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Intro to immunology > Innate Immunity > Flashcards

Innate Immunity Flashcards

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
Q

Describe stage 2 of phagocytosis (2)

A

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
Q

Describe stage 3 of phagocytosis (4)

A

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
Q

What kind of process is phagocytosis? (1)

A

Actin-dependent

28
Q

Which processes are used to kill pathogens by macrophages and dendritic cells? (4)

A

Proteolytic and hydrolytic enzymes

Reactive oxygen species/reactive nitrogen species

Antimicrobial peptides - sophisticated but effective way

Nutrient deprivation

29
Q

How do antimicrobial peptides kill pathogens? (3)

A

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
Q

What are the outcomes of phagocytosis by macrophages and dendritic cells? (4)

A

Killing
Presentation of antigen
Removal of apoptotic cells
Production of cytokines and inflammatory molecules - critical for or inflammation

31
Q

What are cytokines? (1)

A

Group of soluble proteins that have various immunomodulating effect

32
Q

What is inflammation? (2)

A

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
Q

What are the stages of inflammation? (3)

A

Initiation
Recruitment of effector cells (mainly neutrophils)
Resolution (switching off and removal of cells)

34
Q

During acute inflammation, why can swelling (edema) be seen in tissues of patients? (2)

A

Vascular leakage
Plasma proteins go out of circulation between endothelial cells of capillaries and out into the tissue

35
Q

What are the cells involved in acute inflammation? (2)

A

Neutrophils (which come first)
Macrophages (come later)

36
Q

How does initiation of inflammation occur? (4)

A

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
Q

What are the main stages of leukocytes recruitment? (4)

A

Rolling
Activation (by chemokines)
Firm Adhesion
Extravasation (diapedesis)

38
Q

What is the model called for leukocyte migration and recruitment? (1)

A

Postcode model

39
Q

How is leukocyte adhesion and migration mediated? (3)

A

Via cell surface adhesion receptors and chemokine receptors
Found on leukocytes and endothelial cells

40
Q

What acts a postcode for leukocyte migration? (3)

A

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
Q

Once at the site of inflammation, the normally tightly regulated neutrophils are activated by what? (2)

A

PAMPs and proinflammatory cytokines and unload their formidable arsenal.

42
Q

What are natural killer cells and describe features of them (NK) (6)

A

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
Q

How do NK cells kill? (3)

A

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
Q

How is tissue damage or infection recognised? (1)

A

By tissue cells (endothelial cells, mast cells and macrophages)

45
Q

Name the cells of the innate immune system (9)

A

Myeloid cells:
- Neutrophils
- Dendritic cells
- macrophage
Secretory cells, myeloid cells:
- Eosinophils
- Mast cells
Lymphoid, targeted secretory cells:
- natural killer cells

46
Q

Where are haematopoietic stem cells found? (1)

A

In the bone marrow

47
Q

Role of haematopoietic stem cells (1)

A

Generate leukocytes and erythrocytes
Sustain blood cells throughout life
Capable of self-renewal

48
Q

What are multipotent cells? (1)

A

Cells that can generate multiple lineages

49
Q

What is the major function of leukocytes of the innate immune response? (1)

A

Can become phagocytic cells

50
Q

Example of bacterial PAMPS (1)

A

Cell wall components

51
Q

Example of bacterial MAMPS (1)

A

Bacterial DNA
Certain bacterial proteins

52
Q

Example of viral PAMPS/MAMPS (1)

A

ssRNA
dsRNA
sugars

53
Q

When are DAMPs not released and why is this important? (2)

A

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
Q

Give examples of potential molecules released from damaged tissues and dying cells (4)

A

HSPs
ATP
Nuclear proteins (HMGB-1)
Extracellular matrix components
(hyaluronic acid)

55
Q

What happens after microbial recognition? (1)

A

Uptake/phagocytosis by neutrophils, macrophages and dendritic cells

56
Q

Describe how a phagocyte engulfs (8)

A

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
Q

Apart from pathogens, what can phagocytes also uptake? (1)

A

Apoptic cells - such as dying red blood cells

58
Q

What are the clinical signs of inflammation? (5)

A

Swelling
Pain
Redness
Heat
Loss of function

59
Q

How is the importance of neutrophils studied? (3)

A

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
Q

What do neutrophils release? (7)

A

Multiple anti-microbial molecules
Primary granules
Secondary granules
Tertiary granules
Cytoplasm
Host-tissue damage

Neutrophil extracellular traps (NETs)

61
Q

What are Neutrophil extracellular traps (NETs)? (1)

A

Nets that trap bacteria and neutrophil elastase

62
Q

How are neutrophils switched off? (3)

A

By macrophages

Proresolving cytokines
and other mediators
Prevents further neutrophil recruitment, increases
macrophage recruitment to “clean up”

Intro to immunology (13 decks)

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