Lecture 2 Notes

The lecture continues discussing the second line of defense in the immune system, having previously covered recognition, inflammation, and phagocytosis.
The focus is now on the complement system and interferons.

Part of the innate immune system and is a non-specific host defense.
Consists of a series of serum proteins that perform coordinated functions to amplify immune responses and interface with both innate and acquired immunity.
Approximately 20 complement proteins are involved.

Classical Pathway:
- The first pathway discovered, it activates through antibodies already bound to antigens on a microbe's surface.
- Involves proteins denoted as C, such as C1, C2, C4, and C3.
Mannose-Binding Lectin (MBL) Pathway:
- Activated when MBL binds to carbohydrates on microbial surfaces.
- Functions similarly to the classical pathway but uses innate recognition.
Alternative Pathway:
- Slowly activated through the spontaneous hydrolysis of C3.
- Requires unique factors for stabilization and amplifies its signal through feedback.

Complement proteins bind to surfaces of microbes or antibodies.
This sets off a cascade of reactions.
Initiation can resemble an avalanche where a small trigger results in a large reaction.

Amplifier effect leads to a significant increase in the number of reactive molecules.
Amplified response significant for fighting infections effectively.

Forms holes in bacterial membranes leading to lysis, especially in Gram-negative bacteria.
Complement proteins assemble in a complex to create a pore in the target cell's membrane.

Antibody binds to an antigen.
C1 complexes bind to this antibody.
C1 activates and cleaves C4 into C4a & C4b.
- C4b adheres to the microbe surface.
C1 also cleaves C2, producing C2a and C2b.
C2a and C4b combine to form C3 convertase, an enzyme that splits C3 into C3A and C3B.
C3A diffuses and acts as a chemokine for recruitment, triggering inflammation.
C3B binds to the pathogen's surface marking it for opsonization and aiding C5 cleavage to initiate MAC.

C1 complex is replaced with MBL which binds carbohydrates on microbial surfaces.
Still uses components from the classical pathway to activate the same terminal cascade.
Important for the body to defend against previously unencountered pathogens through innate mechanisms.

Spontaneous hydrolysis of C3 occurs, forming C3B.
C3B binds to factor B, allowing factor D to cleave factor B.
This creates a C3 convertase that amplifies the response using feedback mechanisms.
Important for early responses when antibodies are absent.

Sets up inflammatory reactions (C3A, C5A).
Opsonizes pathogens to enhance phagocytosis.
Directly kills susceptible organisms via the MAC.
Essential for maintaining homeostasis by clearing dead cells and debris from immune responses.

Healthy self-cells express degrading enzymes that prevent C3 activation on their surfaces, protecting them from complement fixation.

Plasma proteins that help interrupt viral spread.
Two main types:
- Type 1 Interferons (alpha and beta): Secreted by many cell types in response to viral infections, acting locally to protect neighboring cells.
- Interferon Gamma: A unique type, important for activating macrophages.

Cells detect viral infection through innate sensors programmed to detect viral nucleic acids.
This activates interferon genes and results in the synthesis and secretion of interferon proteins.
Neighboring cells respond via interferon receptors, inducing the expression of antiviral proteins that degrade viral components and restrict replication, effectively alerting them to the infection.
This process may lead to cell death, but it is vital for alerting other cells and preventing viral spread.

Involves humoral immunity mediated by antibodies produced by B lymphocytes, primarily targeting extracellular microbes.
T cells mediate cell-mediated immunity targeting intracellular pathogens (viruses and some bacteria).

Antigens: Substances that generate an immune response recognized by the adaptive immune system; epitopes are the precise molecular structures recognized.
Antigenicity: Measure of a substance's ability to stimulate an immune response, influenced by size and structure.

Macrophages: Breakdown and present antigens from pathogens to T lymphocytes (Antigen Presenting Cells).
Dendritic Cells: Capture antigens and migrate to lymph nodes to present them.
Helper T Cells (CD4): Orchestrate the immune response by receiving signals from antigen-presenting cells and helping B cells and macrophages.
Regulatory T Cells: Prevent overactivity of the immune response; regulate and maintain homeostasis.
Cytotoxic T Cells (CD8): Kill infected host cells and recognize foreign peptides displayed by MHC.
B Cells: Manufacture and secrete antibodies after receiving signals from helper T cells.
Memory T and B Cells: Long-lived cells that provide rapid and robust responses upon re-encountering the same pathogen.

B and T cells originate from stem cells in the bone marrow; T cell maturation also occurs in the thymus.

Primary lymphoid organs: Bone Marrow (B cell maturation) and Thymus (T cell maturation).
Secondary lymphoid organs: Lymph nodes and spleen that filter and survey materials from lymph and blood.
Mucosal Associated Lymphoid Tissues (MALT): Positioned throughout the entry points of the body to survey for pathogens (e.g., tonsils).

Blood: Circulation of immune cells and proteins.
Extracellular fluid: Bathes tissue cells and enables diffusion for immune surveillance.
Reticuloendothelial system and lymphatics: Network crucial for survey and response to infections.

Understanding lymphoid organs and their location helps in comprehending immune surveillance and responses within the body.
The interplay of different immune responses (innate and adaptive) is vital for a robust defense against pathogens.