Immune System Effector Functions

Immune System Functions: How Immune Cells and Molecules Eliminate Microbes

Outline the effector modules of immunity and list the class of pathogens for which they provide protection.
Discuss key effector mechanisms of the innate immune system.
Describe the activation of B and T cells.
Explain key effector mechanisms of the humoral and cell-mediated adaptive immune systems.

The immune system needs to recognize and combat potential pathogens of different:
- Sizes (viruses to parasites).
- Locations (extracellular, intracellular in cytosol or vesicles).
- Life cycles (viral vs. bacterial).
- Mechanisms of disease (toxins).
Innate Immunity: Broadly specific, quick response.
Adaptive Immunity: Highly specific, slower response, more effective, provides memory.
Classification of the immune system:
- Innate vs. Adaptive.
- Immune effector modules (integrated innate and adaptive).

Targets macroscopic pathogens.
Involves:
- Granulocytes (eosinophils, basophils, mast cells - innate).
- Th2 cells (adaptive).
- B cells (adaptive - not explicitly listed but important).

Pathogens encounter a series of barriers upon exposure.
Defense mechanisms:
- Nonspecific.
- Broadly specific.
- Highly specific.
Layers:
- Anatomic barriers.
- Complement and antimicrobial proteins.
- Innate immune cells.
- Adaptive immune cells.
First three layers comprise the innate immune system.
Last layer is the adaptive immune system.
Pathogens face increasingly sophisticated mechanisms as they breach each layer.

Prevent infection.
Contain pathogens via anatomical barriers.
Mechanisms at different barrier types (skin, gut, lungs, eyes, nose, mouth).
Mechanical barriers:
- Epithelial cells with tight junctions.
- Mucus.
- Cilia.
Chemical barriers:
- Low pH.
- Defensins.
- Lysozyme.
Normal microbiota (commensals):
- Non-pathogenic.
- Shape the immune system.
- Provide protection from pathogenic microorganisms.

Part of the innate immune system, also used in adaptive (humoral) immunity.
Soluble proteins in circulation (serum and plasma).
Circulate in an inactive form.
Activation:
- Recognition of pathogen surface directly.
- Recognition of antibody bound to a pathogen (link to humoral immunity).
Proteolytic enzyme cascade.
Three outcomes for the elimination of microbes:
- Inflammatory response.
- Phagocytic response.
- Lysis.
Complement proteins as inflammatory mediators recruit innate cells to the site of infection.
Opsonization: coating pathogens for phagocytosis.
Lysis: membrane attack complex forms a pore in the bacteria membrane.

Cells recognize pathogen-associated molecular patterns (PAMPs) on microbes using pattern recognition receptors (PRRs).
Response to damaged host cells (DAMPs) also occurs, important for tissue repair.
Recognition results in signaling and activation of innate immune cells.
Cells produce mediators and enact effector responses.
Key innate immune cells: macrophages, neutrophils, and dendritic cells.
Bacterial LPS recognized by Toll-like receptor.
Signaling cascade leads to mediators (cytokines) production.
Acute inflammation and activation of adaptive immune response.
Type one interferons for antiviral response.

Produced by immune (and non-immune) cells in response to pathogen or antigen recognition.
Soluble signaling molecules that orchestrate the immune response.
Produced in response to pathogen or antigen recognition, danger signals, or cytokine receptor engagement.
Functions:
- Communication between cells.
- Cell survival, proliferation, and differentiation.
- Cell migration (chemokines).
- Inflammatory mediators.
Act in autocrine, paracrine, or endocrine manners.
Act locally or have systemic effects (e.g., fever).

Innate immune response that brings cells and molecules to the site of infection or tissue damage.
Contain and eliminate microbes, also important for tissue repair.
Signs: Redness, heat, swelling, pain, loss of function.
Process:
- Bacteria enters through a cut in the skin.
- Innate immune cells (sentinels) are activated through pattern recognition receptors.
- Production of inflammatory mediators.
- Vasculature becomes permeable: gaps in endothelial cells form.
- Proteins and fluid exit into the site of infection.
- Recruitment of neutrophils to phagocytose microbes.
- Monocytes enter the tissue and differentiate into macrophages.
- Macrophages are important for phagocytosis and tissue repair.
- Neutrophils respond quickly (minutes to hours), macrophages respond later (hours to days).

Process of engulfing microscopic extracellular pathogens.
Microbes recognized by pattern recognition receptors and complement receptors.
Phagocyte engulfs microbe into a phagosome.
Phagosome fuses with lysosome to form phagolysosome.
Activation of the phagocyte and "oxidative burst".
Enhanced when microbes are flagged with complement and antibodies (opsonization).
The principal function of neutrophils and macrophages.
Dendritic cells phagocytose for antigen presentation.

Method for both microscopic and macroscopic pathogens.
Neutrophils: Target extracellular bacteria and fungi.
Eosinophils, basophils, and mast cells: Target large parasites such as worms. Associated with allergic responses.
Granule contents:
- Preformed toxic substances that kill bacteria, fungi, or worms.
Activated by various methods (not detailed in the lecture).
Quick release of substances leads to pathogen killing.

Function through cytotoxicity (killing of other cells).
Important for virally infected cells and cancer cells.
Mediated through:
- Receptors that recognize molecules expressed on infected or stressed cells.
- Antibodies.
Activating and inhibitory receptors:
- If both engaged, the cell is not killed.
- Virus-infected cells may downregulate MHC, leading to NK cell activation and killing.
- Antibody-coated cells can also activate NK cells.
Activation leads to the release of granules:
- Induce apoptosis of the target cell.