Immunity in Class Part 1 - BIO4311 Pathophysiology I PDF

## Immunity ### Immunity - Defense Mechanisms - Defense mechanisms - Lymphocytes - Cytokines - MHCS - Humoral vs cell-mediated ### The Immune System The immune system is comprised of many different cells, tissues, and organs that work together to protect the body. - **Innate Immunity**...

## Immunity ### Immunity - Defense Mechanisms - Defense mechanisms - Lymphocytes - Cytokines - MHCS - Humoral vs cell-mediated ### The Immune System The immune system is comprised of many different cells, tissues, and organs that work together to protect the body. - **Innate Immunity** - **First Line of Defense**: The intact skin and mucous membranes, protective chemicals of the skin and mucous membranes. - **Second Line of Defense**: Phagocytes, antimicrobial proteins, natural killer cells, and inflammation - **Adaptive Immunity** - **Humoral Immunity**: B cells - **Cellular Immunity**: T cells ### Physical Barriers **1st Line of Defense** - **Skin** - An intact epidermis acts as a mechanical barrier to pathogens. - Keratin is a protein made by keratinocytes, that provides waterproofing and is resistance to some weak acids and bases as well as bacteria - **Mucous Membranes** - Together with their secretions these line our “inner” epithelial linings. - When intact, these membranes help to protect the body cavities from the external environment. - **Mucus**: to trap microorganisms and other particles in the respiratory and digestive tracts. - **Cilia**: to move mucus and the debris stuck in the mucus out of the lower respiratory tract. - **Tears**: these lacrimal secretions constantly clean the eye and contain lysozyme. - **Saliva**: cleans the oral cavity and contain lysozyme. - **Urine**: cleanses the lower urinary tract, acidic pH inhibits bacterial growth. ### **2nd Line of Defense** - **Phagocytosis** - Pathogens that get through the first line of defence will be attacked by phagocytes. - These immune cells are capable of engulfing many different microorganisms via phagocytosis. - The four steps are: 1. A phagocyte recognizes and adheres to a pathogen or debris. 2. Phagocyte engulfs the particle and creates a phagosome. 3. Lysosomes fuse with the phagosome to forms a phagolysosome. 4. Enzymes destroy he pathogen within the phagolysosome. ### Phagocytes **Roles in phagocytosis** - Elimination of invading microorganisms by intracellular degradation - Elimination of exogenous pathogens as well as host-derived molecules including dead cells. **Physiological roles** - Induction of adaptive immunity by presenting antigens to T cells. - Elimination of neighboring dead cells. **Neutrophils:** - Most abundant type of WBC. - Become phagocytic when it encounters a pathogen. **Macrophages:** - “Big eaters” - Derived from monocytes (WBC). - Monocytes become macrophages when they leave the blood and enter tissue. **Two main types:** - Free macrophages: Wander tissue spaces, looking for cell waste or pathogens. - Fixed macrophages: Permanent residents in a specific organ - Examples: Stellate macrophages (liver), microglia cells (CNS). ### Examples of Protective Chemicals - **Acidity of skin (pH 3 to 5)** inhibits bacterial growth. - **Bactericidal action of oil from sebaceous glands** - **Hydrochloric acid secreted by stomach** - **Saliva and tears contain lysozyme** – an antibacterial enzyme - **Mucus produced in digestive and respiratory tracts traps microorganisms.** - **Ciliated mucous membranes in the respiratory tract move trapped microorganisms to be swallowed and digested by stomach acid and the mucus-coated nose hairs help to trap particles.** ### Inflammation - Part of the body's 2nd line of defenses. - Is a NON-SPECIFIC response, often due to physical damage (abrasions, sprains, burns etc.), chemical damage, ischemia, allergic reactions, infections etc. - Is USUALLY a rapid response - Regardless of the cause the process is ALWAYS THE SAME. **Acute inflammation is:** - Protective - Normal - Intended to localize/remove an injurious agent - May act as a warning sign. **Cardinal signs:** heat, redness, swelling, pain and loss of use. ### Inflammatory Chemicals - Immediately following tissue injury, the inflammatory process begins with a chemical "alarm." Released from the injured tissue cells, or nearby immune cells (e.g., mast cells, kinins, and prostaglandins). **All contribute to vasodilation and increased capillary permeability:** - **Mast cells release histamines**, which are vasodilators - **Kinins are created by the breakdown of a protein called kininogen**, which contribute to vasodilation, chemotaxis, and pain sensation - **Prostaglandins are produced by a variety of cells**, contribute to vasodilation, chemotaxis, and pain sensation - **Cytokines are released by immune cells**. Large variety; contribute to various aspects of the immune response. ### Vasodilation - Causes redness and heat to local inflamed areas ### Increased capillary permeability - Allows clotting factors, antibodies to move out of the blood and into the tissues, but causes Edema... albumin leaks from the blood to the interstitium and causes a pull via osmotic pressure to leak MORE fluid from the blood when it's usual job is to keep fluid IN the blood! ### Acute vs. Chronic inflammation - **If the cause of an inflammatory response is brief, the inflammatory response will be brief, (i.e., acute inflammation)** - Examples: touching a hot object (resolves within ~ 48 hours), a superficial cut to the skin (resolves within ~ 1 week) - **Chronic inflammation** - A state of low-grade, long-term inflammation, characterized by the activation of immune mechanisms in response to the long-term presence of certain biological, psychological, pathological, environmental, and/or social factors. - **Typically develops two ways:** 1. **From an episode of acute inflammation when the cause of the inflammation is ongoing (e.g., > 2 weeks)** - Can be local (at injury site) or systemic (in cases of infection) 2. **Gradually due to the long-term presence of an irritant** - Examples: Smoking, long-term infections, abnormal immune responses. - Usually systemic. ### Acute vs Chronic Inflammation **Acute** - Causative agent: pathogens, irritants, damage. **Chronic** - Causative agent: Persistent acute inflammation due to non-degradable pathogens, persistent foreign bodies, or autoimmune reactions. **Major cells:** - **Acute:** neutrophils, basophils, eosinophils, monocytes, macrophages. - **Chronic:** Monocytes, macrophages, lymphocytes, plasma cells, fibroblasts **Onset:** - **Acute:** Immediate - **Chronic:** Delayed **Duration:** - **Acute:** Few days. - **Chronic:** Up to many months, or years **Outcomes:** - **Acute:** Resolution, abscess formation, chronic - **Chronic:** Tissue destruction, fibrosis ### Systemic effects of inflammation - May include: Malaise, Fatigue, Headache, Loss of appetite, Pyrexia ### Fever - The medical term for fever. - Abnormally high body temperature. - Is a systemic response to often help kill off invading organisms or increase the metabolic rate of your cells. - Is a non-specific line of defense. - Over 42oC or 1080 are considered dangerous and may be life threatening as they disturb mitochondria function and cellular proteins, possibly triggering apoptosis. - **Occurs when a WBC encounters a foreign substance and releases pyrogens** (interleukin 1, interleukin 6, tumor necrosis factor). - **These pyrogens circulate through the blood and arrive at the hypothalamus where it triggers us to temporarily raise our normal body temperature.** ### Adaptive immunity - This defense mechanism helps clear specific foreign matter. - Takes longer to mount than innate mechanisms but is more effective. - Includes the immune system, central and peripheral lymphoid tissues. - Major players are **lymphocytes:** T and B lymphocytes & antibodies. - Also important are macrophages and dendritic cells ### Antigens - Describes substances that are foreign to the host that can induce an immune response also known as an immunogen. - Antigens are recognized by receptors on immune cells as well as (or immunoglobulins), proteins that are produced in response to the antigen. - Examples of antigens – bacteria, virus, fungus, pollen, poison ivy plant resin, insect venom and transplanted organs. ### Antigenic Determinants - Immune cells and antibodies recognize small pieces of the antigen called antigenic determinants or epitopes. - A single antigen may have several epitopes that can each elicit an immune response. - A **hapten** is a small substance that usually does not elicit an immune response, but can stimulate the immune system when bound to a larger carrier protein. ### Immune Cells - The major players are T- and B-lymphocytes, part of the agranular white blood cells. - Other cells are macrophages and dendritic cells which help process antigen and activate the lymphocytes. - Regulatory cells help to coordinate and control the immune response (e.g. T helper lymphocytes). - The immune cells act as regulatory or effector cells. - Effector cells help to destroy and clear the antigen (e.g. **T cytotoxic lymphocyte**) ### Lymphocytes - Lymphocytes are produced in the bone marrow from stem cells called hemocytoblasts. - After production, the lymphocytes must become “educated” - i.e. immunocompetent – able to recognize foreign cells and be self tolerant; able to recognize cells of the host. - After education, T- and B-lymphocytes can be found in lymph nodes, spleen and mucosal tissues where they await a challenge by a specific antigen. ### Major Histocompatibility Complex - Cell surface molecule that helps distinguish normal "self" cells/ molecules and foreign invaders. - Each individual has a unique set of MHC proteins. - Also known as Human Leukocyte Antigens (HLA) because they were first discovered in white blood cells. - Two classes of cells: Class I and Class II ### Class I MHC - Cell surface glycoproteins that interact with antigen receptors and the CD8 molecule on T cytotoxic cells. - Contain a groove to bind a peptide fragment of antigen; binding of peptide fragment to the Class I molecule will alert the immune system that a cell has been infected by a virus or has become cancerous. - T-cytotoxic cells will be activated only after it binds to the MHC Class I molecule/antigen complex. ### Class II MHC - Interact with CD4 T-helper cells. - After phagocytosis, digested fragments are bound to Class II MHC. - T-helper cells recognize the Class II/antigen complex and become activated. - Activated T-helper cells release cytokines to enhance the response by other lymphocytes. ### Macrophages - Develop from monocytes as they migrate to various tissues. - Can be free and wander throughout tissue looking for foreign invaders or fixed and permanent residents of a particular organ (e.g. Kupffer cells in the liver, microglia in the brain). - Function as part of the second line of defense or can help with the immune response by: - Helping digest foreign substances when coated with antibody. - Secreting cytokines to activate T and B-cells. - Acting as antigen-presenting cells (by presenting a digested antigen with an MHC Class II molecule attached to T-helper cells). - Destroying virus-infected cells or tumor cells when appropriately stimulated by T-cell cytokines. ### Dendritic Cells - Star-shaped cells that act as APCs. - Located in lymphoid tissue and other areas where foreign invaders might enter the body. - Dendritic cells found in the skin are called Langerhans' cells; in lymph nodes they are called follicular dendritic cells. - Big MHC-II binders!