Immune System First Line of Defense

Innate Immune Response

• Rapid, early response to microbes
• Non-specific, always the same response
• Involves inflammation, fever, and other mechanisms
• Primarily reacts to microbes
• Relies on phagocytes and antimicrobials
• Includes external physical barriers like skin and mucous membranes
• Easy for microbes to adapt to
• Stimulates adaptive responses

First Line of Defense

• Skin and mucous membranes
• Sebum on skin forms a protective film that inhibits growth of certain microbes
• Mucous can trap microbes which can be then expectorated or sneezed out of the body
• Hairs in nose and respiratory tract trap and sweep microbes away
• Tears and saliva contain lysozyme, an enzyme that breaks down cell walls of some bacteria

Second Line of Defense

• Antimicrobial substances, natural killer (NK) cells, and phagocytes
• Involves activation of the complement system
• Antimicrobial substances include interferons, iron-binding proteins, and antimicrobial proteins

Adaptive Response

• Specific response to specific attributes of an invader
• Develops with exposure to various organisms and substances
• Slower to kick in, develops in response to specific attributes of an invader
• Works with the innate response system to enhance reactivity
• Attacks microbes and antigens
• Generates immunologic memory, leading to a more rapid response upon subsequent exposure

Immune Cells

• Primary cells of adaptive immunity are B-lymphocytes (B-cells) and T-lymphocytes (T-cells)
• Lymphocytes act as regulator cells, assisting in controlling and orchestrating the immune response
• Lymphocytes can identify self from non-self through HLA (Human Leukocyte Antigens)

Acquiring Immunity

• Immunity can be acquired in four ways:
• Active natural immunity: develops through direct exposure to an antigen and the immune system develops antibodies
• Active artificial immunity: develops when the body is purposefully introduced to an antigen and subsequently reacts by developing antibodies (e.g., vaccines)
• Passive immunity: passed from a mother to fetus, to protect the infant during the first few months of life as they develop their own immune system
• Passive artificial immunity: when antibodies are injected from one system to another, used to help fight a current infection if the individual has not been immunized against the specific organism

Auto-Immunity

• Ability to distinguish between self- and non-self antigens is referred to as immunologic self-tolerance
• Auto-immunity is the mounting of an immune response against the body's own tissues
• Can occur when mechanisms fail to eliminate T- or B-cells that fail to differentiate between self- and non-self antigens

Hypersensitivity Reactions

Type I - Anaphylactic Reactions

• Systemic, life-threatening hypersensitivity reaction
• Characterized by itching, generalized flushing, headache, difficulty breathing, and a drop in blood pressure
• Caused by smooth muscle contraction and vascular dilation as a reaction to released mediators
• Common allergens are food, chemicals, insect stings, and drugs

Type II - Antibody-Mediated Hypersensitivity

• Mediated by IgM or IgG, directed against target antigens on cell surfaces or in extracellular tissue
• Commonly involves the formation of antibodies directed against blood cells and their destruction
• Examples:
• Erythroblastosis Fetalis: hemolytic disease that affects neonates, caused by Rh- mother and Rh+ fetus
• Autoimmune Hemolytic Anemia: antibodies produced by a patient's own body are responsible for the hemolysis of erythrocytes
• Blood Transfusion Reactions: triggered by incompatible blood type, manifests as fever, chills, and renal failure due to hemolysis of red blood cells
• Autoimmune Thrombocytopenia (AITP): body produces antibodies that are directed against platelets, manifests as petechiae, purpura, and mucosal bleeding

Type III - Immune Complex Mediated Hypersensitivity

• Mediated by formation of antigen-immunoglobulin complexes, complement fixation, and localized inflammation
• Involves IgM and IgG antibodies
• Examples:
• Arthus Reaction: local response, typically performed for experimental purposes, involves the injection of a foreign substance, resulting in complex formation and localized skin reactions
• Serum Sickness: systemic response, caused by animal serum or drugs, resulting in the formation of an antigen-antibody complex, which gets lodged in small vessels and causes an inflammatory reaction
• Glomerulonephritis: local effects, caused by acute streptococcal infection, resulting in the formation of an immune complex, which is deposited on the glomerular basement membrane, leading to inflammation of the glomerulus
• Polyarteritis Nodosa: systemic effects, characterized by inflammation and necrosis of medium-sized arteries with secondary ischemia of the tissues supplied by the affected blood vessels

Type IV - Delayed or Cell-Mediated Hypersensitivity

• Mediated by specifically sensitized T-lymphocytes
• Manifests as sub-acute or chronic inflammation with infiltration of the tissue by the lymphocytes and macrophages, resulting in variable degrees of necrosis
• Examples:
• Contact Dermatitis: acute or chronic delayed type of hypersensitive response to allergens placed on the skin surface, caused by plants, drugs, cosmetics, dyes, paints, and jewelry
• Graft Rejection: caused by a delayed hypersensitivity reaction, resulting in chronic inflammation and necrosis of the graft