Unit 3

immunity

innate vs adaptive immunity

innate: “natural”

adaptive: complex series of interactions between components of the immune system and the antigens of a foreign pathogen

• lymphocytes: primary cells of adaptive immune response

  • B lymphocytes: originate from Bone marrow (humoral immunity), migrate to lymphoid tissues to fully mature, → memory B cells OR antibody-secreting plasma cells, become committed to specific antibody

  • T lymphocytes: produced in the bone marrow, migrate to the Thymus (cell-mediated immunity)

  • memory B & T lymphocytes: appear after 1st encounter, remember exact antigen, respond rapidly during 2nd encounter

• antigens: substances that are foreign to the body and trigger production of antibodies (ex: bacteria, fungi, virus, protozoa, parasite, plant pollen, insect venom, transplanted organs)

• antibodies: protein molecules aka immunoglobulins

  • IgG: most of the protective activity against infections, only Ig that crosses placenta (responsible for protection of newborn)

  • IgA: protects mucous membranes, located in body secretions (saliva, nasal/resp secretions, breast milk)

  • IgM: early immune response, 1st antibody produced by developing fetus

  • IgD: needed for B cell maturation

  • IgE: binds to mast cells & basophils, involved in parasitic/allergic/hypersensitivity reactions

• lymphoid organs: responsible for the production, maturation, & storage of immune system cells

  • central lymphoid organs: bone marrow, thymus

  • peripheral lymphoid organs: lymph nodes, spleen

active vs passive immunity

active: host mounts an immune response to an antigen, requires host’s immune system, long lasting

ex: vaccination, environmental exposure

passive: immunity transferred from another source, short-term degree of protection from infection

ex: from placenta or breastmilk

• tolerance: ability of the immune system to react to foreign antigens but remain nonreactive to self-antigens, protects body from harmful autoimmune responses

immune response

naive B cell → 1* response + activated B cell → memory B cell → 2* response + activated B cell

primary immune response: develops during 1st encounter with antigen

ex: initial vaccination (causes production of plasma & memory cells)

secondary immune response: “memory phase” that occurs on subsequent exposure to the antigen

ex: booster immunization (produces an immediate antigen-antibody response, stimulates an immediate rise in antibody levels)

***elderly immune system: decrease in size of thymus, biological clock of T cells, altered responses of immune cells to antigen stimulate, decline in immune responsiveness

cellular regulation

cancer

cancer: overgrowth of abnormal cells

• carcinoma in situ: cancer in location it originated, not yet malignant

• metastasis: development of secondary tumor in a distant location from primary tumor

• oncogenes: mutated genes that promote cell proliferation & are capable of triggering cancerous characteristics (must be activated for cancer to occur)

• tumor-suppressor genes: (must be inactivated for cancer to occur)

HOW CANCER SPREADS:

1. direct invasion & extension

2. seeding of cancer cells in body cavities

3. spread through blood or lymph pathways

• staging: extent & spread of disease

• grading of tumors: level of differentiation & number of mitoses of cancer cells

  • grade I: neoplasms are well differentiated

  • grade IV: neoplasms are poorly differentiated, display marked anaplasia

• tumor markers: antigens expressed on surface of tumor cells OR substances released from normal cells in response to presence of tumor (hormones, enzymes, proteins),

  • used for screening, establishing prognosis, monitoring treatment, & detecting recurrent disease - NOT specific enough for diagnosis

infection

stages of infection

1. incubation period: no symptoms

2. prodromal stage: onset of vague symptoms

3. acute stage: most specific symptoms

4. convalescent stage: improvement of symptoms

5. resolution stage: absence of manifestations of infection

immunoglobulin = passive immunity

immunization = active immunity

perfusion

fetal circulation

R side is HIGH PRESSURE, L side is LOW PRESSURE

• ductus venosus: connects umbilical vein to inferior vena cava

• ductus arteriosus: connects pulmonary artery to the aorta

• foramen ovale: allow blood to go from R → L atria (skips pulmonary circuit)

AT BIRTH:

1. cord clamped/cut: ductus venosus severed

2. first breath → pulmonary system becomes low pressure, foramen ovale shuts

congenital heart defects (CHDs)

transposition of the great arteries: aorta arises from R ventricle, pulmonary artery arises from L ventricle, incompatible w/ life unless there is a PDA or VSD

• no shunting

• 2 separate circuits: unoxygenated blood circulates systemically, oxygenated blood circulates through pulmonary circulation

• manifestations: cyanosis

ventricular septal defect: oxygenated blood from L ventricle → R ventricle (d/t high pressure of L ventricle)

• L → R shunt

• manifestations: loud, harsh murmur

patent ductus arteriosus: increased blood flow to pulmonary circuit (d/t opening between pulmonary artery and aorta)

• L → R shunt

• manifestations: “machinery” murmur, bounding pulses, widened pulse pressure

coarctation of the aorta: narrowed (obstructed) aorta → reduced blood flow to LEs, increased blood flow to UEs

• L → R shunt

• manifestations: pulse difference >20 mmHg in arm vs leg, pulmonary congestion, high BP/bounding pulses (UEs), low BP/decreased pulses (LEs)

tetralogy of Fallot: recurrent “tet” spells, requires surgical intervention

1. VSD

2. overriding aorta (blood coming from R & L ventricles)

3. pulmonary stenosis

4. R ventricle hypertrophy (d/t increased pressure)

• R → L shunt

• manifestations: cyanosis, harsh murmur

EXEMPLARS

rheumatoid arthritis (RA): chronic, systemic, autoimmune, inflammatory disorder due to failure to differentiate self from non-self (autoantibodies)

pathophysiology: inflammation of connective tissue initiated by 1) activation of helper T cells, 2) release of cytokines, 3) antibody formation → irreversible joint destruction

manifestations: fever, fatigue, weakness, anorexia, weight loss, aching, stiffness, exacerbations & remissions, symmetrical/polyarticular painful warm swollen joints, ruddy/cyanotic/thin/shiny skin, ulnar deviation, swan-neck deformity

• rheumatoid factor (RF): autoantibody that binds with self antigens in blood & synovial membrane, forms immune complexes, 70-80% test +

systemic lupus erythematosus (SLE): chronic, systemic, inflammatory, autoimmune disease, most common in females (esp. African Americans, Hispanics, and Asians), diagnosed between 15-45 years old

pathophysiology: autoantibodies formed → type III hypersensitivity reaction

manifestations: arthralgias & arthritis, joint pain, deformities of joints, articular destruction is RARE, exacerbations & remissions, butterfly rash across cheeks & nose, photosensitivity, discoid lesions, splinter hemorrhages, alopecia

leukemia: “blood cancer” chronic malignant disorders of WBCs and WBC precursors (usual ratio of RBCs : WBCs is reversed)

classified by predominant cell of origin (myelocytic or lymphocytic) and rate of progression (acute or chronic)

etiology: radiation exposure, chemotherapy, genetic predisposition, chromosomal changes

• acute leukemias: more dangerous, cancers of hematopoietic progenitor cells, sudden onset, fatigue (low RBCs), bleeding (low platelets), infection (low neutrophils), night sweats, fever, weight loss

  • ALL (acute lymphocytic leukemia): occurs mostly in children (least common overall), lymphoblasts

  • AML (acute myelogenous leukemia): most common in adults and occurs mostly in older adults, more serious (higher mortality)

• chronic leukemias:

  • CLL (chronic lymphocytic leukemia): lymphocytosis, most common in adults

  • CML (chronic myelogenous leukemia): leukocytosis

• lymphocytic leukemia: involve immature lymphocytes and progenitor cells in bone marrow

• myelocytic leukemia: more severe

• tumor lysis syndrome: massive necrosis of malignant cells can occur during initial phase of chemo tx, may → life-threatening metabolic disorders)

infective endocarditis (IE): infection & inflammation of endocardium → vegetations that can damage/destroy heart valves, most commonly caused by bacteria

1. microbes enter bloodstream: dental or surgical procedure, contaminated injection, other source of infection in oral cavity or gut

2. preexisting endothelial injury: congenital heart disease, valve disease, prosthetic valves or implanted devices → inflammatory reaction

3. infective endocardial vegetations formed: → aneurysm, valvular regurgitation, valve perforation, pericarditis