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Lecture 13 – Ch. 43: Immune SystemLecture 13 – Ch. 43: Immune SystemI. Overview
II. Innate ImmunityA. componentsB. cells
IIII. Adaptive/acquired immunity
A. Lymphocytesi. B-cellsii. T-cells
B. humoral vs. cell-mediated immunityC. AntibodiesD. MHC molecules
IV. Immune memory
V. Immune System Problems
VI. Preparation for next lecture
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Why do we not get sick EVERY time someone near us sneezes?
Thought Question:
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Overview
PathogensVirusesBacteriaMacroparasites
For example…
Virus Bacteria Macroparasites
Influenza Strep Malaria
Ebola Black Plague Sleeping Sickness
Chicken Pox Salmonella River Blindness
West Nile Virus E. Coli Elephantiasis
IrritantsPollenDust
pollen
cilia of tracheal cells
dust
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Disease Defenses
A Way In?
Mucus membranes
Eyes
Nose
Mouth
Vagina
Urethra
Skin breeches (cuts, punctures, scrapes)
Antigens = foreign molecules specific to the invader
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Immunity Overview
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Which cells are exclusively part of the adaptive immune system?
1. Dendritic cells
2. Macrophages
3. B cells
4. Natural killer cells
5. White blood cells
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External Barriers
Innate Immunity
Skin
Dry dead cells
Constantly sloughed off
Secretions
Contain natural antibiotics
Mucus physically traps microbes
Dendritic cells – detect foreign particles alert innate and adaptive immune systems
Mast cells – cause inflammation and alert of damaged tissues
Internal Barriers
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Innate ImmunityLeukocytes
Phagocytes - ingest foreign particles & cellular debrisMacrophages – consume
many cells
Neutrophils – die upon consumption
Natural killer cells
Attack cancerous or infected body cells
Use proteins & enzymes to lyse cells
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Inflammation
Initiated by damaged or infected cells
Histamine release by mast cells
Capillary flow and permeability increased
Phagocytes drawn to area
Innate Immunity
Cytokines – recruit more lymphocytes leads to pus, swelling, redness, heat
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Inflammatory “Symptoms”
Warm, red, painful
Result of leaky capillaries
Increased fluid secretions
Removal of dead cells and waste
Pain
Swelling, chemical response
Alerts injured organism
NSAIDs
Innate Immunity
Leukocytes and fluid = pus
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Antimicrobial peptides in vertebrates:
the complement – family of proteins, inactivate and lyse infected cells
Interferons – cytokine made by host cells, boosts immune response
Innate ImmunityAntimicrobial peptides first discovered in insects (like Drosophila).
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One immune similarity between insects and humans is…..
1. Both use B and T cells
2. Both have skin as a barrier
3. Both engage antimicrobial peptides
4. Both have adaptive immunity
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Adaptive Immune System
Acquired/ adaptive immunity –consists of lymphocytes B cells and T cells
Responsible for circulating antibodies, remembering pathogens, destroying infected cells
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B cells
Made and mature in bone marrow
Lymphocytes that make antibodies – either secreted or embedded in B cell membrane
Humoral immunity
B cells and antibodies attack pathogens before they enter cells
After encounter pathogen, B cells differentiate into memory B cells and plasma cells
Adaptive Immune System
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Clonal Selection:
Adaptive Immune System
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B cell Plasma cell
Adaptive Immune System
Plasma cells make and secrete TONS of antibodies, as opposed to memory B cells
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Which is NOT a function of B cells?
1. Produce memory cells
2. Secrete antibodies
3. Attack infected cells
4. Make clones of plasma cells
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Antibody action
Defend against pathogens in blood or fluid
Can inactivate pathogens by binding to epitopes
Can stimulate phagocytosis
Can neutralize toxins or block adhesion
Can trigger complement system where blood proteins destroy invaders
Adaptive Immune System
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Antibodies
Produced by B cells
Each composed of two heavy chains and two light chainsConstant region is same
Variable region is unique to antibody
Bind antigens at each end of “fork”
Adaptive Immune System
Genes are unique in that can recombine into millions of combinations in different B cells. Transmembrane antigen
receptors inserted in B cells
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Immunospecificity
Antibodies are “pieced together” from many genes
Random combinations allow for millions of possibilities
Adaptive Immune System
Each B cell produces unique antibodies
Over 100 million different antibodies in body chances of an antigen encountering one that fits are high
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How does our body mount an immune attack to a new pathogen (not previously encountered)?
1. By using memory B cells
2. By chance encounter with a B-cell receptor
3. By attacking with macrophages
4. Both (b) and (c)
5. Both (a) and (c)
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Adaptive Immune SystemT cells
Made in bone marrow, mature in thymus
Lymphocytes that cozy up to infected cells – two types:
Helper T cells – recognize and bind infected cells
Cytotoxic T cells – bind and lyse infected cells
Cell-mediated immunity
T cells find and attack pathogen-infected cells
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Cell-mediated immunityCytotoxic T cells: Insert pores in infected cells, enzymes break down cells
Helper T cells stimulate lymphocyte division
Some T cells develop into memory cells – future protection
Adaptive Immune System
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T cell receptors – recognize pathogen epitopes ‘presented’ on infected cells
Composed of one alpha chain, one beta chainHave a variable and constant region, similar to B-antibodies
Adaptive Immune System
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Self-tolerance
Adaptive Immune System
All cells have MHC molecules – most body cells have class I (lymphocytes have class II)
MHC molecules displayed on cell surface – each binds a specific peptide foreign fragment then “displays” it on surface.
MHC = major histocompatibility complex
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Self-tolerance
Adaptive Immune System
T-cells (cytotoxic or helper T) bind to MHC presented antigens
Self-reactive lymphocytes with receptors to self epitopes are eliminated before they leave bone marrow and mature
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Which cells have MHC molecules displayed?
1. Most body cells
2. Cancerous cells
3. Immune system cells
4. Transplanted cells
5. All white blood cells
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Immune system must remember past victories...
• Memory cells “remember” specific antigens
• May survive for years
• Respond faster and larger to repeat invasion
Adaptive Immune System
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Memory
Memory B and T cells are able to recognize pathogens and fight off infections immediately
Adaptive Immune System
Then why do you keep catching a cold every year?
100+ rhinoviruses
Cold viruses can mutate quickly
Vaccinations take advantage of the immune response
Body is exposed to antigens to stimulate memory cells
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Antibiotics aid disease fight
Reduce growth and reproduction of living pathogens (not viruses)
Give immune system time to fight infection
Humans have misused antibiotics “superbugs”Overuse of antibacterial
products
Failure to complete full course of antibiotics
Non-medicinal use of antibiotics
Antibiotics
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Allergies
Immune overreaction to harmless antigens
Histamine triggers inflammation
Extreme response can trigger anaphylaxis
Immune System Problems
Autoimmune DisordersImmune system attacks healthy body cells
Lupus, Rheumatoid Arthritis, Multiple Sclerosis, Type 1 Diabetes, Celiac disease, Crohn’s disease
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Immune Deficiency Syndromes
Severe Combined Immune Deficiency (SCID): Few/no immune cells produced genetic
Acquired Immune Deficiency Syndrome (AIDS): Due to Human Immunodeficiency Virus (HIV)
Destroys helper T cells
Immune System ProblemsImmune rejection
When tissue without “self” MHC molecules (aka HLA) contact immune system, response mounted
Can be countered by immunosuppressive drugs
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What can you do to fortify your immune system?
Thought Question:
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Things To Do After Lecture 13…Reading and Preparation:
1. Re-read today’s lecture, highlight all vocabulary you do not understand, and look up terms.
2. Ch. 43 Self-Quiz: #1 – 7 (correct answers in back of book)
3. Read chapter 43, focus on material covered in lecture (terms, concepts, and figures!)
4. Skim next lecture.
“HOMEWORK” (NOT COLLECTED – but things to think about for studying):
1. Compare and contrast: T cells and B cells, the humoral response compared to the cell-mediated immune response.
2. Explain the function and parts of the human innate immune system.
3. Describe the problem with each of the following: allergies, autoimmune disorders, immune deficiency syndromes.
4. Why are people concerned about over-use or misuse of antibiotics?