CHAPTER 43 THE BODY’S DEFENSES. Nonspecific mechanisms and general barriers Skin-water proof and impenetrable if unbroken; acidity of sweat and normal.

CHAPTER 43THE BODY’S DEFENSES

Nonspecific mechanisms and general barriers

Skin-water proof and impenetrable if unbroken; acidity of sweat and normal bacteria flora inhibit pathogens

Lysozymes in perspiration, tears and saliva attacks cell walls of many bacteria

Stomach acid kill most bacteria in food

Hair and cilia in

respiratory tracts

traps bacteria

and viruses

Neutrophils-most numerous, attracted by chemical signals, become amoeboid, phagocytic, living only a few days Monocytes-macrophages-larger, longer lived, wander through interstitial fluid, found in connective tissue, lymph nodes, and spleen, interact with T-cells

Eosinophils-enzymes against parasitic worms

Natural killer cells-lyse infected or abnormal cells, similar to cytotoxic T’s but less discriminatory

Basophils (circulating)-and mast cells (in connective tissue) degranulate releasing histamines that cause vasodilation of local capillaries and makes them leakier

Dendritic cells-are a type of blood cell that have the ability to stimulate an immune response against specific targets and are being widely pursued as a new treatment for cancer and viral diseases. Phagocytic, and interact with T & B cells

Cytotoxic T cells killinga cancerous cell

Inflammatory ResponseInjured tissue releases prostaglandins and histamines

that cause basophils and mast cells to release more histamines causing:– Vasodilation of capillaries and increased blood flow– Capillaries to become leakier– Increased metabolic rate and local temperature

rises– Neutrophils become amoeboid and leave capillaries

and begin to phagocytize– Monocytes become macrophages and move into

the area and begin phagocytizing then become antigen presenting cells and release interleukin 1 to attract T cells

-- Dendritic cells phagocytize and present antigens to T & B cells

Inflammatory Response• Toxins and pyrogens cause fever

• Various chemicals released cause pluripotent stem cells to divide more rapidly

• Natural killers in area check locals cell’s MHC I’s for antigens

• Viral infected cells release interferon

• Complements stick to pathogens and lyse or induce opsonization

• T lymphocytes and B lymphocytes are alerted and move into the area

Phagocytosis by a macrophage

Clonal Selection-the antibodies of eachB cell only recognize certain antibodies but collectively they should recognize any antigen

B lymphocyte

Cytotoxic T perforating acell

Specific defense mechanisms IMMUNE RESPONSE

1. Macrophages phagocytize pathogen; attach a piece to their MHC-II’s and release interleukin I to attract Helper T’s2. Helper T's confirm antigen and divide forming memory and active helper T’s 3. Active Helper T’s also secrete interleukin II that causes: a. macrophages to go and attack more pathogens b. Cytotoxic T's check cells in the area for antigens on their MHC-I's When they find one they divide forming memory and active cells which: 1. release lymphokines to attract more macrophages 2. release perforins-kill infected cells 3. release interferon

Specific defense mechanisms c. Meanwhile; the interleukin II also alerts B-cells to check antigens on activated helper T’s antigen receptors for fit with their preformed antibodies 1. B cell which fits checks with Helper T 2. Helper T secretes interleukins which causes B cell to proliferate 3. B cell divides to form plasma cells and memory cells 4. rearrangement of the antibody DNA for perfect fit antibody

Specific defense mechanisms4. Antibody Functions a. Agglutination–stick to antigens, clump pathogens together b. Neutralization–interfere with life functions of pathogens c. Precipitation of soluble d. Activation–join with complement to lyse pathogen e. Opsonization–attract macrophages to phagocytize pathogens5. suppressor T's release interleukin 10; slow down the immune system after the infection is killed off

Some people overreact to specific allergens and produce IgE antibodies that stick to the membranes of mast cells. Then when the allergen attaches to the IgE it causes the mast cell to degranulate and release histamines.

Arthritis

T cell infected with HIV

Close-up of T cell infected with HIV

HIV budding

Neutrophil phagocytizing a bacteria

Mold that is a

common allergen

Monoclonal Antibodies

Myelomacells

Rh factor• When an Rh+ fetus is carried by an Rh- mother,

during birth or the last few days before birth, some Rh+ blood can go into the mother’s body and she will make antibodies against it. That child will not have a problem because it is born before the antibodies are produced. However any subsequent Rh+ fetus will get antibodies form the mother that will attack its blood resulting in hemolytic anemia and death.

• To prevent this problem, Rh- mothers are given an injection of Rhogan that contains small amounts of Rh+ antibodies two or three times during their pregnancies.

• Anaphylactic shock-a severe systemic allergic reaction to an antigen; causes rapid drop in blood pressure and often death

• Cyclosporine-the best antirejection drug; only affects cytotoxic T cells

T cells contribute to the immune defenses in two major ways. Regulatory T cells are vital to orchestrating the elaborate system. (B cells, for instance, cannot make antibody against most substances without T cell help). Cytotoxic T cells, on the other hand, directly attack body cells that are infected or malignant. Chief among the regulatory T cells are "helper/inducer" cells. Typically identifiable by the T4 cell marker, helper T cells are essential for activating B cells and other T cells as well as natural killer cells and macrophages. Another subset of T cells acts to turn off or "suppress" these cells. Cytotoxic T cells, which usually carry the T8

marker, are killer cells. In addition to ridding the body of cells that have been infected by viruses or transformed by cancer, they are responsible for the rejection of tissue and organ grafts. (Although suppressor/ cytotoxic T cells are often called T8 cells, in reality the two are not always synonymous. The T8 molecule, like the T4 molecule, determines which MHC molecule-class I or class II-the T cell will recognize, but not how the T cell will behave.)

T cells work primarily by secreting substances known as cytokines or, more specifically, lymphokines. Lymphokines (which are also secreted by B cells) and their relatives, the monokines produced by monocytes and macrophages, are diverse and potent chemical messengers. Binding to specific receptors on target cells, lymphokines call into play many other cells and substances, including the elements of the inflammatory response. They encourage cell growth, promote cell activation, direct cellular traffic, destroy target cells, and incite macrophages. A single cytokine may have many functions; conversely, several different cytokines may be able to produce the same effect.

One of the first cytokines to be discovered was interferon. Produced by T cells and macrophages (as well as by cells outside the immune system), interferons are a family of proteins with antiviral properties. Interferon from immune cells, known as immune interferon or gamma interferon, activates macrophages. Two other cytokines, closely related to one another, are lymphotoxin (from lymphocytes) and tumor necrosis factor (from macrophages). Both kill tumor cells; tumor necrosis factor (TNF) also inhibits parasites and viruses.

Many cytokines are initially given descriptive names but, as their basic structure is identified, they are renamed as "interleukins"-messengers between leukocytes, or white cells. Interleukin-1, or IL-1, is a product of macrophages (and many other cells) that helps to activate B cells and T cells. IL-2, originally known as T cell growth factor, or TCGF, is produced by antigen-activated T cells and promotes the rapid growth or differentiation of mature T cells and B cells. IL-3 is a T-cell derived member of the family of protein mediators known as colony-stimulating factors (CSF); one of its many functions is to nurture the development of immature precursor cells into a variety of mature blood cells. IL-4, IL-5, and IL-6 help B cells grow and differentiate; IL-4 also affects T cells, macrophages, mast cells, and granulocytes.