Lecture 5 - Immune & Lymphatic System Flashcards
Immune System Review
I. Natural or innate immunity: A nonspecific response
physical barriers like skin, mucosa, and cilia
fever
chemical barriers like digestive enzymes, perspiration, vaginal secretions, skin acid
complement proteins in blood
phagocytes like neutrophils & macrophages (in both natural and acquired immunity)
inflammation (in both natural and acquired immunity)
II. Acquired immunity: a specific response using lymphocytes to recognize and attack foreign invaders or pathogens and remember them for next time
Humoral (Antibody-mediated) immunity involves B cells
Cellular (Cell-mediated) immunity involves T cells
We have two main types of lymphocytes:
B cells: mature in red bone marrow,
T cells: complete their maturation in the thymus
When the T and B cells have matured, they travel to lymphatic tissues all over the body (lymph nodes, the lymphatic tissue inside the spleen, or lymphatic nodules, which are clusters of lymphatic tissue embedded in the mucous membranes).
For T and B cells to mount an immune response, they need to come into contact and interact with the pathogen. This occurs in 3 ways:
travels through lymphatic vessels and lymphatic fluids to a lymph node
travels through the bloodstream to lymphatic tissue in the spleen
penetrates mucous membranes and comes into contact with embedded lymphatic nodules.
B and T cells come into contact with the pathogen and become activated for that specific pathogen. They then clone themselves. This accounts for the swelling of lymph nodes during infection.
T cells leave the lymphatic tissue and kill that specific pathogen as they come across it.
Helper T cells secrete hormones to stimulate both B and T cells
Cytotoxic T cells outright kill any cells infected by a pathogen.
Memory cells stay after the infection is contained to recognize the pathogen if it invades again.
B cells produce antibodies that leave the lymphatic tissue and circulate in body fluids and in the bloodstream. They inactivate pathogens as they come across them.
Autoimmune Disease
In an autoimmune disease, the B and T cells are unable to distinguish the body’s own normal, healthy tissues from something that is foreign to the body or a pathogen.
Examples of common autoimmune diseases:
Rheumatoid arthritis: the immune system attacks the synovial lining of joints, causing ongoing inflammation and damage.
Multiple sclerosis: the immune system attacks the myelin sheath surrounding neurons in the central nervous system.
Type 1 diabetes mellitus: the immune system attacks the insulin-producing cells of the pancreas.
Hypersensitivity Reactions: Allergic Disorders
This is an exaggerated or inappropriate abnormal immune response to an exogenous antigen (from the outside world) or a reaction to an endogenous (inside the body) auto-antigen. These are basically “over reactions” to something that is normal.
We have four types depending on the mechanism:
Type I Immediate Hypersensitivity: anaphylactic or atopic reactions
Type II Cytotoxic antibody mediated reaction
Type III Immune complex mediated reaction
Type IV Cell mediated or Delayed type reaction
Hypersensitivity Reactions
(Allergic disorders)
Type I Immediate Hypersensitivity: Anaphylactic or atopic reactions:
Mediated by: IgE, mast cells or basophils
Process: IgE is sensitized to a foreign antigen like pollen, 2nd time exposed to this foreign substance leads to the formation of antibody/antigen complexes on the surface of mast cells. This triggers an immediate release of a vasoactive substances called histamine stored in the mast cells granules and other inflammatory mediators like prostaglandins & leukotrienes that enhance and prolong the effects of histamine.
Symptoms: systemic vasodilation, bronchospasm, increased mucus secretions and edema all referred to as anaphylaxis. This causes increased vascular permeability, an accumulation of inflammatory cells (eosinophils especially), also have a late phase response 4-6 hours later mediated by arachidonic acid (leukotrienes & prostaglandins) common in asthma (coughing, shortness of breath, excessive mucus production), bee stings are the most common, other triggers: penicillin, foods, animal dander, children, semen, latex
Common symptoms: wheezing, hypotension, swelling, urticaria (welts), rhinorrhea, sneezing, may be life threatening, need an injection of epinephrine to restore blood pressure
Examples: hay fever, allergic rhinitis, atopic dermatitis, bronchial asthma, anaphylactic shock
Hypersensitivity Reactions
(Allergic Disorders)
Hay Fever
Description: Hay fever, allergic rhinitis, seasonal allergy to foreign substances not normally pathological
Etiology: inhaled pollens, other plant substances, cat dander or house dust trigger an abnormal response from the immune system
Pathogenesis: the inhaled pollens trigger a release of histamine that causes swelling and inflammation of the nasal passages and conjunctiva
Clinical Features: itching, runny nose, itchy watery eyes, sneezing, swollen skin under eyes, coughing (all similar to the common cold).
Treatment: desensitization to allergens and antihistamines
Hypersensitivity Reactions
(Allergic Disorders)
Atopic Dermatitis - Eczema
Description: a chronic skin irritation known as eczema, usually in childhood only, effects 10% of children, family history is common
Etiology: abnormal response to environmental allergens that come into direct skin contact
Pathogenesis: hyperproduction of IgE in response to environmental allergens
Clinical Features: improves with age
Treatment: moisturizers, anti itch cream, corticosteroid cream, phototherapy
Hypersensitivity Reactions
(Allergic disorders)
Asthma
Description: affects the bronchi
Etiology abnormal response to inhaled allergens
Pathogenesis: leukotrienes and prostaglandins released constrict the bronchioles and cause an overproduction of mucus
Clinical Features: coughing, wheezing, excess mucus
Treatment: inhaled corticosteroids (to open airways and reduce swelling of bronchioles), prevention (recognizing triggers), allergy shots (immunotherapy)
Hypersensitivity Reactions
(Allergic disorders)
Anaphylactic Shock
Description: a severe, life threatening systemic response to an allergen
Etiology: abnormal response or reaction to a normal substance
Pathogenesis: causes a massive release of histamine and other vasoactive substances into the bloodstream, results in edema in cutaneous tissues (hives) and respiratory tissues, bronchoconstriction occurs, causes acute respiratory failure, generalized vasodilation causes shock
Clinical Features: stridor (high pitched sound during breathing caused by vocal cord spasm), choking, wheezing, shortness of breath, fainting
Treatment: epinephrine injected immediately, oxygen, intravenous antihistamines, cortisone, beta agonist
Hemolytic Anemia (Review)
Description: red blood cells are destroyed (hemolysis) faster than they can be produced in the bone marrow and are also defective. This impedes their ability to carry oxygen. There are less and less functioning red blood cells to carry oxygen.
Etiology: red blood cells are destroyed (hemolysis) by auto antibodies, faster than they can be produced, may be caused by a mismatched blood transfusion, genetic defects, toxins, or infections
Pathogenesis: less functional RBC’s means less oxygen to tissues and organs (hypoxia),
Clinical features: fewer RBC’s, reduced life span, increased numbers of immature reticulocytes, fatigue, headache, chest pain, irregular heart beat, cold intolerance, shortness of breath, pallor, dizziness, brittle hair, spoon shaped nails, delayed wound healing, swollen ankles, beefy red tongue, cracked lips, intermittent calf pain.
Treatment: RBC transfusions, immunosuppressants, steroids
Pathology - Immune System
Hypersensitivity Reactions
Type II Cytotoxic Antibody mediated reaction
Mediated by: IgG and IgM
Process: IgG and IgM form antigen-antibody complexes on usually normal cell membranes which activates the complement system (causing cell lysis and also phagocytosis), these complexes react with antigens (both foreign or extrinsic: drugs, chemicals, bacterial secretions and from within or intrinsic: proteins, RNA, DNA), our body attacks normal substances for an unknown reason (autoimmune diseases).
Symptoms: depends on the tissue reacting
Examples: hemolytic anemia, Goodpasture’s syndrome, Graves Disease, Myasthenia Gravis
Hypersensitivity Reactions
(Allergic disorders)
Goodpasture’s Syndrome
( bệnh kháng màng đáy cầu thận)
Description: autoimmune disease affecting kidneys and lungs. Antibodies produced attack a component of collagen (Type IV) that affects the alveoli of the lungs and the glomerulus of the kidneys. Highest incidence in young (20-30 years) caucasian men or over 60.
Etiology: autoimmune, exposure to chemicals and cigarette smoke, cocaine, virus
Pathogenesis: antibodies attack collagen in the basement membrane of tissues in lungs and kidneys, causing inflammation and destruction of cells of the glomeruli of the kidneys and cause massive pulmonary hemorrhage in the lungs.
Clinical Features:
Lungs: fatigue, nausea, vomiting, difficulty breathing or shortness of breath, cough and pale skin.
Kidney: blood in urine, painful urination, foamy urine, hands and feet swelling, hypertension and flank pain.
Treatment: immunosuppressants, corticosteroids and plasmapheresis: removing antibodies from blood.
Hyperthyroidism
Graves Disease
Description: an autoimmune disorder causing hyperactivity of the thyroid gland or hyperthyroidism with a resultant goiter (enlargement of the thyroid gland). Excessive thyroid hormone secretions increase the body’s metabolic rate 60% to 100%. Graves disease is more common in women than in men and manifestations occur after age 20 years. Thyroid hormones act to increase the basal metabolic rate, affect protein synthesis, help regulate long bone growth, neuronal maturation and increase the body’s sensitivity to catecholamines. The thyroid hormones are essential to proper development and differentiation of all cells of the human body. They also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energy and they also stimulate vitamin metabolism. Thyroid hormone leads to heat generation.
Etiology: autoimmune disorder, genetics
Pathogenesis: antibodies are produced in reaction to thyroid hormones and attack regulatory thyroid hormones causing overproduction.
Clinical Features: anxiety, hand tremors, weight loss (despite normal or increased food intake), diarrhea, fatigue, insomnia, tachycardia, flushed and warm skin with profuse sweating, heat intolerance, erectile dysfunction, brittle or loss of hair, goiter, joints are often hypermobile, protrusion of the eyeballs (exophthalmos) and Graves dermopathy (pretibial myxedema). The latter is reddening and swelling seen on the shins and tops of the feet.
Treatment: decrease thyroid hormone production and control symptoms, especially tachycardia. Medications include beta-blockers and anti-thyroidal drugs. Surgery (thyroidectomy) or irradiated to kill some of it.
Myasthenia Gravis
Description: impaired impulse transmission of motor neurons caused by antibodies that attack and destroy acetylcholine receptors at the neuromuscular junction with an excess of cholinesterase (an enzyme that deactivates acetylcholine). With less or no receptors and no enzyme to deactivate it, there is an excess of acetylcholine in the synaptic cleft and less nerve signals going to the muscles, this causes a reduction of stimulation of muscles and weakness that is progressive that eventually leads to paralysis. Most often seen in women 20-30 years old and in men aged 50. If respiratory muscles are involved there are recurrent respiratory infections and a risk of breathing dysfunction. Eye muscles, muscles of facial expression, throat muscles and muscles of mastication are affected 20% of the time, so chewing talking and swallowing are difficult. May cause weakness in neck, arm and leg muscles also.
Etiology: autoimmune disease, but also 75% of sufferers have a thymus disorder (tumour).
Pathogenesis: unclear, but antibodies are produced by B cells and converted into plasma cells that activate T helper cells that also activate the antibodies. This all happens in the thymus gland. Thymus plays a key role in activating and developing T cells. The antibodies block the receptors.
Clinical findings: Facial weakness and loss of expression, muscles of the eyes, mouth, throat and neck are all affected. Ptosis: eyelids droop, face may falsely express sadness and attempts to smile may result in a snarl, impaired vision, difficulty chewing and swallowing, impaired speech often produces a sound similar to a nasal monotone, head droops forward as a result of weak neck muscles and fatigue is a frequent complaint.
Treatment: no cure, manage symptoms with medications: cholinesterase inhibitors, corticosteroids, immunosuppressants, surgery if tumour in thymus.
Pathology - Immune System
Hypersensitivity Reactions
(allergic disorders)
Type III Immune complex mediated reaction
Mediated by: immune complexes are formed between antigens and antibodies and deposited into tissues (blood vessel walls often-called vasculitis) which also activates the complement system. This causes inflammation and local tissue injury, effects the skin causing wheals, joints causing synovitis, kidneys causing nephritis, pleura causing pleuritis and pericardium causing pericarditis
Process: When these complexes are circulating they affect the whole body and are systemic and if these complexes stay local they affect specific tissues only. They commonly are found in small blood vessels, joints and in the glomeruli of the kidneys causing symptoms. These complexes activate the complement system, attract PMN’s and result in acute inflammation with fibrinoid necrosis.
Symptoms: variable depending on systems effected
Examples: systemic lupus erythematosus (SLE), poststreptococcal glomerulonephritis, polyarteritis nodosa
Hypersensitivity Reactions
(Allergic disorders)
Systemic Lupus Erythematosus (SLE)
Definition or description: has various autoantigens reacting with antibodies and effects multiple systems in the body, 10 x more common in women, any age but most often young adults, most severe among african americans, is familial
Etiology (cause): autoimmune disease, unknown cause, maybe a virus
Pathogenesis: the antigens reacting with antibodies form complexes that deposit into tissues in clumps. Malfunctioning T cells activate B cells that secrete auto antibodies.
Clinical Features: many variable symptoms, fever, malaise, headache, loss of appetite, often affects skin, kidneys, joints and blood.
Skin: SLE Butterfly rash, inflammation of the joints (arthritis): swelling, redness and pain
Kidney: 75% of the time are involved, hematuria, proteinuria, glomerulonephritis is common,
Joints: arthralgia
Blood: circulating antibodies damage RBC’s and cause anemia
Treatment: immunosuppressant drugs, hydroxychloroquine (anti malaria drug), corticosteroids and NSAIDS
Hypersensitivity Reactions
(Allergic disorders)
Post-streptococcal Glomerulonephritis
Definition or description: renal disease after an upper respiratory tract infection with streptococcal producing antigen/antibody complexes in the glomerulus
Etiology (cause): group A streptococcus infection, unknown
Pathogenesis: these antigen/antibody complexes stick to the glomerular basement membrane and invoke an inflammatory response, kidneys are less efficient at filtering
Clinical Features: after pharyngitis or a skin infection, loss of glomerular function, dark urine, proteinuria, high blood pressure, facial swelling, swelling in hands & feet, malaise and lethargy.
Treatment: blood pressure medication, decrease swelling, diuretics (increases urine output)
