Innate Immune Cells (MT1)

What physical characteristics can be used to identify innate immune cells?

What physical characteristics can be used to identify innate immune cells?

Granules, multi-lobed nuclei

Where do innate immune cells come from? From which cells do they develop?

Innate immune cells are produced in the bone marrow, they develop from pluripotent hematopoietic stem cells.

Define; Pluripotent Hematopoietic Stem Cells

Self-renewing stem cells in the bone marrow capable of giving rise to several different cell types, they produce all blood related cells (immune and non-immune).

What gives rise to different cells from stem cells?

Lineage development and cell differentiation are mediated by the coordinated and regulated expression of transcription factors

Define: Colony Stimulating Factors

Cytokines that determine what a pluripotent hematopoietic stem cell will develop into.

Define: Common Progenitor Cells

Pluripotent hematopoietic stem cells do not directly differentiate into immune cells, common progenitors are intermediate stages capable of giving rise to multiple cell types but no longer capable of differentiating into all type of blood cells

Define: Monocyte

Present in the blood where they traffic to various tissues, once entering a tissue the monocyte differentiates into a macrophage

Define: Macrophage

Cells that:

• Detect pathogens (using PRRs)

• Clear and kill infection (via phagocytosis)

• Activate adaptive immune system by presenting pathogens molecules to T cells

• Shape/direct adaptive immune response (Cytokines)

Define: Dendritic Cells

Unusually shaped phagocytic cells with long, spindly membrane processes. They are the single most important cell type for the activation of naïve T-cells.

Define: Neutrophils

Frontline workhorse of the innate immune system, that ive in the blood and must be recruited out of the blood vessels into an infected tissue. Identified by distinctive tri-lobed nuclei. Consists of granules full of toxins/acids (bleach, think of these as a powder keg of hate. Voracious phagocytes that eat and kill effectively

Contains lots of pre-synthesized effector molecules that are stored in granules – thus neutrophils are granulocytes

What are the four types of Granulocytes?

Eosinophil, Basophil, Mast Cells, Neutrophils

Define: Mast Cells

Differentiate in the tissue and phenotype varies depending on location Located at host-environment interfaces (skin, lung, gut) Closely apposed to blood vessels Very granular (packed FULL of granulocytes that burst out of cell in seconds when activated) Mast cells are also involved in many innate, adaptive and pathologic immune responses (cause our allergies)

Define: Natural Killer Cells

Large granular lymphocytes Non-clonal No markers for B or T-cells (definitively not a lymphocyte) Ability to kill target cells without prior immunization (unlike B and T-cells) Regulated by a balance between activating and inhibiting receptors Can recognize targets labeled with antibody

What are the effector mechanisms of Neutrophils?

• Phagocytosis (Eat the infecting pathogen)

• Degranulation (Dump cytotoxic granular contents on the target)

• Oxidative Burst (Generation of reactive oxygen species (ROS) and reactive nitrogen species (NOS) that can be used to make hydrogen peroxide and hypochloric acid)

• Cytokines (Inflammation, activation of other cells)

• NETs (Neutrophil Extracellular Traps)

How do Monocytes and Macrophages differ?

Macrophages are 5 - 10x larger, they have more intracellular organelles, increased phagocytic ability (more pseudopods), increased amounts of hydrolytic enzymes, and are capable of secreting a variety of soluble factors

How do Dendritic Cells and Macrophages differ?

Dendritic cells take the antigens and transport them to our lymph nodes where T-cells can learn the antigen

What are the three types of granules in Neutrophils?

1. Azurophilic (primary), includes defensins

2. Specific (secondary): includes lactoferrin + collagenase

3. Gelatinase (tertiary): includes gelatinase + lysozyme

How do granules perform their function? Why are they considered risky to our own cells?

Granules can either fuse with the phagosome or can be released into the extracellular environment, this poses a great risk of collateral damage to our own cells.

How do Macrophages enhance inflammatory responses?

1. They contain/isolate the pathogen

2. They secrete cytokines

3. This raises body temperature

4. Finally, they recruit additional cells (neutrophils, T-cells)

Define: Antibody-Dependent Cellular Cytotoxicity (ADCC)

The ability for cells to recognize targets labeled with antibody, NK cells in particular do this.

How do Natural Killer cells know not to kill our own cells?

NK cells are regulated by a balance between activating and inhibiting receptors. Our own cells have inhibiting receptors that block signals from activating receptors so that NK cells do not kill our own cells. Pathogens lack these inhibiting receptors.