Immunology- Pt 1B

Innate Immunity: Pathogen Recognition

• PAMPs (pathogen-associated molecular patterns) are components shared among different pathogens, differing from self, and are only found in microbes.
• PAMPs play a crucial role in recognizing pathogens.
• DAMPs (damage-associated molecular patterns) are released when cells die or are generated when connective tissue is damaged.
• DAMPs recognize damage to one's own cells.

Pattern Recognition Receptors (PRRs)

• PRRs are receptors of innate immunity that recognize PAMPs and DAMPs.
• PRRs can be soluble or membrane-bound.
• They are found in various areas of the body (intracellular or membrane-bound).
• PRRs can be phagocytic or play a signaling role.
• Signaling PRRs trigger cytokine production and granule release.
• Phagocytic PRRs are located on the cell surface.

Sentinel Cells

• Sentinel cells are cells with high quantities of PRRs, allowing for better surveillance of PAMPs and DAMPs.
• Sentinel cells are majorly involved in immune surveillance and threat recognition.
• Examples of sentinel cells include dendritic cells, macrophages, and mast cells.
• These cells recognize PAMPs and DAMPs, activate pro-inflammatory and antimicrobial mediators, and produce histamine, cytokines, and prostaglandins.

Innate Immunity: Inflammation

• Inflammation occurs when sentinel cells are exposed to PAMPs, DAMPs, or pro-inflammatory cytokines.
• Inflammation needs to be strictly regulated to a specific site, rather than becoming systemic.
• Uncontrolled systemic inflammation is problematic.
• Inflammation can lead to various symptoms, such as fever, anorexia, sleepiness, and depression, depending on the affected site.

Mast Cells and Chemokines

• Mast cells release histamine and serotonin, causing vasodilation and increased vascular permeability, allowing neutrophils to migrate towards microbes.
• Chemokines are a type of cytokine that guides and directs leukocyte migration towards pathogens.
• Chemokines bind to neutrophil receptors, altering the cytoskeleton, and propelling neutrophils towards the microbe.

Inflammation: Leukocyte Kinetics

• Step 1: Neutrophils predominate during acute inflammation, using phagocytosis to kill pathogens.
• Step 2: Monocytes/macrophages predominate at the later stages of inflammation.
• Step 3: Lymphocytes are present once the adaptive immune system is engaged in the response.

Innate Immunity: Phagocytosis

• Phagocytosis is an active process of capturing and ingesting foreign objects/microbes by phagocytes, such as neutrophils and macrophages.
• Phagocytosis involves the destruction of microorganisms, damaged cells, and cellular debris, and foreign objects.
• Phagocytosis induces cytokine production and processing and presentation of antigens.

Phagocytosis: Steps

• Step 1: The phagocyte detects and binds to its target.
• Step 2: It surrounds the captured object with pseudopodia and engulfs the object via endocytosis.
• Step 3: The endocytosed object becomes enclosed in the phagosome.
• Step 4: The phagosome fuses with the lysosome to form a phagolysosome.
• Step 5: The contents of the lysosome are released into the phagolysosome.

Phagocytosis: Intracellular Killing Mechanisms

• Phagocytosis utilizes an oxidative pathway, involving the respiratory burst, and reactive oxygen and nitrogen species.
• Phagocytosis also utilizes a non-oxidative pathway, dependent on the actions of toxic substances present in lysosomes.
• Cationic proteins, lysozyme, lactoferrin, and proteolytic and hydrolytic enzymes are involved in the killing of bacteria.

Innate Immunity: Complement System

• The complement system is a collection of circulating and membrane-associated proteins, activated in a sequential manner.
• Many complement proteins are proteolytic enzymes.
• There are three possible activation pathways: Alternative, Classical, and Lectin pathways.
• All activation pathways have the same outcome, but differ in their initiation.
• The alternative and lectin pathways are part of the innate immune response, while the classical pathway is involved in the adaptive immune response.