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MICR2209 > 3 - Innate immunity > Flashcards

3 - Innate immunity Flashcards

1
Q

Innate immune system

A
  • First line of host defence against infections
  • Starts acting immediately on encounter with infectious agents
  • Instructs adaptive immune system to respond to different microbes
  • Role in clearance of dead tissues and initiation of repair
  • Responds in same way to repeat encounters (No memory)
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2
Q

4 examples of chemical and anatomic barriers that protect against pathogens

A
  1. Lysozyme in tears (dissolves cell walls)
  2. Mucus and cilia lining trachea (move pathogens out of body)
  3. Skin (barrier that produces antibacterial peptides)
  4. Stomach acidity (pH 2) inhibits microbial growth
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3
Q

3 more examples of chemical and anatomic barriers that protect against pathogens

A
  1. Normal flora (compete with pathogens in gut and on skin)
  2. Flushing of urinary tract prevents infection
  3. Mucus, antibacterial peptides and phagocytes prevent infection in lungs
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4
Q

3 examples of mechanical barriers

A
  • Epithelial cells joined by tight junctions
  • Longitudinal flow of air or fluid
  • Movement of mucus by cilia
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5
Q

3 examples of chemical barriers

A
  • Fatty acids
  • Low pH
  • Antibacterial peptides (defensins)
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6
Q

Example of microbiological barriers

A

Normal flora

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7
Q

Complement system

A

Includes several plasma proteins that work together to
opsonise microbes, promote phagocyte recruitment, and directly kill microbes

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8
Q

Opsonisation

A

Process by which a microorganism is coated by serum components enhancing recognition and ingestion by phagocytic cells

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9
Q

Outcomes of the complement system

A
  • Direct killing of some
    bacteria (Gram negative more susceptible)
  • Production of C3b (opsonin) leading to phagocytosis
  • Release of C3a and C5a involved in inflammation
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10
Q

Role of complement system in inflammation

A
  • Attract and activate neutrophils
  • Activates mast cells (release of histamine and leukotriene contributes to increased vascular permeability)
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11
Q

Cytokines

A

Generic term for any soluble protein secreted by immune cells that affects the behaviour of cells bearing appropriate receptors

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12
Q

How many cytokines are there

A

More than 60, produced by many different cell types

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13
Q

Effects of cytokines

A
  • Can change expression of adhesion molecules and receptors in the target membrane
  • Activate cell proliferation and differentiation or modulate effector functions
  • Signal cells to survive or die
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14
Q

Examples of cytokines

A
  • Interleukins/Hematipoietins (IL)
  • Interferons (IFN)
  • Tumour Necrosis Factors (TNF)
  • Colony Stimulating Factors (CSF)
  • Chemokines
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15
Q

Granulocytes

A
  • Neutrophil
  • Eosinophil
  • Basophil
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16
Q

Neutrophils

A

The most abundant population of circulating white blood cell and the principal cell type in acute inflammatory reactions

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17
Q

Characteristics of neutrophils

A
  • Multilobed nuclei connected by thin chromatin bridges.
  • Cytoplasmic granules have enzymes such as lysozyme, collagenase, and defensins
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18
Q

Functions of neutrophils

A
  • Phagocytosis
  • Degranulation and the release of neutrophil extracellular traps (NETs)
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19
Q

Functions of eosinophils

A
  • Killing of antibody coated parasites
  • Triggered by infectious and non infectious (allergies) processes
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20
Q

Characteristics of Eosinophils

A

bilobed nucleus with large specific granules that store cytokines, cationic proteins and enzymes

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21
Q

Mast cells

A

Release of granules containing histamine and active agents

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22
Q

Basophils

A

Found in blood, representing less than 1% of circulating white blood cells

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23
Q

Function of mast cells and basophils

A

Roles in parasitic diseases and allergic reactions

24
Q

Granules of mast cells and basophils

A

contain vasoactive mediators (histamine, heparin, leukotrienes). have roles in vasodilation, angiogenesis and regulation of many cell types

25
Q

Macrophages

A

Phagocytes, widely distributed in all organs and connective tissues

26
Q

Two types of macrophages

A
  • Blood circulating monocytes that migrate into tissues and mature into macrophages
  • Long lived, tissue resident macrophages derived from yolk sac
27
Q

Functions of macrophages

A

Phagocytosis (pathogens and necrotic or apoptotic host cells) and antigen presentation

28
Q

Types of dendritic cells

A
  • Conventional dendritic cells
  • Plasmacytoid dendritic cells
  • Follicular dendritic cells
  • Tissue resident DCs (e.g., Langerhans cells)
29
Q

Dendritic cells

A
  • Most effective antigen presenting cell
  • Act as bridge between innate and adaptive immune responses
  • Sample antigen from throughout the body, and migrate to lymph nodes (via the draining lymphatics) to present antigen to T cells
30
Q

Innate lymphoid cells

A
  • Arise from the same common lymphoid precursor as T and B cells, but lack clonally distributed diverse receptors
  • Stimulated by same types of stress signals that alert neutrophils, macrophages and dendritic cells
31
Q

Three major subsets of innate lymphoid cells

A

ILC1, ILC2 and ILC 3

32
Q

ILC1

A

Intracellular pathogen stimulus, promote macrophage activation

33
Q

ILC2

A

Parasite stimulus, promote mucus production, vasodilation, macrophage activation and thermoregulation

34
Q

ILC3

A

Extracellular pathogens (microbiome) stimulus, promote phagocytosis, release of antimicrobial peptides, and epithelial cell survival

35
Q

Natural killer cells functions

A
  • Kill infected (e.g., virus) and unhealthy/ tumour cells using perforin and granzymes
  • Secrete cytokines
  • Antibody-dependent mediated cytotoxicity (type II hypersensitivity)
36
Q

Antibody dependent mediated cytotoxicity

A
  • Antibodies bind to a malignant cell, or a host cell infected with a virus
  • NK cells have a specific antibody receptors on their surface
  • The antibodies bridges the infected cell with the NK cell so that the target is close enough for enzymatic activity
37
Q

What are the main phagocytic cells

A

Neutrophils and macrophages

37
Q

Steps of phagocytosis

A
  1. Pattern recognition receptors (PRRs) on phagocytic cells recognise microbe associated molecular patterns (MAMPS) on microbes
  2. Microbes are engulfed within a phagosome
  3. Lysosomes fuse with phagosome, forming phagolysosome. Respiratory burst generates toxic reactive oxygen species (ROS)
  4. Intracellular digestion mediated by lytic enzymes and ROS
  5. Microbial debris exits phagocyte by exocytosis
37
Q

What causes ingestion/activation of the internalisation process of phagocytosis

A

Reorganisation of actin
cytoskeleton and changes in
the membrane

37
Q

Phagocytosis

A

actin-dependent process of specifically internalising
particulate targets, which may include microorganisms, dead or dying cells or environmental debris.

38
Q

Phagolysosome

A

contain antimicrobial agents including antimicrobial proteins (defensins),
hydrolytic enzymes (lysozyme and proteases) and low pH

39
Q

Exocytosis

A

release of microbial
fragments

40
Q

Antigen presentation

A

microbial fragments are united with glycoproteins (major histocompatibility [MHC] proteins) and presented at the cell surface where it is then presented to T lymphocytes, triggering adaptive immune
responses

41
Q

What happens to neutrophils after phagocytosis

A

Continue until they become exhausted and die

42
Q

What happens to macrophages and dendritic
cells after phagocytosis

A

they become antigen presenting cells

43
Q

Pathogen recognition receptors (PRRs)

A

Recognise unique microbial
macromolecules by the presence of repetitive
structural proteins

44
Q

Characteristics of PRRs

A
  • PRRs are non-clonal (identical receptors
    on all cells of the same lineage)
  • Self/non-self-discrimination (healthy host cells are not recognised)
  • May be located on the cell surface or intracellularly
45
Q

Types of PRRs

A
  • Toll-like receptors (TLRs)
  • NOD-like receptor (NLRs)
  • RIG-like receptors (RLRs)
  • C-type lectin receptors (CLRs)
  • Cytosolic DNA sensors (CDSs)
46
Q

What are the two principal types of reactions of the innate immune system

A

Inflammation and antiviral defence

47
Q

What does activation of transcription factors increase

A
  • Expression of inflammatory genes, inducing acute inflammation and stimulation of adaptive immunity
  • Secretion of IFN-α and IFN-β induce an antiviral state
48
Q

Innate immune system pathway

A

Microbial ligands (PAMPS) –> Host receptors –> Adaptor proteins –> Cytoplasmic signal transduction –> Activation of transcription factors –> Transcription and production of cytokines

49
Q

Inflammatory mediators released by macrophages

A

TNF, IL-1, IL-6

50
Q

Local effects of inflammatory mediators

A
  • Tumour necrosis factor (TNF) and interleukin
    (IL-1) act on leukocytes and endothelium to induce acute inflammation
  • TNF and IL-1 induce the expression of IL-6 from
    leukocytes and other cell types
51
Q

Systemic protective effects of inflammatory mediators

A

Induction of fever, acute-phase protein synthesis by the liver, and increased production of leukocytes by the bone marrow

52
Q

Systemic pathologic effects of inflammatory mediators

A

Decreased cardiac function, shock, thrombosis and capillary leak, and metabolic abnormalities due to insulin resistance

53
Q

Cardinal signs of inflammation

A
  • redness (rubor)
  • warmth (calor)
  • pain (dolor)
  • swelling (tumor)
  • loss (altered) of function (functio laesa)
54
Q

Steps of inflammation

A
  1. Injury, barrier break, microbe entry
  2. Sentinel cells activated
  3. Sentinel cells secrete inflammatory mediators
  4. Increased vascular permeability
  5. Complement, antibodies, and anti-microbial proteins kill microbes
  6. Adhesion molecules and chemokines cause leukocyte migration into tissue
  7. Phagocytosis and killing of microbes

MICR2209 (26 decks)

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