Immunology and Early Vaccination Practices

An ancient practice in China where dry smallpox pustules were injected to induce a mild infection and immunity.

The person credited with pioneering vaccination campaigns against smallpox in 1798.

Louis Pasteur's theory that proposes diseases are caused by microscopic organisms.

The idea of injecting patients with bacteria to shrink tumors, proposed by William Coley based on his observations.

Ehrlich's theory suggesting the immune system constantly patrols for and destroys cancerous cells.

An experiment using syngeneic mice to study cancer cell recognition by immune cells.

Lack of experimental evidence, which was a major critique of the Immunosurveillance Theory.

The immune system can prevent cancer, but can also assist tumor growth.

Inspired by Coley's work using bacterial infections, this approach focuses on stimulating the immune system to target cancer cells.

A type of immune response involving T cells and B cells, providing a targeted and specific immune response to antigens.

How T cells recognize antigens: by detecting antigen-MHC complexes on the surface of infected or cancerous cells.

When a T cell recognizes a self-antigen in the thymus, it undergoes elimination to prevent autoimmune reactions.

Cells like neutrophils and macrophages that are responsible for engulfing and destroying pathogens in the innate immune system.

A type of T cell that plays a critical role in suppressing other immune cells, preventing autoimmune reactions and maintaining immune tolerance.

A molecule crucial for antigen presentation on cells. It presents processed antigens to T cells, triggering an immune response.

The first line of defense against infection, involving non-specific mechanisms like physical barriers and phagocytosis.

The primary role of B cells is to produce antibodies, which recognize and neutralize specific pathogens.

A potentially life-threatening situation caused by an overwhelming release of inflammatory cytokines, leading to widespread organ damage.

A type of immune response where the immune system mistakenly attacks the body's own tissues, leading to autoimmune diseases.

The first phase of the immunoediting process where the immune system actively eliminates nascent tumor cells.

A cytokine released during the elimination phase that helps kill tumor cells.

The phase where tumor cells and immune cells exist in a dynamic balance, showcasing Darwinian micro-evolution as tumor cells evolve to evade the immune system.

The concept that tumor cells undergo evolutionary changes to evade the immune system through mutations and selective pressure.

The phase where tumor cells gain the ability to suppress the immune system and evade immune destruction, leading to clinically detectable tumors.

The point where tumor cells have successfully bypassed the immune system, resulting in the formation of clinically detectable tumors.

A mutated protein found only in cancer cells, recognized as foreign by the immune system.

The phase where the immune system continuously attacks the tumor cells but cannot eliminate them due to tumor evolution.

Cancer-Associated Fibroblasts (CAFs) build a protective collagen barrier around tumors, preventing immune cell infiltration.

Tumors can evade T-cell recognition by downregulating MHC-I, reducing antigen presentation to immune cells.

A molecule that promotes angiogenesis, the formation of new blood vessels, which can supply nutrients and oxygen to tumors and suppress immune cells.

Tumors secrete Fas ligand (FasL) to induce apoptosis in immune cells at a distance, suppressing the immune response.

Tumor cells produce antagonistic ligands for CXCR3, hijacking the immune cell navigation system and preventing immune cell infiltration.

IL-10, an anti-inflammatory cytokine, is produced by tumor cells and suppresses T-cell function.

Tumors express CXCL12, a chemokine that repels immune cells, creating a protective space around the tumor.

Tumor cells can downregulate the Fas receptor, making them resistant to apoptosis triggered by Fas ligand (FasL) from immune cells.

The Warburg effect refers to the preferential use of glycolysis, even in the presence of oxygen, by tumor cells to produce energy.

Due to the Warburg Effect, tumor cells consume excessive glucose, depleting the tumor microenvironment of this crucial nutrient.

Lactic acid, a byproduct of glycolysis, accumulates in the tumor microenvironment, contributing to its acidic nature.

Acidity in the tumor microenvironment impairs immune cell function and induces anergy, preventing an effective immune response.

Hypoxia, or oxygen deficiency, in the tumor microenvironment impair immune cell activity as immune cells rely heavily on aerobic metabolism.

Tumors upregulate GLUT1, a glucose transporter, to maximize their glucose uptake, fueling their rapid growth and contributing to glucose depletion in the TME.

Lactate accumulation in the TME contributes to its acidity, which can inhibit immune cell function and create a favorable environment for tumor growth.

Immune cells in a glucose-depleted TME become anergic, their activity is suppressed, and their ability to fight cancer is compromised.

Tumor cells manipulate fibroblasts, converting them into CAFs through TGF-β signaling, which helps establish a protective barrier around tumors.

CAFs create physical barriers of collagen around tumors, blocking immune cell infiltration and impeding an effective immune response.

High levels of TGF-β in the TME induce conversion of CD4+ T cells into Tregs, further suppressing the immune response and protecting the tumor.

Tumors release factors that polarize M1 macrophages, which are normally pro-inflammatory, into M2 macrophages, which promote tumor growth and suppress anti-tumor immunity.

M2 macrophages, induced by tumors, have an anti-inflammatory and tumor-promoting effect, suppressing immune cell activity and enhancing tumor survival.

Tregs in the TME suppress effector T cells, which are crucial for killing tumor cells, thus protecting the tumor from immune destruction.

The primary function of Tregs in the tumor microenvironment is to inhibit the immune response, promoting tumor survival and hindering the body's ability to fight cancer.

TGF-β, secreted by tumors, promotes the conversion of macrophages into the M2 phenotype, which contributes to the tumor-promoting environment.

CAFs serve as a physical barrier that prevents immune cells from reaching and attacking the tumor, contributing significantly to immune evasion.

Hypoxia in the TME can impair the function of CD8+ cytotoxic T cells, making them less effective at killing tumor cells and contributing to tumor escape.