorganisms and is anti-parasitic (MBP)
What is MBP?
Major Basic Protein - a potent antiparasitic enzyme toxin that drives cellular lysis
What does ADCC rely on?
antibodies produced by B cells
Which immune cells carry out phagocytosis?
Phagocytes (neutrophils, macrophages, dendritic cells)
Overview of phagocytosis
degradation, antigen presentation, safe break down and dispose of apoptotic and necrotic cells
Stages of phagocytosis
recognition, engulfment, phagosome formation, phagolysosome formation, cell digestion/degradation, exocytosis / antigen presentation
Opsonization definition
tagging of cells for removal
What are initiating factors of phagocytosis?
Antibodies / complement components bind to antigens (opsonization) which is detected by Pattern Recognition Receptors / Fc receptors on phagocytes
Efferocytosis definition
removal of apoptotic or necrotic cells
How is innate immunity linked to adaptive immunity?
Antigen presentation
How does antigen presentation occur?
Antigens are presented to T cells via Major Histocompatibility Complex receptors (MHC) at the end of phagocytosis
What is MHC?
Major Histocompatibility Complex - set of genes that present proteins within the host cell to T cells to initiate the adaptive immune response.
What is MHC class I involved with?
MHCI presents endogenous proteins (viral, tumour cells) to T cells. (found on all nucleated cells)
Which MHC class is present on all nucleated cells?
MHCI (so all cells can initiate immune response)
What is MHC class II involved with?
MHCII presents exogenous proteins (post-phagocytosis / antigen presenting cells)
Which cells detect MHCI?
CD8 (cytotoxic T cells) and T cells
Which cells detect MHCII?
CD4 (T helper cells) and T cells
What is the largest component of human blood?
Plasma (55%)
Name the four enzymatic cascade systems in plasma
Complement, Kinins, Coagulation factors, Fibrinolytic system
What are complement proteins?
a collection of soluble pro-inflammatory proteins present in circulation
Where are complement proteins produced?
By immune cells in the liver
Function of complement proteins
Drive opsonization and inflammatory responses, forms membrane attack complexes which creates pores on microbial cells causing lysis.
How are complement proteins pro-inflammatory?
Increase vascular permeability by increasing interstitial space, fluid leakage and diapedesis (so more immune cells migrate)
Which complement proteins drive anaphylaxis?
C5a and C3a
What are the complement proteins C5a and C3a called?
anaphylatoxins
What are the 3 pathways of complement?
Classical pathway (antigen-antibody complexes), Lectin pathway (MBL-MASP complexes directed by microorganism), Alternative pathway (microbial components e.g. proteins, enzymes, virulence factors)
How is the classical pathway for complement triggered?
Via antibody-antigen complexes or allergens
How is the lectin pathway for complement triggered?
via MBL-MASP complexes directed by microorganism (mannan-binding lectin and MBL associated serine protease)
How is the alternative pathway for complement triggered?
via microbial components e.g. proteins, enzymes, virulence factors. Also allergens
Which complement pathways can allergens stimulate?
Classical and alternative pathway
