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Two Mechanisms of defense
- 1. Nonspecific (innate) immunity
- 2. Specific (acquired) immunity
Nonspecific (innate) immunity
- natural, nonspecific; essentially unregulated (i.e. always active)
- Does not distinguish one threat from another
Specific (acquired) immunity
- specific, inducible, diverse, discriminatiory (self vs. non-self), self limiting, has "memory"
- Turns on when a pathogen is detected.
- Includes physical barriers, phagocytic cells, complement proteins, general inflammatory response and fever.
What is included in the Specific immune system?
- physical barriers
- phagocytic cells
- complement proteins
- general inflammatory response ; fever
What is the primary surface barrier?
- skin, mucous membranes, secretions
- a. Stratified, desmosomes, keratinization.
- Hair fur
How do secretions support the nonspecific immune system?
- Secretions are acidic and contain bactericides, fatty acids, etc.
- Saliva contains lysozyme-puts holes in bacteria
- Mucous traps bacteria
What is the role of mucous/ the respiratory elevator?
- Mucous traps bacteria
- Respiratory Elevator: cillia in bronchioles continuously move dust and debris up and away from the lungs.
what are the 2 types of Cellular and Chemical defenses?
- 1. Phagocytes
- 2. Opsonization
What is a Phagocyte?
Phagocytes engulf particles in a phagosome which is then combined with lysosome to form a phagolysosome. Free radicals are also produced in the phagolysosome
the name of a combined lysosome and phagosome (phagocyte)
What are the 2 major types of Phagocytic cells?
- 1. Macrophages- monocytes
- 1. Microphages- neutrophils and eosiniphils
- formed from monocytes that leave the bloodstream and enter tissue
- a. specific receptors for complement proteins and antibodies; can be "activated" ; nonspecific
- b. express antigen fragments of surface for interaction with T-cells
Fixed macrophages are found only in specific areas of the body. What are these two areas?
- Kupffer cells- liver
- Alveolar macrophages- alveoli
- Diapedesis- squeezing between endothelial cells of the blood vessels
- Chemotaxis- attraction of neutrophils
- Neutrophils can produce defensin, bleach, and hydrogen peroxide.
- a. self destruct after they engulf something
squeezing between endothelial cells of the blood vessels
the attraction of neutrophils
- weakly phagocytic
- more important against parasites
which type of denfense cell is more important agaisnt parasites?
usually associated with allergies, may have phagocytic properties
foreign particles coated with antibodies, complement proteins.
Natural Killer Cells
- 1. Lyse cancer cells and virus-infected cells
- 2. large granular lymphocytes called null cells / third population cells (TPC)
- 3. detect cell surface changes on ANY cell (nonspecific)
- 4. destroy infected cell by release of cytolytic chemicals (perforins)
What is the name of cytolytic chemicals released by Natural Killer cells?
What is the name of tissue's response to injury?
What is the purpose of inflammation?
- 1. prevent spread of damaging agent
- 2. dispose of cell debris and pathogens
- 3. set stage for repair process
Process of vasodilation involving Macrophages
Macrophages lining boundary tissue contain surface receptors called Toll-like receptors. When stimulated, TLR cause release of cytokines with attract WBC
Mediators released from cells to initiate vasodialition
- Histamine, kinins, PGs, complement
- Macrophages' Toll-like receptors release cytokines to attract WBC
Bacterial toxins and edema cause pain
Broad spectrum antibiotics that come from neutrophils
Injured cells release chemicals which cause bone marrow to release neutrophils
- neutrophils line inner walls of capillaries
- Diapedesis- squeeze between the endothelial cells and out of the blood vessel
- Chemotaxis- monocytes follow the neutrophils and eventually convert to macrophages
What is the name of Cell Adhesion Molecules located on neutrophils?
What is the name of cell adhesion molecule produces by endothelial cells?
What is pus?
- dead and dying neutrophils, broken down tissue cells, and living and dead pathogens.
- Abscess- sac of pus that can be walled off by collagen fibers
What are the two categories of Antimicrobial Protein action?
- 1. Interferon
- 2. Complement proteins
What is Interferon?
what are its effects?
- protein secreted by cells infected with viruses
- a. IFN are not virus specific
- Causes neighboring cells to produce PKR which inhibits viral replication.
- Interferons also activate macrophages and natural killer cells
How do Complement proteins work?
- group of plasma proteins which, when activated, enhance inflammation and cause lysis.
- Two Pathways:
- a. classical
- b. alternative
- Important component of humoral immunity
What is the classical pathway of Complement proteins?
- Antibodies bind to invader and change its shape exposing complement binding site of C region
- C3 is cleaved into C3a and C3b
- C3b causes the insertion of Membrance Attack Complex (MAC)
- In addition, C3b coat microorganism providing sites that macrophages recognize and attack (opsinization)
How is C-reactive protein involved in the classical pathway of Complement proteins?
C-reactive protein is formed by liver in response to inflammatory molecules. Binds to C1 of the classical pathway and results in deposition of C3 on bacteria wall
Alternative pathway of Complement proteins
- Complement does not require antibodies
- MAC forbed by other substances in yeasts, viruses, virus-infected cells, and protozoan parasites.
- part of nonspecific immune responce
Specific Body Defenses (Adaptive immune system)
- specificity- eliminates particular antigens by producing specialized lymphocytes and antibodies
- Diversity- recognizes millions of antigens
- Self/ non-self recognition
- Involves antibodies secreted from lymphocytes and complement
- a. 5 classes of Ab
- Against toxins, free bacteria, and viruses
- Direct action of cells
- bacteria and viruses inside host's cells; fungi, protozoans and worms
- tissue transplants
Definition of Antigen
Substances that can mobilize the immune system and provoke and immune response.
2 classes of antigens
- 1. complete- stimulate prolifereation of specific lymphocytes
- reactivity: ability to react with activated lymphocytes
- 2 incomplete- by themselves cannot cause immune response, but when linked to bodies own proteins can then be recognized.
Only the antigen determinant part of an antigen is immunogenic
Self Antigens: MHC proteins
- on the surface of all cells
- practically infinite number if gene combinations for MHC, like a finger print
2 main classes of Major Histomatibility Complexes
- Class I- nucleated cells
- a. display self antigens (endogenous antigens)
- Class II- macrophages and B lymphocytes
- a. can display foreign antigens ( exogenous)
Cells of Adaptive Immune System
Includes Lymphocytes and Antigen-Presenting Cells
2 Classes of lymphocytes
- 1. B-cells- bone marrow; humoral immunity
- 2. T-Cells- bone marrow to Thymus gland; cell-mediated immunity
how are T-cells selected?
- Positive selection: fetal T-cells that can recognize self MHC are retained. If unable to recognize self, then they undergo apoptosis
- Negative selection: T-cells that bind too strongly to self MHC are eliminated
How are B-cells selected?
- 1. Anergy: Self reactive B cells are inactivated by process called anergy
- 2. Clonal deletion: Other B-Cells killed outright or physically eliminated.
- Engulf antigens and present fragments of antigens on their surface in MHC class II.
- Includes Macrophages and activated B lymphocytes.
Specific locations of some APC
- Dendritic cells- in connective tissue
- Langerhan's cells- skin epidermis
How are T cells activated (adaptive immune system)
- Dendritic cells and macrophages secrete soluble proteins that activate T cells
- Activated T cells then mobilize and cause maturation of dendritic cells and activate macrophages.
how do Lymphocytes leave the blood system?
Lymphocytes leave system because of cell adhesion molecules CAM found of endothelial cells.
Humoral Immunity Response (2 steps)
- 1. Antigen binds to receptor on B-cell
- 2. Macrophages and helper t-cells
Clonal Selection and Differentiation of B-cells
A B-cell is activated by binding an antigen to its surface, then internalizing it. The B-cell grows and creates clones. Most progeny become plasma cells; some become memory cells
- 1. Primary immune response- 3-6 day lag
- 2. Secondary immune response- quicker and more aggressive
What is the structure of an antibody?
- 4 polypeptide chains linked by disulfide bridge: 2 light chains and 2 heavy chains.
- a. constant region
- b. variable region- antigen binding site
what portion of blood are antibodies located in?
Constitute gamma globulin portion of blood
How do immunoglobulins interact with antigens?
- Soluble proteins: interact with epitope on antigens
- epitope: a small, restricted site on an antigen molecule that induces immunity through specific binding with either an antibody or a T-cell receptor.
how many classes of antibodies are there?
Why/ how are antibodies so diverse?
Enbryonic DNA has multiple variable, four joiner regions and one constant region. These can be manipulated to form nearly infinite combinations
Antibody Targets and Function
- 1. Complement fixation and activation
- 2. Neutralization: Binding of antigen causes neutralization
- 3. Agglutination: think of lots of people tackling a gunman
- 4. Precipitation
What properties of monoclonal antibodies allow them to be used for clinical testing?
very specific; can be produced by fusing tumor cells and B lymphocytes to form hybridomas. Hybridomas proliferate indefinitely in culture and produce a single type of antibody.
Cell- Mediated immunity targets pathogens where?
cell mediated immunity battles pathogens already inside cells
What is the key component of cell mediated immunity?
- 2 major populations:
- a. CD4- helper T cells
- b. CD8-cytotoxic T-cells
CD4- Helper T cells
- activate B cells to secrete Antibodies; also activate other T-cells
- Only recognizes antigen in type II MHC, Antigen Presenting Cells (macrophages and B-cells)
- For Helper T-cells to activate other lymphocytes, cytokines must be present.
CD8- Cytotoxic T-cells
- destroy other cells; only T cells that actually kill other cells
- recognize antigens associated with class I MHC markers
- Cytotoxic T-cells attack as long as appropriate antigen and co-stimulatory signal present.
- not activated by free antigens; activated only by antigenic epitopes displayed on surfaces of bodies own cells.
- must be able to recognize foreign and self through MHC
Class I MHC
- displayed on virtually all cells of body except for red blood cells.
- recognized by CD8- Cytotoxic T-cells
Class II MHC
- found on some mature B cells, some T cells and Antigen Presenting Cells
- enable cells of the immune system to recognize each other.
- Class II MHC only recognizes exogenous antigens (foreign antigens phagocytized and borken down in phagolysosome)
- are recognized by CD4 helper T-cells
What is the role of cytokines in Helper T cell actions?
- Cytokines are molecules which regulate neighboring cells
- For helper T-cells to activate other lymphocytes, cytokines must be present
How is Interleukin-1 produced and what is its effect?
- Binding of helper T-cells causes macrophages to release interleukin-1
- interleukin-1 signals helper t-cells to release interleukin-2
- Stimulates helper T-cells to grow and divide
What kinds of cytokines can activated T cells produce?
- Tumor necrosis factor-kills cells
- interferon- enhances ability of macrophages.
- interleukin-2 stimulates B-cells to produce Ab
- Cytokines can also stimulate T-lymphocytes to differentiate into cytotoxic T-cells
T-cell independent antigens
- Antigens that stimulate B cells without help from T-helper cells
- produce weak responses
T-cell dependent antigens
- require T-helper cells
- more potent antigens
What do Cytotoxic T-cells target?
only T-cells that actually kill other cells: attach virus-infected cells, and cells infected by intracellular bacteria, parasites, cancer cells, and foreign cells
What is the "lethal hit sequence" of cytotoxic T-cells?
- Tc release perforin and granzymes which form lesion in infected cell's membrane
- with calcium present, perforin polymerize and create transmembrane hole
- granzymes enter target cell through holes and then degrade cellular contents causing apoptosis
- some Tc release lymphotoxin, TNF, or gamma interferon to cause cell death
What is perforin?
puts hole in cell membrane. part of Tc lethal hit sequence
what are granzymes?
interfere with the membrane of a cell and degrade cellular contents as part of Tc lethal hit sequence
Other types of T cells (other than Helper and Cytotoxic)
Suppressor T-cells: suppress activity of B cells and other T cells; helps keep immune system in check.
- 1. Lupus erythematosis and rheumatoid arthritis
- 2. Insulin-dependent diabetes: attacking own beta cells
- 3. Rheumatic fever
- 4. Grave's disease- attack Thyroid
- 5. Multiple Schlerosis- attack myelin sheath
is AIDS an autoimmune disease, and allergy, or an immunodeficiency?
- Explanation: type A blood has A antigens, so if you put A blood in a type B person, formation of "anti A antigens" antibodies will occur.
- Rh factor: Rh-negative mother can develop antibodies against fetus, treat mother with anti-Rh antibodies after birth
What is responsible for tissue rejection in tissue grafts?
- MHC is responsible for tissue rejection
- causes cytotoxic T-cells to mount cell-mediated immune response.