Pathophysiology Chapter 9
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3rd line of defense
- Inheritance of parental MHC to determine "self" from "non-self"
- Immune Response
- Occurs more slowly
- Provides long-lasting protection
What is natural immunity?
Present at birth, not produced by immune response
What is acquired immunity?
Gained after birth, result from the immune response
What is a primary immune response?
- Occurs 5-7 days after the initial exposure to most antigens
- Active immune response is marked by detection of IgM in large amounts; falls to very low levels following active response
- Through the formation of memory cells, "primes" the immune system for the possible second exposure to the same antigen
What is a secondary immune response?
- Occurs when there is a second exposure to an antigen
- More rapid production of antibody, d/t memory cells
- IgG is the predominant antibody produced
- IgG antibody levels remain high for years
What is active acquired immunity?
Produced by host after natural exposure to antigen or immunization
What is passive acquired immunity?
Doesn't involve host's immune response but rather is "given" to the organism
What is cell-mediated immune response?
- Occurs via the lymphocytes that migrate and differentiate in the Thymus gland into T lymphocytes
- T cells encounter antigen, become sensitized and recognize and DIRECTLY attack specific
- 5 different types of T cells are produced
What is a humoral immune response?
- Occurs as a result of lymphocytes that migrate and differentiate in bone marrow, B lymphocytes
- B cells differentiate into antigen induced mature plasma cells that will produce antibodies specific to an antigen
- -5 different antibodies produced
- -B "memory" cells are generated
What is an antigen?
Any substance foreign to the body that evokes an immune response either alone or after forming a complex with a larger molecule and that is capable of binding with a product of the immune response
What is a self antigen?
Any molecule or chemical group of an organism which acts as an antigen in inducing antibody formation in another organism but to which the healthy immune system of the parent organism is tolerant
What is tolerance?
Immune system prevents recognition of self antigens by lymphocytes or antibodies
What are Immunoglobulins?
- Constructed to respond to a specific antigen
- Serve as receptors on the surface of mature B lymphocytes
Where are MHC I antigens found?
On almost all body cells except RBCs
Where are MHC II antigens found?
Only present on macrophages, dendritic cells, and B lymphocytes
What is the primary function of MHC II antigens?
To present foreign antigens to the immune system in order to better induce the immune response
What is the role of MHC proteins?
- Defends body against infection
- Initiates the immune response that destroys invasive "foreign" proteins
- Regulates the quality and quantity of theh immune response
- Distinguishes each individual's tissue from the tissue of others
Identify the "Antigen-presenting" cells or proteins.
- Macrophages and other phagocytes
- MHC I molecules-found on all nucleated cells and platelets
- MHC II molecules- found on B lymphocytes, macrophages, dendritic cells, and some epithelial cells
- CD1 antigens-unique set of molecules on the surface of APCs that present lipid antigens
- CD4 antigens-restricted to binding wiht MHC II proteins, significantly found on pre T-helper cell
What are cytokines?
Regulatory molecules that facilitate communication among macrophages and various lymphocytes, or among different types of cells
What are the different types of cytokines?
- Tumor necrosis factors
- Colony stimulating factors
What do interleukins do?
Sent from one leukocyte to another to enhance the response to foreign substances
Where are lymphokines produced?
Produced by lymphocytes
Where are Monokines produced?
Produced by monocytes/macrophages
What are Interferon?
A type of lymphokine that defends against tumor cells and viruses
What are Tumor necrosis factors?
Produced by macrophages, T cells and NK cells in response to infection by gram-negative bacteria, and other conditions of inflammation
What do Colony stimulating factors do?
Stimulate the differentiation of blood cells
Describe the basic elements of the Humoral Immune Response.
- Antigen binds to surface receptors of a mature B cell and generate
- -->Plasma cells which manufacture
- ----->5 classes based on antigenic, structural , and functional differences
- ------->IgG, IgA, IgM, IgE, IgD
- -->Memory cells, important in creating the secondary immune response
Describe the functions of antibodies.
- Render the antigen inactive
- Activate components of inflammatory response
How does and antibody render the antigen inactive?
- Binding with and thus inactivating the production of toxic chemicals produced by bacteria
- Neutralize viruses by attaching to the surface structures so they cannot lock onto their target body cell membrane receptors
What are the antibody's direct effects?
- Always begins with antigen binding
- Can precipitate a cellular reaction
- Burst the cell
- Render it ineffective
- Make it a target for macrophages, NK cells, T cytotoxic cells
How do antibodies activate components of inflammatory response?
- One end binds with the antigen, the other non-specific end "informs" nonspecific amplifiers of the inflammatory response that there is a foreign invader
- Promotes clustering of combined circulating antigen and antibody
- -Activation of the complement cascade
- -Recognition and binding to receptors on surfaces of inflammatory cells such as neutrophils and macrophages
- -Activation of T cytotoxic and/or NK cells
- Constitutes 80-85% of circulating Ig
- Responsible for precipitation, agglutination, complement cascade activation
- Formed on SECOND exposure to an antigen
- Lives many years
- Crosses the placenta into fetal blood and confers immunity to the fetus and newborn for about 3 mos, crosses into breastmilk
- Primary antibody in the secretory immune system
- Protects against the attachment and invasion of pathogens through mucosal membranes in the GI, GU tracts, and the pulmonary system
- Largest immunoglobulin
- Largely disappears after target antigen has been eliminated
- Can be synthesized early in neonatal life
Develops on the surface of immature B cells
Principle antibody in an allergic response, least concentrated
Identify the Components and function of the Secretory Immune System.
- First line of defense
- Provides local protection
- Functional components are IgA antibodies
- -->Lymphocytes of systemic immune system travel through spleen and lymph nodes
- -->Lymphocytes of secretary immune system have traveled through lacrimal and salivary glands and lymphoid tissue in the gut, breast, bronchi, and GU tract
What is the difference between Systemic Immune System and the Secretory Immune System?
- Secretory: at external surfaces of body
- Systemic: the immune system within the body
Identify immune function in the neonate.
- IgG is passed from mom to fetus through placenta by active transport (at adult level at birth)
- IgG declines over 2-3 months unless breastfed
- Once breastfeeding declines baby has to make his own IgG, through his own primary and secondary immune responses
What are the different types of Granulocytes?
What are the different types of Agranulocytes?
- Act as phagocytes and produce inflammatory chemicals
- Particularly active during acute bacterial infections
- Differentiate into mast cells when they leave the circulation
- Basophils and mast cells primarily release histamine
- Display IgE and participate in allergic responses.
- Particulary activer during parasitic worm infections
- Release inflammatory chemicals
- T cells function in cell-mediated specific immune responses and release inflammatory chemicals
- B cells function in humoral specific immune responses (antibody-mediated)
- NK cells function in innate immune response to intracellular infection and malignancy
- The major circulating phagocytes
- Differentiate into macrophages when they leave the bloodstream
- Macrophages play important roles in both innate and specific immune responses
What are chemical mediators?
What are complement?
- 20 plasma proteins that up inflammation, opsonization, chemotaxis, and cell lysis
- Circulate in inactive form - activated when needed
What are kinins?
- Polypeptides --> strong vasodilation
- Activated with the clotting system
- Increased vascular permeability, smooth muscle contraction, pain signals
What are cytokines?
- Polypeptides that stimulate surface receptors of other cells
- Communication proteins
- Functions: chemotactic factors, antiviral factors, inflammation mediators, heatopoietic factors, antivates specific WBCs
What is the purpose of inflammation?
- Neutralize/destroy pathogens
- Limit spread of harmful stuff
- Prepare damaged tissues for repair
- Dilutes irritating/ toxic pathogens
- Facilitates neutrophil emigration
What are vasoactive chemicals?
- Histamines-->powerful, early vasodilator
- Prostaglandins & Leukotrienes-->made from Arachidonic Acid
- Prstaglandins-->vasodilation, increased permeability, chemotactic agent for neutrophils, increased pain sensitivity
- Leukotrienes-->chemotactic agent for lymphocytes, increased smooth muscle contractions, bronchospasms, increased vasular permeability
What are inflammatory exudates?
Fluid that leaks from blood vessels, mixes with neutrophils and phagocytotic debris
What are the purposes of Inflammatory Exudates?
- Delivery of WBCs and antibodies
- Transport of nutrients
What are the types of Inflammatory Exudate?
- Serous: watery stuff
- Fibrinous: sticky and thick, can wall off infectious material
- Purulent: PUS, severe inflammation
- Hemorrhagic: lots of RBCs, most severe inflammation
What is the systemic involvement of Inflammation?
Fever, neutrophilia, lethargy, muscle catabolism
What are the effects of Systemic Inflammation on the brain?
- Appetite Suppression
How is a fever produced?
- External pyrogens cause immune cells to release cytokines
- Cytokines (IL-1, IL-6, TNF-a) stimulate immune cells to produce internal pyrogen, PGE-2, from arachidonic acid
- PGE-2 acts on the hypothalamus to produce fever
What are the effects of inflammation on Skeletal Muscle tissue?
- Cytokines induce the breakdown of muscle proteins
- Provides a pool of free amino acids to be used for the production of inflammatory proteins and antibody molecules
What is the liver's response to inflammation?
- Complement components
- Clotting factors
- Protease inhibitors
- -->c-reactive protein
- -->serum amyloid A
What limits and controls inflammation?
- Influx of clotting proteins walls off damaged tissue
- Influx of eosinophils
How does inflammation prevent further infection and damage?
- Phagocytes and NK cells remove bacteria
- Influx of fluid to dilute toxins
- Influx of plasma proteins that destroy bacteria
What are the healing phases after inflammation?
- Reconstructive phase
- Maturation phase
What are the Adaptive Immune Response Lymphocytes?
- T cells
- B cells
- Requirements for Lymphocyte maturity
- Self-tolerance Antigen
What are the two ways that MHC present non-self antigens?
- --> antigen is engulfed by cell and presented to naive T cells
- --> antigen is synthesized within the cell that displays them
What is the difference between MHC I and MHC II presentation?
MHC I --> sign post made in rough ER and sent to plasma membrane surface
MHC II --> antigen is engulfed, proteins made in the rough ER, then pick up foreign antigens in the phagosome, sent to plasma membrane
What is the difference between an effector cell and a memory cell?
Effectors react to the initial antigen challenge
Memory cells react to the subsequent challenges.
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