Immune System class1.pdf

Systems- Immune System IMMUNE SYSTEM The immune system is the body system that defends against foreign invaders. These invaders include bacteria, viruses, other organisms, foreign bodies/substances, abnormal molecules, and cells that develop abnormally in the body (c...

Systems- Immune System IMMUNE SYSTEM The immune system is the body system that defends against foreign invaders. These invaders include bacteria, viruses, other organisms, foreign bodies/substances, abnormal molecules, and cells that develop abnormally in the body (cancerous cells). Essential to immunity is the capacity to recognize foreign invaders (non-self). Problems arise when the response to an invader is excessive (allergies, hypersensitivities) or when self tissue is perceived as foreign or dangerous (auto-immunity). HANDY DEFINITIONS Microbe: a type of microorganism that is too small to see with the unaided eye; ex. bacteria, viruses, fungi. A microbe that causes disease is called a pathogen. Antimicrobial substance: tends to kill or damage microbes – ex. lysosomal enzymes released by immune cells Antigen: large molecules (usually proteins or polysaccharides) on cell surfaces that elicit specific responses from hosts; can be on self-cells and foreign-cells Epitope (antigenic determinant): a specific, discrete component of an antigen that is used as an identifier and binding site by host immune cells Antibody: a protein in the immune system that is responsible for binding to an epitope and initiating the destruction of the associated organism IMMUNE RESPONSES From Porth: collected coordinated response of the cells and molecules of the immune system to protect against infectious disease. The immune system has two responses: 1. The innate response 2. The adaptive response 1 Systems- Immune System 1) The Innate Response The innate response is something that we are born with. It is our non-specific initial line of defence. It’s a rapid, early response It’s always the same (non-specific) Inflammation, fever, etc It primarily reacts to microbes It relies on phagocytes and antimicrobials It includes external physical barriers like the skin and mucous membranes It’s fairly easy for microbes to adapt to it It stimulates adaptive responses The first line of defence is the skin and our mucous membranes. Sebum on the skin forms a protective film that inhibits the growth of certain microbes. Mucous can trap microbes which can be then expectorated or sneezed out of the body. Hairs in the nose and respiratory tract trap and sweep microbes away. Tears and saliva contain lysozyme, an enzyme that breaks down the cell wall of some bacteria. The second line of defence, or internal defences consists of antimicrobial substances, natural killer (NK) cells, and phagocytes. It involves activation of the complement system. Antimicrobial substances include interferons, iron binding proteins, and antimicrobial proteins. 2) The Adaptive Response This is a specific response. It develops with exposure to various organisms and substances. It’s slower to kick in and develops in response to specific attributes of an invader It works with the innate response system to enhance reactivity It attacks microbes and antigens It generates immunologic memory, meaning that subsequent exposures lead to a more rapid response 2 Systems- Immune System IMMUNE CELLS The primary cells of adaptive immunity are B-Lymphocytes (B-cells), and T-Lymphocytes (T-cells). Lymphocytes do two things: 1. They act as regulator cells, which assist in controlling and orchestration of the immune response (ie. by activating other cells). 2. They act as effector cells, by killing and eliminating the microbe or antigen. Accessory cells are phagocytes (macrophages, neutrophils, eosinophils) that kill or break apart an invader. Dendritic cells present antigens and epitopes to killers. IMMUNE CELL LOCATIONS There are always a high number of immune cells and other immune materials (like antibodies) circulating in the blood and lymph. This is known as humoral immunity. Immune cells are also located in various tissues and organs: Lymph nodes Bone marrow Thymus Tonsils Spleen Skin Mucosa Vital organs When signalled by the presence of microbes or antigens, or by other immune cells, they rapidly reproduce to create populations (clones) of targeted cell types. 3 Systems- Immune System B-CELLS B-Cells are key players in humoral immunity. They are very good at recognizing microbes and antigens (assisted by T-helper cells). They also produce antibodies. When a B-cell binds to its associated antigen, it becomes activated. Upon activation, it selects the type of clone needed: plasma cell or memory cell. Plasma cells: When it reaches full maturation, plasma cells produce and secrete antibodies (aka immunoglobulins) designed for a specific antigen. Antibodies bind to epitopes and either kill or neutralize the invader, or present them to T-cells or macrophages. Memory cells: Memory cells do not participate in the initial immune response. They stay in the body to respond quickly if a secondary exposure to the same antigen occurs. TYPES OF ANTIBODIES IgG 75% of antibodies are IgG The only Ig to cross the placenta (protects neonates) à passive immunity in newborn Diffuses readily out of the vascular zone into the tissues Antiviral, antitoxin, antibacterial actions Activates killer cells Activates the complement system 4 Systems- Immune System IgA Predominant in saliva, tears, nasal, GI, and respiratory secretions Found in breast milk (protects neonates) Blocks entry of organisms to the eyes, gut, respiratory, and urinary tracts Protects mucosa IgM Doesn’t leave the blood or lymph Early responder First Ig formed after immunization or initial exposure to a pathogen Activates the complement system Forms natural ABO antibodies IgD Present in small amounts in serum Needed for B-cell maturation IgE Found in tiny amounts in plasma Binds to mast cells and liberates histamine and other inflammatory substances Attracts eosinophils Responds to parasites IgE overreaction à allergic/hypersensitivity reactions, asthma, etc. Can be a genetic predisposition to producing excess IgE ANTIGEN PRESENTING CELLS These are cells that bind to and/or break down antigens. They present epitopes on their surfaces, or alter the antigen to make it more recognizable. B-cells, macrophages, and dendritic cells all act as presenting cells. Also, the antibodies can work in the same way. Antigen presenting cells present antigens to T-cells. However, sometimes they are presented to phagocytosing cells. 5 Systems- Immune System T-CELLS T-cells are responsible for what is called cell-mediated, or cellular immunity. They work via cell- to-cell contact or by secreting messenger compounds that communicate with immune system cells. This will: Attract cells Prevent cells from leaving the area Amplify the effectiveness of cells Increase or decrease cell reactions Activate and regulate B-cells Signal natural killer cells Increase local blood flow to facilitate immune cell movement Determine if humoral or cellular immunity is needed T-cells also: Activate most cells and IgE’s in allergen responses Are involved in rejection of foreign tissue grafts Control intracellular (viral) infections Kill tumour cells N.B. T-cells are involved in differentiating between self vs. non-self recognition and reaction. TYPES OF T-CELLS T-Helper cells (a.k.a. CD-4 cells); up regulation – The key regulatory cells of the immune system. They release various T-messenger compounds that activate and regulate the activities of the other cell types. They activate B and T cells correctly depending on the type of immune challenge. Regulatory T-cells (a.k.a. Tregs); down regulation – These suppress/modify immune responses. They decrease immune cell production. They control the mechanism to help ensure the response matches the situation, and that healthy self-cells are not killed. T-cytotoxic cells (a.k.a. CD-8 cells) – They destroy identified/presented antigens. They kill virus- infected cells by various means (lytic enzymes, cytotoxins, perforins, interferon). They are involved in attacking cellular problems that antibodies cannot influence. 6 Systems- Immune System SELF vs. NON-SELF In order for T-cells to recognize and respond to an antigen, it must be presented by another cell or an antibody. It must be coded by a Major Histocompatibility Complex (MHC). MHC are a group of genes on chromosome 6 that determine tissue and blood compatibility. In humans, they are often called Human Leukocyte Antigens (HLA). There are two classes of HLA. Class I are on all cell surfaces. Class II are on immune system cells. HLA are key factors in determining self from non-self. However, they can also identify self-targets (cells infected by a virus; cancerous cells). They lead to T-cells attacking, or ignoring an antigen. They are genetically determined self-markers. Acquiring Immunity Immunity is acquired in four ways: Active natural immunity – develops through direct exposure to an antigen and the in response, the immune system develops antibodies Active artificial immunity – develops when the body is purposefully introduced to an antigen and subsequently reacts by developing antibodies (ie. vaccines) Passive immunity – passed from a mother to fetus, to protect the infant during the first few months of life as they develop their own immune system (ie. IgG crossing the placenta, IgA passed on in breast milk) Passive artificial immunity – when antibodies are injected from one system to another; used to help fight a current infection if the individual has not been immunized against the specific organism (ex. hepatitis B infections; rabies antiserum, snake antivenom) 7 Systems- Immune System AUTO-IMMUNITY The ability to distinguish between self- and non-self antigens is referred to as immunologic self- tolerance. In a healthy individual, mechanisms are put in place to eliminate T- or B-cells that fail to differentiate between the two antigens. When these mechanisms fail, autoimmune disorders arise. Auto-immunity is the mounting of an immune response against the body’s own tissues. This happens for various reasons: The attacked body tissue may have similar characteristics to a microbe the immune system has just battled (ex. Rheumatic fever). In this case, the foreign antigen is believed to be immunologically similar to auto-antigens (shares some of the same epitopes). Some HLA inheritance corresponds to activation of autoimmune disease. Exposure to a microbe or foreign material (like a breast implant) can initiate an autoimmune disease. Some examples would be rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, diabetes, etc. Sometimes there is an over response of immune activities. For instance, in SLE (lupus) there is a hyper-reactivity of B-cells and an overproduction of antibodies. SLE may be triggered by a hyper reactivity to UV light. Sometimes there is a reduced T-cell suppressor response (ex. MS exacerbations are associated with drops in T-suppressor cell counts). Auto-immunity tends to involve the production of auto-antibodies: In rheumatoid arthritis (RA), there is an autoimmune response to self-IgG. The resulting body is called rheumatoid factor. RA involves an immune system attack on synovial membranes of joints, eventually leading to bone erosion and joint deformities. § Tender, warm, painful joints; joint stiffness following inactivity In MS, auto-antibodies create an immune attack on self-myelin in the CNS’s neurons (specifically the neuroglial cell: ___________________). Depending on what region of the brain is affected, there will be varying outcomes. In Myasthenia Gravis, acetylcholine receptors at the neuromuscular junction are destroyed by immune cells after having been bonded by auto antibodies. 8 Systems- Immune System Auto antibodies bind with self molecules to create immune complexes: In RA and SLE, such immune complexes travel in the bloodstream to target tissues like joints. By gathering in these tissues, the immune complexes subject them to intense tissue destruction from immune system responses and their sequelae. There may be mistaken targeting of self cells as dangerous: Since some self cells (ex. virus infected cells, or cancerous cells) are identified and presented for destruction, misidentification is possible. This has been found to occur in reactions to drugs and viruses that appear to have altered cellular markers in the affected person’s body. Auto-immunity can have elements of hypersensitivity reactions: Immune complexes attract inflammatory and cytotoxic reactions where the tissue damage is the result of intense responses related to complement activation and killer cell activity. This component of diseases like RA and SLE is a type III hypersensitivity reaction. The response is more destructive than the stimulus warrants. In these examples the stimulus is an autoimmune one. There is a gender relationship observed, but not well understood. Autoimmune diseases are typically more common in women than men. It is thought that there may be a hormonal component in the development of autoimmune conditions. Treatment tends to involve the use of corticosteroids and immunosuppressive drugs to try to counter or reduce the cellular damage being caused by the immune system response. 9 Systems- Immune System HYPERSENSITIVITY DISORDERS Hypersensitivity disorders refer to excessive or inappropriate activation of the immune system to exogenous and endogenous antigens that produce inflammation and cause tissue damage. There are four categories of hypersensitivity responses. TYPE I – IMMEDIATE HYPERSENSITIVITY: Mediated by IgE which leads to the release of inflammatory mediators from sensitized mast cells. The reaction takes place with the second and subsequent exposures to the antigen, not with the initial exposure. This response begins rapidly, often within minutes of an antigen challenge. Often referred to as Allergic Reactions, the antigen in this case would be referred to as an allergen. Type I responses vary in severity: Mild, but annoying (ex. seasonal allergies) Severely debilitating (ex. asthma) Life threatening (ex. anaphylaxis) They can vary based upon site of involvement: Local (atopic) reactions Systemic reactions (anaphylaxis) Local/Atopic Reactions: 1. Allergic Rhinitis Edema and hypersecretion of mucosal lining of the nasopharyngeal cavities by allergens like pollen. May be aggravated by high humidity, irritating vapours, and upper respiratory tract infections. Lasts for days to weeks. Can lead to complications like sinusitis or nasal polyps. 2. Asthma Lung disorder characterized by bronchoconstriction, edema, and increased secretion of thick mucus in the bronchi à constriction of airways. 3. Urticaria (hives) Local wheals and erythema in the upper dermis Associated with pruritis (itchiness) Develops rapidly after exposure to an allergen Allergens can be ingested (eg. food, medication) or introduced through the skin (ex. bee stings) 4. Angioedema (aka Quincke’s edema, Angioneurotic edema) Generalized edema of skin, lips, face, tongue, pharynx, and/or mucosa Allergens are similar to urticaria Similar to hives, but the swelling takes place deeper in the dermis 10 Systems- Immune System 5. Gastrointestinal food allergies Allergic reaction in GI tract begins shortly after food ingestion Symptoms are primarily seen in the GI tract, skin, and respiratory system (ex. nausea, vomiting, abdominal cramps, diarrhea, hives, asthma); anaphylaxis A common allergen is shellfish Systemic/ Anaphylactic Reactions: Anaphylaxis is a systemic life-threatening hypersensitivity reaction. An acute generalized reaction characterized by itching, generalized flushing, headache, difficulty breathing, and a drop in blood pressure which can lead to shock and loss of consciousness. Caused by smooth muscle contraction and vascular dilation as a reaction to released mediators. Common allergens are food, chemicals, insect stings, and drugs. Treatment is subcutaneous administration of epinephrine. TYPE II – ANTIBODY MEDIATED HYPERSENSITIVITY aka CYTOTOXIC HYPERSENSITIVITY: Mediated by IgM or IgG, this response is directed against target antigens on cell surfaces or in extracellular tissue. These reactions commonly involve the formation of antibodies directed against blood cells and their destruction. 1. Erythroblastosis Fetalis This is a hemolytic disease that affects neonates à hemolytic anemia/ erythroblastosis neonatorum in neonates It occurs if the mother is Rh- and fetus is Rh+ in subsequent pregnancies. Rh+ antibodies formed in mother’s system from her first Rh+ pregnancy, cause hemolysis of the red blood cells during second pregnancy à anemia, jaundice, and edema of the child. 2. Autoimmune Hemolytic Anemia Antibodies produced by a patient’s own body are responsible for the hemolysis of erythrocytes It is manifested as anemia Treatment includes use of corticosteroids and/ or a splenectomy 11 Systems- Immune System 3. Blood Transfusion Reactions This is triggered when an incompatible blood type is administered It manifests as fever, chills, and renal failure due to hemolysis of red blood cells It can be prevented by checking blood groups and doing cross-matching before blood transfusion 4. Autoimmune Thrombocytopenia (AITP) The body produces antibodies that are directed against platelets The response manifests as petechiae (small hemorrhages), purpura (bruising) and mucosal bleeding (nose, stomach, vagina) Treatment includes use of corticosteroids and/ or a splenectomy TYPE III – IMMUNE COMPLEX MEDIATED HYPERSENSITIVITY: Mediated by formation of antigen-immunoglobulin complexes, complement fixation, and localized inflammation; this response involves IgM and IgG antibodies. Immune complexes formed in the body’s circulatory system are deposited in different areas of the body (ie. Blood vessels, joint spaces) à the subsequent immune response causes inflammation and tissue destruction of the surrounding structures. 1. Arthus Reaction – local response; performed for experimental purposes and involves the injection of a foreign substance. This usually results in complex formation and localized skin reactions (edema, hemorrhage, necrosis) 2. Serum Sickness – systemic response Caused by animal serum or drugs (ex. penicillin) Antibodies are developed to a serum or drug antigen, which results in the formation of an antigen-antibody complex Complexes get lodged in small vessels and cause an inflammatory reaction (acute vasculitis) Symptoms include fever, painful joints, enlarged lymph nodes and spleen, and urticaria 12 Systems- Immune System 3. Glomerulonephritis – local effects An acute streptococcal infection is responsible for the formation of antibodies Streptococcus antigen and antibodies form an immune complex This complex is deposited on the glomerular basement membrane, leading to inflammation of the glomerulus Symptoms include hematuria and proteinuria 4. Polyarteritis nodosa – systemic effects This disease is characterized by the inflammation and necrosis of medium-sized arteries with secondary ischemia of the tissues supplied by the affected blood vessels Inflammation is caused by immune complex formation The antigen can be penicillin or hepatitis B virus This can lead to fatal complications such as occlusion or rupture of blood vessels TYPE IV – DELAYED OR CELL-MEDIATED HYPERSENSITIVITY: Mediated by specifically sensitized T-lymphocytes, this response manifests as sub-acute or chronic inflammation with infiltration of the tissue by the lymphocytes and macrophages, resulting in variable degrees of necrosis. (Type I, II, III are antibody-mediated and immediate; Type IV is cell-mediated and delayed) 1. Contact Dermatitis An acute or chronic delayed type of hypersensitive response to allergens placed on the skin surface Caused by plants (eg. poison ivy, poison oak), drugs, cosmetics, dyes, paints, and jewelry Symptoms usually occur 12-24 hours after exposure and can last from a few days to weeks It manifests as skin erythema, edema, pruritis, vascular eruption, necrosis 2. Graft Rejection This is cause by a delayed hypersensitivity reaction Development of chronic inflammation because of infiltration of the graft by lymphocytes and macrophages. This leads to necrosis of the graft. **Latex allergies can be Type I and/or Type IV Type I latex reactions are immediate and often life-threatening Type IV latex reactions are more common and tend to manifest as contact dermatitis 13