Immune System
Why do viruses invade cells of the body?
They lack cellular machinery to generate ATP or synthesize proteins. They do their dirty work in the body by invading tissue cells and taking over the cellular metabolic machinery needed to reproduce
Where do immature lymphocytes originate? From what undifferentiated cell do they originate?
They originate in red bone marrow from hematopoietic stem cells.
What role do NK cells play in defending the body?
Unlike the adaptive immune system which only react and recognize against specific infected or tumor cells, NK cells are far less picky. They eliminate a variety of infected or cancerous cells by detecting general abnormalities such as lack of "self" cell-surface proteins called MHC. They are not phagocytotic, they kill by directly targeting the cell inducing it to undergo apoptosis.
What is a virus?
an infective agent that typically consists of a nucleic acid molecule in a protein coat, is too small to be seen by light microscopy, and is able to multiply only within the living cells of a host.
What is an antigen ?
any substance that can mobilize the immune system & provoke an immune response large complex molecules that are not normally present in the body
Explain the difference between deletion (i.e. apoptosis) and anergy
apoptosis: elimination or deletion of cells anergy: cell is highly monitored and made inactive
What two properties characterize a complete antigen?
immunogenicity: the ability to trigger an immune response reactivity: the ability to react specifically with the cells or antibodies produced in the immune response
What is the difference between a complete and incomplete antigen?
incomplete antigens are not immunogenic by themselves. they can react with the immune response but they cannot mount an immune response
What cellular organelle contains the enzymes required for intracellular digestion of microbes and particulate matter?
lysosomes
Identify and describe the three basic stages of the antibody-mediated immune response?
1) Antigen binding - an immunocompetent but naive B cell is activated when matching antigens bind to its surface receptors and cross-link adjacent receptors together 2) Receptor-mediated endocytosis: - receptor + antigen will be enclosed in a vesicle and taken into the cell - antigen will be taken to class II MHC and then to membrane 3) Proliferation and differentiation - once activated, the lymphocyte proliferates to form an army of cells exactly like it (colonal selection) - most cells of the clone differentiate into plasma cells that secrete antibodies - clone cells that don't become plasma cells become long-lived memory cells that can mount almost an immediate humoral response if they encounter the same antigen.
Identify and describe the major events of the inflammation process
1) Chemical alarm: injured or stressed tissue release chemicals such as histamine, kinins, prostaglandins or cytokines. If pathogens caused inflammation, then complement is activated to form potent inflammatory chemicals 2) Vasodilation and vascular permeability: vasodilation of local arteries causes hyperemia (increased blood flow). More cells and chemicals rush to the site. Increased permeability allows exudate (which has antibodies and clotting factors) to seep from the blood into tissue spaces. 3) Phagocyte mobilization: pahgocytes flood the area
Identify and briefly describe the three pathways of complement activation
1) Classical pathway: involves antibodies (adaptive immunity). When antibodies bind pathogens, they also bind complement components. 2) Lectin pathway: involves lectins, water-soluble protein molecules that the innate immune system produces to recognize foreign invaders. They bind and activate complement. 3) Alternative pathway: triggered when C3 is spontaneously activated and other complement factors interact on the surface of microorganisms
Describe the process of phagocytic mobilization
1) Leukocytosis: injured cells release leukocytosis-inducing factors. White blood cells (neutrophils) rush into the area 2) Margination: phagocytes cling to the inner walls of capillaries to bind endothelial cells tightly 3) Diapedesis: chemical signals prompt the neutrophils to flatten and squeeze between the endothelial cells of capillary walls 4) Chemotaxis: inflammatory chemicals act as homing devices that attract WBCs and neutrophils to site of injury to devour foreign material
Name and describe the five general steps involved in phagocytosis
1) phagocyte adheres to pathogens or debris (using receptors) 2) Phagocyte forms pseudopods that eventually engulf the particles, forming a phagosome. 3) Lysosome fuses with the phagocytic vesicle, forming a phagolysosome. 4) Toxic compounds and lysosomal enzymes destroy pathogens 5) Sometimes exocytosis of the vesicle removes indigestible and residual material.
What the two characteristics which clearly distinguish immunity from the body's nonspecific defenses?
1) specificity: attack directed against a specific antigen 2) memory: they can attack an antigen they previously encountered
What is the function of major histocompatibility complex (MHC) antigens?
A group of glycoproteins that act as cell surface proteins which allow you to identify a cell as your self (not antigenic).
What is a natural killer (NK) cell?
A unique group of defensive cells that can kill cancer cells and virus-infected body cells before the adaptive immune system is activated.
Identify the accessory structures and secretions which increase the effectiveness of these mechanical barriers
Acid: the acidity of skin, vaginal, and stomach secretions - the acid mantle - inhibits bacterial growth Enzymes: lysozyme found in saliva, respiratory mucus and lacrimal fluid of the eye - destroys bacteria. Mucin: dissolved in water forms thick, sticky mucus that lines the digestive and respiratory passageways. Traps microorganisms and washes them out. Defensins: Mucous membrane and skin secrete small amounts of antimicrobial peptides and help to control bacterial and fungal colonization in the exposed areas
Distinguish between active and passive immunity
Active immunity is Immunity due to the production of antibodies by the organism itself after the body's defense mechanisms are stimulated by antigens. (ex. vaccination by presenting pathogen in an attenuated form) Passive immunity is Immunity due to the acquisition of antibodies from another organism in which active immunity has been stimulated. (does not make antibodies or memory cells) (ex. mother passes antibodies to fetus.
Identify and describe the mechanisms of antibody action
An antibody binds to an antigen and is inactivate by - Neutralization: (masks dangerous parts of bacterial exotoxins; viruses) - Agglutination: (clumping of cell-bound antigens) - Precipitation: soluble molecules are cross-linked into large complexes that settle out of solution. Makes it easier for phagocytes to attack - Complement activation: antibodies bind close together on the same cell, complement portion aligns, and activated complement system and lysis and cell
Identify and describe the three basic stages of the cell-mediated immune response?
Antigen recognition: inactive t cells have receptors that recognize Ag by MHC CD8 cells recognize MHC-1 CD4 recognize MHC-2 Costimulation: If the T cell is going to be activated effectively, costimulation signal must be delivered to the lymphocyte at the same time Ag recognition occurs. Costimulation caused by interleukin2 CD40/CD40L. Proliferation and Differentiation: T cell clone. Diff into..... 1. Memory cells 2. Suppressor cells: control/mediate immune response (tcell/bcell) 3. cytotoxic: attack and destroy Elimination
What type of molecules make up the complement system?
At least 20 plasma proteins that normally circulate in the blood in an inactive state. They are activated and subsequently amplify the inflammatory process.
Which subset of T cells expresses CD4 antigen? CD8?
CD4: T Helper cells CD8: cytotoxic T cells
How do APCs interact with T lymphocytes to activate a cell-mediated immune response?
CD8+ T cells recognize antigens presented by the MHC-I cells CD4+ T cells recognize antigens presented by the MHC-II. APCs present antigen and active T lymphocyte
What lymphocyte type is associated with cell-mediated immunity? with humoral immunity?
Cell mediated = T cells Humoral = B cells
What are the two classes of MHC proteins? Which cells of the body express each type?
Class I MHC: present in the membranes of all nucleated body cells Class II MHC: present only in the membrane of antigen-presenting cells activated lymphocytes and certain cells of the thymus.
What three types of cells function as antigen presenting cells?
Dendritic cells (DCs), macrophages, activated B lymphocytes
Where do B cells develop immunocompetence and self-tolerance?
During maturation in the bone marrow
Describe the general structure of an antibody
Each antibody consists of four looping polypeptide chains linked together by disulfide bonds. The four chains combined form a molecule called an antibody monomer. Made of 2 identical heavy chains and 2 identical short light chains Each chain forming an antibody has a variable region and a constant region. C regions are the same in all antibodies of a given class and V regions have the antigen-binding site
Explain how each of the above types of antigens is processed and complexed with MHC proteins
Endogenous antigens: 1) antigen degraded by protease 2) enter ER via transport protein 3) loaded into MHC-I 4) Presented on surface Exogenous antigens: 1) ingestion of Ag 2) Ag digestion & MHC-II synthesis 3) fusion of vesicles (phagolysozome and MHC complex) 4) assembly of Ag-MHC-II complexes (in phagolysozome) 5) Ag-MHC-II complexes inserted into plasma membrane
Describe the difference between endogenous and exogenous antigens
Endogenous: foreign particles that are synthesized within a body cell (if a cell become cancerous and starts producing abnormal proteins) Exogenous antigens: these are foreign antigens that have been phagocytized and degraded within a phagosome
Describe the physiology of fevers.
Fever is an abnormally high body temperature. A systemic response to invading microorganisms. Pyrogens are released and they raise the body's temperature. Fever causes the liver and spleen to sequester iron and zinc, which makes them less available to support bacterial growth. Additionally, fever increases the metabolic rate of tissue cells and may speed up repair processes.
Compare and contrast free and fixed phagocytosis
Free macrophages wander throughout the tissue spaces in search of cellular debris or foreign invaders Fixed macrophages such as stellate macrophages in the liver are permanent residents of particular organs
Identify the five classes of antibodies and describe the general role of each
IgD: membrane-bound on mature B cells, where it serves as an Ag-receptor IgM: attached to B cell membrane where it serves as Ag receptor - confound to blood vessels and quickly clumps Ag to activate complement system IgG: main Ig of both primary and secondary immune responses. only Ig which crosses placenta to provide passive immune protection to neonate. Activates complement, also involved in neutralization, agglutination and opsonization IgA: predominant class of secretory Ig, present in tears, saliva, nasal secretions, bronchial and digestive tract mucus & mammary glad secretions IgE: secreted by plasma cells - responsbile for allergic response in immediate hypersensitivity reactions
What are the three results that can occur when complement protein C3 is activated by being split into C3a and C3b?
Inflammation is enhanced, phagocytosis is promoted and cells can lyse.
Differentiate between nonspecific and specific defenses
Innate Nonspecific defenses: - first line of defense followed by second line (born with defenses) - responds within minutes - skin defenses and internal defenses (phagocytes, antimicrobial response, fever and inflammation) Adaptive Specific defenses: - functions like an elite fighting force - acquired after birth - third line of defense - takes longer to respond - carried out by T and B lymphocytes
Where do T and B lymphocytes mature and become immunocompetent?
Lymphocyte precursors destined to become T cells travel to thymus. B cells mature in the bone marrow.
What two signals are required to activate T cells?
MHC presentation and costimulation
What class of MHC protein is complexed with endogenous antigens? with exogenous antigens?
MHC-I with endogenous MHC-II with exogenous
Describe the steps required for B-cell activation
Matching antigens bind to the surface receptors and form cross-links between nearby receptors. The receptor-mediated endocytosis then occurs as the cross linked antigen-receptor complexes are brought in. Then proliferation and differentiation occurs
Which of the above stages is the basis of self-tolerance?
Negative selection
Which pre-T cells are eliminated during the second stage of T cell maturation? What is this stage called? Where (specifically) does this stage take place?
Negative selection occurs in the medulla of the thymus. T cells that recognize & respond to self-antigens presented on the MHC via apoptosis or anergy (eliminates self-recognized T cells that could cause autoimmune diseases).
What are the two primary types of phagocytes in the body?
Neutrophils and macrophages
What is the importance of memory cells?
to be able to remember the antigen so that the immune response will be faster upon the next encounter
Name the specialized type of B lymphocyte which secretes antibodies
Plasma cells
Which pre-T cells are eliminated during the first stage of T cell maturation? What is this stage called? Where (specifically) does this stage take place?
Positive selection occurs in the cortex of the thymus pre-T cells that cannot recognize self-MHC are eliminated via apoptosis
Describe the difference between a primary and secondary immune response
Primary immune response: occurs on first expsure to antigen and occurs after a short delay Secondary immune response: when you are reexposed to the same antigen. Faster, more prolonged and more effective because the immune response has already been primed to the antigen.
What are the four cardinal signs of inflammation?
Redness Heat Swelling Pain
What physiologic events underlie each of cardinal signs of inflammation?
Redness and heat: hyperemia (increased blood flow) Swelling and pain: increased fluid due to vascular permeability presses on adjacent nerve endings.
What are interferons?
Small proteins that help protect cells that have not been infected yet. The IFNs diffuse to nearby cells and stimulate them to synthesize proteins that block further protein synthesis and degrade viral RNA.
What are the two primary classes of T lymphocytes involved in an immune response?
T Helper cells (CD4 positive) = - adaptive immunity - Activate B and T cells to proliferate Cytototoxic T cells (CD8 positive) = - T cells that can directly attack and kill other cells
What is the function of the constant region of an antibody molecule? of the variable region?
The constant region determine antibody class The variable region houses the specific antigen-binding site
What is an antigenic determinant? (epitopes)
The region of an Ag that is immunogenic --> they bind to antibodies or lymphocyte receptors (the specific area where if something binds, it can proliferate a humoral or cellular response in the immune system)
What is the role of antigen-presenting cells (APCs) in an immune response?
They activate lymphocytes - engulf antigens and present them so that T lymphocytes can identify them
What role do the skin and mucous membranes play in protecting the body?
They are surface barriers that behave as a first line of defense that keep invaders out of the body by being a physical barrier.
What roles do interferons play in enhancing the body's resistance to infection and disease?
They interfere with viral replication by stimulating cells to block further protein synthesis.
