Topic 2 - Innate Immunity 1 (Inflammation + Phagocytosis)

True or False: Both Innate and Adaptive immunity Only exist in higher organisms?

False

• Innate immunity exists in most/all organisms

• Adaptive only exists in bony fish+ higher organisms

Innate vs. Adaptive immunity

• What type of defense is each

• What makes up the defense for each?

  • 1st, 2nd + 3rd line

INNATE: Non-specific defense

• 1st line of defense = skin, mucous membranes + chemicals eg. enzymes, pH AMPs from lecture 1)

• 2nd line = Innate immune cells (Phagocytosis, complement, interferon, inflammation + fever)

ADAPTIVE = Specific defense

• 3rd line = Lymphocytes + Antibodies

***Fundamentals of INNATE immunity: 4 differences with Adaptive

1. Non-specific recognizes general patterns present on most pathogens using PRR (pattern recognizing receptors - physl) Adaptive recognizes specific markers on specific pathogens

2. Exists before infection, already in pace + ready to act (Adaptive immunity is developed after infection)

3. Rapid response encoded (adaptive immunity takes days)

4. Identical response with repeat infection (adaptive response typically gets stronger with repeat infection)

Where is the rapid response of Innate immunity encoded?

In the germ line DNA in sperm + egg cells

About how long does it take for Adaptive immunity to develop vs. innate

Adaptive ~ 6 days

Innate = hours

What were the innate immune cells listed throughout the slides?

• Define/describe each if needed

(don’t know if need to know the details at this stage)

1. Phagocytes - eg. Neutrophils(have unique nucleus shape)

2. Dendritic cells - Good at presenting pathogens to the lymph nodes for recognition

3. Complement - similar to AMPs (OIL, opsonization, inflammation + Lysis)

4. NK cells (natural killer cells) - ONLY INNATE LYMPHOCYTE. A type of WBC that are rapid + innate

5. Mast cells - Located in TISSUE near skin surface for easy release upon infection. Release things that trigger Inflammation + recruit immune cells

What are the 2 main Innate immunity responses covered in these slides?

Inflammation

Phagocytosis

What is one Function/ purpose of inflammation?

MOBILIZING bodily defenses at site of infection

What are 2 aspects of Inflammation, what is the purpose of each aspect + What is the result?

1. Vasodilation of CAPILLARIES = Increase volume = slow down blood flow in the area to allow for WBC to have time to interact with capillary walls = allow for leukocyte rolling

2. Increase in capillary permeability = allow for more cells into tissue eg. WBC

Result = Influx of immune cells to affected tissues

What are the 4 signs of inflammation + what are the causes of each?

1. Redness: Vasodilation = increase blood volume

2. Heat: Increase blood volume

3. Edema: swelling due to accumulation of fluid from blood in affected tissue

4. Pain: Some inflammatory mediators trigger pain response

What was the Experiment that was Evidence for Inflammation

• Who

• What was the method

• What was observed

Elie Metchnikoff 1800s

Experiment:

• Insult starfish larvae with thorn (contained Bacteria)

Observations:

• Rapid localization of cells to site of insult

• Break down of thorn by cells

Inflammatory response steps + cells involved

1. Detection of infection by MAST cells in tissue

2. Release of inflammatory mediators by MAST cells

3. Causes Vascular change: The 2 aspects of inflammation - Vasodilation + increased permeability

4. Mediators act on Endothelial cells to express adhesion molecules

5. NEUTROPHILS arrive first to site + aggregate at site of infection (margination) + other innate WBC follow

6. Chemotaxis to infection + Phagocytosis

****What are the 4 steps to make WBC move past the endothelial cells (barrier) from blood to tissue?

• describe what occurs at each step

1. Margination - WBC move to vessel wall near site of infection

2. Diapedesis - Mediators change WBC shape to allow them to squeeze between endothelial cells into the tissue

3. Chemotaxis

4. Phagocytosis

Where was PHAGOCYTOSIS first observed?

Starfish larvae + thorn experiment (Elie Metchnikoff 1800s)

***What are the steps of Phagocytosis?

1. Receptors on surface of phagocyte recognize pathogens (primitive way)

2. Reach out + Engulf the pathogen intracellularly into a Vesicle

3. A lysosome fuses with the vesicle

4. Break down + digestion of contents

5. The fused vesicles fuses with the PM + exocytosis the Garbage (inert/non-infectious) into extracellular space

Expand upon the “primitive way” That phagocytes recognize pathogens

Recognize entire classes of pathogens, non-specific

What is the Initial Intracellular vesicle containing the pathogen called?

Where do they lysosomes come from?

What is the Lysosome fused vesicle now called?

Phagosome = Initial vesicle containing only pathogen

Lysosomes originate from the GOLGI

Phagolysosome = The Lysosome + Phagosome fused

True or False: Phagocytosis is highly CONSERVED throughout evolution

TRUE

****What are the 3 examples of Phagocytes mentioned in the slides?

1. Macrophage (differentiated Monocyte)

2. Monocyte (precursors that circulate in the blood)

3. Neutrophil

*****Phagocytes perform what 2 processes?

2 step process:

1. CHEMOTAXIS

2. PHAGOCYTOSIS

What is the main idea of this image?

• General receptors on phagocyte recognize microbe

• Recognition results in activation of signal transduction pathways

• Convergent intracellular signaling - all the different pathways CONVERGE INTO ONE SIGNALING PATHWAYS

• The converged signaling activates pathways involved in cytoskeletal changes for engulfment

****What are the 5/6 steps of Phagocytosis listed on the slides

1. Phagocyte detects + engages microbe

2. Detection of microbe initiates cytoskeletal rearrangements that drive phagocytosis

3. Microbe is internalized into a specialized phagosome

4. Phagosome fuses with lysosome = phagolysosome

5. ROI (reactive oxygen + Nitrogen intermediates) NO killing

6. Lysosomal enzymes killing

Are Lysosomal enzymes and NO + ROI the same thing?

• functions

NO they are 2 different methods of killing

• Lysosomal enzymes (O2 independent - physl)= destroy ingested microbes

  • stored in lysosomes

• ROI + NO (O2 dependent - Physl) = destroy microbial proteins, genomes + walls

  • produced

Describe the Macrophage Development Process

• 3 steps

1. Arise from undifferentiated stem cells in the bone marrow (Like all blood cells)

2. Monocytes = differentiated from stem sites. Leave the bone marrow to circulate in the blood

3. Inflammation recruits monocytes to sites of infection where they differentiate in resident macrophages

*What are resident macrophages?

LONG LIVED “professional” Phagocytes that ingest large amounts of extra cellular material

• Macrophages differentiate to best fit the tissue that they are in

Since macrophages differentiate to best suit their tissue, they also have different names corresponding to their tissue. What are the 4 different macrophages mentioned in the slides + What tissue do they specialize in?

1. Microglia = CNS

2. Kupfter cells = liver

3. Alveolar macrophage = lungs

4. Osteoclasts = bone

***Is the only function of Phagocytes to eliminate microbes?

No

• they also ACTIVATE NEIGHBOURING CELLS

How do phagocytes activate neighbouring cells?

By releasing cytokines + Chemokines

***Are CYTOKINES + CHEMOKINE the same thing?

• define each if applicable + differentiate

• Functions?

No

• Cytokine = Secreted Protein that drive immune + inflammatory reactions

  • larger molecule + BROADER FUNCTION

  • One function = Induce proteins in the endothelium that make the endothelium more adherent for passing leukocytes → leads to diapedesis

  • Produced by: Macrophages + NK cells

• Chemokine: Large family of structurally related, low molecular weight cytokines that stimulate LEUKOCYTE MOVEMENT (chemotaxis) + regulate migration of leukocytes from the blood to tissues

Expand on “Everything comes at a cost”

Immune system is not perfect. If it can’t regulate self, prolonged immune response results in CHRONIC INFLAMMATION