Immunity

Body Defenses First line - barriers Skin and mucous membranes Flushing action –Antimicrobial substances Lysozyme, acids, salts, normal microbiota

Second line defenses Cells – neutrophils, macrophages, natural killer cells –Toll-like receptors on phagocytes recognize carbohydrates on the surface of bacteria Inflammation Proteins –Complement –Interferon Fever

All of the previous mechanisms are NON-SPECIFIC Third line – immune response 1.Specific 2.Memory 3.Inducibility

Antigens - substances recognized as “non- self” These can be: Infectious agents - bacteria, viruses, fungi or parasites Noninfectious substances – Environmental - pollen, foods, bee venoms Drugs, vaccines, transfusions and transplanted tissues

Antigen Antibody Generator The best antigens are: 1. large 2.recognized as foreign 3.complex

proteins and complex carbohydrates – good nucleic acids and lipids – not good Haptens – too small by themselves, piggy- back on larger molecules, us. Proteins Epitopes (antigenic determinants) – regions of large molecules recognized by the immune system

Two cell types give us the immune response; both are lymphocytes, which are a type of leukocyte, or white blood cell. B lymphocytes or B cells T lymphocytes or T cells

The cells of the immune response differ from the cells of the inflammatory response in three ways: 1. They are SPECIFIC and each cell recognizes only one specific antigen. B cells produce antibodies Tc cells attack antigen directly

2. Both produce groups of cells called “memory cells” that act quickly the second time the antigen is encountered. 3. An antigen induces an immune response. Only small amounts of antibodies or T Cells are present before encountering an antigen.

Long lasting protection against a specific antigen is immunity. Natural immunity: Not produced by the immune response Species specific

Acquired immunity Active – person produces immunity (by producing antibodies or Tc cells) natural artificial Passive – temporary immunity is given (by giving antibodies) natural artificial

Lymphocytes Originate : in liver, spleen and bone marrow of fetus in bone marrow after birth From stem cells – hemocytoblasts – that produce all blood cells.

To become mature, immunocompetent cells, they must pass through lymphoid tissues in other parts of the body. As they do so, they become committed to becoming either T cells or B cells Cells that migrate through the bone marrow (bursal equivalent) become B cells, and will produce antigens and participate in humoral immunity.

Cells that migrate through the thymus glands become T cells and participate in Cell-mediated immunity.

Humoral Immunity Humoral immune response : B cells that produce antibodies that travel through the blood. Antibodies are proteins that match the molecular structure of an antigen, and bind to that antigen. This leads to the destruction of the antigen.

Antibody

B cells mature in the human bursal equivalent – in bone marrow – and obtain the ability to bind antigens and produce antibodies. Clonal selection theory: During fetal development, B cells are produced which can bind with any potential antigen. Each B cell binds only one antigen.

When antigen binds to antibody receptors on the surface of the B cell, the B cell divides and differentiates into antibody producing plasma cells and also memory cells.

Immunoglobulins IgG - monomer (crosses placenta) IgA – dimer – 2 units - in secretions IgM – pentamer – 5 units IgD – monomer – on surface of B cells IgE – monomer – involved in hypersensitivities

Cell-mediated immunity Produced through Tcytoxic or Tc Cells (T 8 cell) DO NOT produce antibodies Attack invaders directly May produce toxic chemicals – such as perforins, cytolytic enzymes, etc. May stimulate cell’s self-destruct mechanism

Primary and Secondary Immune Responses Primary response –Latent period –IgM produced –IgG produced later

Secondary response Anamnestic response –much more rapid due to memory cells Primarily IgG

Cellular Interactions in the Immune Response Few antigens can activate B cells all by themselves For activation of B cells and Tc Cells need a second signal – cytokine ( “cell mover”)

Antigen-Presenting cells (macrophages) place antigen on their cell surface in combination with the MHC II complex Antigen is presented to a specific helper T cell that has receptors that match the antigen – MHC II complex

After binding, the APC produces Interleukin -1 (IL-1) which stimulates the T H Cell to produce IL-2 and/or IL-4 Interleukin-2 has an autocrine function, causes T H Cell to clone itself, and make more IL-2 and /or IL-4

Helper T cells T H1 cells produce IL -2 and IFN- ɣ and influence cell-mediated immunity T H2 cells produce IL -4 (and other IL’s) and influence antibody-mediated (humoral) immunity

When B cell comes in contact with the antigen and IL-4, the B cell produces plasma cells and memory cells Tc Cells come in contact with the antigen on the surface of infected cells in combination with the MHC 1 complex. When also have binding with IL-2, cells produce activated Tc Cells and memory cells.

Hypersensitivities “The Immune System Gone Bad”

Hypersensitivities 1.Allergies – Exaggerated immune response against environmental antigens 2.Autoimmunity – immune response against host’s own cells 3.Alloimmunity – immune response against beneficial foreign tissues, such as transfusions or transplants

These immune processes initiate inflammation and destroy healthy tissue. Four types: Type I – IgE-mediated allergic reactions immediate type hypersensitivity Type II – tissue-specific reactions antibody-dependent cytotoxicity Type III – immune-complex-mediated reactions Type IV - cell-mediated reactions delayed-type hypersensitivity

Type I - IgE-mediated allergic reactions or immediate hypersensitivity Characterized by production of IgE Most common allergic reactions Most Type I reactions are against environmental antigens - allergens

Selected B cells produce IgE Need repeated exposure to large quantities of allergen to become sensitized IgE binds by Fc end to mast cells after first exposure

Second exposure (and subsequent exposures) – antigen binds with Fab portion of antibody on mast cells, and cross-links adjacent antibodies, causing mast cell to release granules. Response is immediate ( minutes)

Sometimes beneficial to host – IgE-mediated destruction of parasites, especially parasitic worms.

Histamine release: Increases vascular permeability, causing edema Causes vasodilation Constricts bronchial smooth muscle Stimulates secretion from nasal, bronchial and gastric glands Also hives (skin), conjunctivitis (eyes) and rhinitis (mucous membranes of nose).

Late phase reaction 2 – 8 hours; lasts for days Other mediators that take longer to be released or act: –Chemotactic factors for eosinophils and neutrophils –Leukotrienes –Prostaglandins –Platelet-activating factor –Protein-digesting enzymes

Genetic predisposition Allergy prone or atopic Can be life threatening, so individuals should be aware Skin tests – injection – see wheal and flare Lab tests for circulating IgE

Treatment First wave – antihistamines or epinephrine (blocks mast cell degranulation) Second wave – corticosteroids and nonsteroidal anti-inflammatory agents that block synthesis of leukotrienes and prostaglandins Desensitization by repeated injections of allergen – formation of IgG

Anaphylaxis – Type I allergic reaction may be localized or general immediate – within a few minutes of exposure Systemic anaphylaxis: pruritus(intense itching) urticaria (hives) Wheezing; dyspnea; swelling of the larynx Give epinephrine

Anaphylactic shock Hypotension, edema (esp. of larynx), rash, tachycardia, pale cool skin, convulsions and cyanosis Treatment: –Maintain airway –Epinephrine, antihistamines, corticosteroids –Fluids –Oxygen

Type II – Tissue specific reactions (antibody-dependent cytotoxicity) Most tissues have specific antigens in their membranes expressed only by that tissue Antibodies bind to cells or surface of a solid tissue (glomerular basement membrane)

Destruction of tissue occurs: –Destruction by Tc Cells which are not antigen specific- K cells –Complement-mediated lysis –Phagocytosis by macrophages (“frustrated phagocytosis”) –Binding of antibody causes cell to malfunction

Type III – Immune-complex- mediated reactions Caused by antigen-antibody complexes formed in circulation and deposited in vessel walls or other tissues Not organ specific Effects caused by activation of complement – chemotaxis of neutrophils Neutrophils release lysosomal enzymes into tissues (“frustrated phagocytosis”)

Type IV- Cell-mediated reactions Sensitized T lymphocytes – either Tc Cells or lymphokine producing Td cells Takes 24 – 72 hours to develop Damage by Tc Cell or inflammatory response by Td Cells (lymphokines) Graft rejection, tumor rejection, TB reaction, poison ivy and metal reactions Immune diseases Tissue rejection

Systemic lupus erythematosus SLE Autoanitbodies against nucleic acids and other self components Graft vs. Host disease host is immunocompromised transplant has immunocompetent cells