Must defend from the many dangerous pathogens it may encounter in the environment
Detect invader/foreign cells
Communicate alarm & recruit immune cells
Suppress or destroy invader
Two major kinds of defense have evolved that counter these threats
Innate immunity and acquired immunity
Innate Immunity
Innate immunity provides broad defenses against infection
Present before any exposure to pathogens and is effective from the time of birth
Involves nonspecific responses to pathogens
A pathogen that successfully breaks through an animal’s external defenses encounters several innate cellular and chemical mechanisms that impede its attack on the body
Innate Immunity
Non-selective
No lag time – immediate response
No previous exposure required
Protects against infections, toxins
Works with specific (acquired) immune response
Acquired (Adaptive) Immune Response
Depends on B and T lymphocytes
Specific immune response directed attack against pathogens (antigen)
Resident macrophages remove microbes and debris from lymph
Lymphocytes produce antibodies and sensitized T cells released in lymph
Spleen – Exchange Lymphocytes with blood, residents produce antibodies and sensitized T cells released in blood
Lymphocytes
B and T cells originate in bone marrow
B cells remain in bone marrow for maturation
T cells leave bone marrow, and migrate to thymus gland for maturation
Lymphocytes – B and T cells
B cells – Antibody-mediated immunity (grenade launchers)
T cells – Cell-mediated immunity (hand-to-hand combat)
Antigens
An antigen is any foreign molecule that is specifically recognized by lymphocytes and elicits a response from them
A lymphocyte actually recognizes and binds to just a small, accessible portion of the antigen called an epitope or antigenic determinant
Antigenic determinants - Specific regions of a given antigen recognized by a lymphocyte
Antigenic receptors -Surface of lymphocyte that combines with antigenic determinant
Antigen Recognition by Lymphocytes
A single B cell or T cell has about 100,000 identical antigen receptors
All antigen receptors on a single cell recognize the same epitope
Cell-Mediated Immunity – T Cells
Antigens that stimulate this response are mainly intracellular (cell to cell).
Requires constant presence of antigen to remain effective
Involves numerous cytokines, over 100 have been identified
Stimulate and/or regulate immune responses
Interleukins: Communication between WBCs
Interferons: Protect against viral infections
Chemotaxins: Attract WBCs to infected areas
Lymphocyte Communication
Over 18 different types of interleukins are known; designated IL-1, IL-2…IL-18, etc.
IL-1 and IL-2 are primarily responsible for activating T and B lymphocytes, with IL-2 being a stimulant of T- and B-cell growth and maturation
IL-1, along with IL-6, is also a mediator of inflammation.
IL-4 often leads to an increase in antibody secretion by B lymphocytes
IL-12 causes a greater number of the leukocytes cytotoxic T cells and natural killer cells to be made
The set of interleukins produced by the presence of a specific infectious agent determines which cells will respond to the infection
Types of T cells
Cytotoxic T cells – attack foreign cells
Helper T cells - activate other T cells and B cells
Suppressor T cells– inhibit the activation of T and B cells
Memory T cells – function during a second exposure to antigen
T cell membranes contain CD markers:
CD3 markers present on all T cells
CD8 markers on cytotoxic and suppressor T cells
CD4 markers on helper T cells
T Cell Activation
T cells are activated when they detect and bind to small fragments of antigens that are combined with to cell-surface glycoproteins called major histocompatibility complex (MHC) molecules
Lymphocytes respond to antigens bound to either class I or class II MHC proteins depending on the source of the MHC molecule and theantigen presenting cell
Class I MHC molecules are displayed on the surface of infected nucleated cells
Class II MHC molecules are displayed on the surface of phagocytes
Class I MHC molecules
Infected cells produce Class I MHC molecules which bind to antigen fragments and then are transported to the cell surface in a process called antigen presentation
Binds and activates with Cytotoxic T cell receptor
Cytotoxic T cell response:
Clonal production of cytotoxic T cells and memory cells
Destruction of virus-infected cells, tumor cells, and tissue transplants
Cytotoxic T (TC) Cells – CD8
Recognize and destroy host cells that are infected with viruses or bacteria, cancer cells, transplanted tissue
Release protein called perforin which forms a pore in target cell, causing lysis of infected cells.
Produce cytokines, which promote phagocytosis and inflammation
Undergo apoptosis when stimulating antigen is gone.
Class II MHC molecules
Produced by dendritic cells, macrophages, and B cells
Macrophages & dendritic cells phagocytize antigens, proteins broken down into antigen fragments (peptides) and combined with Class II MHC molecules
Binds and activates Helper T cells
Clonal production of Helper T cells
Activation of Cytotoxic T cells
Activation of B cells
T Helper (TH) Cells – CD4
T Helper (TH) Cells: main role in immune response
Recognize antigen on the surface of antigen presenting cells
Secrete Interleukin II (T-cell growth factor), interferon and cytokines which stimulate lymphocyte activity
Production and activation of Cytotoxic T cells and more Helper T cells
Stimulate B cells to produce antibodies
T Cell Overview
Memory T-Cells
Can survive a long time and give lifelong immunity from infection
Can stimulate memory B-cells to produce antibodies
Thymosin - hormone important in T cell lineage, enhances capabilities of existing T cells and the proliferation of new T cells in lymphoid tissues - decreases after age 30-40
Proliferation of Lymphocytes
Antibody-Mediated (Humoral) Immunity
Involves production of antibodies against foreign antigens
Plasma cells - B cells that are stimulated and begin actively secrete antibodies
Antibodies (immunoglobulins, Ig) are Y-shaped proteins found in extracellular fluids (blood plasma, lymph, mucus, etc.) and the surface of B cells
Defend against bacteria, bacterial toxins, and viruses that circulate freely in body fluids, before they enter cells
Also cause certain reactions against transplanted tissue
Antibody-Mediated (Humoral) Immunity
1000s of different B cells, each recognizes a different antigen on the surface of a macrophage (specificity)
Each antigen stimulates production of a single specific antibody that the B cells (along with T cells) come in contact with
They are stimulated (by TH cells) to produce many clones, plasma cells, which make antibodies.
Memory B cells provide secondary response (faster, more sensitive)
Antibody Structure
Antibodies or Immunoglobulins (Ig)
Classes: IgG, IgM, IgA, IgE, IgD
Structure
Variable region - combines with anitgenic determinant of antigen
Constant region - responsible for other binding activities
Consequences of Antigen-Antibody Binding
Agglutination - antibodies cause antigens (microbes) to clump together
Opsonization and Phagocytosis – coating foreign substance with antibodies, allowing Phagocytes to grip and engulf the invader
Complement System / Inflammatory Response – lyse the invader and attract other immune cells (chemotaxis)
Neutralization – coat foreign substance, rendering it harmless
Antibody dependent NK/eosinophil cell response – Directly attack and lyse the cell using perforins
Consequences of Antigen-Antibody Binding
Antigen-Antibody Complex On B Cell
Activate B lymphocyte production of:
Memory B cells for secondary immune response to that antigen
Location: Blood, lymph, intestine, Only lg that crosses placenta, thus conferring passive immunity on fetus
Promotes opsonization, neutralization, and agglutination of antigens, protects fetus and newborn.
IgA
Percentage serum antibodies: 10-15%
Location: Secretions (tears, saliva, intestine, breast milk), blood and lymph
Provides localized defense of mucous membranes by agglutination and neutralization of antigens
Localized protection of mucosal surfaces. Presence in breast milk confers passive immunity on nursing infant
IgM
Percentage serum antibodies: 5-10%
Location: Blood, lymph, B cell surface (monomer)
First antibodies produced during an infection. Effective against microbes, complement activation and agglutinating antigens
IgD
Percentage serum antibodies: 0.2%
Location: Found primarily on surface of naive B cells that have not been exposed to antigens
Acts as antigen receptor in antigen-stimulated proliferation and differentiation of B cells (clonal selection)
IgE
Percentage serum antibodies: 0.002%
Location: Bound to mast cells and basophils throughout body
Triggers release of histamine and other chemicals that cause allergic reactions
B Cell Sensitization And Activation
Sensitization – the binding of antigens to the B cell membrane antibodies
Activation - Helper T cells present same antigen to stimulate B cell
Division - Stimulated B cells divide into many clones called plasma cells, which actively secrete antibodies
Secretion - Each B cell secrete antibodies that will recognize only one antigenic determinant
Differentiation - Active B cells also differentiate into Memory B Cells
Immunological Memory
Primary Response:
After initial exposure to antigen, no antibodies are found in serum for several days. A gradual increase number of Abs, first of IgM and then of IgG is observed.
Most B cells become plasma cells, but some B cells become long living memory cells. Gradual decline of antibodies follows.
Secondary Response:
Subsequent exposure to the same antigen displays a faster/more intense response due to the existence of memory cells, which rapidly produce plasma cells upon antigen stimulation
Clonal Selection
Clonal Selection: B cells (and T cells) that encounter stimulating antigen will proliferate into a large group of cells.
Why don’t we produce antibodies against our own antigens? We have developed tolerance to them.
Tolerance: To prevent the immune system from responding to self-antigens
Clonal Deletion: B and T cells that react against self antigens are normally destroyed during fetal development
Preventing activation of lymphocytes – activate Suppressor T cells, control the immune system when the antigen / pathogen has been destroyed
Apoptosis
Apoptosis - Programmed cell death (“Falling away”)
Human body makes 100 million lymphocytes every day. If an equivalent number doesn’t die, will develop leukemia
B cells that do not encounter stimulating antigen will self-destruct and send signals to phagocytes to dispose of their remains
Many virus infected cells will undergo apoptosis, to help prevent spread of the infection
Autoimmune Diseases: Failure of “Self-Tolerance”
Some diabetes mellitus – attack - cells
Multiple sclerosis – attack on myelin nerve sheath
Rheumatoid arthritis – attack joint cartilage
Myasthenia gravis – ACh-receptors at endplate attacked
Allergic Response: Inflammation Reaction to Non-pathogen
First exposure: sensitization
Activation
Clone B cells
Form antibodies
Memory cells
Re-exposure
Many antibodies
Activated T cells
Intensified
Inflammation
Hemagglutination
Agglutination of red blood cells used to determine ABO blood types and to detect influenza and measles viruses
Summary
Body defends itself with barriers, chemicals & immune responses
WBCs and relatives conduct direct cellular attack: phagocytosis, activated NK & cytotoxic T cells and produce attack proteins (i.e. antibodies, complement, & membrane attack complex)
Cytokines, communicate cell activation, recruitment, swelling, pain, & fever in the inflammation response
Defense against bacteria is mostly innate while viral defense relies more on acquired immune responses
Autoimmune diseases are a failure of self-tolerance
