InnateImm_

Innate Immunity

Nonspecific Defenses of the Host

• First Line of Defense:

  • Intact skin

  • Mucous membranes and their secretions

  • Normal microbiota

  • Toll-like receptors

  • Specialized lymphocytes: T cells and B cells

  • Antibodies

• Second Line of Defense:

  • Phagocytes: Neutrophils, eosinophils, dendritic cells, macrophages

  • Inflammation

  • Fever

  • Antimicrobial substances

• Third Line of Defense:

  • Adaptive immunity and specifically targeted responses against pathogens.

Concepts of Immunity

• Susceptibility: Lack of resistance to disease.

• Immunity: Ability to resist disease.

• Innate Immunity: General defenses against any pathogen, including normal body functions.

• Adaptive Immunity: Specific immunity or resistance to particular pathogens.

Physical/Mechanical Factors of Innate Immunity

• First Line of Defense:

  • Skin:

    • The epidermis consists of tightly packed cells containing keratin, a protective protein.

  • Mucous membranes:

    • Mucus traps microbes.

    • Ciliary escalator transports trapped microbes away from lungs.

  • Lacrimal apparatus:

    • Washes eyes.

  • Saliva:

    • Washes microbes off surface.

  • Urine:

    • Flows out, helping to prevent colonization.

  • Vaginal secretions:

    • Flow out, providing protective benefits.

Chemical Factors of Innate Immunity

• Sebum: Contains fungistatic fatty acids.

• pH Levels:

  • Skin pH: 3-5

  • Gastric juice pH: 1.2-3.0

  • Vaginal secretions pH: 3-5

• Enzymes:

  • Lysozyme present in perspiration, tears, saliva, and urine.

Normal Microbiota and Innate Immunity

• Microbial antagonism: Normal microbiota compete with pathogens or alter the environment.

• Commensal microbiota: One organism benefits (microbe) while the other (host) remains unharmed.

• Opportunistic Pathogens: Normally harmless microbes that can cause disease under certain conditions.

Toll-like Receptors (TLRs) and Immune Responses

• TLRs attach to pathogen-associated molecular patterns (PAMPs), leading to the activation of the immune response through cytokine release that regulates the intensity and duration of the immune response.

Blood Components in Immunity

Formed Elements in Blood

• Erythrocytes (Red Blood Cells):

  • Function: Transport of O2 and CO2

• Leukocytes (White Blood Cells):

  • Agranulocytes

    • Monocytes: Phagocytosis (when they mature into macrophages).

    • Dendritic cells: Phagocytosis & initiation of adaptive immune responses.

    • Lymphocytes: Natural killer (NK) cells, T cells (cell-mediated immunity), and B cells (produce antibodies).

  • Granulocytes

    • Neutrophils: Phagocytosis (60-70% of leukocytes).

    • Basophils: Produces histamine.

    • Eosinophils: Produce toxic proteins against certain parasites; some phagocytosis.

  • Plates: Blood clotting.

Lymphatic System Components

• Main Components:

  • Lymphatic vessels, lymph nodes, spleen, thymus, tonsils, red bone marrow.

• Functions:

  • Transport of lymph, fluid balance, filtering pathogens, and initiation of immune responses.

Phagocytosis

• Phagocytes:

  • Types include neutrophils, fixed macrophages, wandering macrophages, and dendritic cells.

• Process of Phagocytosis:

  • Chemotaxis and adherence of phagocyte to microbe

  • Ingestion of microbe by phagocyte

  • Formation of phagosome

  • Fusion of phagosome with lysosome to form a phagolysosome

  • Digestion of ingested microbes by enzymes in the phagolysosome

  • Formation of residual body with indigestible material

  • Discharge of waste materials.

Inflammation

• Process:

  • Activation of acute-phase proteins and cytokines leading to vasodilation and increased permeability of blood vessels, causing redness, swelling (edema), pain, and heat.

• Phagocyte Migration:

  • Margination: Phagocytes adhere to endothelium.

  • Diapedesis: Phagocytes squeeze between endothelial cells.

Fever

• Definition:

  • Abnormally high body temperature, usually set at 37°C in the hypothalamus.

• Causes and Effects:

  • Gram-negative endotoxins trigger phagocytes to release interleukin-1 (IL-1), increasing body temperature.

  • Advantages include increased transferrins, heightened IL-1 activity, and reduced survival of many microbes.

  • Disadvantages may include tachycardia, acidosis, dehydration, and potentially fatal at temperatures above 44-46°C.

The Complement System

• Function:

  • A cascade of serum proteins activated to enhance inflammation, attract phagocytes, and cause cytolysis of pathogens.

• Outcomes:

  • Opsonization, membrane attack complex (MAC), and inflammatory mediator release.

Adaptive Immunity

• Definition:

  • Specific defenses that include an antibody response and lymphocyte reactions to antigens.

• Types:

  • Natural Immunity:

    • Active: Resulting from infection.

    • Passive: Transplacental or through breast milk.

  • Artificial Immunity:

    • Active: Via immunization.

    • Passive: Injection of antibodies.

Antigens and Antibodies

• Antigens:

  • Substances that the body recognizes as foreign and evoke an immune response.

• Antibodies:

  • Proteins produced in response to specific antigens by plasma cells derived from B cells.

  • Different classes include IgG, IgM, IgA, IgE, and IgD, each having specific functions in immunity.

Immune Testing

• Types:

  • Direct testing: Detect presence of antigens.

  • Indirect testing: Detect antibodies formed against antigens.

• Tests:

  • Enzyme-linked immunosorbent assay (ELISA), western blot test, immunochromatography for rapid diagnostics, and various precipitation or agglutination tests.

Hypersensitivities

• Types of Hypersensitivity:

  • Type I: Immediate; allergies.

  • Type II: Cytotoxic; blood transfusion reactions.

  • Type III: Immune complex-mediated; systemic lupus erythematosus.

  • Type IV: Delayed/cell-mediated; graft rejection and contact dermatitis.