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Define the term “attenuate.”
Discuss the clonal-selection theory.
Is the theory that a lymphocyte expresses membrane receptors that are specific for a certain antigen à this is determined before exposure to an antigen. When the antigen binds to the cell, this activates the cell which in turn allows it to clone itself with immunity specific to the parent cell.
How did Pasteur’s work differ from that of Jenner?
Pasteur worked with chicken cholera. He was inoculating chickens with bacteria, he used the same strain that he was fighting however he accidently discovered an attenuated cholera that allowed the chickens to live. He then inoculated chickens with this strain. This was the basis for immunology.
Why is an attenuated pathogen more suitable for vaccination
It is less likely to cause the actual disease. Also you don’t have to find a weakened strain out in nature, you can attenuate the strain yourself.
What are the active molecules in the immunoglobulin fraction of serum? For what activities might molecules be responsible?
he active molecules are antibodies , Antibodies are responsible for recognizing and reacting with antigen.
Differentiate between active and passive immunity.
Active immunity is self-made immunity, developed by cells in response to an infection, it is long lasting. It is immunization with an antigen to provoke adaptive immunity.
Passive immunity is the short lived immunity that is introduced by introducing readymade antibodies.
Ex Polio, smallpox, flu, measles. Aids
Ex. Tuberculosis, Tetanus, Whooping cough
Ex Thrush, Ringworm
How does the immune response may differ depending on the nature of the pathogen.?
Recognizes and kills virus infected cells
Recognition of antibodies or soluble molecules, followed by cellular /molecular mechanisms to eliminate cell
Body has pre-existing immunity
These are opportunistic infections and works when the immune system is compromised
Acts a toxin
Can develop antibodies to toxin but must be developed
Name the organism that causes tetanus, and outline the symptoms of the disease. How is this disease controlled?
Organism that causes tetanus is a bacteria called Clostiridium tetani. It attacks the nervous system and causes death, The disease is controlled through vaccination.
· First line of defense
· Response time: hours
· Repeat response is same as first response
o Phagocytes and
o Pattern recognition molecules
· Specificity is limited and fixed
· Response time :Days
· Repeat response is faster than primary response
o Antigen specific receptors
· Specificity is diverse and improves
Explain how innate and adaptive immunity work together to maximize the immune response.
· Do this through signalling
· Innate sends out signals that stimulates adaptive immune response (ex , ligand reacts with receptor that leads to metabolic changes in the cell , as with cytokines)
Discuss the role of signal transduction in the coordination of the innate and adaptive immune response.
Signal transduction allows for the synthesis/secretion of certain proteins, differentiation or initiation or cessation of specific functions. Adaptive system produces signals components that increase effectiveness of the innate response.
Define “antigenic specificity.”
Immunity that can be transferred from an immune individual to a non-immune through the transfer of serum antibodies. (B cell response)
Cellular Immune response: Immunity that can be transferred only by administration of T –cells from an immune individual. (T-cell response)
Describe clonal selection.
Antigen mediated activation and proliferation of members of a clone of B cells that have receptors for the antigen . (or for complexes of MHC and peptides derived from the antigen , like in T cells)
· Low magnitude , shorter duration of response
· Activation of naïve B cells by antigen and T H cells for proliferation
· Greater in magnitude and duration
· Antibody levels are much higher (this is because of clonally expanded population of memory B cells)
· Memory cells respond faster than naïve B cells
Discuss the concept of immune dysfunction.
1. Allergies and Asthma (inappropriate immune response)
2. Graft rejection and graft vs. host disease (transplant viewed as foreign object and not as host)
3. Autoimmune disease (loses sense of self ex MS)
4. Immunodeficiency (genetic abnormality or damage by physical chemical or biological agent)
Immediate type hypersensitivity reaction , triggered by Ig-E mediated mast cells degranulation. Exposure to antigen leads to hypersensitivity.
Physical barriers such as skin, mucus membranes don’t allow pathogens in
Acidity of the stomach kills bacteria, bacteria cannot grow in acidic conditions
Lysozyme present in tears , kill bacteria..
List and describe the soluble molecules that contribute to innate immunity.
Enzymes such as lysozyme are present in tears, and mucus secretions attack bacteria , can cleave the peptoglycan layer of the bacterial cell wall .
Interferon , a soluble molecule compromises a group of proteins are produced by virus infecting cells , interferons can bind to nearby cells and induce a generalized antiviral state.
Complement is a group of soluble proteins that circulate in an inactive state, once activated can damage membranes of pathogenic organisms
· Signal binds to receptor
· Signal leads to the generation of a second messenger which carries message to cells interior
· Phosphorylation /dehosphorylation cycles under control of signaling pathway to activate or deactivate pathway components.
· Signals are amplified by enzyme cascade
· Protein is synthesized and secreted
· Leads to metabolic adaptations in the cell(make targets , produce cytokines)
Antigen specificity is the ability of adaptive system to distinguish between antigens. Can respond to a diverse set of pathogens , and can distinguish between different protein moloecules.It recognizes billions of unique structures.
What happens when a naïve B lymphocyte encounters the corresponding antigen?
When a naïve B cell meets its matching antigen , it causes it to divide rapidly and its progeny differentiate in to memory B cells and effector B cells(plasma cells)
The antigen binding component of a T lymphocyte id the T cell receptor (TCR).
The two subpopulations are
· Tc cytotoxic cells with express CD8,
· TH helper cells which express CD4
T cells only recognize antigens that are bound to a MHC molecule found on cell membranes.
Which types of MHC molecules result in the activation of which types of T cells?
· Is in all nucleated vertebrate cells
· Tc cells generally combine with MHC 1MHC II
· MHC II generally combines with TH
In clonal selection an antigen binds to a particular B or T cell and stimulates it to divide into a clone of the cell. It has specificity because only lymphocytes whose receptor is for a specific antigen are clonally expanded to be mobilized for an immune response. The self non self-discrimination is accomplished because during development the system eliminates lymphocytes bearing self-reactive receptors during development/
Common manifestations are
· Allergy /asthma
· Graft rejection and graft vs. host disease
· Autoimmune disease
What are the possible causes of immunodeficiency?
Genetic factors abnormalities, environmental damage such as chemical, physical and biological agents
Explain the process of hematopoiesis.
HSC cells (hematopoietic stem cells) which are self-renewing
· In embryo in yolk sac , cell differentiate into primitive erythroid cells that have hemoglobin. By third month HSC cells migrate to fetal liver , colonize spleen . After that it is the bone marrow that becomes main differentiator of blood cells.
· 2 pathways initially : (once a progenitor , they cannot self-renew)
° Myeloid Progenitor cell- Generate RBC, WBC and platelet generating cells called megakaryocytes
° Lymphoid Progenitor cell Give rise to B, T and NK cells
° Expresses membrane- bound antibody which recognizes antigen alone
° Mature in Bone marrow
° Naïve B cells become effector cells, plasma cells and memory B cells
° Expresses membrane bound antibody
° Mature in the Thymus
° T cell receptors can only recognize antigen that is bound to cell membrane proteins called major histocompatibility complex (MHC) molecules
° When T cells recognizes antigen combined with MHC molecule , the T cell proliferates and differentiates into various effector and memory T cells
° Two subpopulations of T cells à Th and Tc but also T reg cells
Natural killer cells
° Are large granular lymphocytes
° No surface markers
° Display cytotoxic activity against a wide range of tumor cells , and cells infected with some viruses
° Do not have T cell receptors or immunoglobin
° Has antibody dependant cell mediated cytotoxicity (ADCC)
· Mononuclear phagocytes
° Consists of both the monocytes circulating in the blood and macrophages in the tissue.
° During hematopoiesis , when develop into monocytes they circulate in the blood for 8 hours where they enlarge migrate into the tissue and differentiate into specific tissue macrophages in various tissues (gut, lung, connective, liver, kidney, brain and bone)
° Macrophages capable of digesting exogenous antigens
· Granulocytic cells
° Neutrophils, Eosinophils or Basophils
° Multilobes nucleus and contains granulated cytoplasm
° Neutrophils and Eosinophils are phagocytic (Basophils aren’t)
° Neutrophils constitute 50-70% of WBC
· Mast cells
° Do not differentiate until they leave blood and enter tissue
° Found in epithelial cells, connective tissue, digestive tract
° Have large number of cytoplasmic granules that contain histamine and pharmacological active substances
° Role in development of allergies
° Bone marrow derived cells that descend through myeloid and lymphoid lineages and are specialized for antigen presentation to helper T cells
° Express class II molecules
Follicular dendritic cells
° A cell with extensive dendritic extensions that is found in the follicles of lymph nodes.
° Do not express MHC class II molecules
° Do express high levels of membrane receptors for antibodies
Primary: Thymus and bone marrow , where maturation of lymphocytes takes place
· Thymus functions
° Site for T cells to develop
° Bilobed organ situated above the heart
° Function if the thymus is to generate and select a repertoire of T cells that protect body from infection
° Induces the death of T cells that cannot recognize antigen MHC complexes and those that react with self-antigen (enough to cause autoimmune disease)
Bone marrow functions
° Site of hematopoiesis and fat depot
° Site of B cell origin and development (for mammals and humans anyway)
° Also has a selection process that gets rid of self-reactive B cells
· Lymphatic system functions
° Network of vessels and nodes that conveys lymph. Returns plasma derived interstitial fluid to the blood stream
° Important for the immune system
° Traps foreign antigen, becomes enriched in lymphocytes-> transport system
· Lymph nodes functions
° A secondary lymphoid organ that contains lymphocytes, macrophages and dendritic cells that serves as a site for filtration of antigen and for activation and proliferation of lymphocytes.
° Site where response is mounted to antigen
· Spleen functions
° Secondary lymphoid organ where old erythrocytes are destroyed and blood borne antigens are trapped and presented to lymphocytes in the PALS and marginal zone.
° Left abdominal cavity
° Filters blood
° Is not supplied by lymphatic vessels, blood borne agents are carried to spleen by through splenic artery
· Mucosa-associated lymphoid tissue functions
° Protective Lymphoid tissue situated along the mucous membranes that line the digestive, respiratory and urogenital tract.
° Less organized than the spleen and lymph node cells
° Major site of entry for most pathogens
° Has a large population of antibody producing plasma cells
· Cutaneous-associated lymphoid tissue functions
° Skin defense system
° Skin cells called keratinocytes secrete cytokines to induce local inflammatory response
What types of immune cells arise from each type of progenitor cell?
The two types are Myeloid which generate RBC , WBC and megakaryocytes and Lymphoid which give rise to B, T and K cells.
Define “apoptosis.” Discuss its role in hematopoiesis.
Apoptosis is the programmed cell death of cells that has morphological changes such as nuclear fragmentation, blebbing and release of apoptic bodies which a phagocytized. This is needed when there is a problem with a cell also important for an immunological response
When a B cell that has never encountered an antigen that matches the cell proliferates quickly . These then become Effector cells (plasma cells ) and Memory B cells. The plasma cells do not have membrane bound antibody (the have antibody you have to secrete) and do not divide, they only last one to two weeks.Memory cells live a lot longer and have the same membrane bound antibody as parent cells
1) T helper cells (TH)
2) T cytotoxic (Tc)
3) T regulatory (Treg)
CD8 glycoproteins is generally associated with Tc
What is the function of a helper T cell (TH) once it is activated by interaction with appropriate antigen-MHC complexes?
Once activated , A T helper cell differentiates into an effector cell that enable or “help” the activation of B cells , Tc cells, macrophages and other cells that participate in an immune response.
What is the role of a cytotoxic T cell (TC cell) following activation?
The role of a Tc cell following activation , triggers it to proliferate and differentiate into an effector cell called a cytotoxic T lymphocyte (CTL) or into a memory cell.
What is the general function of a Treg cell?
T reg cell (have CD4 and CD25) , T reg suppress the immune response (they are negative regulators).
Define the term “clone” with regard to lymphocytes.
Clone means , that it is a cell arising from a single progenitor cell. If given lymphocyte divides to form two daughter cells, both daughter have antigen receptors with specificity identical to each other and so will any descendants . This population is a clone.
The function of a natural killer T cell is don’t have membrane molecules and are part of our innate immune system that display cytotoxic activity against a wide range of tumour cells and some but not all viruses.
Recognize targets by
i.) Nk cell employs NK receptors to distinguish abnormalities (unusual profiles, reduction in MHC)
ii.) Antibody dependant cell mediated cytotoxicitySome tumour cells display : antigens connected to antibodies . NK cells express CD16 for a region of the antibody molecule and can attach and destroy the cell
What changes occur in the differentiation of monocytes into macrophages?
Monocytes circle blood stream for 8 hours , enlarge , and differentiate in to macrophages.
· Cell enlarges 5-10 times
· Intracellular organelles increase in number and complexity
· Acquires increased phagocytic ability
· Produces higher amount of hydrolytic enzymes
· Begins to secrete a variety of soluble factors
Why are activated macrophages more effective at eliminating pathogens?
Activated macrophages are more effective at eliminating pathogens because
· They exhibit greater phagocytic ability
· Increased secretion of inflammatory mediators
· Increased ability to activate T cells
· Secrete various cytotoxic proteins that help them eliminate a broad range of targets
· Antigen sticks to the macrophage cell membrane
· Extended membrane protrusions called pseudopodia extend around the attached material
· It sticks around to make a bubble called the phagosome which goes towards the cell interior
· This then fuses with a lysosome and is called the phagolysosome, where hydrolytic enzymes digest the material
· Then it is eliminated by exocytosis
Describe the three types of granulocytes .
° First to arrive at inflammation site, indicative of infection
° Generate a variety of antimicrobial agents
° Are phagocytic
° Nonphagocytic granulocytes
° Release pharmacologically active substances from their cytoplasm granules
° Play a major role in certain allergic responses
° Motile phagocytic cells (phagocytic role less important)
° Can migrate into tissue spaces
How do follicular dendritic cells differ in their function from dendritic cells?
Follicular dendritic cells are different because they do not arise from bone marrow and do not express MHC II and do not function as antigen presenting cells for TH cell activation.
Components of the lymphoid system are:
● immune cells – B cell lymphocytes and plasma cells, dendritic cells, granulocytes, macrophages, monocytes of mononuclear phagocyte system (MPS), T cell lymphocytes
● lymph ducts and vessels and lymph nodes (right)
● lymphoid organs including reticuloendothelial system – bone marrow, (lymph vermiform appendix
Define the term “immunocompetent.”
A mature lymphocyte capable of recognizing a specific antigen and mediating an immune response.
What is the difference between a primary follicle and a secondary follicle?
A primary follicle is a lymphoid follicle prior to stimulation with antigen that contains a network of dendritic cells and small resting B cells. After antigenic stimulation it becomes a secondary follicle which develops a ring of concentric packed B cells surrounding a germinal center.
Describe and outline the function of M cells.
M cells (or micro fold cells) are cells found in the follicle-associated epithelium of the Peyer's patch as well as in BALT (Bronchus-associated lymphoid tissue). They transport organisms and particles from the gut lumen to immune cells across the epithelial barrier, and thus are important in stimulating mucosal immunity.
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