ePathoPlusPage

Immune Dysfuntion

Outline

A. Infectious Mononucleosis

    1. caused by Epstein Barr virus (EBV) which infects B
    lymphocytes of oropharyngeal tissue

B. Agranulocytosis (decrease in granulocytes, mostly neutrophils)

    a.Causes

        1. cancer chemotherapy

        2. irradiation

        3. aplastic anemia

        4. drug related suppression of bone marrow

        5. infections

        6. autoimmune disorders

  C. Leukemia

    1.characterized by diffuse replacement of bone marrow with leukemic cells, (white blood cell precursors in the bone marrow that have become cancerous).The cancerous cells monopolizes resources in  bone marrow, leading to a decrease in other elements: red blood cells, (causing anemia) other wbc's (causing increased suceptibiity to infection) and platelets (causing thrombocytopnia).

        a. Acute Myelogenous Leukemia (AML)- myeloid precursor cell
        beomes cancerous

        b. Acute Lymphocytic Leukemia (ALL) - lymphoid precursor cell
        becomes cancerous

D. Lymphomas (cancer occuring in lymphatic tissue)

    1. Hodgkins

        a. about 40% of malignant lymphomas

        b. characterized by painless, progresive enlargement of lymphoid
        tissue, usually a single node or group of nodes

        c. diagnosis made by presence of Reed Sternberg Cells

    2. Non Hodgkins Lymphoma   

        a. involves more lymph nodes in early stages than Hodgkins and spreads more easily to other tissue sof the body

        b. viral etiology suspected

        c. affects humoral response > then cellular response

E. Multiple Myeloma

    a. a plasma cell cancer of osseous tissue, leading to uncontrolled proliferation of immunoglobulin, usually IgG or IgA

    b. Bence jones proteins present in urine

F. Autoimmune Diseases

    a. Mechanisms

        1. alterations in antigen, T Cell receptor and MHC Interactions

        2. disorders of immune regulatory or surveillance function

            a. e.g. multiple sclerosis in which there is a disordered ratio of helper to suppressor T cells

        3. Molecular mimicry

     a. a foreign antigen closely resembles a self antigen, so that antibodies produced against the foreign antigen attack self  antigens, e.g. rheumatic fever

    b. Systemic Lupus Erythematosus (SLE)

        1. discoid vs systemic

        2. ANA (aninuclear antibodies)

        3. systemic can involve

            1. skin

            2. joints

            3. kidneys

            4. circualtory vessels

            5. eye

            6. neurological system

            7. gastrointestinal system

    c. Polymyositis (dermatomyositis)

        1. inflamatory dx of striated muscle

    d. Scleroderma (Progressive systemic sclerosis)

        1. involves connective tissue throughout body

    e. Sjorgen's Syndrome

        1. chronic inflamatory disorder affecting lacrimal and parotid glands

    f. Rheumatoid arhtritis

        1. chronic systemic disease, often manifesting as inflammation of joints

G. Hypersensitivity Reactions

Type I. IgE Mediated Sensitivity Reaction

Discussion

  Immune system disorders can be characterized as either under reaction or over reaction to antigen or self antigen. In the case of an antigen: over reaction results in hypersensitivity disorders, wheras under reaction results in infection. In the case of self antigens (i.e. normally occuring proteins on the surface of one's own cells): over reaction results in autoimmune disease wheras under reaction (failure of immune surveillance) results in cancer.
    A great number of factors can influence the immune system. Age is an important factor. In newborns the immune system is still immature, suppressor T cells are high. As one ages you get an involution of the thymus affecting maturation of T cells and you get quantitiative and qualitative decreases in cellular immunity. Genetics plays a role. There are obvious genetic disorders, many of which result in immune deficiency disorders because of the inability of the body to produce one or more immune elements. For example,  Bruton's Hypogammagloulinemia is an X linked genetic disorder resulting in a deficiency of B cells. Severe combined immunodeficiency syndrome (SCID) is a defect in the ability to produce both T and B cells. Gender plays a role. Females (perhaps because of the stimulatory effect of estrogens on the immune system) have a higher rate of autoimmune diseases than do males. Temperature is a factor. Lymphocytes perform best at 40 degrees centigrade. Sleep wake cycles play a role. Sleep deprivation decreases the ability of neutrophils to phagocytize. Cortisol, produced in greatest amounts at 5AM suppresses immune functioning. Nutrition plays a role, both malnutrition and obesity increases the incidence of infectious diseases. Finally, stress and emotions can either decrease or increase the immune response through two way communication with endorphins and through stimulation of the hypothalmic- pituitary- adrenal axis.

Clinically  

The treatment for refractory leukemia is a bone marrow transplant. Because the leukemic cells reside in the bone marrow, total irradiation of the bone marrow is done in order to fully destroy all the leukemic cells. Of course, total irradiation also kills the normal elements including the plurioptential stem cells. An individual could not survive long without the pluriopotential stem cell which is needed to continuously replace the formed elements of the ciculatory system, so this procedure cannot be done unless a well matched transplant of bone marrow from a donor is standing by. Donation requires the removal of a small amount of bone marrow from a healthy individual who is a good HLA match to the recipient. General anesthesia is usually administered to the donor and the bone marrow is removed from the iliac crest (or some other suitable bone). The donor can quickly replace the lost bone marrow. The bone marrow from the donor is then infused (via a peripheral line) into the recipient. The cells of the bone marrow immediately head for the bone marrow of the recipient and begin making new rbc's, wbc's and platelets. A frequent complication of this procedure is Graft versus Host Disease, in which the graft (basically a transplanted immune system) begins to attack the hosts own tissue because of HLA tissue incompatibility (it is almost impossible to get a perfect match).This is the reverse of what usually happens when an organ other than bone marrow is transplanted- in these cases the hosts immune system attacks the graft. Graft versus host disease causes pruritic maculopapular rash on the soles and palms but often extending to the entire surface of the body, it may also cause bloody diarrhea, abdominal pain and involve the liver leading to bleeding diorders and coma. Treatment with immunosuppressive drugs such as cyclosporine is often effective.