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Immunology > Phagocytosis and Phagocytes > Flashcards

Phagocytosis and Phagocytes Flashcards

1
Q

Elie Metchnikov

A

First to describe phagocytosis

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2
Q

Stages of phagocytosis

A
  1. Chemotaxis- cell migrates towards material
  2. Adherence and ingestion- material is being ingested
  3. Microbial killing- material is phagocytosed and destroyed in phagolysosome
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3
Q

Chemotaxis

A

Neutrophils travel towards the signal (most often IL-8 which is secreted by other body and immune cells)

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4
Q

Adherence and ingestion (opsonization)

A

Pathogen will bind to neutrophil by either complement receptors or antibodies (Fc-receptor). Or neutrophils will use trapping method (NETS- neutrophil extracellular traps)
- Endocytosis and pinocytosis will take up the material

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5
Q

Neutrophil nets

A

Neutrophils make nets out of chromatin anf then release them to catch extracellular material

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6
Q

Microbial Killing

A

Neutrophils ingest bacteria through respiratory burst (within seconds of ingestion)
- Oxygen consumption increases 100-fold
- Produce hypochlorous acid (similar to bleach)
- Lytic enzymes: lysozyme, proteases, acid hydrolases, myeloperoxidase
- Nitric oxides

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7
Q

Different phagocytes

A
  1. Neutrophils
  2. Macrophages
  3. Dendritic cells
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8
Q

Neutrophils

A
  • First to arrive at site of infection
  • Predominant blood leukocyte
  • 10-20 micrometers in size
  • Only live a few days
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9
Q

Hematopoiesis and neutrophils

A
  • About 2/3rds of hemopoietic activity is devoted to neutrophils
  • Appear within 12 hours at tissues
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10
Q

Neutrophil distribution in carnivores, horse, and cattle, sheep, goats, rodents

A
  • Carnivores: between 60-75% of all leukocytes
  • Horse: about 50%
  • Cattle, sheep, goat, rodents: about 20-30%
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11
Q

Granulocytes

A
  • Myeloid stem cell lineage
  • Produced in bone marrow
  • Cytoplasm with granules
  • Characteristic lobulated irregular nucleus (polymorphonuclear)
  • Neutrophils (phagocytes), eosinophils, basophils, mast cells
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12
Q

Cell distribution

A
  • Majority of cells are normally within small capillaries in liver, spleen, lungs and bone marrow
  • During infections, the number of circulating neutrophils in the blood many increase significantly
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13
Q

What regulates the production of neutrophils?

A
  • Granulocyte Colony-stimulating factor (G-CSF)
  • Will be stimulated by dying neutrophils when they produce IL-23. (IL-23 stimulates IL-17 which stimulates G-CSF)
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14
Q

Where do neutrophils die?

A

They will die by apoptosis while in tissues. Macrophages will come and phagocytose them

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15
Q

Neutropenia (Granylocytopenia) and possible causes

A

Lower than normal cell count for neutrophils. Will result in the animal becoming very susceptible to pathogens that would otherwise be normally overcome

Possible causes:
- Chemotherapy
- Infectious disease (parvo, FeLV, FIV in cats)
- Sepsis as a result of bacterial infections
- Immune-mediated
- Drug-related

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16
Q

Macrophages

A
  • Means “large-eating”
  • Derived from myeloid stem cells
  • Form about 5% of total leukocyte population (between 5-15%)
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17
Q

Two general roles of macrophages

A
  1. Phagocytes
  2. Antigen presenting cells
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18
Q

Macrophage types:

A
  1. M1 macrophages (inflammatory)
  2. M2 macrophages (non-inflammatory)
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19
Q

Macrophage functions

A
  • Act as sentinel cells- detecting and killing pathogens (M1)
  • Release cytokines that trigger innate and adaptive immunity (M1)
  • Control inflammation (M1)
  • Repair tissue through removal of dead cells, and promote tissue healing (M2)
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20
Q

Immature and mature macrophages

A
  • Monocyte: immature macrophage, in blood
  • Macrophage: mature, in tissues
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21
Q

Macrophage specific names

A

Tissue specific names for macrophages.

Eg. Histiocytes (connective tissues), Kupffer cells (liver), alveolar macrophages (lung), microglia (brain), Macrophages (elsewhere)

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22
Q

Macrophage Steps as sentinel cells and phagocytosis

A
  1. Macrophages undergo tissue surveillance and express pattern-recognition receptors to detect pathogens or tissue damage.
  2. Once pathogens have been identified, macrophages release cytokines and antimicrobial peptides to recruit other immune cells
  3. Macrophages phagocytose pathogens by engulfing them and destroying them inside the cell (phagolysosome). Mechanisms inside the phagolysosome include both oxidative and non-oxidative mechanisms.
  4. In addition to pathogens, macrophages also engulf dying neutrophils and their exosomes
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23
Q

Phagolysosome

A

The combination of a phagosome and lysosome during phagocytosis to destroy pathogen inside cell

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24
Q

Macrophage phagocytosis: oxidative and non-oxidative mechanism release

A
  • Antimicrobial peptides
  • Nitric oxide
  • Enzymes (proteases)
  • Also can release collagenases, elastases, proteases etc. that destroy/soften up tissue
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25
Q

What happens when M1 macrophages undergo classical activation?

A

Danger signal binds to resting macrophage and activates it

Increased:
- Size
- Movement
- Membrane activity (more receptors)
- Lysosomal enzymes
- Phagocytosis
- Bactericidal activity
- MHC class II expression
- Nitric oxide production

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26
Q

Types of surface receptors on macrophages

A
  • Complement receptors
  • Pattern recognition receptors
  • Antibody receptors
  • Transport receptors
  • Cytokines receptors
27
Q

Phagocytosis

A
  1. Chemotaxis and adherence of microbe to phagocyte
  2. Ingestion of microbe by phagocyte
  3. Formation of a phagosome
  4. Fusion of the phagosome with a lysosome to form a phagolysosome
  5. Digestion of ingested microbe by enzymes
  6. Formation of residual body containing indigestible material
  7. Discharge of waste materials
28
Q

Macrophages as antigen presenting cells

A
  1. Macrophages grab, destroy, and presents antigen
  2. Macrophages will migrate back to the local lymph node and present the antigen to the lymphocytes at the lymph nodes
  3. Lymphocytes become activated and differentiate/specialize which starts the adaptive immune response. They will then move out of lymph nodes and begin looking for the pathogen
29
Q

Antigen

A

Foreign material that is being recognized through specific receptors on lymphocytes (adaptive immune system) and against which an immune response is directed

30
Q

3 types of antigen presenting cells

A
  1. Macrophages
  2. Dendritic cells
  3. B-cells
31
Q

Alternative activation of M2 Macrophages

A
  • Activated by interleukins
  • Will bring us back to normal (recovery from inflammation)

Results in:
- Increased tissue repair
- Increased MHC class II expression (presents antigens)
- Reduced microbial killing
- Destroying normal apoptotic cells

32
Q

Dendritic cells

A
  • First described by R. Steinman in 1973
  • Found essentially at all surfaces (including mucosal surfaces)
  • Better at antigen presenting than macrophages
33
Q

Function of dendritic cells

A

Modulate immune response by determining the type of immune response needed
- Links innate and adaptive immunity

Antigen presenters! (MOST IMPORTANT)

Also involved in phagocytosis (sentinel cells)

34
Q

Types of dendritic cells

A
  1. Immature dendritic cells: found in tissues, mainly phagocytic
  2. Mature dendritic cells: found in lymph nodes, highly effective antigen presenters. They have already encountered the foreign material.
35
Q

Subpopulations of dendritic cells

A
  1. Myeloid dendritic cells
  2. Plasmacytoid dendritic cells
  3. Langerhans dendritic cells
  4. Follicular dendritic cells
36
Q

Dendritic cell maturation

A

Receptors will change based on the maturation of the dendrites
1. Immature dendritic cell- have lots of pattern recognition receptors specific to recognize danger signals and undergo phagocytosis
2. Mature dendritic cell- Occurs when immature dendritic cell encounters a danger signal. I then displays antigens (MHC upregulation) and migrate through lymphatics to lymphoid organs
3. T cell activation- Mature dendritic cells at the lymphoid organs will activate the lymphocytes making T cells which can go and destroy pathogens

37
Q

Immune modulation through dendritic cells

A

Dendritic cells present antigen to the lymphocytes. Lymphocytes will differentiate and specialize for either intracellular or extracellular pathogens. Lymphocytes will know where to go.

38
Q

Granulocytes

A
  • Mast cells, basophil, eosinophils, neutrophils
  • Characterized by the presence of granula in their cytoplasm and polymorphonuclear
  • Release molecules to kill pathogens, recruit other immune cells, and modulate/facilitate immune response
  • Most abundant is neutrophil, others less frequent
39
Q

Eosinophil staining

A
  • H & E staining
  • Will appear red
40
Q

Eosinophils

A
  • First described by Paul Ehrlich in 1879
  • Granulocytic leukocytes
  • Originate in bone marrow
  • Granules contain arginine-rich basic proteins (acidic eosin stains them red)
  • Very few in circulation, short half-life of about 18hours. Normally found only in tissue (connective tissues right underneath epithelium)
41
Q

Eosinophil surface receptors

A

Have a variety of surface receptors
- Immunoglobulin receptors
- Complement receptors
- Cytokine receptors
- Toll-like receptors
- MORE!

42
Q

Eosinophil function

A
  • Pro-inflammatory
  • Very important immune response to parasites and allergic reactions
  • Some antiviral capabilities and role in tumour immunity
43
Q

Continued presence of eosinophils

A

Characteristic of chronic inflammation

44
Q

Effector functions of eosinophils

A
  1. Release highly toxic proteins and free radicals
  2. Release chemical mediators including prostaglandins and leukotrienes
  3. Release cytokines to modulate immune response = Th2 immunity (extracellular pathogens)
45
Q

Toxic proteins and free radicals released by eosinophils

A
  • Major basic protein (MBP)
  • Eosinophilic cationic protein (ECP)
  • Eosinophil peroxidase (EPX)
  • Eosinophil-derived neurotox (EDN)
46
Q

General mechanism for eosinophils fighting parasites

A

Parasites are surrounded by eosinophils that are releasing granula that breaks down the parasites from the outside
- Important for pathogens that are too large to be phagocytosed

47
Q

Eosinophils during allergic reactions

A

Eosinophils are recruited when allergen is present. Begin releasing granula to break down allergen

48
Q

Salt poisoning in animals

A
  • Dehydrated animals who continue to eat can get salt poisoning
  • Symptoms: restless, wandering around, running into walls, convulsions, itching of mouth
  • Characteristic: eosinophils surrounding blood vessels in the brain
49
Q

Basophils

A
  • Discovered by Paul Ehrich in 1879
  • Least common granulocyte (~0.5-1% of the circulating WBCs)
  • Largest type of granulocyte (large cytoplasmic granules)
  • Mediators of inflammation associated with parasitic infections and allergies, more potent modulators than eosinophils
50
Q

Basophil staining

A

Basophilic staining of granula = blue

51
Q

Basophils functions

A
  • Pro-inflammatory response
  • Release histamine, serotonin, and heparin = increase blood flow
  • Release Th2 cytokines (eg. IL-4) = Th2 type immune response
52
Q

What type of reactions are basophils involved in?

A
  • Inflammatory reactions
  • Allergic reactions
  • Anaphylaxis
  • Asthma
  • Atopic dermatitis
  • Parasitic infections
53
Q

Basophil receptors

A
  • TLRs
  • Complement receptors
  • Fc-receptors
54
Q

Basophils and immunomodulatory functions

A

Many different receptors that have the ability to modulate many different immune responses

Eg. Basophils presenting to dendritic cells can result in activation of Th2

55
Q

Mast cells

A
  • Discovered by Paul Ehrlich
  • Look like flattened cells (Mastzellen), very large
  • Found in a variety of tissues, but especially in mucosal tissues
  • Secrete a variety of molecules including histamine, prostaglandins, leukotrienes, chemokines
56
Q

Mast cell degranulation

A
  • Release of granula
  • Very quick, within a few seconds
57
Q

What can activate mast cells?

A
  • Danger signals
  • Antibodies
  • Complement
58
Q

Antibody receptors on mast cells

A
  • Binds Fc fragment of IgE antibody on the Fc(epsilon)RI and Fc(epsilon)RII, and Fc(gamma)R
  • Can result in starting a lot of different functions
59
Q

What causes mast cells to grow?

A

Grow in the presence of Th2 cytokines

60
Q

Mast cell function

A

Response during allergic reactions and anaphylaxis

61
Q

3 ways of mast cell activation

A
  1. Direct interactions with pathogens- danger signals bind
  2. Fc-receptor mediated- couple antibodies bind
  3. Complement receptor mediated- proteins of complement bind and cause granula to be released
62
Q

Cells with the largest complexity of receptors

A
  • Mammalian mast cells and basophils are equipped with the largest complexity of receptors
  • Evolved over time
63
Q

Mast cells half life

A
  • They can live on mucosal surfaces for a long time
  • Means that antibodies from an allergen can be bound for a long time, and when we encounter the pathogen again a response/attack will occur quickly

Immunology (8 decks)

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