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Microimmunology > Innate Immunity > Flashcards

Innate Immunity Flashcards

1
Q

What is the main function of epithelial cells and what barriers do they provide?

A

Main Function: block the entry of pathogens
Physical Barrier
Mechanical Barrier - cilia, keratin, mucous
Microbiological Barrier - Microbiota
Chemical Barrier - Anti-microbial enzymes

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2
Q

How are Pathogens recognized?

A

Pattern Recognition Receptors (PRRs) which are bound to the cell membrane (surface) or cytoplasm (inside)

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3
Q

What are the 4 classes of PRRs and where is each class located?

A 
Membrane bound:
	Toll-like receptors (TLR)
	C-type Lectin receptors
Cytoplasmic bound:
	Toll-like receptors (TLR)
	(RIG)-I-like receptors
	NOD-like receptors
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4
Q

How does PRR bind to a pathogen?

A

PAMP: Pathogen-Associated Molecular Patterns
(only on pathogens so no auto-immune response also highly conserved/ low mutation rate)

  • PRR and PAMP fit together like lock and key
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5
Q

PAMPs are essential for what in a pathogen?

A

Structural integrity
Replication
Critical for a pathogen’s pathogenicity

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6
Q

Can a PRR only bind to one pathogen?

A

NO, any given PRRs can bind to a variety of pathogens

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7
Q

What are 4 ways pathogens can enter the body?

A

Broken Skin
GI tract
Respiratory tract
Sexually transmitted

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8
Q

Name the main cells of innate immunity

A 
Phagocytes: (use Phagocytosis to kill)
	Neutrophils
	Macrophage
	Immature Dendritic Cell
Lymphocytes:
	Natural Killer Cell (uses apoptosis to kill)
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9
Q

Extracellular Pathogens are destroyed by what mechanism?

Describe the steps.

A

Phagocytosis

  • PRR binding to PAMP triggers phagocytosis to start
  • Cell membrane extends around the pathogen envelopes and internalizes it (= phagosome)
  • Phagosome fuses with lysosomewhich empties antimicrobial mediators (acids and enzymes) (= phagolysosome)
  • Kills pathogen
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10
Q

What are the enzymes used in the phagolysosome?

A
  1. Defensins, lysozyme - damage pathogen cell wall
  2. NADPH oxidase - produces toxic oxygen metabolites
    superoxide –> H_2O_2 + HOCl = Respiratory burst
  3. Nitric oxide synthetase - produces toxic nitric oxide
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11
Q

What mechanisms may a pathogen use to resist phagocytosis?

A
  • Cover PAMPs (encapsulated)
  • Block uptake
  • Escape from phagosome
  • Resistant to contents of the lysosome/blocks lysosome from fusing
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12
Q

What type of pathogen is innate immunity ineffective at dealing with?

A

Intracellular Bacteria

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13
Q 
What phagocyte:
- Is most abundant Leukocyte (60-70%)
- Short-lived
- Rapidly differentiates from stem cells in response to infection 
(> 2x)
A

Neutrophil

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14
Q

What is Neutropenia?

A

Low Neutrophil count (<500 cells/uL of blood) normal = 1500

  • Very susceptible to bacterial infections
  • Septic shock = Neutropenic Sepsis
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15
Q

Where are macrophages located and what is their main function?

A

Location: Below epithelial cells
Function: Phagocytosis of extracellular pathogens & helps instruct adaptive immunity

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16
Q

What role in immune response does an immature dendritic cell play compared to a mature one?

A

Immature DC = phagocyte, circulate in blood/lymph and resides in tissue near epithelial cells

Mature DC = role in adaptive immunity

17
Q

What cell:

  • Is the lymphocyte of innate immunity
  • Is important in early defence of intracellular pathogens
  • Has cytoplasmic granules that contain: perforin & granzyme
A

Natural Killer Cells

18
Q

What is the role of perforin and granzyme in the destruction of intracellular pathogens?

A

Perforin: forms a pore in infected cell allowing granzyme to enter
Granzyme: degrades cell DNA

  • This kills the virus-infected cell and intracellular virus (Apoptosis)
  • Same mechanism as cytotoxic T cell
19
Q

What kind of infection are people susceptible to w/o natural killer cells?

A

Viral infections

- especially herpes (only NK cells destroy herpes virus)

20
Q

What are Cytokines and what is their function?

A
  • Proteins secreted by ACTIVATED cells (secrete many types of cytokines simultaneously)
  • Messengers (help cells communicated with other cells and itself)
  • Activates or suppresses most cell behaviour
  • Paracrine or autocrine
  • PRR-PAMP binding releases cytokines
  • Binds to cytokine receptors
  • Regulates haematopoiesis
21
Q

What Cytokines are key to innate immunity?

A

Chemokines:
- Secreted by virus infected cells
- Attract immune cells
- Cells leave blood and get recruited to site of infection
Interferon (IFN) - Type 1:
- IFN-Alpha and IFN-Beta are secreted by virus-infected cells very early after infection(antiviral)
- Tells NK cell it is infected and to kill it
- Signals uninfected cells to produce antiviral enzymes which inhibit viral replication
- Used to treat viral infections but hepatitis B & C are becoming resistant
Tumour Necrosis factor (TNF)
- Secreted by activated phagocytes
- Activates endothelial cells (via binding) to vasodilate
- Increases blood vessel permeability allowing more immune cells to respond to infection

22
Q

What are the key components to Inflammation?

A
  1. Activated phagocytes secrete chemokines, TNF and other cytokines
  2. Vasodialation and increased permiability cause redness, heat and swelling
  3. Inflammatory cells migrate into tissue releasing inflammatory mediators which cause pain

(Phagocytosis and Cytokines are KEY)

23
Q

What are the circulating Innate cells and can they permeate through all types of blood vessels?

A
  • Neutrophils, NK cells, immature DC, Monocytes Macrophages

- These cells cannot pass through the artery wall, it is too thick and blood flows faster

24
Q

The TNF activates the hypothalamus to produce prostaglandins, what is the purpose of this?

A

This causes a Fever

  • Fever is a sign of a healthy immune system
  • higher temps =
    • Less pathogenic replication (most pathogens prefer lower temp to replicate efficiently)
    • Enhanced antigen presentation
25
Q

Cytokines (including TNF) activate hepatocytes (liver cells) to secrete what? What purpose do these have?

A

Acute-phase proteins = acute-phase response
Complement proteins = complement system
- Both have similar function
- Important in the destruction of extracellular pathogens (especially bacteria)
- Rapidly synthesized by liver cells
- Clinically plasma levels of acute-phase and complement proteins can be used to confirm and monitor inflammation
- Both help attach bacteria to the phagocyte by binding to bacteria’s surface
- They enhance bacterial recognition by phagocytes by increasing the # of pathogen recognizing molecules in innate immunity

26
Q

What receptors on phagocytes bind to extracellular pathogens?

A 
Pattern Recognition Receptor (PRR)
Acute-phase Receptor (APR)
Complement Receptor (CR)
- APR & CR bind to bacterial surface and help attach bacteria to phagocytes
^ALL TRIGGER PHAGOCYTOSIS^
27
Q

Name 3 functions of Complement proteins

A
  1. Destruction of pathogen by phagocytosis
  2. Destruction of certain pathogen by lysis
    • creates pore in pathogen cell wall
    • fluids flow into pathogen and it blows up
  3. Inflammation
    • Activates endothelial cells to vasodilate (like TNF)

Microimmunology (10 decks)

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