blsy2 immunology 1
TRANSCRIPT
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Introduction to Immunology
Dr. Catherine Gerald Mkindi
MVM, BVM, SUA
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What is immunology?
Immune (Latin- “immunus”)To be free, exemptPeople survived ravages of epidemic diseases when faced with the same disease again
The study of physiological mechanisms that humans and other animals use to defend their bodies from invading organisms
Bacteria - VirusesFungi - Parasites - Toxins
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Immune response• The immune response is the host reaction to
infection/invasion.• The body is under constant attack by microorganisms in
the environment.
• pathogen : an infectious agent that causes disease• Infectious disease occurs when a microorganism
succeeds in evading or overwhelming host defenses to establish a local site of infection and replication. In order for a pathogen to enter the body it must first overcome the innate immune response and the adaptive immune response.
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Types of Immunity
• Innate Immunity– Host defense mechanisms that act from the
start of an infection but do not adapt to a particular pathogen
– Recognize “patterns’ of a.a., saccharides, etc..
• Adaptive Immunity– Response of an antigen specific B and T
lymphocytes to an antigen– Immunological memory
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Types of Immunity
• Humoral immunity– Immunity that is mediated by antibodies– Can be transferred by to a non-immune
recipient by serum
• Cell Mediated Immunity– Immune response in which antigen specific T
cells dominate
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Humoral and cellular immunity (antibody mediated or cellular)
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Immune System
Innate/Nonspecific
Adaptive/Specific/Acquired
Protects/re-exposure
Cellular Components Humoral ComponentsHumoral ComponentsCellular Components
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Development of the Immune System
• Many cells of the immune system derived from the bone marrow
• Hematopoetic stem cell differentiation
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Cells of the immune system
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Lymphocytes
Important in bothhumoral and cellmediated immunity
B-cells produce antibodiesT- cells– Cytotoxic T cells– Helper T cells
Memory cells
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• Natural Killer cells– Kills cells
infected with certain viruses
– Both innate and adaptive
– Antigen presentation
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Monocytes/Macrophage
• Phagocytosis and killing of microorganisms– Activation of T cells and
initation of immune response
• Monocyte is a young macrophage in blood
• There are tissue-specific macrophages
• Antigen Presentation
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Dendritic Cells
• Activation of T cells and initiate adaptive immunity
• Found mainly in lymphoid tissue
• Function as antigen presenting cells (APC)
• Most potent stimulator of T-cell response
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Mast Cells
• Expulsion of parasites through release of granules
• Histamine, leukotrienes, chemokines, cytokines
• Also involved in allergic responses
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Neutrophil
• Granulocyte– Cytoplasmic granules
• Polymorphonuclear• Phagocytosis• Short life span (hours)• Very important at
“clearing” bacterial infections
• Innate Immunity• CD 66 membrane
marker
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Eosinophils
• Kills Ab-coated parasites through degranulation
• Involved in allergic inflammation
• A granulocyte• Double Lobed nucleus• Orange granules
contain toxic compounds
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Lymphoid organs
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Function of the Immune System(Self/Non-self Discrimination
• To protect from pathogens• Intracellular (e.g. viruses and some bacteria
and parasites)• Extracellular (e.g. most bacteria, fungi and
parasites)
• To eliminate modified or altered self
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Innate immune responses
Anatomical barriers– Mechanical factors– Chemical factors– Biological factors
• Humoral components– Complement– Coagulation system– Cytokines
• Cellular components– Neutrophils– Monocytes and macrophages– NK cells– Eosinophils
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Anatomical Barriers - Mechanical Factors
System or Organ Cell type Mechanism
Skin Squamous epithelium Physical barrier
Desquamation
Mucous Membranes Non-ciliated epithelium (e.g. GI tract)
Peristalsis
Ciliated epithelium (e.g. respiratory tract)
Mucociliary elevator
Epithelium (e.g. nasopharynx)
Flushing action of tears, saliva, mucus, urine
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Anatomical Barriers - Chemical Factors Anatomical Barriers - Chemical Factors
System or Organ Component Mechanism
Skin Sweat Anti-microbial fatty acids
Mucous Membranes HCl (parietal cells)
Tears and saliva
Low pH
Lysozyme and phospholipase A
Defensins (respiratory & GI tract)
Antimicrobial
Sufactants (lung) Opsonin
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Anatomical Barriers - Biological Factors
System or Organ Component Mechanism
Skin and mucous membranes
Normal flora Antimicrobial substances
Competition for nutrients and colonization
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Humoral Components
Complement Lysis of bacteria and some viruses
Opsonin
Increase in vascular permeability
Recruitment and activation of phagocytic cells
Coagulation system Increase vascular permeability
Recruitment of phagocytic cells
Β-lysin from platelets – a cationic detergent
Lactoferrin and transferrin
Compete with bacteria for iron
Lysozyme Breaks down bacterial cell walls
Cytokines Various effects
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Cellular Components
Cell Functions
Neutrophils Phagocytosis and intracellular killing
Inflammation and tissue damage
Macrophages Phagocytosis and intracellular killing
Extracellular killing of infected or altered self targets
Tissue repair
Antigen presentation for specific immune response
NK and LAK cells Killing of virus-infected and altered self targets
Eosinophils Killing of certain parasites
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Adaptive/ Acquired/ Specific Immunity
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Key characteristics of the adaptive immune responses
• Specificity
• Adaptability
• Memory
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Types of Acquired Immunity
I. Naturally Acquired Immunity: Obtained in the course of daily life.A. Naturally Acquired Active Immunity: – Antigens or pathogens enter body naturally. – Body generates an immune response to antigens.– Immunity may be lifelong (chickenpox or mumps) or
temporary (influenza or intestinal infections).B. Naturally Acquired Passive Immunity: – Antibodies pass from mother to fetus via placenta or breast
feeding (colostrum).– No immune response to antigens.– Immunity is usually short-lived (weeks to months).– Protection until child’s immune system develops.
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Types of Acquired Immunity (Continued)
II. Artificially Acquired Immunity: Obtained by receiving a vaccine or immune serum.1. Artificially Acquired Active Immunity: – Antigens are introduced in vaccines (immunization). – Body generates an immune response to antigens.– Immunity can be lifelong (oral polio vaccine) or temporary
(tetanus toxoid).2. Artificially Acquired Passive Immunity: – Preformed antibodies (antiserum) are introduced into body
by injection. • Snake antivenom injection from horses or rabbits.
– Immunity is short lived (half life three weeks).– Host immune system does not respond to antigens.
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Cells of adaptive immune responses
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B lymphocytes
Cell group Surface components
Function
T-lymphocytes CD3 molecule
B-cell receptor (BCR, Ag recognition)
Involved in humoral
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T-lymphocytes
Cell group Surface components
Function
T-lymphocytes CD3 molecule
T-cell receptor (TCR, Ag recognition)
Involved in both humoral and cell-mediated responses
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T helper cells (CD 4+ cells)
Cell group
Surface components
Function
Helper T-cells (TH)
CD4 molecule 1. Recognizes antigen presented within Class II MHC
2. Promotes differentiation of B-cells and cytotoxic T-cells
3. Activates Macrophages
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Cytotoxic T cells (CD 8+ cells)
Cell group Surface components
Function
Cytotoxic T-cells (CTL)
CD8 molecule Recognizes antigen presented within Class I MHC
Kills cells expressing appropriate antigen
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T Suppressor Cells (CD 8+ cells)
Cell group Surface components
Function
Suppressor T-cells (TS)
CD8 molecule Downregulates the activities of other cells
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Macrophages
Cell group Surface components
Function
Macrophages 1. Immunoglobulin Fc receptor
2. Complement component C3b receptor
3. Class II MHC molecule
Bind Fc portion of immunoglobulin (enhances phagocytosis)
Bind complement component C3b (enhances phagocytosis)
Antigen presentation within Class II MHC
Secrete IL-1 (macrokine) promoting T-cell differentiation and proliferation
Can be "activated" by T-cell lymphokines
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Dendritic Cells
Cell group Surface components
Function
Dendritic cells Class II MHC molecule
Antigen presentation within Class II MHC
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Primary and Secondary Immune Responses
1o and 2o immune responses
[Ab]in serum
Time (days)10 20 60 70 80
1st injection of Ag A2nd injection of Ag A
React only withA, not B, C, etc
1o
2o
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• The figure illustrates the production of antibody in response to antigenic substances. In this figure, an animal was injected with Antigen A at day 0. Antigen A invokes a primary response beginning about day 4, as indicated by a rise in the specific antibody titer (titer = measure of the amount of antibody in the animal's serum per unit volume). Initially, this antibody is mostly IgM (and some IgG). After a peak titer between days 7 and 10, the response decreases rapidly. If the animal is then reinjected with Antigen A at day 28, the production of antibody begins almost immediately and reaches a level 1000-fold greater that that seen in the primary response. This is known as the secondary response and the principal antibody produced is IgG. If a second antigen (Antigen B) is also injected at the same time as the reinjection of Antigen A, however, only a primary response to Antigen B is observed. These results demonstrate that:
• The immune response is specific. • The immune response has memory.
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Comparison of Innate and Adaptive Immunity
• Innate Immunity:• Fast-acting • Less specific recognition• Early during evolution • e.g. phagocytes, barriers to infection
such as skin and mucus surfaces• Adaptive Immunity:• Specificity• Distinguish antigens sometimes present
from those always present• Memory and Recall