Immuno Test 1 part 1 up to page 36 Flashcards
The word immunity means what?
Means “exempt” from charges. For nearly a Century it has meant resistance to possible attack by an infectious agent. Resistance to certain diseases have been observed even in ancient times
What did the Chinese do in the eleventh century?
Introduced small pox to infants to protect them later in life, the technique is known as variolation
Who performed the first effective immunization? Explain?
Edward Jenner, an English physician in 1798. He observed milk maids infected with cow pox were resistance to small pox.
What is formol used for?
Used for the detoxification of toxins and venoms. Serpa Pinto reported this from his travels though central Africa.
What term replaced variolation?
Vaccination
How did Louis Pasteur influence immunology?
He investigated the possibility of protection against infection by vaccinations with attenuated strains of microorganisms 1st observation was Pasturella aviseptica (chicken cholera) Pasteur concluded that this culture contained attenuated microbes and he extended the term vaccination to mean conferring immunity by injection.
Using attenuated strains of microorganisms as a vaccine was confirmed by ____________ when he applied it to anthrax. How were these strains rendered avirulent?
Pasteur He rendered the organism avirulent by growing them at an unusually high temperature.
How did Elie Metchnikoff study the role of motile cells of a transparent starfish larva?
He introduced a rose thorn into the larva and noticed a few hours later the thorn was surrounded by motile cells.
How did the rabies vaccine come to be?
Pasteur allowed spinal cords taken from rabies infected rabbits to dry, and then used the dry cords as his vaccine material, since the drying process rendered the rabies virus avirulent.
What did Metchnikoff prove?
That Leukocytes will engulf microorganisms. He called this phagocytosis Phagocytosis was greatly enhanced in animals recovering from an infection or after a vaccine against those particular microorganisms
What are the 2 circulating types of cells shown by Metchnikoff to be capable of phagocytosis? What are these cells termed??
Polymorphonuclear Leukocytes (neutrophils) and the macrophages as well as certain fixed cells capable of phagocytosis The cells are termed phagocytes.
What did Wright and Douglas do?
They used washed cells to prove the immune a system used an active enzyme known as opsonin. They proposed a term opsonization.
What did Wright and Douglas do?
They used washed cells to prove the immune a system used an active enzyme known as opsonin. They proposed a term opsonization. (resolution for the humoral and cellular theories)
What is an Antigen?
Any substance capable of inducing a reaction against itself.
Lymphocyte is responsible for both ______ and ________.
Cellular and humoral immunity
What is in Antibody?
Factor present in the serum possessing this activity (inducing a reaction against itself)
What is the instructional theory?
1930-1940 suggest a particular antigen would serve as a template around which antibody would fold. The antibody molecule would therefore assume a configuration complementary to that of the antigen template This theory was discredited as knowledge of DNA RNA and proteins were accumulated.
What is the Selective theory?
In 1900 Paul Ehhrlich proposed that cells expressed a variety of “side-chain” receptors that could react with infectious agents. This binding resulted from a complementary lock and key type interaction. (he further suggested that binding of an infectious agent to the side chain receptor released the side chain and inured production and release of more side-chain receptors from the cell with the same specificity – antigen selected the appropriate side chain and side chain specificity was determined prior to antigen exposure)
Where did the Clonal selection theory come from?
in 1950 the selection theory was refined into the clonal selection theory by Sir F. Macfarlane Burnet.
What did Sir F. Macfarlane do?
Refined the selection theory to the Clonal Selection theory. he proposed that individual lymphocytes express membrane receptors that are specific for particular antigens. The receptor specificity is determined prior to antigen exposure.
Binding of antigen to a specific receptor activates the cell, resulting in?
its proliferation into a clone of cells, each with the same immunologic specificity as the original parent cell.
What is now accepted as the underlying paradigm of modern immunology?
The Clonal Selection Theory.
What is the Immune system in host defense described as?
A criminal invades a town, threatening its safety; but before he can do any damage, he is surrounded by police and then hauled off and confined in the local jail.
What are the 2 types of immunity?
Innate Immunity (natural, Native, or Nonspecific immunity) Adaptive immunity ( Acquired or Specific immunity)
What is Innate immunity??
it is present in all individuals or animals at all times, hence it is the initial response to microbial invasion.
True or False- innate immunity improves on repeated exposure to a given pathogen and does not discriminate between pathogens.
FALSE BITCHES! Innate immunity does NOT improve on repeated exposure to a given pathogen (i.e no memory) and does not discriminate between pathogens.
Innate immunity constitutes which line of host defenses?
The first and second lines of host defenses.
What mediates adaptive immunity?
T and B lymphocytes
Adaptive immunity is highly specific for a particular _______
Pathogen
How long does it take for adaptive immunity to become fully functional?
it takes several days after a pathogen invades the body
What is the difference between innate immunity and adaptive immunity?
Unlike innate immune response, the adaptive response improves with each successive encounter with the same pathogen (i.e. immunologic memory)
What line of defense is adaptive immunity?
third line of defense
What happens when a microbe eludes innate immune responses?
Adaptive immune response is then enlisted. However, acquired immunity does not operate independently of innate immunity; rather, it supplements and augments the nonspecific defense mechanisms, producing a more effective total response.
What is the first line of defense against microoorganisms?
the first line of defense against mircroorganisms is the intact skin and mucous membranes lining the gastrointestinal, respiratory, and genitourinary tracts.
If a microorganism does breach the skin and mucous membranes and enters the body what other components help destroy the invader?
Neutorphils and macrophages, etc
Name the first lines of defenses… there are 3
1.) intact skin 2.)mucous membranes and their secretions, eg, mucus 3,) Normal flora
Name the second lines of defenses… there are 3
1.) phagocytosis 2.)Inflammation and fever 3.) Antimicrobial substances
Who are much more susceptible to infectious agents because of their immune responses?
The very young and the Very old because their immune responses are Suboptimal
What is a result of loss of taste or smell with age?
As individuals age, they sometimes lose sense of smell and taste. as a result, appetites may decrease and vitamin deficiencies increase. Dietary components such as protein and vitamin A, D, C and B complex are necessary for healthy immune responses.
The skin is a mechanical barrier than helps protect from entry of microorganisms and the epithelia also produce _____ that helps with this. How?
Peptides. Peptides that are produced have a natural antibiotic function (defensins and phagocytosis)
What is the epithelial turnover in humans?
Where the epidermis is completely renewed every 15-30 days
How does sebum help with innate immunity in the first line of defense?
Sebum is produced by sebaceous glands. Sebum forms a protective film over the surface of the skin. Contains lactic and fatty acids that inhibit the growth of many microorganisms (pH 3-5)
How does perspiration help protect the body?
It flushes microorganisms from the surface of the skin. Sweat also contains lysozyme.
How does the oral cavity help keep microorganisms out?
Saliva washes microorganisms from teeth and gums. It also contains antibacterial agents, (lysozymes)
what are the 4 main properties of the gastrointestinal tract?
1.) Low pH of the stomach 2.) Normal Flora 3.) Peristaltic movement, (vomiting and diarrhea) 4.)(Antimicrobial Substances) Proteolytic enzymes, Bile acids, and pancreatic secretions.
What are examples of Antimicrobial substances of the second line of defense?
Complement proteins, lysozymes, bacteriocins, digestive enzymes, low pH (stomach), Defensins
What can pH do to proteins and enzymes?
protein denaturation. High or Low pH can change the shape of an enzyme
Acidophiles grow best at what pH? Neutrophiles grow best at what pH? Alkalophiles grow best at what pH?
Acidophiles- 3.0-4.0 Neutrophiles- 6.5-7.5 Alkalophiles- pH> 8.0
3 main properties of the Respiratory tract in relation to immunity and protection?
1.) mucociliary escalator 2.) Coughing and sneezing (speeds up the escalator) 3.) Alveolar macrophages
How do eyes help keep out microorganisms?
Flushing action of tears. Tears also contain lysozyme
How does the genitourinary tract help keep out microorganisms?
Urine. Flushing action of urine; acidity of urine. Urine contains lysozyme. Vaginal lactic acid
What is normal flora?
These are microorganisms (mostly bacteria, fungi, protozoa) that colonize a host without causing disease. However, under certain circumstances, some flora can cause disease. They contribute to host defense by preventing potential pathogens from colonizing the host.
What is the role of the normal flora? (i.e. how does normal flora contribute to host defense)
1.) Competition for attachment sites and nutrients (competitive exclusion) 2.) Produces substances that are harmful to pathogens, eg. bacteriocins (antimicrobial peptides produced by bacteria that kill or inhibit other bacteria) In the large intestines, E. Coli producins colicins that inhibit the growth of Salmonella spp. and Shigella spp. 3.) Altering conditions that affect the survival of pathogens, eg, pH and O2 availability. Lactobacillus acidophilus in the vagina alters its pH to prevent over population by Candida albicans.
What are iron- binding proteins?
These are proteins that sequester iron thereby reducing iron available to a pathogen, Eg, transferrin, lactoferrin, and haptoglobin.
What critical role does iron play in bacterial respiration?
as a component of the cytochromes and the iron-sulfide proteins involved in electron transport chain.
What are siderophores?
Iron-chelating compounds produced by various pathogenic bacteria that facilitate the uptake of iron by the bacterial cell.
What is oxygen tension or oxygen concentration?
toxic derivatives of oxygen such as H2O2, superoxide anion, etc, inhibit the growth of obligate anaerobic bacteria, especially in the lungs.
What is complement in terms of a component of innate immunity?
Plasma and cell surface proteins associate with lysis of Gram negative bacteria, chemotaxis of pahgocytes, and opsonization ( the coating of an antigen or particle that facilitates its uptake into a phagocytic cell).
What are interferons?
Low molecular weight glycoproteins produced by certain cells in response to viral infections. IFNs have antiviral and immune regulatory activity.
How does temperature effect microbial growth?
Body temperature inhibits replication of some pathogens, fever enhances phagocytosis. Also antibody production and T cell proliferation are more efficient at higher body temperatures than at normal levels
What can induce fever?
Fever can be induced by bacterial endotoxin (lipopolysaccharide (LPS)) and interleukin-1
What is inflammation?
This is a process which begins following sublethal injury to tissue and ends with complete healing. Cause may be microbiological, physical, or chemical. Inflammation results in the bringing of blood components and cells of the immune system to the site of tissue damage.
2 Main components of Specific immunity?
1.) Antibody- mediated (humoral) immunity 2.) Cell- mediated immunity
What is Antibody- mediated (humoral) immunity?
Antibodies are soluble proteins produced as a result of interaction between a B lymphocyte and an antigen. The antibody has the ability to combine with the antigen that stimulated its production.
Where are Antibodies found?
they are found in plasma, lymph and tissue fluids of the body. They are most effective in eliminating extracellular antigens and bacterial toxins.
What is Cell-mediated immunity?
An adaptive immune response in which antigen specific T cells play the main role. Macrophages and natural killer cells (although non specific cells) are included with T cells in cell-mediated immune responses.
Cell Mediated responses are most important against______________?
Most important against intracellular parasites, in allograft rejection, and in delayed hypersensitivity reactions.
The adaptive immune response is divided into what 3 phases? 1.) ____2.)_____3.)_______
1.) the recognition of antigen by antigen-specific lymphocytes 2.) the activation of the lymphocytes 3.) the effector phase which results in destruction of the antigen.
What does Activation of Lymphocytes result in?`
Clonal expansion
What is clonal expansion?
The proliferation of antigen specific T and B lymphocytes in response to antigenic stimulation and precedes their differentiation into effector cells and memory cells. ( this is important b/c it allows increases in numbers of T and B cells so they can effectively fight)
What happens after the elimination of the antigen?
The immune response subsides and homeostasis is restored.
Fill in the gaps on this chart
A - Antigen recognition
B- Lymphocyte activation
B1- Differentiation
B2- Clonal expansion
C - Antigen elimination
C1-cell-mediated immunity
C2-Humoral immunity
C3- elimination of antigens
D- Contraction (homeostasis)
D1- Apoptosis
E - Memory
What are the two main lines of differentiation of pluripotent stem cells?
1.) The myeloid lineage 2.) the lymphoid lineage
What does the myeloid lineage produce?
it produces monocytes neutrophils, basophils, eosinophils, and other cells.
What does the Lymphoid Lineage produce?
produces lymphocytes
Plasma proteins represent a mix of what two types of properties?
What are the major plasma proteins?
structural and functional
Albumin, Fibrinogen, and Globulin.
Where are the major plasma proteins produced?
virtually all the albumin and fibrinogen, and 50% to 80% of globulins are produced in the LIVER!! the remaining globulin proteins are produced in the lymphoid organs and tissues.
What are Globulins?
They are principally responsible for the body’s innate and adaptive immune responses against invading pathogens. They are comprised of complement proteins and antibodies.
What can Hosts immune responses result in (related to immunopathology)?
1.) Autoimmunity: Response is directed against self- antigens 2.) Immunodeficiency: Ineffective immune response. 3.) Hypersensitivity: overactive immune response resulting in allergies. 4.) Transplantation reaction: Rejection allograft.
How are CD molecules identified?
By using monoclonal antibody. They may be used as markers to differentiate different tcell populations, such as CD 4+ T cell ( T Helper cell) or CD8+ T cell ( Cytolytic T lymphocyte)
What is an Antigen?
What must it be capable of?
Any substance that can induce humoral and/ or cell - mediated immune responses when introduced into an individual or animal.
The antigen must be capable of reacting with specific receptors on T and B cells and with the antibodies produced against it.
What are microbial antigens?
Bacteria, fungi, viruses, protozoa and helminth parasites.
What are non microbial antigens?
Foreign proteins, food antigens, plant antigens ( eg. Pollen), cell surface proteins ( eg red blood cells antigens) etc.
What influences the degree of antigenicity of a molecule?
1.) Foreignness 2.) Chemical Complexity 3.) Molecular size 4.) Stability 5.) Degradability 6.) Genetic makeup of the host. 7.) method of administration.
What is foreigness?
How does it relate to antigenicity?
What are the four types?
Self vs Non self. The macromolecule must come from a foreign source.
The more foreign the antigen, the more vigorous the immune response.
autologous, syngeneic (isogeneic), allogeneic, xenogeneic
What are autologous antigens?
Antigens found within the same individual
What are Synegenic (isogeneic) antigens?
Antigens found in genetically identical indiciduals, (Twins or inbred mice)
What are allogeneic antigens?
Antigens found in genetically dissimilar members of the same species, Eg, blood- group antigens.
What are Xenogeneic antigens?
Antigens found in different species.
What does chemical complexity mean (relative to antigenicity?)
The more complex a molecule, the more varied the epitope (antigenic determinant) composition, Hence the more likely different (individual) immune responses will be induced.
What are the most complex organic compounds therefore they are the most antigenic?
Proteins - They are often composed of 18 or more amino acids. -This diversity imparts epitopes of differeing specificities to the protein.
Simple polysaccharides are _______ antigens. Why?
Weak antigens, because they do not possess sufficient chemical complexity, additionally, they are rapidly degraded before the immune system has had time to respond to them.
More complex polysaccharides are ________. (compared to simple polysaccharides in terms of antigenicity requirements)
Antigenic (capsular polysaccharides and lipopolysaccharides.)
How is antigenicity of polysaccharides enhanced?
IF they are coupled to proteins as glycoproteins.
Why are Lipids weak antigens?
Due to their structural simplicity and rapid metabolism. However, immune responses to lipids may be enhaced when they are conjugated to proteins (lipoproteins) or polysaccharides (glycolipids)
The most potent antigens are proteins with high____________.
Molecular weights ( above 100,000)
In general molecules with weights below _______ are weak antigenic
10,000 and very small ones, ex amino acids are non antigenic.
What is an example of an non antigenic molecules?
Amino acids.
The number and variety of epitopes increase proportionately with_______
the size of the protein.
With carbohydrate antigens, the number if epitopes may increase with size but__________ does not.
diversity
Why are highly flexible molecules that have no fixed shape poor antigens??
Because the Lymphocyte antigen receptor recognizes an antigen by its shape.
T Cells respond only to _______ antigens.
What must APCs do to an antigen before it can be expressed?
Processed.
they must first degrade the antigen before they can express antigenic peptides noncovalently bound to MHC molecules on their cell surface
Macromolecules that cannot be degraded and presented with MHC molecules are _________ antigens.
Poor
The genetic constitution of the host determines whether a given molecule will stimulate an ______ _______.
immune response.
low does of an antigen may not stimulate an immune response either because the amount given fails to activate enough lymphocytes or renders the lymphocytes unresponsive. On the other hand a very high dose of antigen may lead to _______ _______
Immune Paralysis.
What does the route of antigen administration determine?
Which organs and cell populations will initiate the immune response.
Antigens administered _________, usually elicit the strongest response.
Explain.
Subcutaneously. The antigens are taken up by Langerhans cells present in the skin, Carried to local lymph nodes, where they are processed and presented to T cells.
What are Epitopes?
The sites on or within the antigen that stimulate the immune response and against which that response is directed. Thus, epitopes determine the specificity of the antigen molecule.
When are internal epitopes expressed?
Only after the antigen has been partially degraded in vivo by antigen- presenting cells.
What does it mean that many antigens are polyvalent or multivalent?
What does polyvalent mean?
What does multivalent mean?
Simultaneous immune responses may be mounted against the various epitopes on theses antigens.
polyvalent - many epitopes of different specificities
multivalent - many epitopes of the same specificities
Why can antibodies produced to one antigen cross react with an unrelated antigen?
does the antibody have the same affinity for both antigens?
it is possible because the two unrelated antigens share on or more identical or very similar epitope(s)
No, the affinit of the antibody will be higher for the original epitope
What does Cross reactivity (heterophile antigens) provide the basis for?
- Some autoimmune diseases, -heterologous vaccines (measles distemper) -false positive diagnosis.
What is a B cell receptor?
This is the cell surface receptor of B cells that recognizes a specific antigen. It consists of a membrane immunoglobulin molecule in association with the signal transduction molecules IgA and IgB
Cytokines usually act _______.
Locally, however on occasion, they may exhibit endocrine action.
Proinflammatory cytokines act in concert with _______ and _______ to ensure the development of physiologic responses to a wide variety of stimuli, such as microbial infections and tissue injury.
Chemokines and hematopoietic cytokines
How are chemokines classified?
into subfamilies based on the position of two of the four highly conserved NH2 terminal cysteine residues they possess.
C3b can combine with other complement components to generate__________?
C5 convertase, the enzyme that leads to the terminal pathway that produces the membrane attack complex (MAC)
Fill in the missing information
Soluble C1 inhibitor covalently binds to active_______and ______
C1r2 and C1s2 and dissociates them from C1q, thus stopping activation by the classic pathway.
Membrane bound decay accelerating factor (DAF) displaces Bb from……
C3bBb or C2b from C4b2b, the alternative and classic pathway C3 convertase.
What does Fluid phase (soluble) Factor I do?
Cleaves cell -associated C3b and C4b. C3b is cleaved to yield iC3b, C3c, C3d, C3f, and C3dg.
Factor I is active only in the presence of ________________? Explain the 3 examples from the book.
regulatory proteins or cofactors.
1) Membrane bound membrane-cofactor protein (MCP, CD46) and complement-receptor 1 (CR1) block the formation of C3 convertase by binding C4b or C3b. Cofactor for factor I-mediated cleavage of C3b or C4b.
2) soluble factor H – cofactor for cleavage of C3b by factor I
3) soluble C4b-binding protein (C4BP) - binds to C4b on cell surface and competitively inhibits the binding of C2; prevents formation of the C3 convertase. Cofactor for factor I-mediated cleavage of C4b into C4b and C4d.
S protein (vitronectin) Binds to_____________?
What happens as a result of this?
C5b67 complex, preventing the complex from inserting into cell membranes.
In this way, S protein can diminish the potentially indiscriminate lysis of host cells (bystander lysis) by insertion of soluble C5b67 complexes released from other activation surfaces
How does Cd59 work?
What can most nucleated cells do to fight this?
by binding to C5b678 on the cell surface and preventing C9 polymerization.
most nucleated cells can endocytose C5b-8 or the entire MAC. Therefore if C5b-8 is removed early enough, the cell is able to repair any membrane damage and restor its osmotic stability.
Fill in the cells from this lineage
Add in the details from this chart:
What are the 4 “isms” that can apply to cytokines?
Pleiotropism - a single cytokine may have multiple activities
redundancy - a single activity can be caused by multiple cytokines
synergism - a cytokine may work best in assoication with another cytokine
antagonism - a cytokine may antagonize the effects of another cytokine
What is another name for MAC?
C5b6789
(The membrane attack complex)
