Bio 20.2 Biology: Innate Defenses

External Innate Defenses

• Mucin is a protein that dissolves in water to form mucus, which traps pathogens in the respiratory, digestive, and urogenital tracts.
• Lysozyme is an enzyme that kills bacteria by disrupting bacterial cell walls and is secreted into saliva, tears, and respiratory mucus.
• Defensins are peptides produced by epithelial cells and immune cells that destroy pathogens (bacteria, viruses, fungi).
• Dermcidin is a peptide found in sweat that kills bacteria and fungi.
• Cilia on cells of the upper respiratory tract sweep mucus and trapped pathogens upward toward the mouth, where they can be swallowed and destroyed by gastric juice.
• Tears and saliva wash pathogens from the eyes and oral cavity.
• Urine flow helps remove pathogens from the lower urinary tract.

Internal Innate Defenses

• Pathogens that evade external defenses are met by internal defenses.
• Internal defenses are not specific to pathogens but respond to a broad range of microorganisms and harmful substances.
• Pattern recognition receptors (PRRs) on body cells bind to pathogen-associated molecular patterns (PAMPs) present on microorganisms and viruses.
• Binding of PAMPs to PRRs activates internal innate defenses.

Internal Innate Defenses: Leukocytes

• Macrophages (derived from monocytes) and neutrophils both engage in phagocytosis, engulfing and destroying pathogens.

Adaptive Immunity

• Adaptive immunity is specific to particular pathogens and relies on cell-mediated immunity and humoral immunity.
• Pathogens possess distinct antigens, which are molecules that trigger an immune response by being recognized as foreign.
• T lymphocytes (T cells) and B lymphocytes (B cells) have surface receptors that bind to specific antigens.
• Each lymphocyte possesses numerous antigen receptors with the same specificity, allowing it to recognize and respond to only one specific antigen.
• Naïve lymphocytes are mature lymphocytes that have not encountered antigens.
• Activation of naïve lymphocytes is required for them to fight an invader.
• This activation happens only to lymphocytes with receptors that bind the invader's antigen.
• Clonal selection occurs when an activated lymphocyte proliferates to form a large number of identical cells.
• This process ensures that only cells capable of responding to a specific antigen are replicated.

Adaptive Immunity: Primary and Secondary Immune Responses

• Effector cells immediately combat the pathogen that stimulated clone production.
• Memory cells are long-lived cells held in reserve for future responses.
• The initial response to a new pathogen is a primary immune response.
• Subsequent responses to the same pathogen are secondary immune responses.
• Memory cells are responsible for immunological memory, making subsequent responses faster and more effective.

Antigen Presentation

• Lymphocyte activation requires recognition and binding of foreign antigens to B-cell and T-cell receptors.
• B-cell receptors can bind unaltered, isolated antigens.
• T-cell receptors recognize antigens only when they are presented on the surface of cells in association with major histocompatibility complex (MHC) proteins.
• This process is called antigen presentation.
• There are two classes of MHC proteins: MHC I and MHC II.
• MHC I proteins are present on all nucleated cells, while MHC II proteins are found only on antigen-presenting cells (APCs), which include dendritic cells, macrophages, and B cells.
• MHC I molecules display fragments of antigens produced within the cell presenting them.
• MHC II proteins display fragments of foreign antigens taken into APCs via phagocytosis.

Cell-Mediated Immunity

• Cell-mediated immunity defends against intracellular pathogens, cancer cells, and foreign cells through the activity of various T cells.
• Cytotoxic T (TC) cells (CD8+ cells) are effector cells that directly destroy infected or abnormal cells.
• T cell activation requires interactions between naïve T cells and APCs.
• Helper T (TH) cells (CD4+ cells) become activated when presented with a foreign antigen in association with MHC II on an APC.
• Activated TH cells replicate to form a clone of effector cells.
• TH cells stimulate APCs to present co-stimulatory molecules to TC cells, completing TC cell activation.
• Activated TC cells are stimulated by cytokines (secreted by TH cells) to divide and form a clone of effector and memory cells.
• TC effector cells release cytotoxins to induce apoptosis in cells displaying the targeted antigen.
• Regulatory T (TReg) cells suppress the immune response, preventing overactive responses that could damage healthy tissues.

Phagocytosis

• Phagocytes (immune cells) engulf pathogens or other materials and enclose them in vesicles called phagosomes.
• Hydrogen ions are pumped into phagosomes, acidifying them.
• Acidified phagosomes fuse with lysosomes, forming phagolysosomes.
• Phagolysosomes contain hydrolytic enzymes that digest and destroy the engulfed material.

Other Immune Cell Functions

• Macrophages activate lymphocytes involved in adaptive immunity.
• Neutrophils undergo degranulation, releasing defensive substances like antimicrobial molecules (defensins) and cytokines.
• Natural killer (NK) cells induce virus-infected and cancer cells to undergo apoptosis.
• Mast cells, basophils, and eosinophils participate in inflammatory responses, defense against parasites, and allergic reactions.
• Mast cells release histamine, leading to vasodilation and increased capillary permeability.

Antimicrobial Proteins

• Interferons are proteins produced by virus-infected cells that interfere with viral replication and regulate leukocyte activity.
• Complement is a system of over 30 proteins that enhance phagocyte efficiency, regulate inflammation, and form membrane attack complexes (MACs) that lyse pathogens.

Adaptive Immunity

• Adaptive immunity is specific and targets particular pathogens.
• Pathogens possess distinct antigens, molecules that trigger an immune response by being recognized as foreign.
• Adaptive immunity relies on lymphocytes: T lymphocytes (T cells) and B lymphocytes (B cells).
• T and B cells have surface receptors that bind to specific antigens.
• Naïve lymphocytes are mature lymphocytes that haven't encountered their specific antigens.
• Upon activation, naïve lymphocytes proliferate to form a clone of identical cells. This process is called clonal selection.
• Clones differentiate into effector cells that combat pathogens and memory cells that are held in reserve.

Cell-Mediated Immunity

• Cytotoxic T (TC) cells destroy infected or abnormal body cells.
• Helper T (TH) cells become activated when presented with a foreign antigen in association with MHC II on an antigen-presenting cell (APC).
• Activated TH cells replicate and form a clone of effector cells.
• TH cells stimulate APCs to present co-stimulatory molecules to TC cells, completing their activation.
• Activated TC cells release cytotoxins to induce apoptosis in cells displaying the targeted antigen.
• Regulatory T (TReg) cells suppress overactive immune responses.

Humoral Immunity

• Humoral immunity involves B cells and antibodies.
• Antibodies are secreted by activated B cells.
• Humoral immunity is also known as antibody-mediated immunity.
• B cell antigen receptors have the same structure as antibodies but are anchored to the B cell membrane.
• Some antigens activate B cells directly, while most require TH cell participation.
• B cells act as APCs, presenting antigens to TH cells, leading to their activation.
• Activated B cells differentiate into plasma cells, which secrete antibodies.
• Antibodies facilitate innate immunity by activating complement and acting as opsonins.

Autoimmunity

• The immune system normally distinguishes between self-antigens and foreign antigens.
• Autoreactive lymphocytes are eliminated or inactivated during development.
• Autoimmunity occurs when the immune system attacks self-antigens, resulting in autoantibodies and autoreactive TC cells.
• Autoimmune diseases can lead to the destruction of healthy cells.