Microbiology

Chapter 6 - Host Defense Mechanisms

• Many of the resistance mechanisms of the body are non-specific in that they operate against microbes as a whole and operate against non-living foreign matter.
• Mononuclear phagocyte system (MNPS) and Reticuloendothelial system (RES)

1. Entrance Barriers

1. Architecture of the skin & mucous membranes

• Continuous layer
• Covered with keratin
• Underlying dense CT
• Goblet cells
• Cilia
• Phagocytic cells (alveoli)
• Acid bath
• Saliva

1. Physiology of Superficial Tissue

• Skin Secretions - sebaceous & sweat glands
• Lysozyme - tears, saliva
• Gastric secretions
• Mucous film - genitourinary tract

1. Blood Barriers

• Means of carrying away waste products
• Plasma & cellular components important in control of microbes

1. Plasma

• Transport antimicrobial agents and drugs
• Carry immune cells and gamma globulin (antibodies)
• Transport complement proteins

1. Cellular Components

• White blood cells
• Chemotactic agents

1. Lymphatic System

• Antibody production
• Filter foreign particles & micro-organisms

1. Mononuclear Phagocyte System (MNPS)

• MNPS => general term refering to all phagocytic cells found throughout the tissues of the body
• Includes both free and fixed macrophages (microglia, kuppfer cells and alveolar macrophage)
• Function to remove foreign debris or particles by phagocytosis
• Also maintain the integrity of the internal environment by clearing old and dying cells.
• First step in the immune response.

1. Phagocytosis

• The process of phagocytosis consists of four steps: contact, ingestion, intracellular digestion and exocytosis
• Fig. 6.6
• Some micro-organisms can resist phagocytosis because of the presence of a capsule covering their cell wall
• If an organisms is encapsulated, an antibody is required for identification and phagocytosis
• Some pathogens (brucella) can actually multiply within the phagocytic cell and in the process usually kill the cell.

1. Inflammatory Response

• Includes both specific and non-specific defense responses
• Fig. 6.7
• Function is to localize and prevent the spread of a micro-organism.
• Chemotactic mechanisms
• Exudate => collection of fluid & cells in injured area
• Abscess formation in deeper tissues
• ESR - sed rate => as the number of plasma proteins increase (due to the production of proteins) red blood cells settle at an increased rate.

1. Other Factors

1. C-Reactive Protein
2. Cytokines => Interferons, Tumor Necrosis Factor, Interleukins

1. Specific Resistance to Infection

1. Development and Functions of the Immune System

• Non-specific and Specific immune response
• Specific resistance is directed against a particular organism
• Learning, Recognition, Memory and Self-Tolerance
• Humoral and Cell-Mediated Immunity
• Lymphocytes, Antibodies & Complement

1. Antigens, Immunogens and Antibodies

• Immunogen => Any substance that induces an immune response and specifically binds to the resulting antibody
• Antigen => An agent that binds specifically to an antibody but may not evoke the immune response.
• Epitopes => Site on an antigen molecule that promotes the immune response

1. Microbial Immunogens and Antigens

• Many microbes consist of proteins and carbohydrates. Both of wich are very immunogenic
• Some microbes make toxins that are immunogenic
• Somatic antigens, Capsular antigens, Flagellar antigens, Exotoxins
• Diagnostic uses

1. Antibodies

• Protein produced by B lymphocytes against a specific immunogen
• Two light and two heavy chains connected by disulfide bonds
• Fab region => antigen binding region
• Fc region => area of attachment of complement protein

1. Antigen-Antibody Specificity

• The combining surfaces of the antigen and antibody are reciprocal
• High level of specificty

1. Classes of Immunoglobulins

• Five different classes of immunoglobulins
• IgG, IgA, IgE, IgD and IgM

1. IgM

• Major component of the primary antibody reaction
• Appears first in an immune response
• Very large molecule consisting of five antibody units connected together in a circle
• Found almost exclusively in the bloodstream
• Comprises about 7% of the total IgG
• Fairly non-specific
• Responsible for containing an infection until the secondary immune response as the levels of specific immunoglobulins rise.
• Detection of IgM is indicative of a recent or continuing infection

1. IgG

• Principal antibody of the secondary immune response
• Appears at high levels during subsequent exposures to an antigen
• Comprises 75-80% of the circulating IgG's
• Only immunoglobulin capable of crossing the placental barrier

1. IgA

• Found primarily in secretions such as tears, saliva, bile and urine
• Constructed of two immunoglobulin units connected at the Fc regions
• Important in resisting infection of the surface tissues/mucous membranes
• Found in colostrum to confer passive immunity to a newborn

1. IgD

• Found in only small quantities in the serum
• Levels increase during chronic infections
• Found on the surface of B-cells

1. IgE

• Important role in allergic reactions (hypersensitivity)
• Will attach to mast cells and basophils and facilitate the release of cehmical agents such as histamine

1. Immune Functions of the Lymphoid System

• The immune system is regulated by the specialization of certain white blood cells
• Bone marrow, spleen, lymph nodes and thymus are important organs in the development and maturation of the lymphocytic cells

1. B Lymphocytes

• Produce antibodies
• Humoral-mediated immunity
• B-cells: Memory cells and Plasma cells
• Class switching => the same plasma cell can produce a variety of immunoglobulins
• Antibodies for a particular immunogen are not present in the serum until an exposure has occurred
• Primary event => first exposure
• Anamnestic response => secondary exposure

1. T Lymphocytes

• Important for self-recognition
• Maturation in the Thymus
• Longer life span than B-cells
• Cell-mediated immunity
• Regulate both humoral and cell-mediated immunity
• Helper, suppressor and cytotoxic T-cells

1. Role of Complement in the Immune System

• Proteins found in the bloodstream
• C1 => C9
• Cascade pathway
• Participate in changes in vascular system, phagocytosis, chemotaxis and lysis of microbial cells

1. Review of Immune System Function

1. Humoral-mediated immunity
2. Cell-mediated immunity
3. NK cells

1. Interactions of Antigens and Antibodies

1. Clinical Tests

1. Plate diffusion
2. ELISA

1. Monoclonal Antibodies

1. Mechanisms of Immunization

• Active and Passive Immunity
• Acquired and Artificial Immunity

1. Active Immunity

1. Aquired Immunity

• As a result of an infection by a micro-organism

1. Artificial Immunity

• Vaccines: Killed, Attenuated, Toxoids or Recombinants

1. Passive Immunity

1. Aquired Immunity

• Placental transfer of antibodies

1. Artificial Immunity

• Temporary protection to a very hazardous infection
• From human or animal source
• Elderly or immuno-compromised individuals

1. Disorders of the Immune System

1. Hypersensitivity

• Excessive response
• Increased capillary permeability => edema and inflammation
• Release of chemotactic agents => histamine, lymphokines
• Reaction mediated by antibodies (immediate) or T lymphocytes (delayed)

1. Immediate Hypersensitivity

• Manifestations depend on the nature of the antigen, the frequency /route of antigen contact and the type of immunoglobulin reacting with it.
• Sensitizing dose and eliciting dose.
• Parental entry => systemic involvement
• Superficial entry => localized effects
• Allergens of atopy include pollen, dust , animal dander, feathers and food.
• Allergens of injection include animal serums, bee venom and drugs.
• Antibody involved is IgE
• Sequence of events:

1. Anaphylaxis

• Condition brought on by an allergic reaction
• Requires injection of the allergen

1. Atopic Allergy

• Occur through inhalation, ingestion and physical contact.
• Asthma, hay fever, hives

1. Delayed Hypersensitivity

• Caused by sensitized T lymphocytes
• Takes 48-72 hours to present
• Important in contact dermatitis and microbial allergies

1. Autoimmune Diseases

• Failure to recognize self
• Mechanisms not always clearly understood
• Environmental? Genetic? Physical?
• Rheumatoid arthritis, Lupus

1. Graft Rejection
2. Tumor Immunity