Week 2 Chapters 10, 11, 13, 14 & 15 Study Guide

Alterations in Immune Function: Immune System

-       Defends body against invasion or infection by antigens

-       Patrols for and destroys abnormal or damaged cells

Types of Alterations: Excessive immune response

-       Over- or hyper-functioning of immune system

Types of Alterations: Deficient immune response

-       Ineffective immune response

Excessive Immune Responses Types: Autoimmunity**

-       Immune system attacks own tissues

Cause: abnormal excessive immune responses toward own tissues

-       MHC genes (HLA) appear to increase risk of autoimmune disorders females at higher risk

Excessive Immune Responses Types: Hypersensitivity

-       Describes the mechanism of injury

-       May or may not involve autoimmunity

Both types will eventually lead to inflammation**.

Autoimmunity (Cont.): Treatment

Individualized immunosuppressive therapy

1.     Corticosteroids and cytotoxins (MTX)

2.     Tumor necrosis factor inhibitors and immunomodulators

3.     Therapeutic plasmapheresis

Know all hypersensitivity types, mechanism of pathogenesis with some examples:

Type	Mechanism of Pathogenesis	Key Immune Components	Examples
Type I (Immediate)	Allergen exposure causes IgE production. IgE binds mast cells and basophils. Re-exposure triggers histamine release and inflammation.	IgE, mast cells, histamine	Allergic rhinitis (hay fever), asthma, anaphylaxis, food allergies
Type II (Antibody-Mediated/Cytotoxic)	IgG or IgM antibodies bind to antigens on cell surfaces, leading to cell destruction through complement activation or phagocytosis.	IgG, IgM, complement	Autoimmune hemolytic anemia, transfusion reactions, hemolytic disease of the newborn, Graves disease
Type III (Immune Complex-Mediated)	Antigen-antibody complexes form in circulation and deposit in tissues, activating complement and causing inflammation and tissue damage.	Immune complexes, complement, neutrophils	Systemic lupus erythematosus (SLE), glomerulonephritis, rheumatoid arthritis, serum sickness
Type IV (Delayed-Type/Cell-Mediated)	Sensitized T cells release cytokines or directly attack cells. Reaction occurs 24–72 hours after exposure.	T lymphocytes, macrophages	Contact dermatitis (poison ivy), tuberculosis skin test (PPD), type 1 diabetes mellitus, multiple sclerosis

Treatment for Type I Hypersensitivity or other types**

-       IgE blocker therapy: Inhibits binding of IgE to mast cells (Only for Type I)

-       Antihistamines: Block the effects of histamine

-       Epinephrine: (counter effects of Histamine)

o   Adrenergic agent given subQ or IV during acute allergic reactions

o   Highly allergic people can carry an EpiPen

-       Beta- adrenergics: Decrease bronchoconstriction

-       Corticosteroids: Decrease inflammatory response

-       Anticholinergics: Block parasympathetic system

Understand the mechanisms of the treatment.

Know about Autoimmune disease etiology and treatment: Etiology (causes):

Autoimmune diseases occur when the body’s immune system mistakenly attacks its own healthy cells and tissues because it cannot distinguish “self” from “non-self.”

Know about Autoimmune disease etiology and treatment: Common Risk factors:

Genetic predisposition: Family history increases the risk of developing autoimmune disorders.

Environmental triggers: Infections, toxins, chemicals, smoking, and UV radiation may trigger an abnormal immune response.

Hormonal factors: Many autoimmune diseases are more common in women, suggesting hormones play a role.

Stress: Physical or emotional stress may contribute to disease onset or flare-ups.

Examples of Autoimmune Diseases:

  Rheumatoid Arthritis

  Systemic Lupus Erythematosus

  Type 1 Diabetes

  Multiple Sclerosis

  Hashimoto's Thyroiditis

Know about Autoimmune disease etiology and treatment: Treatment:

There is no cure, so treatment focuses on controlling symptoms, reducing inflammation, and preventing tissue damage.

-       Anti-inflammatory Medications

o   NSAID’s (ibuprofen, naproxen)

o   Reduce pain and inflammation

-       Corticosteroids

o   Ex: Prednisone

o   Suppress immune system activity and decrease inflammation

-       Immunosuppressant Drugs

o   Ex: Methotrexate and Azathioprine

o   Slow the immune attack on healthy tissues

-       Biologic Therapies

o   Target specific immune system components

o   Ex: adalimumab and infliximab

-       Lifestyle Management

o   Healthy diet

o   Regular exercise

o   Stress reduction

o   Adequate sleep

o   Smoking cessation

Classification of Hematologic Neoplasms:

Categories based on the cell type of the neoplasm rather than its location in the body

-       Myeloid lineage: red blood cells, platelets, monocytes, and granulocytes

-       Lymphoid lineage: B cells, T cells, and natural killer (NK) cells

**Anaplasia of leukemia cells would also decide which types of

blood cells would be affected.

Malignant Disorders of White Blood Cells:

-       Leukemia, lymphoma, and plasma cell myeloma (multiple myeloma)—common neoplastic disorders of the bone marrow and lymphoid tissues

Malignant Disorders of White Blood Cells:  Leukemias

-       circulating tumors that primarily involve blood and bone marrow

Malignant Disorders of White Blood Cells: Lymphoma

-       tends to localize in lymph tissues; is often disseminated to other sites at diagnosis

Malignant Disorders of White Blood Cells: Plasma cell myeloma

-       malignant transformation of B-cell plasma cells; likes to form localized tumors in bony structures

Malignant Disorders of White Blood Cells: Plasma cell myeloma

-       malignant transformation of B-cell plasma cells; likes to form localized tumors in bony structures

Malignant Disorders of White Blood Cells: Typical signs and symptoms

-        Malaise, weakness

-       Unexplained fever, night sweats

-        Recurrent infections

-        Enlarged, nontender lymph nodes (lymphadenopathy) with lymphoma and some leukemias

-        Very high total white blood cell counts or the presence of abnormal cell types

Malignant Disorders of White Blood Cells: Most Common Clinical Manifestations**

-       Anemia

-        Thrombocytopenia

-        Leukopenia

o    Neutropenia

Malignant Disorders of White Blood Cells: Principles of Treatment

-       Combination chemotherapy to remove malignant cells (primary)

-        Stem cell transplant to rescue and restore bone marrow function (primary)

-        Radiation and tissue-specific drug therapy may be indicated in some cases

Know all information on the following: ALL, CML, CLL, Multiple Myeloma, Lymphoma (both types): Acute Myeloid Leukemia/AML

-        Abrupt onset of symptoms

-        80% of cases are adults; median age 64 years

-        Bone marrow aspirate must have >20% blasts

-       Prognosis worse for AML than ALL: <50% children and 30% adults survive long term

Know all information on the following: ALL, CML, CLL, Multiple Myeloma, Lymphoma (both types): Acute Lymphoblastic Leukemia/

Lymphoma/ALL: Pathogenesis and Clinical Manifestations

-       primarily a children’s disorder: most common malignancy in children

-       Peak incidence: between 3 and 7 years; 2^nd peak: middle age

-       Symptom onset

o   Abrupt

o   Bone pain, bruising, fever, infection

o   Children may refuse to walk---why? (Hematothrosis)

o   Loss of appetite, fatigue, abdominal pain

o   Enlarged spleen, liver, lymph nodes

o   3% may present with CNS signs

Know all information on the following: ALL, CML, CLL, Multiple Myeloma, Lymphoma (both types): Acute Lymphoblastic Leukemia/Lymphoma/ALL: Prognosis and Treatment

-       85% 5-year survival rate in children; 30% to 50% in adults (Better prognosis in children than adults)

-       Certain forms of ALL more responsive to therapy

-       Chemotherapy for remission induction

Know all information on the following: ALL, CML, CLL, Multiple Myeloma, Lymphoma (both types): Chronic Myeloid Leukemia (CML)**

-       Average age of onset: 40-50 years/Adult

-       Characterized by malignant granulocytes that carry the Philadelphia chromosome (Ph+): Translocation of chromosomes 9 and 22 to creates a new fusion gene: bcr/abl (increases cell proliferation and reduces apoptotic cell death)

-       Usual clinical presentation

o   High granulocyte count on the CBC

o   Splenomegaly

-       Anti-bcr/abl therapy (imatinib): reduce number of leukemic cells with bcr/abl type to undetectable levels

-       CML does not respond well to chemotherapy: poor overall survival time, untreated patients have median survival 2 years

Know all information on the following: ALL, CML, CLL, Multiple Myeloma, Lymphoma (both types): Chronic Lymphoid Leukemia/CLL

Pathogenesis and Clinical Manifestations

-       CLL accounts for 30% of all cases of leukemia in the United States— most common

-       95% are malignant B-cell precursors

o   Follows an indolent course; asymptomatic

o   Usually found by accident in routine blood examinations

-       5% associated with more aggressive T-cell transformation

Pathogenesis and Clinical Manifestations

-       Symptomatic CLL

o   Fatigue, weight loss, anorexia

o   Increased susceptibility to infections

-       Malignant lymphocytes invade lymphoid tissues and bone marrow--disrupts function

o   Enlarged, painless lymph nodes (lymphadenopathy)

o   Enlarged spleen

-       Bone marrow infiltration

o   Reduces production of red blood cells/platelets---s/s??

o   Preponderance of lymphoid cells

Know all information on the following: ALL, CML, CLL, Multiple Myeloma, Lymphoma (both types): Multiple Myeloma, Lymphoma (both types):

Plasma Cell Myeloma (Multiple

Myeloma)

-       Malignant disorder of mature, antibody-secreting B lymphocytes (plasma cells)

-       Occurs exclusively in adults; usually >40 years; median age 65 years

-       Malignant plasma cells invade bone and form multiple tumor sites

-       May also target other tissues, including lymph nodes, liver, spleen, and kidneys

Know all information on the following: ALL, CML, CLL, Multiple Myeloma, Lymphoma (both types): Multiple Myeloma, Lymphoma (both types): PT2

Pathogenesis and Clinical Manifestations

-       Malignant plasma cells produce excessive identical monoclonal antibodies

o   Accumulate in the bloodstream

o   Detected by serum protein electrophoresis

o   Large amount of one type of antibody; forms a characteristic spike

-       Bence Jones protein: malignant plasma cells produce light-chain antibody fragments that accumulate in blood and urine

o   Helps confirm diagnosis

o   Can accumulate in kidneys and damage them

-       Malignant plasma cells tend to accumulate in bone; pathologic fractures common

o   Bone destruction releases calcium into bloodstream hypercalcemia

-       Most clinical manifestation caused by bone/renal damage

Know all information on the following: ALL, CML, CLL, Multiple Myeloma, Lymphoma (both types): Multiple Myeloma, Lymphoma (both types): PT3

Diagnosis based on:

-       Monoclonal antibody peak

-       Presence of Bence Jones protein

-       Hypercalcemia

-       Evidence of bone lesions

Hodgkin Disease

-       Represents about 30% of malignant lymphoma

-       Occurs across life span; half of cases between ages 20 and 40 years

-       Higher incidence in males; also have worse prognosis

-       Overall 5-year survival rate for all stages treated Hodgkin disease: 85%

Hodgkin Disease: Pathogenesis and Clinical Manifestations

-       Malignant disorder of the lymph nodes

o   Characterized by Reed-Sternberg cells

o   Originate from B cells in germinal centers of lymph nodes

§  Malignant but grow/spread in predictable way; sets HD apart from other lymphomas

-       Usually metastasizes along contiguous lymphatic pathways (Predictable metastasis route)

Pathogenesis and Clinical Manifestations

-       Epstein-Barr virus frequently found in genome of transformed Reed-Sternberg cells; may be important in pathogenesis of HD

-       Usually present in single node or localized node chain

-       Inflammatory cells accumulate within node; Reed-Sternberg cells constitute around 2% of cells in lymph node tumor

Pathogenesis and Clinical Manifestations

-       Clinical manifestations depend on origin site and dissemination stage

o   Early stages: often asymptomatic

-       Painless lymphadenopathy; possibly with fever, night sweats, pruritus, weight loss, malaise

Lymph node enlargement above diaphragm, cervical nodes most common site

Hodgkin Disease: Prognosis and Treatment

-       Stage dictates treatment modality

o   Localized tumors: radiation therapy (most common)

-       Disseminated disease: chemotherapy

B-Cell, T-Cell, and NK-Cell Lymphoma (Non-Hodgkin)

-       Do not have Reed-Sternberg cells

-       Majority arise from lymph nodes, but can originate in any lymphoid tissue

-       95% occur in older adults

-       Males somewhat higher risk than females

-       Incidence increasing, esp. in AIDS populations

-       Most arise from B cells, T cells, or NK cells

B-Cell, T-Cell, and NK-Cell Lymphoma (Non-Hodgkin): Prognosis varies according to type

-       Grouped as indolent or aggressive

o   Indolent: longer survival times

o   Aggressive: disseminated at presentation, generally poor prognosis

-       As a group: spread early and unpredictably when compared to Hodgkin’s

B-Cell, T-Cell, and NK-Cell Lymphoma (Non-Hodgkin):  

Pathogenesis and Clinical Manifestations

-       Similar to other malignancies

-       Tumor cells derived from single mutant precursor cell and are clonal

-       Viruses suspected in development of some lymphomas (e.g., Burkitt lymphoma and Epstein-Barr virus)

-       5-year survival rate: 50%

-       Complications include two serious oncologic emergencies

o   Superior vena cava obstruction

o   Spinal cord compression

-       Other complications: infection, bone metastasis, joint effusions

-       Staging and classification same as Hodgkin disease

B-Cell, T-Cell, and NK-Cell Lymphoma (Non-Hodgkin): Prognosis and Treatment

Common therapies:

-       Radiation

-       Chemotherapy

-       Tissue specific therapies: monoclonal antibodies and BMT