9.2 From notes - Body defense

• The human body has the ability to resist nearly all types of organisms or toxins that damage tissues and organs through immunity.
• Immunity can be classified into innate immunity and acquired immunity.

Innate Immunity (Natural Immunity)

• Innate immunity doesn't develop after the body is first attacked by a specific organism or toxin, instead it results from general processes.
• Key components include phagocytosis by white blood cells and macrophages, destruction of swallowed organisms by stomach acid, skin resistance, and blood chemicals/cells.
• Lysozyme attacks and dissolves bacteria.
• Basic polypeptides inactivate some gram-positive bacteria.
• The complement complex destroys bacteria.
• Natural killer lymphocytes recognize and eliminate foreign and tumor cells.
• Innate immunity provides resistance to certain animal diseases.

Acquired (Adaptive) Immunity

• Acquired immunity is the ability to develop immunity against individual invading agents.
• It is caused by an immune system that forms antibodies and/or activated lymphocytes that attack and destroy the specific invader.
• Immunization is a crucial process for protection against diseases and toxins.
• Humoral immunity (B-cell immunity) involves circulating antibodies produced by B lymphocytes.
• Cell-mediated immunity (T-cell immunity) is achieved through activated T lymphocytes in lymph nodes that directly destroy foreign agents.
• Both antibodies and activated lymphocytes are formed in the lymphoid tissues.

Antigens

• Essential to acquired immunity as they trigger it by being recognized as foreign.
• Antigens are generally proteins or large polysaccharides.
• Antigenic substances typically need a high molecular weight (8000 or more) and regularly recurring molecular groups (epitopes) on their surface.

Lymphocytes

• Lymphocytes are the basis of acquired immunity; their absence prevents its development.
• They are located extensively in lymph nodes and other lymphoid tissues.
• Lymphocytes are divided into two major populations: T lymphocytes (cell-mediated immunity) and B lymphocytes (humoral immunity).
• Both T and B lymphocytes originate from hematopoietic stem cells in the embryo.
• T lymphocytes are preprocessed in the thymus gland.
• B lymphocytes are preprocessed in the liver during mid-fetal life and in the bone marrow later in fetal life and after birth.

Preprocessing of T and B Lymphocytes

• Lymphocyte stem cells require differentiation in processing areas to form activated T lymphocytes or antibodies.
• T lymphocytes migrate to the thymus, divide rapidly, and develop specificity against a single antigen.
• The thymus ensures released T lymphocytes will not react against self-antigens.
• B lymphocytes differ by secreting antibodies and have even greater diversity.
• After preprocessing, both T and B lymphocytes migrate to lymphoid tissue.

Lymphocyte Clones and Antigen Specificity

• When specific antigens contact T and B lymphocytes in lymphoid tissue, some become activated.
• Each preformed lymphocyte forms only one type of antibody or T cell with a single specificity.
• Upon activation, a specific lymphocyte reproduces, forming a clone of identical lymphocytes.
• The diversity of lymphocyte clones arises from random recombination of gene segments during preprocessing.
• Each lymphocyte clone responds to a single type of antigen due to specific antibody molecules on B cells and surface receptor proteins on T cells.

Mechanism of Lymphocyte Clone Activation

• Macrophages in lymphoid tissue phagocytize and partially digest invading organisms, releasing antigenic products.
• Macrophages present antigens directly to lymphocytes, activating specific clones.
• Macrophages secrete interleukin-1, which promotes lymphocyte growth and reproduction.
• T-helper cells secrete lymphokines that enhance B cell activation and antibody production.

B-Lymphocyte System: Humoral Immunity and Antibodies

• Dormant B lymphocyte clones are activated upon entry of a foreign antigen, with macrophages presenting the antigen to B lymphocytes and T cells.
• Activated T-helper cells contribute to B lymphocyte activation.
• B lymphocytes specific for the antigen enlarge into lymphoblasts, which then differentiate into plasmablasts.
• Plasmablasts mature into plasma cells, which produce gamma globulin antibodies (immunoglobulins) at a rapid rate.
• Some lymphoblasts form memory cells, long-lived B lymphocytes of the same specific clone.
• Subsequent exposure to the same antigen triggers a faster and more potent secondary antibody response due to memory cells, which is the basis for multiple doses in immunization.
• Activated B lymphocytes differentiate into short-lived (rapid protection, apoptosis after a few days) and long-lived plasma cells.
• Long-lived plasma cells reside in tissues like bone marrow and gut-associated lymphoid tissue and can continue producing antibodies for years, which provides lifelong immunity.

Nature of Antibodies (Immunoglobulins)

• Antibodies are gamma globulins called immunoglobulins (Igs), constituting about 20% of plasma proteins.
• Immunoglobulins are composed of light and heavy polypeptide chains.
• Each chain has a variable portion (antigen binding) and a constant portion.
• Light and heavy chains are held together by noncovalent and covalent (disulfide) bonds.
• Specificity of antibodies results from the unique amino acid arrangement in the variable portions.
• Binding between antibody and antigen is rapid, tight, and strong due to different types of bonding.
• IgG antibodies have two variable antigen-binding sites, making them bivalent.
• The five general classes of antibodies are IgM, IgG, IgA, IgD, and IgE.
• IgG is bivalent and makes up about 75% of antibodies being important for normal immunity.
• IgE is a small percentage, is involved in allergies.
• IgM is a large share in primary response, has 10 binding sites, so is therefore effective against invaders.

Mechanisms of Action of Antibodies

• Antibodies protect the body through: direct attack on the invader and activation of the complement system.
• Direct action of antibodies is due to their bivalent nature, causing agglutination, precipitation, neutralization, and lysis.

Complement System for Antibody Action

• The complement system enhances antibody and phagocytic cell actions in neutralizing pathogens, removing damaged cells, and promoting inflammation.
• It consists of about 20 proteins, including 11 principal proteins (C1-C9, B, D) present in plasma and tissue spaces.
• The enzyme precursors are normally inactive but can be activated by the classical pathway, initiated by an antigen-antibody reaction.
• Important effects of the complement system include opsonization, lysis via the membrane attack complex, agglutination, neutralization of viruses, chemotaxis, activation of mast cells and basophils, and inflammatory effects.

T-Lymphocyte System: Activated T Cells and Cell-Mediated Immunity

• Upon antigen exposure, specific T lymphocyte clones proliferate and release activated T cells into the lymph.
• T-lymphocyte memory cells are also formed upon antigen activation.
• Subsequent exposure to the same antigen results in a faster and more powerful activated T cell release.
• T cell responses are highly antigen-specific.
• T lymphocytes respond to antigens only when bound to MHC proteins on the surface of antigen-presenting cells (APCs) in lymphoid tissues.
• Major types of APCs are macrophages, B lymphocytes, and dendritic cells (most potent).
• MHC proteins bind peptide fragments of degraded antigen proteins inside APCs and transport them to the cell surface.
• MHC I proteins present antigens to cytotoxic T cells, while MHC II proteins present antigens to T-helper cells.
• Antigens on APC surfaces bind to receptor molecules on T cell surfaces (T-cell receptors).

Different Types of T Cells and Their Functions

• Three major groups of T cells exist: T-helper cells, cytotoxic T cells, and regulatory T cells (suppressor T cells).
• T-helper cells are the most numerous (over 75%).
• They serve as major regulators of immune functions by forming lymphokines.
• Naïve CD4+ T-helper cells can differentiate into subsets (TH1, TH2, TH17) that produce different lymphokines.
• HIV inactivates or destroys T-helper cells, leading to AIDS and severe immunodeficiency.
• Cytotoxic T cells (killer cells) are direct attack cells capable of killing microorganisms and some of the body's own cells.
• Receptor proteins on CD8+ cytotoxic cells bind tightly to target cells with the appropriate antigen.
• They kill by secreting perforins into the target cell membrane and releasing cytotoxic substances directly into the cell.
• Regulatory T cells (suppressor T cells) are capable of suppressing the functions of both cytotoxic and T-helper cells.
• CD4+ regulatory T cells prevent excessive immune reactions by cytotoxic cells.

Tolerance of Acquired Immunity System to the Body's Own Tissues

• The immune system normally recognizes the body's own tissues.
• Most tolerance develops during the preprocessing of T lymphocytes in the thymus and B lymphocytes in the bone marrow (clone selection).
• Failure of the tolerance mechanism causes autoimmune diseases.
• Examples of autoimmune diseases include rheumatic fever, glomerulonephritis, myasthenia gravis, multiple sclerosis, and systemic lupus erythematosus (SLE).

Immunization by Injection of Antigens

• Immunization is used to produce acquired immunity against specific diseases.
• Methods include injecting: dead organisms, chemically treated toxins (toxoids), and live, attenuated organisms.

Passive Immunity

• Passive immunity provides temporary immunity by infusing antibodies or activated T cells from another immunized individual or animal.
• Transfused antibodies last for 2-3 weeks.

Allergy and Hypersensitivity

• Allergy or other immune hypersensitivity can be an undesirable side effect of immunity.
• Allergy caused by activated T cells is a delayed-reaction allergy.
• It involves substances like poison ivy toxin that cause formation of activated helper and cytotoxic T cells upon repeated exposure.
• Atopic allergies are associated with excess IgE antibodies and occur in people with a genetic allergic tendency.
• Allergen: Is an antigen that reacts specifically with a specific type of IgE reagin antibody.
• IgE antibodies attach to mast cells and basophils in large quantities.
• When an allergen binds to IgE antibodies on a mast cell or basophil, it causes an immediate change, leading to rupture or release of special agents.
• Anaphylaxis is a widespread allergic reaction occurring when a specific allergen is injected directly into circulation.
• Urticaria (Hives) are localized anaphylactoid reactions in specific skin areas upon antigen entry.
• Hay Fever is an allergen-reagin reaction in the nose.