Innate Immunity Flashcards
What is innate immunity?
Rapid cellular/soluble component immune response present from birth, using PAMPs/DAMPs to detect microbial structures and damage as well as missing self
Name the 4 types of defensive barrier
Anatomical
Physiological
Phagocytic
Inflammatory
What are the anatomical barriers?
Skin (mechanical)
Mucous membranes
What are the physiological barriers?
Fever
Low Stomach pH
Chemical mediators: Lysozymes, interferons, complement
What are phagocytes?
Cells that ingest material
What is the inflammatory barrier?
Local increased vascular permeability to allow cell escape to enhance immune function
Name the major phagocytic cell types:
All 7 of ‘em!
Neutrophils Eosinophils Basophils Monocytes/Macrophages Mast Cells Dendritic cells Natural Killer Cells
What are neutrophils?
Phagocytes with multi-lobed nuclei.
Short lived; circulate in blood then migrate to tissues
Which cells are first recruited to the site of damage?
Neutrophils
Which cells defend against parasitic infection?
Eosinophils
What are eosinophils?
Phagocytes.
Release granules to defend against parasites
Help B-cells produce IgA
What are basophils?
Granule releasing cells
They act as antigen-presenting cells for antibody mediated immunity
What is the difference between Monocytes and Macrophages?
Monocytes in blood
Macrophages in tissue
What are macrophages?
Important for phagocytosis
“Big Eaters”
Release cytokines
Present antigen fragments to T-cells
What are mast cells?
Release histamine-containing granules
Pro-inflammatory
What do dendritic cells do?
Capture antigens and present them to T-cells
What do Natural Killer Cells do?
Lyse infected cells
(no antigen-specific receptors)
Secreet Interferon-y
How do neutrophils enter tissues?
Diapedesis and Chemotaxis
Simmilar way to Lymphocytes
Selectin Binding (with rollin’)
Then Integrin activation and strong binding, immobilisation and Diapedesis
What proportion of leukocytes are neutrophils?
50-70%
What causes a neutrophil to enter a tissue?
Damage causes chemokines to be released which bind to endothelial layer.
Neutrophils recept these which actiates integrin…
How do Neutrophils know where to go once they enter a tissue?
Chemotaxis:
They follow the gradient of chemokines which gets stronger towards the site of damage/infection
Which molecules function as opsonins?
Antibodies and Complement
What is Opsoninisation?
Coating of microorganism with opsonins (e.g. antibodies) to facilitate phagocytosis.
What are the 2 mechanisms Neutrophils use to kill?
Oxygen independent: Enzymes (hydrolytic, lysozymes etc.) and antimicrobial peptides
Oxygen dependent: Free radicals, H2O2, anything that sounds toxic (e.g. you)
What do neutrophils need to do to fight infection?
List the 4 steps:
Move from circ into tissues
Bind to pathogen
Phagocytose pathogen
Kill it
How do neutrophils trap microbes?
Extracellular traps: they release granule net-like materials which form extracellular fibres to trap microbes
What do macrophages do once they’ve eaten a pathogen?
Release soluble cytokines to recruit further cells
What is (NK) target cell recognition?
Under viral stress, cell upregulates stress-induced molecules that activate natural killer cells and downregulate inhibitory molecules so NK cells are not inhibited to kill cell
What are NK cells useful for fighting?
Viral infections
Tumours
How are NK cells regulated?
Have activatory and inhibitory receptors
Name 5 types of cytokine
Interleukins Interferons Chemokines Growth factors Cytotoxic tumour necrosis factors
What do interferons do?
Interfere with viral replication
What do growth factors do?
Help stem cells differentiate and proliferate
What do cytotoxic tumour necrosis factors do?
Induce programmed cell death in target cells
How do cytokines work?
Producing cell makes them in granules. Exocytose
Bind to receptors on cells, effect gene regulation (up/downregulate)
Name the 3 locational modes of cytokine activity
Autocrine: on self
Paracrine: on nearby cells
Endocrine: via circulation to distant cell
How many types of interferons are there, and what produces them?
2.
Only immune cells produce type 2
Many cells produce type 1
What is complement?
Glycoprotein enzyme that ‘complements’ the action of a specific antibody
Where are the components of the complement system produced?
Mainly liver
+ Monocytes and macrophages
What is the complement system?
Complex system of ~30 glycoproteins that from a triggered enzyme cascade
What happens to the complement system when it is activated?
Inactive precursors are cleaved, and the cleaved sites become pro-inflammatory molecules.
What are the names of the 3 activation pathways of complement?
Classical
Alternative
Lectin
What do all 3 complement activation pathways result in?
Activation of C3b; final common pathway
What is the classical pathway?
Antibody binds to antigen on pathogen.
Conformational change in antibody leads to complement activation
What is the alternative pathway?
Direct activation of complement system by surfaces of pathogens themselves.
What is the Lectin pathway?
Lectin: Carbohydrate binding protein; antibody-independent activation.
Is a pattern recognition receptor, binds to patterns only present on pathogens
What does activation of C3b lead to?
Formation of Membrane Attack Complex (MAC)
What is the membrane attack complex?
What lyses infected cells or pathogens.
What are the control mechanisms of complement?
Short half-life
Regulatory proteins on self cells, prevent complement mediated lysis of self (eg. CD59)
What are the functions of complement?
Cell lysis
Opsoninisation
Pro-inflammatory effects
Clear Immune complexes (antibody-antigen)
What might a systematic ‘acute-phase’ response result in increased production of?
C-reactive protein (clinical measurement of inflam)
Mannan-binding Lectin
Complement
Fibrinogen
