CHI335 - Immune System PDF

CHI335 Diagnosis I  Immune System Function and common disorders To explain the importance of the immune system To identify components of the immune system and their functions To describe the types and causes of some immunodeficiency disorders To explore the characteristics of hypersensitivit...

CHI335 Diagnosis I  Immune System Function and common disorders To explain the importance of the immune system To identify components of the immune system and their functions To describe the types and causes of some immunodeficiency disorders To explore the characteristics of hypersensitivity reactions To describe the pathophysiology of autoimmune disorders and provide some examples Protecting our body against  Bacteria  Viruses  Fungi  Parasites  Cancerous cells The immune system works with the lymphatic system which includes  Thymus  Lymph nodes  Lymphoid tissue  Lymphatic vessels  Spleen Cellular  Works through a range of leukocytes such as lymphocytes, monocytes, eosinophils, basophils, and T-lymphocytes  Responsible for direct cellular immune attack  Key facilitators of general immune response  Activate B-cells and influence antibody production Humoral  Works through five classes of antibody (immunoglobulins) produced by B-lymphocytes  IgA, IgD, IgE, IgG, IgM Leukocyte type Function Granulocytes Neutrophils Phagocytosis: important role in bacterial infection Eosinophils Modulate allergic reactions: important in parasitic infection Basophils Facilitate allergic reactions through the release of histamine, heparin and serotonin Agranulocytes Lymphocytes B-cells differentiate into plasma cells, which secrete Igs T-cells and NK cells attack microorganisms, foreign cells and cancer cells Monocytes (become Phagocytosis: facilitates immune responses of both cell-mediated macrophages) immunity and humoral immunity Ab Function Class IgA Mostly in body secretions, role in local immunity in mucous membranes IgD Binds to B-cells to act as an antigen receptor. Low levels in serum. IgE Binds to basophils and mast cells, involved in allergic reactions. Least common in serum. IgM First in the primary (innate) immune response. Activates complement, involved in the lysis and agglutination of microbes, binds to B-cells as an antigen receptor IgG Binds to immune cells to enhance antigen recognition (long-term immunity). Most common in serum, crosses the placenta, activates complement. Macrophage Body response to an injury or infection Cardinal signs  Erythema, heat, pain, swelling, and loss of function Blood vessels in the injured area first constrict and then dilate  Also become more permeable or “leaky” Neutrophils and monocytes  Leave the blood vessels to fight the infection  Clean up the area Commonly characterised by impairments of the immune system that affect  Antibody activity  Lymphocyte function (i.e. T- and B-cells)  Phagocytosis  or a combination of these Can be further classified as either primary or secondary Can be present at birth (congenital) or develop later in life (acquired) Primary immunodeficiency  Chiefly affects the immune system itself and its parts Secondary immunodeficiency  Affects immune function as a consequence of a secondary cause elsewhere in the body T-cell disorders  Result from impaired T-cells  T-cell activation/T-cell maturation  Often result in frequent opportunistic fungal infections  Example: DiGeorge syndrome  Deletion of part of Chromosome 22  Results in thymic aplasia – frequent opportunistic infection B-cell disorders  Commonly affect antibody production (1, few or all)  May also affect B-cell numbers  Example: Bruton’s agammaglobulinaemia  Inherited X-linked recessive condition  Results in B-cell deficiency – all antibodies , frequent infections  Example: Selective IgA deficiency  Inherited condition, which can be autosomal dominant or recessive  Frequent infections Combined T- and B-cell disorders  Affect development of lymphoid stem cells  Differentiation of both lymphocyte subpopulations  Lymphocyte numbers and/or  Lymphocytes’ function  Example: severe combined immunodeficiency (SCID)  Various types: X-linked recessive, most common  Profoundly susceptible to infections   Antibody production   (or absent) T-cells   (or absent) Natural killer cell Consequence of environmental circumstances  Severe or prolonged stress  Medications  Poor nutrition  Infections  Blood cancers Severe or prolonged stress can result in  Adrenal gland hypertrophy   Glucocorticoid release   Immune response  Atrophy of lymphoid tissue Medications can result in  Immunosuppression effect or side effect  e.g. corticosteroids, immunosuppressants, antineoplastics, and some antibiotics  Inhibit the production of immune/inflammatory mediators  Inhibit the immune cell proliferation  Alter balance between normal flora and opportunistic pathogens Poor nutrition can result in   Proteins to make antibodies or chemical mediators   Vitamins necessary for immunity  e.g. vitamins A, B, C and E   Minerals important for immunity  e.g. zinc and iron Infection may disrupt immune attack by  Neutralising antibody  Impairing (lysosomal) action of phagocytic enzymes  Evading recognition by the immune system Blood cancer can affect  Production or maturation of lymphoid and myeloid tissues  Altered availability and/or function of lymphocytes and monocytes  Inadequate cellular and humoral immune responses Inappropriate excessive immune responses Induce inflammatory responses that can lead to  Tissue damage  Chronic disability  Death (occasionally) Four types, classified by  Speed on onset  Mediated by antibody or direct immune cell attack  Type of antibody concerned  Activation of Complement Symptoms vary depending on what part of the body is involved or exposed to the allergens  Inhalation often causes a runny nose, sneezing, coughing, or wheezing  Ingestion causes nausea, diarrhea, vomiting, or abdominal cramps  Skin exposure to allergens causes rashes, itchiness and urticaria  Systemic allergens (blood entry) are often the most life-threatening because they can affect many organs Source: Adapted from Bullock & Manias (2011), Figure 18.3, p. 178. Clinical manifestation  Localised inflammatory response affecting  Skin → rash  Airways → constriction and obstruction  Gastrointestinal tract → abdominal cramps, diarrhoea  Systemic → multiple organ failure e.g. Anaphylactic shock  Systemic inflammatory response  Blood vessels dilate so quickly that a significant and sudden drop in blood pressure occurs  Increased vessel permeability shifts intravascular fluid to interstitial space to further the drop in BP  Shock  Death A life-threatening condition such as anaphylaxis will push a person into anaphylactic shock and death without treatment, such as  Adrenaline  Airway management  Bronchodilators  Fluid support  IV corticosteroids  Mast cell stabilisers  Antihistamines Most importantly to educate avoidance of causative allergen(s) Examples  Myasthenia gravis  Antibodies bind to and destroy neuromuscular ACh receptors  Mismatched ABO blood transfusion or haemolytic disease of the newborn (HDN)  Antibodies result in the destruction of red blood cells Examples  Arthus reaction → vasculitis and tissue necrosis  Serum sickness → after intravenous administration of antisera  Where antigen-antibody complexes are widely deposited into a variety of tissues Examples  Contact dermatitis  Diabetes mellitus – Type I  Chronic graft rejection  Granulomatous disease  A mass of inflammatory cells occupy a spheroid tissue lesion (granuloma)  Lesion unable to be removed  Lesion becomes fibrotic and necrotic  E.g. tuberculosis Granuloma A loss of tolerance to ‘self ’  The body does not recognise a part of itself  Considers its cells “foreign/antigen” and attacks them Tolerance occurs through  Thymic education of T-cells  Bone marrow education of B-cells  Maintenance of ‘privileged’ sites  Brain  Testicles  Pregnant uterus Loss of ‘self’ tolerance may develop through  Disruption to T-cells education by thymus  A breach in the physical barrier between blood and ‘privileged’ sites  Antigens from infectious organisms being too similar to self-tissues, resulting in cross-reactivity Systemic lupus erythematosus  Clinical presentation, systems involved, and basics of management Rheumatoid arthritis  Clinical presentation and basics of management Infectious Mononucleosis  Causes, clinical presentation Acquired immunodeficiency syndrome  Pathophysiology, routes of transmission