Principles of Chronic Inflammation and Cellular Transformation

What types of cells release inflammatory mediators?

Leukocytes, endothelial cells, and plasma proteins

What are key types of inflammatory mediators?

Cytokines, histamine, serotonin, eicosanoids, coagulation factors

What are key anti-inflammatory cytokines?

IL-4, IL-10, IL-13, TGF-beta

What are the five principles of inflammatory mediators?

Produced locally, concentration-dependent, short-lived, negative feedback regulated, functionally redundant

What chemical causes endothelial contraction and vascular permeability?

Histamine

Where is histamine stored?

Mast cell granules

What are the vascular effects of histamine?

Arteriolar dilation and increased vascular permeability

What drug is a histamine antagonist?

Diphenhydramine (Benadryl)

What are common effects of Benadryl?

Reduces swelling, itching, redness and causes drowsiness

Why does Benadryl cause drowsiness?

It crosses the blood-brain barrier

How long does chronic inflammation last?

Weeks to years

What are common triggers of chronic inflammation?

Persistent infection, autoimmunity, long-term toxicant exposure

What are some diseases associated with chronic inflammation?

Tuberculosis, rheumatoid arthritis, inflammatory bowel disease

Can chronic inflammation cause cancer?

Yes, but it is not always the primary cause

What immune cells use pro-inflammatory mediators to fight tumors?

T cells and macrophages using TNF-alpha

Is cancer risk higher or lower in immunodeficient patients?

Higher

Do anti-inflammatory drugs consistently reduce cancer risk?

No

What are major cancer immunotherapy strategies?

Checkpoint blockade, cancer vaccines, CAR-T cells, suppressor cell neutralization

What molecule causes DNA damage in chronic inflammation?

Reactive oxygen species (ROS)

How do tumor cells adapt to high ROS levels?

They increase their production of antioxidants

What cells predominate in chronic inflammation?

Macrophages

How do macrophages behave in chronic inflammation?

They persist, proliferate, and become hyperactivated

What do hyperactivated macrophages form?

Giant multinucleated cells

What substances do macrophages release?

Proteases, ROS, cytokines, and growth factors

How do macrophages amplify inflammation?

Positive feedback with lymphocytes

What are tumor-associated macrophages (TAMs)?

Macrophages in tumors that support cancer progression

How much of a tumor can be composed of TAMs?

Over 50 percent

Where are TAMs recruited from?

Monocytes and resident macrophages

What do TAMs support?

Angiogenesis, tumor invasion, metastasis, and CTC survival

What is a pre-metastatic niche?

A tumor-supportive environment established by TAMs

What is metaplasia?

Replacement of one mature cell type with another that can withstand the adverse environment better

What causes metaplasia?

Stem cell reprogramming due to chronic stress or injury

Can metaplasia progress to dysplasia?

Yes

What is dysplasia?

Disordered growth and abnormal tissue architecture

Can dysplasia revert or progress?

It can do either

What is neoplasia?

Uncontrolled new growth that can be benign or malignant

What is anaplasia?

Severe loss of differentiation, a hallmark of malignancy

What are features of anaplastic cells?

Enlarged, irregular, hyperchromatic, multinucleated

What are key differences between benign and malignant tumors?

Malignant tumors grow fast, invade tissue, and metastasize

What are oncogenes?

Mutated proto-oncogenes that promote cell survival and growth

What are common types of oncogenes?

Growth factor receptors, Bcl-2 family, VEGF

What are tumor suppressor genes (TSGs)?

Genes that prevent cancer by controlling cell growth and death

What are examples of TSGs?

p53, BRCA1, BRCA2, IFN, TNF families

What happens when oncogenes are overactive or TSGs are lost?

Cells gain survival advantages and proliferate uncontrollably

What balances determine cell fate and cancer risk?

Oncogenes vs tumor suppressors and pro-survival vs pro-apoptotic signals

How many damaged cells are needed to start a tumor?

Just one

What is the Hayflick limit?

The number of times a normal cell can divide (40–60)

What are senescent cells?

Non-dividing cells that secrete inflammatory factors

What is SASP?

Senescence-Associated Secretory Phenotype including growth factors, chemokines, and proteases

What is the role of senescence?

Prevents proliferation but promotes tissue remodeling and inflammation