Case Studies of Human Disease Exam 2

Innate Immunity

Innate Immunity

Quick & nonspecific immune respone (0-4 Hours)

Macrophage

Type of white blood cell that surrounds and kills microorganisms, and stimulates the action of other immune system cells.

Dendritic Cells

Immune cell tat is found in tissues, such as the skin, boosts immune response by showing antigens on its surface to other immune cells.

Monocytes

Type of immune cell that is made in bone marrow and travels through the blood to tissues where it is needed, is then able to change into macrophage of dendritic cells.

Mast Cells

A type of white blood cell that is found in connective tissues all through the body, especially under the skin, near blood vessels and lymph vessels, in nerves, and in the lungs and intestines.

Neutrophils

A type of white blood cell (leukocytes) that act as your immune system's first line of defense. A subset of granulocytes that has a segmented nucleus.

Eosinophil

A type of white blood cell and a subset of granulocytes that is responsible for creating an inflammatory response. Focus on destroying invading germ cells.

Basophil

A type of white blood cell and a subset of granulocyte. Has enzymes which are released during allergic reactions and asthma.

Gamma-delta (γδ) T cells

a subset of T cells that promote the inflammatory responses of lymphoid and myeloid lineages, and are especially vital to the initial inflammatory and immune responses.

Natural Killer T Cell

type of T cell that also have certain features of natural killer (NK) cells. They can kill invading microorganisms, such as bacteria and viruses, by releasing cytokines. They can also kill certain cells, such as cancer cells, either directly or by causing other immune cells to kill them.

Adaptive Immunity

Slow and specific immune response (4-14 days)

Humoral Immunity

Class of adaptive immunity. Production of antibodies and main defense against bacterial infection

Cell-mediated Immunity

Formation of lymphocytes that attack foreign material. The main defense against viruses, fungi, parasites, and some bacteria. Also rejects transplanted organs and eliminates abnormal cells that arise during cell division.

T-lymphocytes

Type of WBC that is diverse and an important group of lymphocytes that mature and undergo a positive and negative selection processes in the thymus. Can wipe out infected or cancerous cells and also maintain immunological memory and self-tolerance.

CD4+

help coordinate the immune response by stimulating other immune cells, such as macrophages, B lymphocytes (B cells), and CD8 T lymphocytes (CD8 cells), to fight infection. Helper T Cells

CD8+

Kill virus-infected cells and produce antiviral cytokines such as interferon-gamma. Have the primary job to kill toxic/target cells. Killer T Cells

B lymphocytes

Proliferate and mature into antibody-forming plasma cells

T lymphocytes

Proliferate to form a diverse population of cells that regulate the immune response and generate a cell-mediated immune reaction to eliminate antigen

Entry of Foreign Antigen Reaction

1) Recognition of foreign antigen

2) Proliferation of lymphocytes that are programmed to respond to the specific antigen form a large group of cells

3) Destruction of the foreign antigen occurs by the proliferated lymphocytes

MHC (Major Histocompatibility Proteins)

Present processed antigen to responding cells of the immune system and generates an immune response

MHC class I

Present on all nucleated cells

MHC class II

Only on B lymphocytes, macrophages, and related antigen-processing cells and some activated T-lymphocytes

Cytotoxic T Cells

Can respond only to antigens complexed with MHC class I proteins displayed on infected host cellsI

IgA

Mucus, Saliva, Tears, Colostrum. Tags pathogens for destruction

IgD

B-Cell receptor stimulates release of IgM

IgE

Binds to mast cells and Basophils. Allergy and antiparasitic activity

IgG (Most Common)

Binds to phagocytes. Main blood antibody for secondary responses. Crosses the Placenta

IgM

Primary first responder to new pathogen. B-cell receptor and immune system memory.

Hypersensitivity Type I

Allergy and Anaphylactic (immediate response). IgE antibodies fix to mast cells and basophils.

Anaphylaxis

Hypersensitivity reaction that may be life threatening. Severe generalized IgE-mediated reaction: Fall in blood pressure, sever respiratory distress

Antihistamine drugs

Often relieve many allergic symptoms.

Atopic person

Allergy-Prone individual

Allergen

Sensitizing antigen

Hypersensitivity Type II

Cytotoxic: Antibody combines with cell or tissue antigen, resulting in complement-mediated lysis of cells or other membrance damage. EX: Rh hemolytic disease, blood transfusion reactions.

Hypersensitivity Type III

Immune Complex: Ag-Ab immune complexes deposited in tissues activate complements; PMN attracted to site, causing tissue damage. EX: Rheumatoid Arthritis

Hypersensitivity Type IV

Delayed hypersensitivity or cell-mediated hypersensitivity: T lymphocytes are sensitized and activated on second contact with same antigen. Lymphokines induce inflammation and activate macrophages. EX: Tuberculosis, fungal and parasitic infections

Autoimmune disease

A patient forms antibodies against his or her own cells and tissues

Pathogenesis

Alteration of patient’s own antigens, causing them to become antigenic, provoking an immune reaction. EX: Systemic lupus erythematosus, Glomerulonephritis, Anemia, Hypothyroidism, Hyperthyroidism

Neoplasia

Tumor Development

Benign

Slow growth rate, Expansion, Remains localized, Well-differentiated cells

Malignant

Rapid growth rate, Infiltration, Metastasis by bloodstream, poorly differentiated cells

Carcinoma

Involves epithelial tissue, most common form of cancer: 85% of all tumors.

Metastasis: Principally through lymph vessels.

Subtypes: Adenocarcinoma (internal organ) and Squamous cell carcinoma (skin)

Sarcoma

Arising from connective tissues, such as fat, bone, cartilage, and muscles.

Less common but spreads more rapidly, Little differentiation, lacks form (anaplasia),

Metastasis: Bloodstream

Leukemia

Neoplasm of blood cells, usually does not form solid tumors

Proliferates diffusely within bone marrow, overgrows and crowds out normal blood forming cells.

Neoplastic cells (blasts) spill over into the bloodstream, and large numner of abnormal cells circulate in the peripheral blood.

Lymphoma

Malignant tumor of lymph node

Melanoma

Malignant skin tumor; melanocytes

Blastoma

Pediatric malignant solid tumor (retionoblastoma - eye / nephroblastoma - kidney)

Adenoma

A term often used to refer to a benign tumor derived from epithelial tissue

Neoplasms

Derive from a single stem cell. An abnormal mass of tissue that forms when cells grow and divide more than they should or do not die when they should.

Cancer (Progression)

Usually the result of multiple genetic insults such as activation of oncogenes or loss of function of one or more tumor suppressor genes

Tumors

• Derive blood supply from tissues they invade

• Malignant tumors frequently induce new blood vessels to proliferate in adjacent normal tissues to supply the demands of the growing tissue

• The malignant tumor may outgrow its blood supply causing necrosis in areas with the poorest blood supply

Metastasis

Tumor spreads from site of origin to sites near and far within the body

Via Blood Vessels (Hematogenous)

Via Lymphatic Vessels (Lymphatic)

Travel Patterns of Spread

Colon → Liver

Breast → Axillary lymph nodes

Lung → Brain

Kidney, Prostate → Bone

Pancreas → Liver

Testicle → Retroperitoneum

Melanoma → Lymph nodes, etc.

Apoptosis

Programed cell death if a cell sustains a significant degree of DNA damage

Ph1 Chromosome

Best known chromosomal abnormality

Reciprocal translocation of ends of chromosomes 9 and 22

Oncogene on translocated piece of chromosome 9 exhibits increased activity

Oncogene

Abnormally functioning gene that stimulates cell growth excessively, leading to unrestricted cell proliferation.

Tumor Suppressor Genes

Function by preventing DNA replication and completion of mitosis

Normally suppress cell proliferation

Exist in pairs at corresponding gene loci on homologous chromosomes

EX: p53: “guardian of the genome”, Rb: function identified in childhood cancer, retinoblastoma, APC: controls cell-cell adhesion, NF1: association with tumors of the nervous system

Mutation

Any change in the normal arrangement of DNA nucleotides on the DNA chain

Early Warning Signs of Tumors

Unintentional Weight Loss

Bleeding tendency

Persistent cough

Change in bowel and bladder habits

Postmenopausal bleeding

Palpable lump

Carcinoembryonic antigen (CEA)

Cancer secreted substance, concentration related to size of tumor and its possible spread

Alpha fetoprotein

Normally produced by fetal tissues in the placenta but not adult cells; elevated in primary carcinoma of the liver

Human chorionic gonadotropin

Normally produced by the placenta; elevated in testicular carcinoma

Prostate specific antigen (PSA)

Normally produced by prostate epithelial cells, may be elevated in prostate cancer

Cancer Antigen 19-9

Elevation in pancreatic cancer

Cancer Antigen CA-153

Elevation in ovarian cancer

Tumor Treatments

Surgery

Radiotherapy

Hormones

Anticancer drugs

Adjuvant chemotherapy

Chemotherapy

Eliminates cells that divide frequently usually found in: Mouth, skin, hair, bone marrow, digestive tract, kidneys, bladder

Pathology

Study of disease

Autopsies - Indications of Death

Homicide

Suicide

Accidental

Natural

Unknown

Historical Roots of Autopsies

Vesalius - Founder of Modern Human Anatomy

Morgagni - First to propose sign and symptoms were due to findings during autopsies

Virchow - Virchow technique (removal and dissection of organs one by one)

Fluorescein

Fluid used for the identification of blood at crime scene by making blood glow fluorescent

Rigor Mortis

Stiffening or contraction of muscles

Loss of oxidative phosphorylation and ATP production

Begins throughout body at same time

Begins 2 hours after death, maximum at 12+hours, remains for 12 hours, resolves over the next 12 hours (12-12-12 rule)

Livor Mortis

Dark “bruise-like” discoloration due to blood settling into dependent parts of the body

Can help determine TOD and can indicate whether a body was moved

A corpse facing upwards will have lividity on back; one laying on left side will have lividity along left side of body

Algor Mortis

Body temperature

Temperature equilibrates between body and surrounding enviornment

Formula: Hrs since death = (98.6 - corpse core temp) / 1.5

Putrefaction

Generalized decay, decomposition

Bloating

Marbling

Insect infestation

Feeding by animals/birds

General Internal Exam

1) Y-Shaped Incision

2) Chest plate removed (Stryker Saw)

3) Organs removed, weighed, examined

4) Calvarium removed, brain removed & weighed

5) Toxicology samples taken

Body Fluids Sampled for Toxicologic Analysis

Bile, Urine, Vitreous Humor (eye fluids best preserved), Blood, Stomach Contents

Serous

Clear, pale yellow

Serosanguinous

Yellow-red with blood

Sanguinous

Bloody

Purulent

Pus containing (exudate)

Pulmonary Embolus

Thromboembolism travels from deep veins of extremities (legs most commonly)