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Immune System How we stay alive though vastly outnumbered. The Immune System – (the big picture). Fig 21.1. Innate (Nonspecific) Immunity Response is localized… Inflammation is hallmark No ‘customizing’… No memory… OYO – Great summary in Tables 21.1 & 21.2, 21.3
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The Immune System – (the big picture) Fig 21.1 • Innate (Nonspecific) Immunity • Response is localized… • Inflammation is hallmark • No ‘customizing’… • No memory… • OYO – Great summary in Tables 21.1 & 21.2, 21.3 • Adaptive (Specific) Immunity • Response is systemic… • Is customized (specific)… • Has memory… • Great Summary Table 21.8, 21.4
Adaptive Immunity (an outline) Antigens Immunocompetence & Self-tolerance Positive vs. Negative selection of B cells and T cells Antigen-Presenting Cells (APCs) needed to activate CD8 T cells and Helper T cells which then activate both B cells and T cells The Humoral Immune Response by B cells The Cellular Immune Response by T cells Vaccinations Organ Transplants & Rejections HIV & AIDS Autoimmune Diseases Hypersensitivities
Antigens and antigenic determinants Fig. 21.7 Most antigens have several. Lg. proteins may have 100s
Immunocompetence Fig. 21.8 Ts Bs Ts Bs Ts Ts Ts Bs
Positive & Negative Selection Fig. 21.9 • Self MHCs = major histocompatibility complexes … • Receptor shapes (binding sites) on new B & T cells are random … • Some “read” (connect) to self MHCs, some don’t • 1) If read self MHC… positive selection • If can’t read … apoptosis • 2) If read self MHCs & react to those with self antigen… negative selection • Survivors (approx. 2%) are “self tolerant” and therefore immunocompetent and self-tolerant
Immunocompetence Fig. 21.8 Lymph node “gauntlet” Bs Ts
Lymph node interior Fig. 20.3
APCs - Antigen Presenting Cells • Phagocytize the foreign antigen • Present the foreign antigenic marker at surface • Are needed to activate CD4 helper Ts and CD8 cytotoxic Ts • Are not needed to activate B cells but do enhance activation via helper Ts • Examples: • Dendritic cells of skin. #1 • Macrophages in lymph nodes, spleen, and connective tissues • Some B lymphocytes – but only to activate CD4 Helper Ts • Dendritic cells, after phagocytizing antigen, move into lymph and “present” antigen to T cells in lymph nodes
Humoral Response - B cells Fig. 21.11 5 days 5 days 2000/sec/cell Location… Activation… Cloning… Plasma cells… 1-2 days
Humoral response (antibodies) effective against extracellular antigens
Actions of antibodies Fig. 21.15 Video of neutrophil chasing bacteria, 15 secs
Humoral Response - B cells Fig. 21.11 5 days Memory cells… 1o vs. 2 o response Vaccines 5 days 1-2 days
Primary vs. Secondary Response Fig. 21.12
The Cell-Mediated Response - T cells Fig. 20.2
Two major types of T cells Fig. 21.16
Action of CD8 cells (a.k.a. cytotoxic Ts, TC, Killer Ts) Fig. 21.19 Perforin and granzymes… Video of Killer attacking cancer cell, 1 min
Cell-mediated T cell response is effective against intracellular antigens And against antigens that are cellular themselves. E.g. Bacteria Cancer cells V V V V V V V V V V
B cell antibodies against extracellular antigens Bs and Ts work together simultaneously T cells attacking intracellular antigens
Central role of helper Ts Fig. 21.18
AIDS due to HIV • AIDS = Acquired Immune Deficiency Syndrome • HIV = human immunodeficiency virus • Reduces the # of helper Ts (CD4) • Helper Ts play a central role in activation of both B cells & T cells • Therefore both responses are suppressed • Pt. now vulnerable to infections – pneumonia, TB, cancer, etc. • Helper T #s determined by CD4 count • Normal = 600 – 1200 cells/uL • Aids pts. typically less than 200 cells/uL
Antibiotics • Chemical substances… • Effective against bacteria • Similar to cytokines (including interferons and interleukins) • Is actually a form of chemotherapy
Tissue Transplant Rejections • Why? • Who? • Prevention? • Immunosuppressive drugs • Advantage? • Disadvantage?
Autoimmune Disorders • Def… • E.g. Myasthenia Gravis • Rheumatoid arthritis • Multiple Sclerosis • Lupus
Hypersensitivites = Allergic Reactions • When… • Your immune reaction is the problem • Antigens now called “Allergens” • Types of Hypersensitivities are determined by • time frame of reaction – immediate vs. delayed • Whether antibodies (B cells) or T cells are involved • Antibodies cause immediate and subacutereactions • T cells cause delayed reactions
Acute (immediate) Hypersensitivity Reactions Fig. 21.21 • Primary response of both B & T cells • IgE antibodies from B cells attach to and act as receptor sites on mast cells and basophils. • Usually asymptomatic at this point • [Mast cells abundant in skin and mucous membranes] • Granules contain and release histamine • Therefore….. • Upon 2nd exposure reaction begins within seconds of exposure • E.g. Asthma
If this response is localized… • mostly just a nuisance • S&S depend upon method of exposure Usually inhaled or ingested
1A) If allergen is airborne (inhaled)… 1A) If reaction includes spasms of airways and mucus plugs = asthma • S&S: • SOB • Wheezing • Hypoxia • Cyanosis
1B) If allergen is ingested… Fig. 23.1 Includes some food allergies Cramping Vomiting Diarrhea
Trtmt • Localized reactions respond well to antihistamines. • Bronchodilators(e.g. albuterol, epi) are beneficial for asthma.
2. If response is systemic … • Called Anaphylactic Shock (a.k.a. anaphylaxis) • Is life threatening • most often due to an injectedallergen (but may also be ingested) • Blood transports it to all mast cells & allbasophils causing massive release of histamine
2. If response is systemic(cont’d)… • Effects: • Tongue swells & bronchioles constrict SOB • Hives • Vessels dilate, BP falls • Vessel permeability increases, fluid shifts out of vessels, BP falls further • Trtmt: Epinephrine - To dilate bronchioles and vasoconstrict vessels
B) Delayed Hypersensitivities • Begins 1-3 daysafter exposure • The allergens (now called Haptens) pass through skin and attach to “self” (MHC1) markers. • Your cells now appear foreign • 1) Macrophages activated by cytokines come for a “feeding frenzy” 2) T cells come & destroy • Most examples are called “Allergic Contact Dermatitis” • (cosmetics, soaps, deodorants, some metals, poison ivy, poison oak, TB test)
B) Delayed Hypersensitivities e.g. cosmetics
Poison ivy Antihistamines not effective Need corticosteroids (e.g. Prednisone)
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