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IAHI Block 1 > 3 - Innate Immunity > Flashcards

3 - Innate Immunity Flashcards

1
Q

What is the function of innate defenses? Describe some that our body uses.

A

Provide physical and chemical barriers via epithelia and commensals.

Rely on phagocytosis (phagocytes)

Produce inhospitable environments (granulocytes) for invading organisms.

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2
Q

During evolution, phagocytes were co-opted to initiate what? What is the best example of this?

A

Adaptive immunity by serving as antigen presenting cells (APCs) to T-cells.

Dendritic cells are the best APCs.

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3
Q

What are three characteristics of ALL innate immune responses?

A
  1. Rely on pathogen recognition and response mechanisms that exist before infection
  2. Capable of responding rapidly
  3. React in the SAME way to repeat infections
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4
Q

What are the four categories of innate immune cells?

A

Epithelia and associates commensals.

Phagocytes/APCs.

Granulocytes.

NK cells.

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5
Q

How does epithelia act in the innate immune system?

A

Provides a physical barrier to infection and produces antibiotic proteins/antimicrobial proteins (APCs) that kill bacteria.

AMPs are targeted towards microbe-containing environments like the GI lumen via a secretory pathway.

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6
Q

What is the function of low pH in innate immunity?

A

H ions associate with low pH disrupt amino acid charges in structures on the surface of invading organisms.

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7
Q

How do Antimicrobial Peptides (AMPs) function in the innate immune system?

A

They’re small peptides that form pores in the membrane of multiple bacteria.

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8
Q

What is the function of lysozyme? What about lactoferrin?

A

Lysozyme: hydrolase that damages bacterial cell walls

Lactoferrin: protein that sequesters free iron, an element necessary for bacterial growth.

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9
Q

What functions do mucous and cilia provide in the innate immune system?

A

Mucus: polymers of mucin proteins; mucous hinders pathogen contact with epithelia.

Cilia: organelles that move particles out of the airway.

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10
Q

What are commensals?

A

Organisms associated with our epithelia.

They compete with virulent organisms and produce AMPs.

Keep innate immune cells attentive.

Lower vaginal pH.

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11
Q

What are the three types of phagocytes?

A

Neutrophils-circulating
Macrophages-resident
Dendritic cells-resident

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12
Q

What are some features of

neutrophils? What can deficiency in neutrophils cause?

A

Also called PMNs or polymorphs. Multilobed nucleus with small granules (smaller than those in eosinophil).

Most abundant leukocyte in circulation.

Deficiency - chronic granulomatous disease causing chronic and severe bacterial and fungal infections.

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13
Q

Neutrophils (PMNs) are the first phagocyte to emigrate into an infected tissue. Describe what happens upon entry to the infected site?

A

They fuse with lysosmes containing lysozyme, defensins, lactoferrin, hydrolases, and myeloperoxidases (MPO).

  • MPO catelyzes production of HOCl from H2O2 and Cl-.
  • NADPH oxidase dependent production of superoxide
  • Inducible NO synthase forms NO from arginine. to kill microbes

Die within a few hours after reaching infected site

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14
Q

What is in pus? What is the medical term for pus?

A

Accumulated live and dead PMNs (neutrophils), their destroyed material, and the enzymes released as a consequence of PMN death.

Purulent exudate.

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15
Q

What are macrophages? What is their function?

A

AKA Mphi

Tissue resident phagocytes that differentiate from circulating monocytes.

Constantly phagocytosing materials in their environment (especially in airways). When they encounter a microbe, they enter an activated state.

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16
Q

What is the role of activated macrophages (Mphi)?

A

Have recognized a pathogen associated molecular pattern (PAMP) through one or more pattern recognition receptor (PRR)

Secrete pro-inflammatory cytokines

Enhance phagocytosis

Process and display microbe on its surface via MHC Class II.

17
Q

What are the characteristics of dendritic cells (DC)? How do they differ from macrophages?

A

Similar to macrophages except:

  • Have extensive dendrites that allow enhanced SA for reception and presentation.
  • More efficient at processing phagocytosed micrbones into antigens (Ag) for presenting
  • More efficient at migrating to draining lymph nodes for Ag presenting to T cells
18
Q

Why are dendritic cells (DC) referred to as sentinels?

A
  1. Constantly sample environment
  2. Unlike macrophages, they migragte via lymphatics to draining lymph node
  3. Once in node, they come into greater contact with T and B cells to initiate the adaptive response
  4. Express high levels of MHCII and increase expression of rproteins CD80, CD86, and CD40 for survival and proliferative signals to T and B cells.
19
Q

Innate lineages are activated following the interaction of pathogen associated products with what? What are two examples?

A

Pattern recognition receptors (PRRs):

  • cell-contact dependent: macrophage exposure to live bacterium
  • cell-contact independent: macrophage exposure to bacterial products

Help facilitate recognition of intracellular patterns.

20
Q

What is one specific type of pattern recognition receptor?

A

Toll-like receptors (TLRs) - an individual receptor that can recognize a broad number of pathogen products that share certain pathogen associated molecular patterns (PAMPs).

21
Q

What happens when the pathogen associated molecular pattern (PAMP) interacts with a pattern recognition receptor (PRR)?

A

Triggers an intracellular signaling cascade that results in transcription and secretion of multiple pro-inflammatory factors.

Membrane associated PRRs recruit adapter proteins that lead to activation of the NFkB which promotes expression of cytokines and transcription and additional pro-inflamm genes.

22
Q

Phagocytes are great defenses against _____ and _____, but are not helpful for what type of pathogens?

A

Great for bacteria and fungal pathogens.

Not good for pathogenic helminths that are too big to be phagocytosed.

23
Q

What are the three types of granulocytes? (for our purposes we will consider a neutrophil a phagocyte even though it has granules). Do they circulate or are they residents? What are the properties of each?

A

Eosinophil-binds acidic dyes; circulating; lL-5 causes increased production and recruitment of eosinophils. Granules contain major basic protein.

Basophil-binds acidic dyes; circulating; very scarce in blood. Granules contain histamine and heparin.

Mast Cells- tissue resident; Involved in allergic reactions and anaphylaxis.

24
Q

What is the function of mast cells? How does degranulation occur?

A

Defend the host by releasing their granules into the extracellular space.

IgE antibodies binds to surface of the granulocytes via FcERI receptors. (IgE is a product of the adaptive immune system).

Crosslinking of IgE/FcERI causes degranulation of the mast cell to release histamines and heparin.

25
Q

What does granulocyte activation depend on?

A

Previous exposure (sensitization) to an Ag (antigen)

26
Q

What happens when a mast cell has been activated by the FC receptor binding the constant region of IgE?

A

It releases its contents into the environment - called degranulation.

27
Q

What types of substances are released when granulocytes are activated?

A
  1. Vasoactive amines: smooth muscle contraction for expulsion
  2. Proteases that disrupt parasite tegument
  3. Prostaglandins and leukotrienes
  4. Cytokines
28
Q

What is the signaling and pathway that takes place when toll-life receptors (TLRs) engage with bacterial or viral molecules?

A

A signaling domain recruits adaptor proteins and activates transcription factors: NF-kD and IRFs (interferon regulatory factors).

NFkB causes acute inflammation and stimulation of adaptive immunity through expression of cytokines and costimulators.

IRFs- produce type 1 interferon and cause an antiviral state.

29
Q

What toll-like receptors are associated with bacterial lipopeptides?

A

TLR-1

TLR-2

30
Q

What toll-like receptors are associated with bacterial peptidoglycans?

A

TLR-2

31
Q

What toll-like receptors are associated with lipopolysaccharide (LPS)? THIS IS IMPORTANT.

A

TLR-4

32
Q

What toll-like receptors are associated with bacterial flagellin?

A

TLR-5

33
Q

What toll-like receptors are associated with bacterial flagellin?

A

TLR-5

34
Q

What toll-like receptors are associated with bacterial lipopeptides?

A

TLR-2

TLR-6

35
Q

What toll-like receptors are located inside the cell?

A

TLR3, 7, 8, and 9

36
Q

What pathway do toll-like receptors (TLRs) activate? What does this result in?

A

NFkB pathway - results in transcription of additional pro-inflammatory genes.

IAHI Block 1 (19 decks)

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