Advanced Physiology Chapter 6: Immune System and Leukocyte Function

The Immune System

• The immune system protects the entire body from invading pathogens and detects and kills virus-infected or cancer cells.
• Immune cells and mediators reside in tissues and travel between tissues through circulation and lymphatic vessels, distinguishing between "self" and "nonself" cells.

Three Levels of Protection

• Skin and mucosal barriers: provide physical barriers against pathogens.
• Innate immunity: includes nonselective macrophages and neutrophils that can immediately phagocytose and kill pathogens, as well as the complement system.
• Adaptive immunity: consists of effectors such as B cells and antibody secretion, and cytotoxic T cells, which are promoted by helper T cells.

Cells of Inflammation

• Myeloid cells: include granulocytes (neutrophils, basophils, eosinophils) and agranulocytes (monocytes that become macrophages).
• Lymphoid cells: include B cells and T cells, with T cells further subdivided into many classes.

Mediators of Inflammation

• Histamine: involved in allergic reactions.
• Prostaglandins and leukotrienes: involved in inflammation.
• Cytokines: signaling molecules involved in inflammation and immune responses.
• Chemotactic factors: attract immune cells to sites of inflammation.
• Acute phase proteins: produced in response to inflammation.

Immune Disorders

• Hypersensitivity reactions: overactive immune responses to normally innocuous stimuli.
• Autoimmune disorders: destructive immune responses to self molecules, cells, and tissues.
• Examples: allergy, atopic dermatitis, rheumatoid arthritis, type 2 diabetes mellitus, myasthenia gravis, systemic lupus erythematosus.

Three Lines of Immune Defense

• Barriers: skin and mucous membranes.
• Innate immunity: nonspecific, rapid onset.
• Adaptive immunity: specific, slow onset, long-lasting.

Hematopoiesis

• Myeloid lineage: granulocytes (neutrophils, basophils, eosinophils) and agranulocytes (monocytes that become macrophages).
• Lymphoid lineage: B cells and T cells.

Antecedents of Adaptive Immunity

• Gene rearrangement precedes transcription and translation of B cell receptors (BCR) and T cell receptors (TCR).
• V(D)J recombination: the process of gene rearrangement.

Generation of a BCR/Antibody

• Step 1: Initial heavy (H) and light (L) chain gene structures with many possible segments.
• Step 2: Rearranged genes in final configuration.
• Step 3: Protein product of rearranged gene becomes the B cell receptor, which later becomes the secreted antibody.

Innate Immune Cells

• Neutrophils: most abundant white blood cell, primarily involved in acute inflammation and phagocytosis.
• Mast cells: involved in allergic reactions and inflammation.
• Macrophages: professional phagocytes involved in the removal of foreign substances and apoptotic cells.
• Dendritic cells: involved in antigen presentation to T cells.

Sequence of Acute Inflammation

• Detection of danger: by cellular pattern recognition receptors (PRRs) in tissue and sentinel cells (mast cells and macrophages).
• Activation of sentinel cells: by pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs).
• Recruitment of leukocytes: to the site of inflammation.
• Healing and resolution: of inflammation.

Innate Immune/Antigen-Presenting Cells

• Macrophages and dendritic cells: able to present fragments of phagocytosed antigen to helper T cells.

Complement System

• Recognition of pathogen features: by Toll-like receptors (TLRs), a class of pattern recognition receptors (PRRs).
• Activation of complement proteins: through the classical, alternative, or lectin pathways.
• Membrane attack complex (MAC): forms a pore in the bacterial membrane, leading to lysis.

Chronic Inflammation

• Rheumatoid arthritis: an autoimmune disorder characterized by chronic inflammation in joints, perpetuated by Th1 and Th17 immune responses.

The Immune System

• The immune system protects the entire body from invading pathogens and detects and kills virus-infected or cancer cells.
• Immune cells and mediators reside in tissues and travel between tissues through circulation and lymphatic vessels, distinguishing between "self" and "nonself" cells.

Three Levels of Protection

• Skin and mucosal barriers: provide physical barriers against pathogens.
• Innate immunity: includes nonselective macrophages and neutrophils that can immediately phagocytose and kill pathogens, as well as the complement system.
• Adaptive immunity: consists of effectors such as B cells and antibody secretion, and cytotoxic T cells, which are promoted by helper T cells.

Cells of Inflammation

• Myeloid cells: include granulocytes (neutrophils, basophils, eosinophils) and agranulocytes (monocytes that become macrophages).
• Lymphoid cells: include B cells and T cells, with T cells further subdivided into many classes.

Mediators of Inflammation

• Histamine: involved in allergic reactions.
• Prostaglandins and leukotrienes: involved in inflammation.
• Cytokines: signaling molecules involved in inflammation and immune responses.
• Chemotactic factors: attract immune cells to sites of inflammation.
• Acute phase proteins: produced in response to inflammation.

Immune Disorders

• Hypersensitivity reactions: overactive immune responses to normally innocuous stimuli.
• Autoimmune disorders: destructive immune responses to self molecules, cells, and tissues.
• Examples: allergy, atopic dermatitis, rheumatoid arthritis, type 2 diabetes mellitus, myasthenia gravis, systemic lupus erythematosus.

Three Lines of Immune Defense

• Barriers: skin and mucous membranes.
• Innate immunity: nonspecific, rapid onset.
• Adaptive immunity: specific, slow onset, long-lasting.

Hematopoiesis

• Myeloid lineage: granulocytes (neutrophils, basophils, eosinophils) and agranulocytes (monocytes that become macrophages).
• Lymphoid lineage: B cells and T cells.

Antecedents of Adaptive Immunity

• Gene rearrangement precedes transcription and translation of B cell receptors (BCR) and T cell receptors (TCR).
• V(D)J recombination: the process of gene rearrangement.

Generation of a BCR/Antibody

• Step 1: Initial heavy (H) and light (L) chain gene structures with many possible segments.
• Step 2: Rearranged genes in final configuration.
• Step 3: Protein product of rearranged gene becomes the B cell receptor, which later becomes the secreted antibody.

Innate Immune Cells

• Neutrophils: most abundant white blood cell, primarily involved in acute inflammation and phagocytosis.
• Mast cells: involved in allergic reactions and inflammation.
• Macrophages: professional phagocytes involved in the removal of foreign substances and apoptotic cells.
• Dendritic cells: involved in antigen presentation to T cells.

Sequence of Acute Inflammation

• Detection of danger: by cellular pattern recognition receptors (PRRs) in tissue and sentinel cells (mast cells and macrophages).
• Activation of sentinel cells: by pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs).
• Recruitment of leukocytes: to the site of inflammation.
• Healing and resolution: of inflammation.

Innate Immune/Antigen-Presenting Cells

• Macrophages and dendritic cells: able to present fragments of phagocytosed antigen to helper T cells.

Complement System

• Recognition of pathogen features: by Toll-like receptors (TLRs), a class of pattern recognition receptors (PRRs).
• Activation of complement proteins: through the classical, alternative, or lectin pathways.
• Membrane attack complex (MAC): forms a pore in the bacterial membrane, leading to lysis.

Chronic Inflammation

• Rheumatoid arthritis: an autoimmune disorder characterized by chronic inflammation in joints, perpetuated by Th1 and Th17 immune responses.