Immunology and Oncology: A Comprehensive Overview

Immune System

• Specialized to defend the body against antigens (toxins, bacterial proteins, foreign blood cells).

• Antigen: Any substance that induces an immune response, especially antibody production.

  • Protein/protein fragment on bacteria, viruses, or organ transplant tissue.

  • The body recognizes it as foreign and evokes an immune response.

• Includes leukocytes (neutrophils + monocytes) and macrophages (phagocytes in blood and tissues).

• Also includes lymphoid organs.

Types of Immunity - Intro / Overview

• The body's ability to resist foreign organisms and toxins.

• Two Types:

  • Natural (Innate) Immunity - resistance present at birth

    •   Think about Jing-Essence (prenatal)

• Adaptive Immunity - resistance acquired through immune system responses to antigens over time

•   Think about post-natal Jing-Essence

Natural (Innate) Immunity:

• Natural passive immunity: a type of temporary immunity in which antibodies are transferred from one individual to another naturally, without the recipient’s immune system producing them.

• Resistance present at birth.

• NOT dependent on exposure to an antigen.

  • Example: White blood cells respond immediately to invading antigens after a bacterial infection.

• Neutrophils travel to the infected area and ingest bacteria.

• Other White Blood Cells (monocytes, macrophages, lymphocytes) also participate.

Adaptive Immunity

• Adaptive immunity (also called acquired immunity) is the part of the immune system that develops specific responses to particular pathogens after exposure. It involves the activation of B cells and T cells, and it remembers antigens for faster responses upon re-exposure.

• The body's ability to recognize and remember specific antigens.

• Includes lymphocytes (B and T cells).

  • T cells recognize and remember specific antigens (ex. Streptococcus bacteria), producing stronger attacks upon each encounter.

  • B cells secrete antibodies against antigens.

    • When exposed to a viral antigen (e.g., a cold), B cells secrete antibodies to destroy the virus, and these antibodies remain in the blood for future immunity.

Modes of Adaptive Immunity

• Vaccination - injection of an attenuated (weakened) virus, does not make you ill but stimulates B cells to secrete antibodies agains virus

• Immediate Adaptive Immunity - poisons (toxins) cause rapid damage and can be countered using anti-toxins

• Immunoglobulins - ready-made antibiotic injections that can boost adaptive immunity before international travel

• Maternal Antibodies - adaptive immunity infants receive from mom via placenta and breast milk

Components of Adaptive Immunity

• Humoral Immunity - Involves B cells producing antibodies (immunoglobulins) after exposure to specific Antigens.

  • Plasma cells secrete antibodies; memory B cells confer long-term immunity.

• Cell-Mediated Immunity - Involves T cells (Helper, Cytotoxic, Suppressor, Memory), which remember and recognize antibodies.

  • Develop in the thymus gland.

• Complement System -

  • A group of proteins that help antibodies kill targets

  • e.g., dendritic cells: antigen-presenting cells

    • immune cells that capture, process, and present antigens to T lymphocytes, initiating a specific immune response.

Types of Adaptive Immunity

• Active Immunity

  • Natural Active Immunity: response to infection

  • Artificial Active Immunity: Through Vaccination: Injection of attenuated virus stimulates B cells to secrete antibodies against the virus without causing illness.

• Passive Immunity

  • Natural Passive Immunity: Maternal Transference: Antibodies infants receive from their mother, via the placenta and breast milk.

    • Includes IgA, IgD, IgE, IgG, IgM.

  • Artificial Passive Immunity: Immediate adaptive immunity using antitoxins for poisons.

    • Antitoxins: Ready-made antibiotic injections can boost adaptive immunity before international travel.

Humoral vs. Cellular Immunity

• Humoral Immunity involves B cells and antibodies.

• Cellular Immunity involves T cells.

  • Includes CD8+ T cells and CD4+ T cells.

Immunotherapy

• Immunotherapy: The prevention or treatment of disease with substances that stimulate the immune response.

• Involves the use of antibodies, B antibodies, and T cells to treat diseases like cancer.

  • Passive Immunotherapy: Immune agents are given to the patient, resistance is passively acquired.

  • Active Immunotherapy: A patient's own immune system is stimulated to actively develop resistance.

Types of Immunotherapy

• Monoclonal antibodies (Passive Immunotherapy) - injections of antibodies for the immune system to use against future attack. ex. COVID vaccine

  • Useful for patients with immunocompromised conditions, elderly patients. Etc

• Vaccines (Active Immunotherapy) - injection of Antigen agents (virus / bacteria / protein, etc).

  • Not effective for patients with compromised / weakened immune systems

• Transfer of immune cells (Passive Immunotherapy) - T-lymphocytes are injected from a healthy donor into sick patient to help a patient’s immune system recognize cancer cells to destroy them

Immunodeficiency

• Immunodeficiency: The decreased ability of the body to fight infections and other diseases. (Ex. Acquired Immunodeficiency Syndrome (AIDS).

• Can be present at birth (primary immunodeficiency) or acquired (AIDS)

• Acquired Immunodeficiency Syndrome (AIDS) - HIV destroys Helper T-Cells, which allows opportunistic infections to occur in a patient with immunodeficiency, which can be life-threatening. Transmitted via bodily fluids (blood, sexual fluids, mother=> newborn)

  • HIV positive patients may be asymptomatic for up to 10 years - testing is crucial

  • Oral Thrush - oral fungal infection; common sign of a weakened immune system. Yeast is present in the mouth in all individuals, but only becomes an infection / overgrowth in individuals with compromised immune systems.

Hypersensitivity - Allergy

• Hypersensitive Immune response: Exaggerated or inappropriate immunologic responses to an antigen or allergen. (Ex. Allergies, auto-immune)

  • Reactions to exposure over time tends to increase (worsens over time)

• Reactions vary in intensity, from allergic rhinitis (seasonal allergies) to systemic anaphylaxis.

• Other Allergies:

  • Asthma: A chronic inflammatory disorder of the airways characterized by wheezing, shortness of breath, chest tightness, and coughing.

  • Hives: A skin reaction marked by raised, red, itchy welts (wheals) that vary in size and shape.

  • Atopic Dermatitis (Eczema): A chronic, itchy inflammatory skin condition commonly associated with allergies. It often begins in childhood and presents as red, dry, scaly patches on the skin, especially in the creases of elbows and knees.

• Involves:

  • Allergen: A substance (usually harmless) that triggers an allergic reaction in sensitized individuals by stimulating an immune response.

    • Examples: Pollen, dust mites, certain foods, insect venom.

    • Allergens activate the production of IgE antibodies in allergic individuals.

  • Fc receptor for IgE antibodies: A receptor found on the surface of certain immune cells (e.g., mast cells, basophils) that binds to the Fc region of IgE antibodies.

    • Full name: FcεRI (high-affinity IgE receptor).

    • Once bound with allergen-specific IgE, these cells become sensitized.

    • On subsequent allergen exposure, cross-linking of these receptors triggers degranulation.

  • Allergen-specific IgE antibodies: a class of immunoglobulins produced by B cells in response to a specific allergen.

    • These antibodies bind to Fc receptors on mast cells/basophils.

    • IgE antibodies trigger the release of histamine from mast cells and basophils, triggering the allergic reaction

    • Upon re-exposure to the same allergen, cross-linking of these bound IgEs activates the allergic response.

  • Degranulation: The process by which mast cells or basophils release the contents of their granules (e.g., histamine, leukotrienes, prostaglandins) into surrounding tissues.

    • Triggered when allergen cross-links IgE bound to FcεRI on the cell surface.

    • Causes allergic symptoms: itching, swelling, mucus production, bronchoconstriction.

Anaphylaxis

• Anaphylaxis: Clinically important condition: an extreme systemic hypersensitivity reaction.

• Leads to a drop in blood pressure, shock, respiratory distress, and angioedema (rapid swelling of the deeper layers of the skin, often around the eyes, lips, or throat).

• Typically occurs seconds to minutes after exposure to an allergen (e.g., peanuts, bee stings).

  • Can take up to 36 hours after exposure when new-onset hypersensitivity allergic reaction

• Can be life-threatening, but survival is possible with prompt treatment:

  • (1) keep the airway OPEN

  • (2) Administer epinephrine / EPI Pen and THEN antihistamines / Benadryl

  • (3) go to the Emergency Room for a 2nd dose of epinephrine, an IV-drip of antihistamines + monitoring

Cancer & Oncology - Overview

• Disease caused by abnormal & excessive cell growth, marked by structural and functional changes at the cellular level

• Tends to occur more frequently in older patients, but can develop at any age

• Local growth, spread by blood stream or lymphatic vessels

• Can result in death - ~50% of patients survive a cancer Dx. 550,000 pts die each year from cancer

• Most common types:

  • Lung > Breast > Colorectal in women;

  • Lung > Prostate > Colorectal in Men

Malignancies - malignant tumors

• Malignancies - malignant tumors pertaining to the immune/lymphatic systems.

• Lymphoma: Malignant tumor of lymph nodes and lymph tissue.

• Multiple Myeloma: Malignant tumor of bone marrow cells.

• Thymoma: Malignant tumor of the thymus gland.

Characteristics of Tumors

• Tumors (neoplasms) are new growths arising from normal tissue.

  • Malignant: Capable of invasion and spread to surrounding or distant sites

  • Benign: Noninvasive and not spreading.

Differences Between Benign and Malignant Tumors

Carcinogenesis - what causes cancer?

• Carcinogenesis: Process by which normal cells transform into cancerous cells through DNA damage & mutations

  • Cause is only partially understood.

  • Malignant transformation results from damage to the cell's DNA, which causes abnormal growth, development, and division (reproduction) from parent => daughter cell, over-and-over

• Cancer cells reproduce almost continuously and produce abnormal proteins.

• These changes interfere with accurate protein synthesis and are passed onto daughter cells as mutations.

Carcinogens

• Carcinogens: Agents such as chemicals, drugs, tobacco smoke, radiation, and viruses which can damage DNA and thus cause cancer.

• DNA damage may be caused by environmental factors (toxic chemicals, sunlight, tobacco smoke, viruses).

Types of Carcinogens:

• Chemical Carcinogens

  • Found in cigarettes, cigars, pipe smoke, automobile exhaust, insecticides, dyes, industrial chemicals, insulation, and hormones.

• Radiation

  • Sources include sunlight, X-rays, and radioactive substances (atomic energy).

  • Interacts with DNA, causing damage and cancerous mutations.

  • Example: Leukemia.

• Viruses

  • Some are carcinogenic (oncogenic viruses).

    • Example: Human Papilloma Virus (HPV) causes cervical cancer.

  • Fall into two categories: DNA viruses and RNA viruses.

  • Pieces of normal DNA (oncogenes) can cause normal cells to become malignant if activated by mutations.

    • Examples of Oncogenes: ras (colon cancer), myc (lymphoma), and abl (chronic myelogenous leukemia [CML]).

Heredity - Cancer may also be caused by inherited factors.

• Susceptibility is transmitted from parents to offspring through defects in DNA.

• Examples of inherited cancers: Retinoblastoma, some forms of colon, breast, and kidney cancer.

• These diseases are caused by a loss or change in DNA coding sequence, leading to improper protein synthesis and carcinogenesis

  • Loss of normal suppressor genes can be a factor as well as carcinogenic mutations

• Cancer Screening: Inherited changes can be detected and/or predicted by analyzing DNA in body tissue/blood cells.

  • Preventative therapies: mastectomy, hysterectomy, etc.

Examples of Genes Implicated in Hereditary Cancers - don’t need to study, just for reference

Classification of Cancerous Tumors

• Almost half of cancer deaths are caused by malignancies in the lung, breast, or colon.

• There are >100 distinct types of cancer, with unique Sx & Tx

• Cancers are divided into broad groups based on histogenesis (cancer typology based on the tissue where the cancer first arises).

• Major Groups at a glance:

  • Carcinomas - Solid tumors derived from epithelial tissue (lining external and internal body surfaces, including skin, glands, digestive, urinary, and reproductive organs).

  • Sarcomas - Derived from connective tissues (bone, fat, muscle, cartilage, bone marrow, and lymphatic cells). Malignant tumors. Less common than carcinomas.

  • Mixed-tissue tumors - Derived from tissue that can differentiate into both epithelial and connective tissue. Uncommon tumors composed of several different types of cells.

Carcinoma

• Largest group.

• Solid tumors derived from epithelial tissue (lining external and internal body surfaces, including skin, glands, digestive, urinary, and reproductive organs).

• ~90% of all malignancies are carcinomas.

• Adenoma: Benign tumors of epithelial origin (not the same as carcinoma, but same tissue origin)

Sarcomas

• Malignant tumors. Less common than carcinomas.

• Derived from connective tissues (bone, fat, muscle, cartilage, bone marrow, and lymphatic cells).

• Mesenchymal tissue: term used to describe embryonic connective tissue from which sarcomas are derived.

• Also includes tumors arising from blood-forming tissue.

Mixed Tissue Tumors

• Derived from tissue that can differentiate into both epithelial and connective tissue.

• Uncommon tumors composed of several different types of cells.

• Examples:

  • Kidney: Wilms tumor (embryonal adenosarcoma).

  • Ovaries and testes: Teratoma, Germ cell tumor.

Grading and Staging Systems

• Tumors are classified based on tissue origin, microscopic appearance, and extent of spread.

• Grade and stage influence prognosis and treatment.

Grades 1 - 4 (I - IV)

• Cancer Grade: Degree of tumor maturity and/or cell differentiation observed under the microscope.

  • Grade I: Well differentiated, closely resemble normal tissues.

  • Grade II and III: Intermediate in appearance, moderately to poorly differentiated.

  • Grade IV: Undifferentiated, don't resemble normal tissues.

Stages 0 - 4

• Cancer Stage: Extent and spread within the body.

• Relies on defining size and spread using CT, PET/CT, MRI scans, and radioactive bone scans.

Tumor-Node-Metastasis (TNM) International Staging System - measure of Size of tumor, number of lymph nodes involved, and measure of metastases involved

• T: Size and local extension of the tumor.

• N: Number of regional lymph nodes invaded by the tumor.

• M: Presence/absence of metastases (spread to distant sites).

• 0 = undetectable, 1, 2, 3, 4 = progressive increase in size or involvement.

Cancer Treatment

• Surgical Removal of Tumor

  • Tumor is discovered before it has spread, and it may be cured / removed by surgical excision.

  • Common cancers where surgery may be curative:

    • stomach, breast, colon, lung, and uterus.

  • Surgical removal prevents local spread or complications, even with distant disease.

• Radiation Cancer Therapy

  • Goal of Tx is to deliver maximal dose of ionizing radiation to tumor tissue and minimal dose to surrounding normal tissue.

  • High-dose irradiation destroys tumor cells + produces DNA damage.

Radiation Therapy Side Effects - determined based on where the radiation occurs (where is the tumor on the body)

• Alopecia (baldness)

• Fibrosis (increase in connective tissue)

• Infertility

• Mucositis (inflammation and ulceration of mucous membranes)

• Myelosuppression (bone marrow depression)

• Nausea + vomiting

• Pneumonitis (inflammation of the lungs)

• Secondary tumors

• Xerostomia (dry mouth)

Other Cancer Treatments

• Chemotherapy Cancer Tx- Cancer Treatment using chemicals (drugs).

  • Standard treatment for many types of cancer.

  • Given w/ surgery and irradiation to improve cure rates

  • Goal: Administer drugs that kill many tumor cells without harming normal cells.

  • Drugs are given according to a written protocol (route, schedule, and frequency of doses).

• Biologic Cancer Therapy - Tx using the body's own defenses to fight tumor cells.

  • Research explores restoring, enhancing, mimicking, and manipulating the immune system.

  • Examples: Interferons (made by lymphocytes), Monoclonal antibodies (made by mouse or human immune cells).

Clinical Procedures

• Bone Marrow Biopsy - Aspiration of bone marrow tissue (via lumbar puncture) and examination under a microscope.

• Bone Marrow/Stem Cell Transplantation - Cells are infused intravenously into a patient. Used for immunodeficient patients

• Core Needle Biopsy - Insertion of a large-bore needle into tissue to remove a core of cells for microscopic exam.

• Mammography - X-ray exam of the breast to detect breast cancer.