Innate Immunity Flashcards
What is immunology? (1)
The study of the body’s defence against infection
What is an antigen? (1)
A molecule that can bind specifically to an antibody or generate peptide fragments that are recognised by a T cell receptor
What are the requirements of an effective immune system? (2)
Distinguish between harmful non-self (pathogens), harmful altered-self (tumors) and self (host)
Elimination of non-self with minimal damage to the host
What is innate immunity? (2)
First line of defence against invading pathogens
Initiate specific adaptive immune response
Describe features of innate immunity (6)
Evolutionary ancient form of immunity
Conserved across a huge number of species
Can recognise the difference between harmful non-self and altered self and self
Immediate/rapid
No memory
Depends on ‘hard-wired’ germ line receptors
What are the three components of innate immunity (steady state-immediate immune response) (3)
Structural (epithelia, mucosal barriers)
Soluble (complement proteins, mannose-binding lectin)
Cellular (phagocytes, NK cells etc)
What are structural barriers and give examples (2)
Anatomic defence - initial defence against infection that prevents exposure of internal tissues to microbes
For example, skin, mucosa, pH
What are soluble molecules (2)
Defensins (antimicrobial peptides), secreted by epithelial cells
Lysozyme secreted by macrophages
The complement system
Name all the cells of the myeloid lineage (5)
Neutrophil
Dendritic cells
Macrophage
Eosinophil
Mast cell
What are phagocytes (2)
Engulfing cells that are able to recognise microbes through specific receptors
Describe features of neutrophils (4)
Short-lived found normally in blood
Migrates during inflammation
Highly phagocytic granulocyte
Produces vast repertoire of antimicrobial factors
Describe features of dendritic cells (3)
Found throughout the body, sentinels of the immune system
Phagocytic
Crucial link between innate and adaptive immune response, via secretion of soluble factors that affect cell function (cytokines) and antigen presentation (to T cells)
Describe features of macrophages (4)
Found in most, if not all tissues
Highly phagocytic and antimicrobial
Directs both innate and adaptive through secretion of cytokines and antigen presentation
Important for non-inflammatory clearance of apoptotic cells
Describe features of eosinophil (4)
Found in blood and also in gut, lungs, urogenital tract
Important in helminth infection
Involved in allergy and asthma
Contains toxic granules and inflammatory mediators
Describe features of mast cells (3)
Found in tissues
Involved in allergy and histamine release (increase vessel permeability)
What is a natural killer (NK) cell (4)
Lymphoid, targeted secretory cell
Found in blood and tissues
Cells are crucial for recognising changes in tumour cells and virally infected cells.
Target and kill these cells
How does the host distinguish self from non-self? (2)
Via recognition of Pathogen Associated Molecular Patterns (PAMPs) and Microbe Associated Molecular Patterns
(MAMPs)
How are PAMPs/MAMPs recognised? (1)
By pattern recognition receptors
What are PAMPs/MAMPs? (4)
Molecular structures which are produced by microorganisms
Essential for microbial survival
These structures are recognised to be foreign/non-self by the cell surface receptors of the host cell
Difficult to mutate to escape the immune response
How are genes involved in immunology discovery? (2)
Loss of function - is the gene necessary
Gain of function - is the gene sufficient?
What are surface pattern recognition receptors? (8)
Recognise various PAMPs
Found in all multicellular organisms
Germ line genes encoded - evolved to recognise PAMPs
‘know’ the difference between harmful and non-harmful entities
Found mainly on phagocytes
Survey all physiological environment
Major classes - toll receptors, carbohydrate binding lectins
Able to signal to produce appropriate responses and production of various cytokines and immune regulators
What are DAMPs? (1)
Endogenous danger molecules that are released from damaged or dying cells and activate the innate immune system by interacting with pattern recognition receptors (PRRs)
What is phagocytosis? (1)
Major mechanism for the uptake and destruction of large particles
Describe stage 1 of phagocytosis (3)
Recognition and binding to receptor:
Recognition is receptor mediated
Direct binding occurs via phagocytic receptors
Indirect pathogen binding occurs via Fc receptor, and complement receptor
Describe stage 2 of phagocytosis (2)
After recognition of the target particle, phagocytic receptors initiate signaling cascades that remodel lipids in the cell membrane and regulate the actin cytoskeleton in order to extend the cell membrane around the particle
Phagocytic receptors engage in a sequential order and cooperate to complete the formation of the phagosome
Describe stage 3 of phagocytosis (4)
Appropriate processing:
Microbial killing (neutrophils, macrophages, dendritic cells)
Production of inflammatory signals (macrophages) or non-inflammatory removal of dead/apoptotic cells (macrophages)
Production of inflammatory signals to alert (cytokines) and recruit (chemoattractants) other cells(macrophages)
Presentation and communication with T cells (by dendritic cells, adaptive response)
What kind of process is phagocytosis? (1)
Actin-dependent
Which processes are used to kill pathogens by macrophages and dendritic cells? (4)
Proteolytic and hydrolytic enzymes
Reactive oxygen species/reactive nitrogen species
Antimicrobial peptides - sophisticated but effective way
Nutrient deprivation
How do antimicrobial peptides kill pathogens? (3)
Exploit differences in membrane found on bacteria and plasma membrane on eukaryotic cell
Due to different lipid composition and charge on membranes, they intercalate on membrane and form pores in membranes
Lead to iron flux in and out of cell destroying bacterial cell
What are the outcomes of phagocytosis by macrophages and dendritic cells? (4)
Killing
Presentation of antigen
Removal of apoptotic cells
Production of cytokines and inflammatory molecules - critical for or inflammation
What are cytokines? (1)
Group of soluble proteins that have various immunomodulating effect
What is inflammation? (2)
The general term for the accumulation of fluid, plasma proteins and leukocytes that is initiated by physical trauma, infection or a local immune response
What are the stages of inflammation? (3)
Initiation
Recruitment of effector cells (mainly neutrophils)
Resolution (switching off and removal of cells)
During acute inflammation, why can swelling (edema) be seen in tissues of patients? (2)
Vascular leakage
Plasma proteins go out of circulation between endothelial cells of capillaries and out into the tissue
What are the cells involved in acute inflammation? (2)
Neutrophils (which come first)
Macrophages (come later)
How does initiation of inflammation occur? (4)
Damaged cells, bacterial uptake by macrophages and mast cell degranulation all lead to increase in vessel permeability
Increased permeability leads to increase in soluble components from blood, antibodies and complement
Chemokines and bacterial products facilitate chemotaxis (movement up a chemical gradient)
Inflammatory cytokines up regulate adhesion molecules on the endothelium and neutrophils allowing the recruitment of cells from the blood
What are the main stages of leukocytes recruitment? (4)
Rolling
Activation (by chemokines)
Firm Adhesion
Extravasation (diapedesis)
What is the model called for leukocyte migration and recruitment? (1)
Postcode model
How is leukocyte adhesion and migration mediated? (3)
Via cell surface adhesion receptors and chemokine receptors
Found on leukocytes and endothelial cells
What acts a postcode for leukocyte migration? (3)
The temporal-spatial expression as well as there activation state of adhesion and chemokine receptors and there ligands act as a “postcode” for leukocyte migration
Once at the site of inflammation, the normally tightly regulated neutrophils are activated by what? (2)
PAMPs and proinflammatory cytokines and unload their formidable arsenal.
What are natural killer cells and describe features of them (NK) (6)
NK cells are specialised granular lymphocytes
Crucial for defence against tumour and virally infected cells
Do not tend to recognise pathogen directly, detect effects of the pathogen on the host cell
Either detect the lack of host proteins or the induction of stress proteins
Have both activating and inhibitory receptors
Able to also recognise antibody coated cells
How do NK cells kill? (3)
Granules contain Perforin and Granzyme B
Perforin forms pores to allow entry on Granzyme B and other granzymes
Granzyme B triggers apoptosis of target cells
How is tissue damage or infection recognised? (1)
By tissue cells (endothelial cells, mast cells and macrophages)
Name the cells of the innate immune system (9)
Myeloid cells:
- Neutrophils
- Dendritic cells
- macrophage
Secretory cells, myeloid cells:
- Eosinophils
- Mast cells
Lymphoid, targeted secretory cells:
- natural killer cells
Where are haematopoietic stem cells found? (1)
In the bone marrow
Role of haematopoietic stem cells (1)
Generate leukocytes and erythrocytes
Sustain blood cells throughout life
Capable of self-renewal
What are multipotent cells? (1)
Cells that can generate multiple lineages
What is the major function of leukocytes of the innate immune response? (1)
Can become phagocytic cells
Example of bacterial PAMPS (1)
Cell wall components
Example of bacterial MAMPS (1)
Bacterial DNA
Certain bacterial proteins
Example of viral PAMPS/MAMPS (1)
ssRNA
dsRNA
sugars
When are DAMPs not released and why is this important? (2)
These are not normally released when cells undergo suicide in a controlled fashion
(apoptosis)
These help distinguish between “naturally” dying cells and damaged/killed cells
Give examples of potential molecules released from damaged tissues and dying cells (4)
HSPs
ATP
Nuclear proteins (HMGB-1)
Extracellular matrix components
(hyaluronic acid)
What happens after microbial recognition? (1)
Uptake/phagocytosis by neutrophils, macrophages and dendritic cells
Describe how a phagocyte engulfs (8)
Actin allows large projection to occur
Recognition of particles
Signalling
Actin-cup formation
Pseudopodia occurs - arms coming around the particle
Through signalling events vacuole forms and matures and fuses with other parts of the endocytic pathway
Different vacuoles in the cell
Different types of endosome will fuse with phagosome and deliver various contents to vesicles
vesicles have different propagates
Increase in acidity and a lysosome
Hydrolytic enzyme carry out their work
Apart from pathogens, what can phagocytes also uptake? (1)
Apoptic cells - such as dying red blood cells
What are the clinical signs of inflammation? (5)
Swelling
Pain
Redness
Heat
Loss of function
How is the importance of neutrophils studied? (3)
Severe congenital neutropenia (born with low numbers of neutrophils)
usually die in infancy of severe infections
Chemotherapy induced neutropenia- can lead to infection/death
AML- acute myeloid leukaemia- (neutrophilia)
immunocompromised due to immature myeloid cells
What do neutrophils release? (7)
Multiple anti-microbial molecules
Primary granules
Secondary granules
Tertiary granules
Cytoplasm
Host-tissue damage
Neutrophil extracellular traps (NETs)
What are Neutrophil extracellular traps (NETs)? (1)
Nets that trap bacteria and neutrophil elastase
How are neutrophils switched off? (3)
By macrophages
Proresolving cytokines
and other mediators
Prevents further neutrophil recruitment, increases
macrophage recruitment to “clean up”
