Immune System How we stay alive though vastly outnumbered

The Immune System – (the big picture) 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 Fig 21.1

OYO

OYO

OYO

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

Great summary of B cells vs. T cells

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 nodes as check points

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

B cell antibodies against extracellular antigens Bs and Ts work together simultaneously B cell antibodies against extracellular antigens T cells attacking intracellular antigens

Central role of helper Ts Fig. 21.18

Good Summary Fig. 21.20 and Table 21.8

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 subacute reactions 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 injected allergen (but may also be ingested) Blood transports it to all mast cells & all basophils 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 days after 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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