3 Innate Immunity Flashcards
*Q: What percentage of leukocytes do neutrophil make? Life? Found? (2) Role?
A: 50-70% of leukocytes
Short-lived
Circulate in blood and migrate to tissues
First to be recruited to the site of tissue damage/infection
*Q: What are the characteristic features of a neutrophil? (4)
A: Multi-lobed nucleus
Primary Granules - sites of the enzymes that are going to kill the phagocytosed pathogen (stain darker than secondary)
Secondary Granules - predominantly involved in replenishing primary granules and regulate the toxins that are produced during the lysis of phagocytosed pathogens
The granules fuse with the vacuole to form a phagolysosome.
Q: How does a neutrophil move into tissues? 2 processes names? Steps. (4)
A: Diapedesis (movement of a cell across the endothelial layer) and Chemotaxis
Chemokines are released from the site of infection where there is damage which bind to the local endothelial layer
- Rolling- Neutrophils will roll along the surface with low affinity interactions (binding to selectin).
Integrin will be in the low-affinity state.
- Integrin activation by chemokines - chemokine receptor on neutrophil binds to chemokine on endothelial surface and activates integrin converting it to the high-affinity state.
- Stable Adhesion - Integrin binds STRONGLY to the integrin ligand and the neutrophil is immobilised
- Cells migration into endothelium (tissue)- the cells then follow a chemokine gradient to figure out where to go - this is chemotaxis
Q: What are the 2 main types of opsonin?
A: bodies
Complement Proteins
Q: What is opsonisation?
A: coating of micro-organisms with proteins to facilitate phagocytosis
Opsonins act as adapter molecules which bind to the pathogen and link it to receptors present on the phagocyte
Q: How does complement help activate a neutrophil? (3)
A: Antibody binds to a receptor on the pathogen
Complement binds to the cell surface of the pathogen
The bound antibody and complement can then bind to the neutrophil and activate it.
(The neutrophil will engulf the bacterium and lyse it)
Q: What are 2 neutrophil killing mechanisms?
A: Oxygen-Independent: Generates a whole series of toxic metabolites - helps create optimal conditions for the enzymes to be able to kill the pathogens-
Enzymes
Lysozyme
Hydrolytic Enzymes
Antimicrobial Peptides (Defensins)
NEUTROPHIL EXTRACELLULAR TRAPS (NETs): When neutrophils become highly activated they release these nets that help trap extracellular bacteria and immobilise them. -> This helps other cells find these trapped bacteria
*Q: Compare macrophages and monocytes. Location? Size? Organelle? Phagocytic? Receptors?
A: Monocytes leave the circulation and differentiate into macrophages
Macrophages > Monocytes (in terms of size)
Macrophages have lysosomes and are phagocytic and They have pattern recognition receptors (PRR)
*Q: How do macrophages function? What does this do? Found?
A: signal infection by releasing soluble mediators (alarm cytokines)
This helps recruit other cells and activate subsequent adaptive immune responses
Dispersed throughout tissues
*Q: What are cytokines? (3) Life?
A: Small secreted proteins
Involved in cell-to-cell communication
Powerful biological effects at low concentrations
Short-lived
*Q: Name the 5 cytokine types. Include descriptions.
A: Interleukins (IL-x) - between leukocytes
Interferons (IFN) - anti-viral effects
Chemokines - chemotaxis and movement
Growth Factors - required for development of cells for immune system
Cytotoxic - tumour necrosis factor (TNF)
Q: What are the types of interferon? Which cells produce them?
A: there are two types of interferon (type 1 and type 2) - only immune cells produce type 2 interferons - lots of other cells can produce type 1 interferon
Q: Describe the way a cytokine acts. 3 main ways. Common way?
A: Cytokines bind to a receptor on target cells leading to complex effects on gene expression.
Autocrine - the cell that secretes the cytokine expresses a receptor for it so the cytokine affects the cell that secreted it.
Paracrine - acts on nearby cells (e.g. type 1 interferon - a virus infected cell will produce type 1 interferon which moves to other cells and triggers an anti-viral state in those cells) ** short distances
Endocrine - long distance - go into the circulation and travel to distant cells.
Q: Which important cytokines are secreted by activated macrophages? (5) Include roles.
A: IL-1: alarm cytokine, FEVER
TNF-a: alarm cytokine
IL-6: acute phase proteins, acts over long distances,
IL-8: chemotactic for neutrophils
IL-12: directs adaptive immunity, activates NK cells
Q: What causes bacterial sepsis shock? What happens? Result? (2)
A: Massive release of alarm cytokines by activated macrophages causes septic shock.
Bacterial endotoxins cause massive release of TNF-a and IL-1 by activated macrophages.
Increased vascular permeability
Severe drop in blood pressure
Q: How do dendritic cells act? Location? Produce? Why are dendritic cells considered as part of innate immunity?
A: Phagocytose
Migrate once they’ve captured the antigen to the lymph nodes to activate T lymphocytes
Produce cytokines once they have been activated
*Q: Describe the complement system. (2) Allows? Process?
A: Complex system of 30 glycoproteins found in quite high concentrations in the serum that interact with one another to aid the body’s defences when antibodies combine with antigens
‘Complements’ the activity of a specific antibody
A small initial response can be rapidly amplified .
Forms a triggered enzyme cascade system:
-once the inactive precursors are activated = active enzymes -> catalyse the cleavage of lots of molecules down the chain -> convert the next molecule along to become an active enzyme
Q: Where are the components of the complement system made? What are components of the complement system synthesised as? Does this change?
A: produced mainly in the liver, but also produced by monocytes and macrophages
INACTIVE PRECURSORS
When activated they become ACTIVE ENZYMES
Q: What are the 3 pathways of complement activation?
A: CLASSICAL PATHWAY
Antibody binds to antigen - conformational change in the antibody leads to complement activation
if you have seen the bacteria before you will have antibodies against it - these antibodies will bind to the antigens and trigger activation of complement.
ALTERNATIVE PATHWAY
Direct activation by surfaces of pathogens themselves
direct contact with the bacterial surface
LECTIN PATHWAY
Antibody-independent activation by lectin (carbohydrate binding protein)
Q: What is a lectin?
A: pattern recognition receptor and binds to carbohydrates that are only present on pathogens
Q: What is the Y of complement? (The relationship between the pathways of activation)
A: Classical and alternative pathways converge at C3 (complement component 3)
Activation of C3 is a common final pathway which leads to the formation of MEMBRANE ATTACK COMPLEX (MAC) which is what lyses infected cells or bacteria.
MAC -> Cell Lysis
*Q: How is the complement pathway controlled? (3)
A: Components have very short half lives
Complement is diluted in body fluids
There are specific regulatory proteins which help regulate the activity of complement- prevent complement mediated lysis of normal cells
*Q: What are pro-inflammatory molecules?
A: fragments that have been cleaved off to activate components of the complement system
*Q: Describe the functions of complement. (4)
A: activates an inflammatory response
lysis
opsonisation
clearance of immune complexes
*Q: Describe the activation of an inflammatory response by the complement system.
A: proinflammatory fragments bind to receptors (e.g. on mast cells) and can cause- mast cell degranulation -attract cells from the circulation as well
Q: Why does the complement system have to clear immune complexes? How?
A: so they don’t cause inflammation of the blood vessels.
Red cells have a receptor for complement which binds to immune complexes and helps take them out of the circulation to be dealt with in the spleen
Q: What are the 2 main types of mast cells?
A: Mucosal - lung
Connective Tissue - skin and peritoneal cavity
Q: What is the role of mast cells? What do they recognise? What activates them? What is the net result?
A: Secrete HISTAMINES (involved in allergic responses)
Can recognise, phagocytose and kill pathogens
Pro-inflammatory fragments of the complement system can activate mast cells - these are anaphylatoxins
NET RESULT: Vasodilation, Increased Vascular Permeability
*Q: Summarise a typical (local acute) inflammatory response to a localised infection involving recruitment of neutrophils, and phagocytosis and killing bacteria.
Macraphages cytokines chemokines complement anaphylatoxins leukocytes neutrophils
A: You have tissue damage and a bacterial infection due to the damage
There will be macrophages in the tissue which have PRRs that can bind to PAMPs on the bacteria and perform phagocytosis.
The macrophages will become activated and secrete alarm cytokines and chemokines.
Alarm cytokines affect local vascular permeability so that circulating neutrophils and lymphocytes will be arrested and migrate into the tissue to the site of infection (directed by chemokines)
Complement will be activated either by the Alternative or Classical Pathways.
Complement activation will lead to production of pro-inflammatory fragments (anaphylatoxins)
Anaphylatoxins bind to receptors on mast cells - they will degranulate and the products of degranulation will affect vascular permeability and increased adhesion of circulating leukocytes.
Some of the products of degranulation are directly chemotactic for neutrophils
*Q: What is a systemic acute phase response? Characteristics? What induces it?
A: Sometimes local inflammatory response is accompanied by a systemic response
Characteristics: fever, increased leukocyte production (leukocytosis), production of acute phase proteins in the liver
Acute phase response is induced by the production of CYTOKINES which can act over a long distance
Q: What are 4 acute phase proteins? What are they all? Include role. (2,2,0,1)
A: Complement proteins themselves are acute phase proteins
C-reactive protein (CRP)
- C polysaccharide of pneumococcus
- Activates complement
Mannan-Binding Lectin (MBL)
- Opsonin for monocytes
- Activates complement
Complement
Fibrinogen
-Clotting
*Q: What are NK cells? What type of cells are they? What do they do? How are they activated? Why are they important?
A: natural killer cells
Large granulated lymphocytes
Cytotoxic - lyse target cells + Secrete interferon gamma
No antigen-specific receptor- They instead have activating and inhibitory receptors - a balance of these signals determines the response.
Have receptors which can bind to antibody-coated cells (ADCC = Antibody Dependent Cell-Mediated Cytotoxicity)
Important in defence against tumour cells and viral infections
Q: What are the 2 types of target recognition of NK cells?
A: Missing Self Recognition
Induced Self Recognition
Q: Describe missing self recognition. (5)
A: type of target recognition of NK cells
Normal Healthy Cells - present MHC Class I - They are bound by receptors on NK cells which sends inhibitory signals (ligation of inhibitory NK receptors = inhibition of target cell killing)
If a cell becomes infected, MHC becomes down-regulated hence they go ‘missing’
This means that there is no longer an inhibitory signal for the inhibiting receptors of the NK cell to bind to
NK cells will try to kill the target cell
Q: Describe induced cell recognition. (5)
A: type of target recognition of NK cells
Cells start expressing molecules that are only induced by STRESS when infected
abnormal pattern of self proteins - stress patterns
NK Cells have activating receptors which recognise stress patterns
Once activated - the NK cells will try to kill the target cell
Q: What may prolonged acute phase responses be accompanied by? Chacterised by?
A: an acute phase response, characterised by fever and increased production of components to fight infection
