The immune system
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THE IMMUNE SYSTEM
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IMMUNOLOGY AND THE IMMUNE SYSTEM
• Immunology– Study of the components and function of the immune system
• Immune System – Molecules, cells, tissues and organs which provide non-specific
and specific protection against• Microorganisms• Microbial toxins• Tumor cells
– Crucial to human survival– Antigens :– Molecules from a pathogen or foreign organism that provoke a
specific immune response.
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The Invaders . . .
• Bacteria
• Viruses
• parasites such as fungi, protista, & worms
worm trichura.jpg
http://www.hhs.gov/asphep/presentation/images/bacteria.jpg
http://www.skidmore.edu/academics/biology/plant_bio/lab13.FUNGI.html
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Types Of Immune System
• Immune response– Innate (non-specific)– Adaptive (specific)
• Primary • Secondary
• These two systems perform many of their functions by cooperative interactions
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Defense Mechanisms
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Chapter 21, Immune System 6
Immunity: Innate (nonspecific)
• immunity an organism is born with.• system responds quickly and consists of:
– First line of defense – intact skin and mucosae prevent entry of microorganisms
– Second line of defense – antimicrobial proteins, phagocytes, and other cells
• Inhibit spread of invaders throughout the body• Inflammation is its hallmark and most important
mechanism
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Chapter 21, Immune System 7
Immunity: Adaptive (specific) defense system
– Third line of defense – mounts attack against particular foreign substance.
– Immunity that an organism develops during life time.
– Develops only after exposure to including agents such as microbs, toxins, or other foreign substances.
• Takes longer to react than the innate system• Works in conjunction with the innate system
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First line of defenses / innate immune system
• The body’s 1st line of defense against pathogens uses mostly physical and chemical barriers such as :
• Skin- acts as a barrier to invasion• Sweat- has chemicals which can kill different pathogens.• Tears – have lysozymes which has powerful digestive abilities
that render antigens harmless .• Saliva – also has lysozymes• Mucus – can trap pathogens, which are than sneezed,
coughed, washed away, or destroyed by chemicals • Stomach acids – destroys pathogens .
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Body Coverings: The Skin
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Chapter 21, Immune System 11
Epithelial Chemical Barriers
• Epithelial membranes produce protective chemicals that destroy microorganisms– Skin acidity (pH of 3 to 5) inhibits bacterial growth– Sebum contains chemicals toxic to bacteria– Stomach mucosae secrete concentrated HCl and
protein-digesting enzymes– Saliva and lacrimal fluid contain lysozyme– Mucus traps microorganisms that enter the
digestive and respiratory systems
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Chapter 21, Immune System 12
Respiratory Tract Mucosae
• Mucus-coated hairs in the nose trap inhaled particles
• Mucosa of the upper respiratory tract is ciliated– Cilia sweep dust- and bacteria-laden mucus away
from lower respiratory passages
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1st line of defense (Respiratory and Digestive System
• The respiratory passage is lined with mucous
• Cilia also lines the respiratory passage
• There is mucous in the respiratory passage that traps invading microbes and other foreign debris with the cilia.
• Acids in the stomach and protein digesting enzymes destroy most of the invading microbes carried into the body with food.
Immune System Overview: Goals
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Second line of defense
• If a pathogen is able to get past the body’s first line of defense, and an infection starts , the body can rely on it’s second line of defense .
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Chapter 21, Immune System 17
Internal Defenses (Second Line of Defense)
• The body uses nonspecific cellular and chemical devices to protect itself
1. Phagocytes 2. natural killer (NK) cells3. Inflammatory response enlists macrophages,
mast cells, WBCs, and chemicals4. Antimicrobial proteins in blood and tissue fluid
• Harmful substances are identified by surface carbohydrates unique to infectious organisms
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Leukocytes• also called white blood cells are large opaque blood cells that engulf invading microbes. They can also produce antibodies.– They have a nucleus (so different
from red blood cells)– The size of the nucleus and the
types of granules that can be found inside of them can be used to classify them into different classes of leukocytes.
• Granulocytes: have cytoplasmic granules and are made in the bone marrow.
• Agranulocytes: do not have a granular cytoplasm and are also made in the bone marrow, but then modified in the lymph nodes.
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Nonspecific Phagocytosis
NeutrophilsMonocytesEosinophils
NeutrophilsMonocytesEosinophils
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Chapter 21, Immune System 20
1. Phagocytes
• Macrophages are the chief phagocytic cells• Free macrophages wander throughout a region in search
of cellular debris• Kupffer cells (liver) and microglia (brain) are fixed
macrophages• Neutrophils become phagocytic when encountering
infectious material• Eosinophils are weakly phagocytic against parasitic
worms• Mast cells bind and ingest a wide range of bacteria
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Chapter 21, Immune System 22
Mechanism of Phagocytosis
• Microbes adhere to the phagocyte• Pseudopods engulf the particle (antigen) into a
phagosome• Phagosomes fuse with a lysosome to form a
phagolysosome• Invaders in the phagolysosome are digested by
proteolytic enzymes• Indigestible and residual material is removed by
exocytosis
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Chapter 21, Immune System 23
Mechanism of Phagocytosis
Figure 21.1a, b
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Natural killer cells
Lymphocytes, such as NK cells, are characterized by their large nuclei that actively absorb Wright stain and therefore appear dark colored under a microscope.
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Chapter 21, Immune System 25
2. Natural Killer (NK) Cells• Cells that can lyse and kill cancer cells and virus-infected
cells• Natural killer cells:
– Are a small, distinct group of large granular lymphocytes – React nonspecifically and eliminate cancerous and virus-
infected cells– Kill their target cells by releasing perforins and other
cytolytic chemicals– Secrete potent chemicals that enhance the
inflammatory response
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Chapter 21, Immune System 27
3. Inflammation: Tissue Response to Injury
• The inflammatory response is triggered whenever body tissues are injured – Prevents the spread of damaging agents to nearby
tissues– Disposes of cell debris and pathogens– Sets the stage for repair processes
• The four cardinal signs of acute inflammation are redness, heat, swelling, and pain
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Inflammatory Response
Histamine & prostaglandins released
Capillaries dilateClotting begins
Chemotactic factors attract phagocytic cells
Phagocytes consume pathogens & cell debris
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Chapter 21, Immune System 29
4. Antimicrobial Proteins
• Enhance the innate defenses by:– Attacking microorganisms directly– Hindering microorganisms’ ability to reproduce
• The most important antimicrobial proteins are:– Interferon– Complement proteins
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Interferon
• Protein secreted by a cell currently infected by a virus
• Interferon warns the neighboring cells of the impending viral infection
• The neighboring cells synthesize proteins that will block the virus from hijacking the cell DNA replication machinery
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Chapter 21, Immune System 31
Interferon (IFN)
Figure 21.4
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Chapter 21, Immune System 32
• Complement helps destroy pathogens• in three ways:• 1. Enhanced inflammation.• Complement proteins are• involved in and amplify the inflammatory response• because certain ones can bind to mast cells (type of• white blood cell in tissues) and trigger histamine• release, and others can attract phagocytes to the scene.• 2.
Complement Pathways
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Chapter 21, Immune System 33
2.Some complement proteins bind to the surface ofpathogens already coated with antibodies, whichensures that the pathogens will be phagocytized by aneutrophil or macrophage.3. Certain other complement proteins join to form amembrane attack complex that produces holes in thesurface of some bacteria and viruses. Fluids and saltsthen enter the bacterial cell or virus to the point that itbursts .
Complement systems
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Formation of membrane attack complexes
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Chapter 21, Immune System 35
• Abnormally high body temperature in response to invading microorganisms
• The body’s thermostat is reset upwards in response to pyrogens, chemicals secreted by leukocytes and macrophages exposed to bacteria and other foreign substances
Fever
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Chapter 21, Immune System 36
• High fevers are dangerous as they can denature enzymes
• Moderate fever can be beneficial, as it causes:– The liver and spleen to sequester iron and zinc
(needed by microorganisms)– An increase in the metabolic rate, which speeds
up tissue repair
Fever
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Adaptive Immunity
• Immunity that an organism develops during lifetime
• Develops after exposure to antigens• Invovles the activity of lymphocytes• Includes 3rd line of defense
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Adaptive Immunity (Specific immunity)
• Specificity
• Memory
• Ability to distinguish b/w self vs non-self
• T and B cell
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Types of Adaptive Immunity
1. Antibody-Mediated Immunity (AMI) or Humoral Immunity– B lymphocytes
2. Cell-Mediated Immunity (CMI) or Cellular Immunity– T lymphocytes
Note: B and T cells ……..blood, lymph, lymphoid tissues such as spleen, lymph nodes etc.
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Cell-Mediated Immune Response
• T cells
• Immune resoponse to infected cells( viruses, bacteria and parasites (Pathogens) within cells)
• Defense against cancer and transplant cells
Chapter 21, Immune System 40
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T-Lymphocytes
• Helper T cells – secrete CYTOKINES help B cells Tc cells to divide• Cytotoxic T cells (killer T cells) Kill infected body cells• Memory T cells remain in body
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How do T cells know a cell is infected?• Infected cells digest some pathogens and MHC
proteins carry pieces to cell surface• Antigen Presenting Cell (APC)• Alerts Helper T cells
MHC proteins displaying foreign antigens
infectedcell
T cell with antigen receptors
TH cell
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Macrophages
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Antigen-Presenting Cells
– B cells– Dendritic cells– macrophages
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Helper T Cells (TH)
• bind to other white blood cells that have previously encountered an antigen– stimulate proliferation of other T cells– Stimulate B cells that have already become bound
to antigen
• Without TH, there is no immune response
Chapter 21, Immune System 45
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The central role of Helper T Cells (Boss)
Chapter 21, Immune System 46Figure 21.17a
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Cytotoxic T Cell (Tc)
• Destroys infected body cells– binds to target cell– secretes perforin protein
• punctures cell membrane of infected cell– apoptosis
Chapter 21, Immune System 47
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Cytotoxic T cells
Killer T cellbinds to
infected cell
• Destroys infected body cells– binds to target cell– secretes perforin protein
• punctures cell membrane of infected cell– apoptosis
infected celldestroyed
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Cytotoxic T cell
1
Accessoryprotein
Class I MHCmolecule
Infectedcell
Antigenreceptor
Antigenfragment
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Cytotoxic T cell
1 2
Accessoryprotein
Class I MHCmolecule
Infectedcell
Antigenreceptor
Antigenfragment
Perforin
Pore
Gran-zymes
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The killing action ofcytoxic T cells on an infected host cell.
Cytotoxic T cell
31 2
Accessoryprotein
Class I MHCmolecule
Infectedcell
Antigenreceptor
Antigenfragment
Perforin
Pore
Gran-zymes
ReleasedcytotoxicT cell
Dyinginfected cell
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Figure 23.11 (1 of 2)
CMI
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• Human Immunodeficiency Virus– virus infects and destroys helper T cells
• helper T cells don’t activate rest of immune system: killer T cells & B cells
• AIDS: Acquired ImmunoDeficiency Syndrome– infections by opportunistic
diseases– death usually from – “opportunistic” infections
• pneumonia, cancers
HIV & AIDS
HIV infected T cell
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ANTIBODY-MEDIATED (HUMORAL) IMMUNITY
• targets extracellular microorganisms (Bacteria and viruses circulating in the blood)
• B-lymphocytes (B cells)………. Antibodies • Antibodies… extracellular fluids and surface of B
cells
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Pathogen
1
Antigen-presentingcell Antigen
fragment
Class IIMHC
molecule
Antigenreceptor
Accessoryprotein
Helper T cell
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Pathogen
1 2
Antigen-presentingcell Antigen
fragment
Class IIMHC
molecule
Antigenreceptor
Accessoryprotein
Helper T cell
B cell
Cytokines
Activatedhelper T cell
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Pathogen
31 2
Antigen-presentingcell Antigen
fragment
Class IIMHC
molecule
Antigenreceptor
Accessoryprotein
Helper T cell
B cell
Cytokines
Activatedhelper T cell
Memory B cells
Plasma cellsSecreted
antibodies
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Antibody-mediated (humoral) immunity = AMI
• 1- Macrophages phagocytize a pathogen and present an antigen to a matching helper-T cell
• 2- At the same time, some pathogens contact B-cells matching the pathogen’s antigens
• The helper-T cells multiply, secrete lymphokines which stimulate the B-cells to multiply and specialize into plasma cells
• The plasma cells secretes antibodies
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The Nature of Antibodies
• Globular proteins called immunoglobulins• Basic antibody structure has 4 polypeptide chains
– 2 identical light chains– 2 identical heavy chains
• Regions of heavy and light chains– Variable– Constant
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Antibody Molecule
antigen binding sites
antigen
light chains heavy chains
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Immunoglobin Classes
IgM1st response to antigenCan’t cross placenta
IgGMost common formCrosses placenta (passive
immunity to fetus)
IgASecreted from mucus membranesIn colostrum
IgDB cell activationCan’t cross placenta
IgEHistamine reactions
and allergies (mast cells, basophils)
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Types of Immunity
Active ImmunityNatural active immunity - acquired due to infectionArtificial active immunity – vaccination
Passive ImmunityNatural passive immunityplacenta to the fetusColostrumArtificial passive immunityInjection of immune serum
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Types of Acquired Immunity
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Summary
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67
QUESTIONS PLEASE