Innate Immunity Flashcards

(62 cards)

1
Q

What is immunology? (1)

A

The study of the body’s defence against infection

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2
Q

What is an antigen? (1)

A

A molecule that can bind specifically to an antibody or generate peptide fragments that are recognised by a T cell receptor

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3
Q

What are the requirements of an effective immune system? (2)

A

Distinguish between harmful non-self (pathogens), harmful altered-self (tumors) and self (host)
Elimination of non-self with minimal damage to the host

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4
Q

What is innate immunity? (2)

A

First line of defence against invading pathogens

Initiate specific adaptive immune response

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5
Q

Describe features of innate immunity (6)

A

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

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6
Q

What are the three components of innate immunity (steady state-immediate immune response) (3)

A

Structural (epithelia, mucosal barriers)
Soluble (complement proteins, mannose-binding lectin)
Cellular (phagocytes, NK cells etc)

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7
Q

What are structural barriers and give examples (2)

A

Anatomic defence - initial defence against infection that prevents exposure of internal tissues to microbes
For example, skin, mucosa, pH

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8
Q

What are soluble molecules (2)

A

Defensins (antimicrobial peptides), secreted by epithelial cells
Lysozyme secreted by macrophages
The complement system

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9
Q

Name all the cells of the myeloid lineage (5)

A

Neutrophil
Dendritic cells
Macrophage
Eosinophil
Mast cell

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10
Q

What are phagocytes (2)

A

Engulfing cells that are able to recognise microbes through specific receptors

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11
Q

Describe features of neutrophils (4)

A

Short-lived found normally in blood
Migrates during inflammation
Highly phagocytic granulocyte
Produces vast repertoire of antimicrobial factors

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12
Q

Describe features of dendritic cells (3)

A

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)

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13
Q

Describe features of macrophages (4)

A

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

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14
Q

Describe features of eosinophil (4)

A

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

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15
Q

Describe features of mast cells (3)

A

Found in tissues
Involved in allergy and histamine release (increase vessel permeability)

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16
Q

What is a natural killer (NK) cell (4)

A

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

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17
Q

How does the host distinguish self from non-self? (2)

A

Via recognition of Pathogen Associated Molecular Patterns (PAMPs) and Microbe Associated Molecular Patterns
(MAMPs)

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18
Q

How are PAMPs/MAMPs recognised? (1)

A

By pattern recognition receptors

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19
Q

What are PAMPs/MAMPs? (4)

A

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

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20
Q

How are genes involved in immunology discovery? (2)

A

Loss of function - is the gene necessary
Gain of function - is the gene sufficient?

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21
Q

What are surface pattern recognition receptors? (8)

A

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

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22
Q

What are DAMPs? (1)

A

Endogenous danger molecules that are released from damaged or dying cells and activate the innate immune system by interacting with pattern recognition receptors (PRRs)

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23
Q

What is phagocytosis? (1)

A

Major mechanism for the uptake and destruction of large particles

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24
Q

Describe stage 1 of phagocytosis (3)

A

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

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25
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
26
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)
27
What kind of process is phagocytosis? (1)
Actin-dependent
28
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
29
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
30
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
31
What are cytokines? (1)
Group of soluble proteins that have various immunomodulating effect
32
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
33
What are the stages of inflammation? (3)
Initiation Recruitment of effector cells (mainly neutrophils) Resolution (switching off and removal of cells)
34
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
35
What are the cells involved in acute inflammation? (2)
Neutrophils (which come first) Macrophages (come later)
36
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
37
What are the main stages of leukocytes recruitment? (4)
Rolling Activation (by chemokines) Firm Adhesion Extravasation (diapedesis)
38
What is the model called for leukocyte migration and recruitment? (1)
Postcode model
39
How is leukocyte adhesion and migration mediated? (3)
Via cell surface adhesion receptors and chemokine receptors Found on leukocytes and endothelial cells
40
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
41
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.
42
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
43
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
44
How is tissue damage or infection recognised? (1)
By tissue cells (endothelial cells, mast cells and macrophages)
45
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
46
Where are haematopoietic stem cells found? (1)
In the bone marrow
47
Role of haematopoietic stem cells (1)
Generate leukocytes and erythrocytes Sustain blood cells throughout life Capable of self-renewal
48
What are multipotent cells? (1)
Cells that can generate multiple lineages
49
What is the major function of leukocytes of the innate immune response? (1)
Can become phagocytic cells
50
Example of bacterial PAMPS (1)
Cell wall components
51
Example of bacterial MAMPS (1)
Bacterial DNA Certain bacterial proteins
52
Example of viral PAMPS/MAMPS (1)
ssRNA dsRNA sugars
53
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
54
Give examples of potential molecules released from damaged tissues and dying cells (4)
HSPs ATP Nuclear proteins (HMGB-1) Extracellular matrix components (hyaluronic acid)
55
What happens after microbial recognition? (1)
Uptake/phagocytosis by neutrophils, macrophages and dendritic cells
56
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
57
Apart from pathogens, what can phagocytes also uptake? (1)
Apoptic cells - such as dying red blood cells
58
What are the clinical signs of inflammation? (5)
Swelling Pain Redness Heat Loss of function
59
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
60
What do neutrophils release? (7)
Multiple anti-microbial molecules Primary granules Secondary granules Tertiary granules Cytoplasm Host-tissue damage Neutrophil extracellular traps (NETs)
61
What are Neutrophil extracellular traps (NETs)? (1)
Nets that trap bacteria and neutrophil elastase
62
How are neutrophils switched off? (3)
By macrophages Proresolving cytokines and other mediators Prevents further neutrophil recruitment, increases macrophage recruitment to “clean up”