Immune System 4: Innate Immunity and PAMPs/PRRs

A comprehensive set of 100 flashcards covering components, functions, and mechanisms of the innate immune system, including leukocytes types, inflammation, and PAMP recognition.

What are the four physical components of the first line of defense?

Skin, Mucus, Saliva, and Vomiting

What are the four chemical components of the first line of defense?

Sebum, Lysozyme, Saliva, and Gastric Juice

How does normal flora function as a barrier to pathogens?

They colonize (occupy space), utilize available nutrients to stop pathogens from obtaining them, and produce substances which can kill pathogens

What line of defense is innate immunity categorized as?

The second line of defense

At what point is the innate immune system activated?

It is activated when the barriers, which are the first line of defense, are defeated or damaged

What does it mean that innate immunity is 'non-specific'?

It responds in the same way to all pathogens

How quickly can the innate immune system detect and destroy bacteria that entered through a skin wound?

Within a few hours

What are the two primary actions of specialized innate immune cells upon arriving at a site of infection?

Ingest and destroy (phagocytosis) or kill extracellularly by releasing toxic chemicals

What is the main component of the innate immunity which is also referred to as leukocytes?

White blood cells (WBCs)

What are the approximate counts of Red Blood Cells (RBC) in every cubic millimeter of blood?

$5$ million

What is the standard range for White Blood Cell (WBC) counts per cubic millimeter of blood?

$4,000$ - $11,000$

What is the range for platelet counts per cubic millimeter of blood mentioned in the transcript?

$150,000$ to $400,0000$

What three types of cells can a lymphocyte be?

NK cells, B-cells, or T-cells

What is the size range of a typical neutrophil?

$$12-14\,\mu m$$

What is the diameter of an eosinophil?

$$12-17\,\mu m$$

What is the size of a basophil?

$$10-14\,\mu m$$

What is the size range of monocytes?

$$16-20\,\mu m$$

What is the percentage of neutrophils in a typical blood film?

$$\sim 60\%$$

What percentage of white blood cells are lymphocytes?

$$\sim 30\%$$

What percentage of white blood cells are monocytes?

$$\sim 8\%$$

What is the percentage of eosinophils in the blood?

$$\sim 2\%$$

What percentage of white blood cells are basophils?

$$< 1\%$$

What are neutrophils also known as due to their multi-lobed nucleus?

Polymorphonuclear leukocytes (PMN)

How many lobes typically connect with fine threads in a neutrophil's nucleus?

$3$ to $5$ lobes

What is the function of neutrophils?

Defend against bacterial and fungal infections

What is the killing mechanism of neutrophils?

Phagocytosis (engulfing microbe and killing within the neutrophil)

Describe the nucleus of an eosinophil.

The nucleus is bi-lobed

What color do cytoplasmic granules in eosinophils stain?

A bright orange-pink color

What is the primary function of eosinophils?

Defend against parasites

What is the killing mechanism utilized by eosinophils?

Release of granule contents (killing the microbe outside the eosinophil)

What shape is the nucleus of a basophil if it is visible?

$S$-shaped

What color do the granules of a basophil stain?

Deep purple

Which chemical is released by basophils in response to an infection?

Histamine

What process does histamine contribute to?

Inflammation

Where do mast cells derive from?

The bone marrow

Where do mast cells undergo their terminal differentiation?

In the tissue

Where are mast cells typically found in the body?

In skin and mucosal tissues, next to small blood vessels and nerves

What are the common functions of mast cells?

Expulsion of parasites, allergic reactions, and serving as key players in the inflammatory response

What are the largest white blood cells in circulation?

Monocytes

What shapes can a monocyte nucleus typically take?

Kidney shaped, bean shaped, or horseshoe shaped

Into what cell type do monocytes differentiate after migrating to tissues?

Macrophages

Describe the appearance of a lymphocyte's nucleus and cytoplasm.

The nucleus is densely stained, round, and fills almost the entire cell, while the cytoplasm appears like a thin rim

Which specific type of lymphocyte is involved in innate immunity?

Natural Killer Cells (NK)

What do NK cell granules contain that allow them to kill tumor or virus-infected cells?

Enzymes

List four changes that occur when a monocyte becomes a macrophage.

1. Nucleus becomes more rounded; 2. Cell increases in size; 3. Number of cytoplasmic granules and enzymes increase; 4. Phagocytic abilities increase

Where are dendritic cells found?

In tissues

What is the structural appearance of a dendritic cell?

It looks like a neuron but is NOT a nerve cell

By what process do dendritic cells ingest fragments of micro-organisms?

Endocytosis

What is the specialized function of dendritic cells regarding the adaptive immune response?

They are very important in activating the adaptive immune response

Which three types of white blood cells reside in tissue and provide host protection?

Mast cells, macrophages, and dendritic cells

What are the three direct elimination methods for microbes mentioned in Part II?

Phagocytosis, release of granule contents, and elimination of infected cells

Which cells act as a bridge between innate and adaptive immunity?

Dendritic cells

What is a phagosome?

A vesicle that buds from the outer membrane containing an ingested microbe

What is the result of the fusion between a lysosome and a phagosome?

Phagolysosome

How do Natural Killer (NK) cells recognize cancer or infected cells?

Activating receptors recognize molecules expressed on the surface of those cells

What molecule on normal healthy cells marks them as 'self' to inhibitory receptors?

$$MHC\;I$$

What happens when inhibitory receptors on NK cells recognize cognate $MHC\;I$?

The NK cell is 'switched off', preventing it from killing

Why are cancer cells and infected cells often vulnerable to NK cell killing?

They often lose their $MHC\;I$

What two substances are contained in NK cell cytotoxic granules?

$Perforin$ and $granzymes$

What is the role of perforin in target cell lysis?

It forms pores for granzymes to enter cells

What are the four symptoms of inflammation?

Redness, swelling, heat, and pain

Which cells trigger inflammation?

Macrophages, neutrophils, and mast cells

What are the three key processes of inflammation?

Vasodilation, increase in vascular permeability, and emigration of neutrophils (extravasation)

What substance is secreted by endothelial cells during inflammation?

Nitric oxide ($NO$)

What are the pro-inflammatory substances made by macrophages?

Cytokines

What is extravasation?

The process by which WBCs migrate out of the blood vessels and into the tissue area

What occurs as an infection is brought under control during inflammation?

Tissue repair begins and capillaries return to normal

How long are the defense mechanisms of innate immunity present in a human?

From birth

What does PAMP stand for?

Pathogen-associated Molecular Patterns

What are PAMPs?

Conserved molecular structures produced by microorganisms that are recognized as foreign by innate immune system receptors

Are PAMPs found in mammalian cells?

No, they are specific to the microorganism and not found in mammalian cells

What signaling pathways are activated by PAMPs?

Pathways leading to inflammation and adaptive immunity

Where are Lipopolysaccharides (LPS) found?

On gram-negative bacterial cell walls

What is flagellin?

A protein that makes up the filament of bacterial flagella

What viral PAMP is specifically mentioned in the notes?

Double-stranded RNA ($dsRNA$)

What are unmethylated CpG motifs?

Bacterial DNA sequences consisting of unmethylated cytosine followed by a guanine (CpG) dinucleotide

What does PRR stand for?

Pattern Recognition Receptors

What are the four families of Pattern Recognition Receptors (PRRs)?

1. Toll-like receptors (TLR); 2. Nucleotide-binding oligomerization domain-like receptors (NLR); 3. C-type lectin receptors (CLR); 4. RIG-1 like receptors (RLR)

Which PRR recognizes Lipopolysaccharides (LPS)?

$$TLR4$$

Which cells carry the $TLR4$ receptor?

Macrophages, dendritic cells, and neutrophils

Which PRR recognizes Flagellin?

$$TLR5$$

Which cells carry the $TLR5$ receptor?

Macrophages and dendritic cells

Which two PRRs recognize double-stranded RNA ($dsRNA$)?

$TLR3$ and $RIG-I$

Which cells carry PRRs for $dsRNA$?

Macrophages and dendritic cells

Which PRR recognizes unmethylated CpG motifs?

$$TLR9$$

Which cells carry the $TLR9$ receptor?

Dendritic cells and B cells

Where are PRRs strategically localized on the cell surface to detect?

Bacteria and fungi

Where are PRRs localized to detect viral nucleic acids?

Endosomes

Where are PRRs localized to detect viral RNA replication intermediates?

Cytoplasm

What is the result of PAMPs binding to PRRs?

It triggers signaling pathways that initiate inflammation and help activate the adaptive immune response

What is the approximate size of a red blood cell (RBC)?

$$\sim 7\,\mu m$$

What percentage of small lymphocytes are large activated lymphocytes?

$$10\%$$

What is the size of small lymphocytes compared to large activated ones?

$6-9\,\mu m$ (small) and larger (activated)

What happens to the signaling balance in an NK cell when it encounters an infected cell?

The activating receptor ligand binds, and if the inhibitory receptor lacks $MHC\;I$ binding, it triggers lysis

Identify the process: Attachment, Ingestion, Phagosome formation, Phagolysosome formation, Destruction, and Elimination of waste.

The steps of phagocytosis

What is the primary role of cytokines in inflammatory reactions?

They are responsible for inflammatory reactions

What causes the redness and heat during inflammation?

Vasodilation which brings more blood to the damaged area

What produces the swelling (edema) during inflammation?

Plasma leaking into the damaged area due to an increase in vascular permeability

Which cell type is the first to arrive at a site of infection as depicted in the inflammatory response diagram?

Neutrophils

What are the common targets of Natural Killer (NK) cells?

Cancer cells or cells infected with a virus