Immunity and the Immune System

Immunity and the Immune System

• Immunity is defined as the resistance to disease.
• The immune system is classified functionally and anatomically.

Innate Defenses: Barriers - First Line of Defense

• Skin provides a physical barrier with keratin and sloughing.
• Skin secretions (sebum) are acidic, with a pH of 3-5, inhibiting bacterial growth.
• Mucus traps pathogens in the digestive and respiratory systems.
• The digestive system uses stomach acid and protein-digesting enzymes.
• The respiratory system utilizes nose hairs and ciliated cells.
• Saliva and lacrimal fluid contain lysozyme, which is a bacteria-destroying enzyme.
• Hookworm larvae and Helicobacter pylori can sometimes bypass these barriers.

Innate Defenses: Internal Mechanisms - 2nd Line

• Nonspecific cellular and chemical protections include phagocytes.
• Natural killer (NK) cells provide nonspecific cellular and chemical protections
• Antimicrobial proteins, such as interferons and complement, are also key.
• The inflammatory response and fever contribute to internal defense mechanisms.
• Harmful substances are identified by surface carbohydrates unique to infectious organisms.

Second Line of Defense: Phagocytes

• Phagocytes: primary type is macrophages.
• Phagocytes destroy invaders through phagocytosis.

Inflammatory Response

• Leukocytosis: Neutrophils enter the blood from bone marrow.
• Margination: Neutrophils cling to the capillary wall.
• Diapedesis: Neutrophils flatten and squeeze out of the capillaries.
• Chemotaxis: Neutrophils follow a chemical trail.

Inflammation

• The inflammatory response is triggered by injured body tissues.
• Inflammation prevents the spread of damaging agents to nearby tissues.
• Inflammation disposes of cell debris and pathogens.
• Inflammation alerts the adaptive immune system and sets the stage for repair processes.
• Signs of acute inflammation include redness, heat, swelling, and pain.
• Chemical mediators released during inflammation increase blood flow, causing heat and redness.
• Chemical mediators attract WBCs and other cells.
• Fluid moves into the area from capillaries, causing pain and swelling.
• Neutrophils and macrophages destroy invaders and clean up the area.

Fever

• Fever is a response to invading microorganisms.
• Leukocytes and macrophages secrete pyrogens.
• High fevers are dangerous.
• A moderate fever can cause the liver and spleen to sequester iron and zinc and increase the metabolic rate, speeding up tissue repair.

Adaptive (Specific) Defenses - 3rd Line of Defense

• Adaptive defense is highly specific, identifying and attacking specific pathogens.
• Adaptive defense has systemic effects, with immunity not restricted to the initial infection site.
• Adaptive defense has "Memory," able to recognize and quickly respond to previously encountered pathogens.
• Adaptive defense consists of humoral (antibody-mediated) and cellular (cell-mediated) immunity.

Antigens

• Antigens are substances and cells that activate the adaptive immune system and provoke an immune response.
• Reactivity is shown in complete antigens.
• Immunogenicity is shown in complete antigens.
• Incomplete antigens only show reactivity and can cause allergic reactions.

Antigenic Determinants

• Antigenic determinants are parts of the antigen's outer surface.
• Antigenic determinants serve as locations where antibodies or activated lymphocytes attach when attacking the antigen.

Self-Antigens: MHC Proteins

• Cells are dotted with self-antigen protein molecules and are strongly antigenic to others.
• MHC proteins mark a cell as self.
• MHC proteins are unique to an individual, identifying cells as "self".

MHC Camouflage

• Schistosomiasis involves worms living in blood vessels.
• Worms incorporate host MHC in their outer coat to camouflage themselves against attack.

Cells of the Adaptive Immune System

• B lymphocytes (B cells) oversee humoral immunity.
• T lymphocytes (T cells) mediate the cell-mediated arm of immunity, not producing antibodies.
• Antigen-presenting cells (APCs) do not respond to specific antigens but play essential auxiliary roles in immunity.

Lymphocytes

• Immature lymphocytes released from bone marrow are essentially identical.
• Whether a lymphocyte matures into a B cell or a T cell depends on where in the body it becomes immunocompetent.
• B cells mature in the bone marrow.
• T cells mature in the thymus.

Immunocompetent B or T cells

• Display a unique type of receptor that responds to a distinct antigen.
• Become immunocompetent before they encounter antigens they may later attack.
• Must show self-tolerance.
• Exported to secondary lymphoid tissues as naïve cells.
• Mature into fully functional antigen-activated cells upon binding with their recognized antigen.

Humoral Immune Response

• Primary response includes initial encounter with antigen.
• B lymphocytes with a specific receptor bind with the antigen (clonal selection), while lymphocytes with noncomplementary receptors remain inactive.
• Plasma cells are effector B cells that secrete antibody molecules.
• Memory B cells primed to respond to the same antigen.
• A clone of cells are identical to ancestral cells.
• Secondary response occurs years later.
• Subsequent challenge by the same antigen results in a larger, more rapid response.

Immunological Memory

• Primary immune response includes cellular differentiation and proliferation, which occurs on the first exposure to a specific antigen.
• Lag period: 3 to 6 days after antigen challenge.
• Secondary immune response includes re-exposure to the same antigen.
• Secondary immune response has a short lag time (2-3 days) and stronger response.
• The secondary immune response may last for years or even a lifetime.

Active and Passive Humoral Immunity

• Differences exist in the antibody source and the degree of protection.
• Active immunity occurs when B cells encounter antigens and produce antibodies against them.
• Memory clones are formed in active immunity.
• Passive immunity occurs when B cells are not challenged by antigens.
• Immunological memory does not occur in passive immunity.
• Protection ends when antibodies naturally degrade in the body with passive immunity.

Types of Acquired Humoral Immunity

• Naturally acquired active immunity comes from infection and contact with a pathogen.
• Artificially acquired active immunity comes from a vaccine of dead or attenuated pathogens.
• Naturally acquired passive immunity occurs when antibodies are passed from a mother to a fetus via the placenta or to an infant in her milk.
• Artificially acquired passive immunity comes from the injection of exogenous antibodies (gamma globulin).

Antibodies

• There are five classes of immunoglobulins.
• Antibodies are soluble proteins secreted by plasma cells in response to a particular antigen.
• Antibodies can bind specifically with that antigen.
• Plasma cells make over a billion different types of antibodies.
• Antibodies themselves do not destroy antigen, but they inactivate and tag it for destruction.
• All antibodies form an antigen-antibody (immune) complex (antibodies bind to antigen).

Mechanisms of Antibody Action

• Neutralization masks dangerous parts of bacterial exotoxins and viruses.
• Agglutination involves cell-bound antigens.
• Precipitation involves soluble antigens.
• Enhances phagocytosis.
• Complement is fixed and activated.
• Inflammation: Chemotaxis and Histamine Release.
• Cell lysis.

Invaders Fight Back

• Parasite continually changes its surface antigens to confuse the host.
• Invaders fight back
• Reduviid bug.

Cell-Mediated Immune Response

• Antibodies are ineffective against intracellular antigens, so cell-mediated immunity is needed.
• Infected, cancerous, or transplanted cells require cell-mediated immunity.
• Two major populations of T cells mediate cellular immunity.
• Helper T cells (TH, CD4) activate B and T cells.
• Cytotoxic T cells (TC, CD8) kill cell targets.
• T cells only recognize processed fragments of antigens, as presented by APCs and other cells.

Antigen Recognition

• MHC proteins show fragments from cell interior.
• MHC proteins ignore T cells if they are complexed with self-protein fragments (healthy cells) and attack when unhealthy.

Mechanisms of T_c Action

• The cytotoxic T cell (T_c) identifies foreign antigens on MHC I proteins and binds tightly to the target cell.
• T_c releases perforin and granzyme molecules from its granules by exocytosis.
• Perforin molecules insert into the target cell membrane, polymerize, and form transmembrane pores similar to those produced by complement activation.
• Granzymes enter the target cell via pores, activating enzymes that trigger apoptosis.
• The T_c detaches and searches for another prey.

T_c Reaction

• Tuberculin PPD test a cell-mediated response that can indicate
• Active disease
• Memory of past exposure

Homeostatic Imbalances of Immunity

• Immunodeficiencies cause defects in immunity.
• SCID is a congenital immunodeficiency.
• Hodgkin's disease (cancer of lymph nodes and B cells).
• AIDS (virus that attacks Helper T cells) is an acquired immunodeficiency.

Autoimmune Diseases

• The immune system no longer distinguishes self from non-self.
• Multiple sclerosis is a homeostatic imbalance of immunity.
• Grave's Disease / Hashimoto's thyroiditis disease is thyroid related and is a homeostatic imbalance of immunity.
• Rheumatoid arthritis is a homeostatic imbalance of immunity.
• Type I diabetes mellitus is a homeostatic imbalance of immunity.

Allergies - Hypersensitivities

• The immune system overreacts to antigens and damages self
• Immediate (allergy, anaphylaxis) is antibody mediated and stimulates mast cells and basophils.
• Delayed (contact dermatitis) is cell mediated and includes poison ivy reactions.