Defenses mechanisms (Immunity) The human body has the ability to resist almost all types of organisms or toxins that tend to damage the tissues. This capacity is called immunity. Body defense against potential pathogens can be grouped in 2 categories: - Innate immunity. - Adaptive immunity.

quick to develop highly targeted, INNATE IMMUNITY antigen non-specific ADAPTIVE IMMUNITY Antigen specific highly targeted, exhibit memory.

Innate immunity a- External defenses:- Inherited, and represent first line of defense. a- External defenses:- * Skin: acts as a physical barrier to penetration by pathogens. * Digestive tract: includes the high acidity of stomach and protection by normal bacteria in colon. * Respiratory tract: include secretion of mucus, movement of mucus by cilia, alveolar macrophages. * Genitourinary tract: include acidity of urine and vaginal lactic acid.

b- Internal defense:- I- Phagocytic cells II- Natural killer cell III- Interferons IV- Endogenous pyrogens

I- Phagocytic cells: There are 3 major groups of phagocytic cells:- - Neutrophils - Monocytes in blood and macrophages (derived from monocytes) in the connective tissues. - Organ specific phagocytes in the liver (kupffer cells), spleen, lymph nodes, lung and brain (microglia).

II- Natural Killer cell lymphokines kills transformed and malignant cells kills malignant cells IFN IFN IL2 IL2

III- Interferons They inhibit replication of viruses. - Alpha and beta interferons can be produced from all cells of the body, - Gamma interferon is produced only by particular lymphocytes and natural killer cells. Alpha interferon is now being used to treat hepatitis C.

IV- Endogenous pyrogen (as interleukin-1, interleukin-6 and tumor necrosis factor) secreted by leukocytes and other cells  produces fever, increased sleepiness and a fall in plasma iron concentration  inhibit bacterial activity.

Adaptive (acquired) immunity It is the ability of human body to develop antibodies and sensitized lymphocytes against individual invading agents such as bacteria, viruses, and toxins. specific highly targeted, exhibit memory

It is of two types 1-Humoral immunity: by circulating antibodies 2-Cell-mediated immunity: by activated lymphocytes

Development of the immune system: During fetal development, lymphocytes precursors come from the bone marrow and mature in 2 sites (1)Thymus gland In this gland, Thymopoietin transfere the lymphocytes precursors into T-lymphocytes  responsible for cellular immunity

(2) Fetal liver and spleen In which the lymphocytes precursors are transformed into B-lymphocytes The B-lymphocytes differentiate into plasma cells (Humoral immunity) and memory B-cells After development the 2 types (T & B) migrate to the lymph nodes and bone marrow

Bone marrow lymphocytes precursors T-lymphocytes Bone marrow lymphocytes precursors Cellular immunity Humoral immunity B-lymphocytes (liver-spleen) (Thymus) Memory T-cells Cytotoxic T-cell (T8) Helper T-cell (T4) Supressor T-cell Stimulation (+) Inhibition (-) Plasma cells Memory B-cells Stim. (+) Inh. (-)

Activation of a clone of lymphocytes When bacterial or other foreign antigens first enter the body ingested by the macrophages  exposure part of the ingested antigen (antigen presentation) on their surfaces . Then these macrophages contact the lymphocytes  activation of helper-T4 cells  secrete lymphokines  proliferation and transformation of B-lymphocytes into plasma cells and memory B-cells or activation of clone of T-lymphocytes and memory T-cells

Humoral immunity The plasma cells secrete large amount of specific antibodies (immunoglobulins) Plasma cells produce about 2000 antibody protein/sec.

Immunoglobulins: Structure: Their basic components are 4 polypeptide chains 2 long (heavy) and 2 short (light) joined by disulfide bridges It has 3 sites - Antigen-binding sites (the variable portion) - Complement binding (the constant portion) - Macrophage binding sites

Types of immunoglobulins (1) IgG Highest blood concentration (73%). Low M.W 160.000 It can cross capillary walls and placenta to reach the fetal circulation and give the fetus passive immunity during early life Responsible for formation anti-Rh antibodies.

(2) IgM It can not cross capillary or the placenta - 7% of serum antibodies High M.W (macroglobulin) = 900.000. It is made of 5 immuno-globulins units linked by disulphide bonds to provide 10 combining sites It can not cross capillary or the placenta It is responsible for ABO system antibodies

(3) IgA - 19% of serum antibodies - Low M.W 170.000 - It is present in the mucous membrane and secretion of the body as respiratory tract secretion, nasal secretion, saliva, tears, intestinal secretion and clostrum of the breasts producing localised protection

(4) IgE (5) IgD -Very low serum level -M.W 190.000 - It is responsible for immediate hypersensitive reactions as in bronchial asthma, hay fever and urticaria. It also increased in parasitic infestations. (5) IgD - Trace amount & its function are unknown

Functions of T lymphocytes in cellular immunity T lymphocytes provide specific immune protection without secreting antibodies. This is provided by the 4 populations of T lymphocytes:- 1- The killer (cytotoxic) cells 2- The helper T lymphocytes 3- The Suppressor T lymphocytes 4- Memory T cell

1- Cytotoxic T8 lymphocytes They must be in physical contact with victim cells. Then they secrete perforins and lysosomal enzymes that enter victim cells and destruct them. Killer T cells defend against viral and fungal infections and are responsible for transplant rejection reactions.

2- Helper-T4 cells (75%) - They increase the activation of T & B cells by interleukin II secretion - They activate macrophage system -The causative virus of AIDS, destroy these cells causing cell immune deficiency

3- Suppressor T8 cells - They suppress the function of B and other T cells so called regulatory T cells - The helper T cells activate the suppressor T cells, which in turn suppress the helper (negative feed-back). - They play a role in limiting the immune system to prevent the autoimmunity

4- Memory T cells They are responsible for the second response of the same antigen, which occur more rapidly and powerful than the first response

Secondary immune response The memory T & B cells persist in the body for years and readily converted to effector cells by exposure to the same antigen  more rapid and greater immune response as in vaccination.

Tissue transplantation T-lymphocytes of the recipient develops immune response to these tissue grafts and rejection occurred. So the patient uses some drugs to depress the cytotoxic T-cells and inhibit helper T-cells e.g., Glucocorticoids Autoimmune disease The body may produce an immune response against it’s own proteins

Acquired immunodeficiency syndrome (AIDs) Human immunodeficiency virus (HIV-retro virus) attacks the helper (T4) lymphocytes blocking its effect on proliferation of T8 cytotoxic and B-cells  loss of immune function  death from mild infections