Lecture 1- Exam 2 Flashcards
(106 cards)
1
Q
What is a pathogen?
A
Any organism with the potential to cause disease
2
Q
Pathogen are divided into 4 kinds: list them
A
- bacteria
- viruses
- fungi
- parasites (unicellular protozosa, multicellular invertebrates, worms)
3
Q
What is the function of IS?
A
- To prevent entry of foreign cells into the body
- Eliminate foreign agents that have entered the body
4
Q
What are foreign agents?
A
microorganisms (bacteria, viruses, yeasts, fungi, parasites) and the products of these organisms (endotoxin/exotoxin), foods, pollen, chemical, drugs)
5
Q
What are exotoxins and endotoxins?
A
- Exotoxin: proteins secreted by certain species of bacteria which diffuse in the surrounding medium
- Endotoxin: usually heat stable lipopolysaccharide-protein complexes which form structural components of the cell wall of gram negative bacteria – released during cell lysis or death of bacteria
6
Q
What else is the function of the IS?
A
- Eliminate abnormal self cells (cells become abnormal due to age, infection, intracellular pathogen, transformed/cancer)
- Some immune cells are also involved in the removal of dead cells or tissues and in the generation of new blood vessels
7
Q
What are examples of external barriers?
A
- Physical barriers – skin – first defense
- Chemical barriers- has the enzyme lysozyme in tears and saliva- antibacterial substance secreted from mucosa. Cilia in the lungs participate in continual cleansing of unwanted material breathed in, acidic environment in the stomach, vagina or skin deters microorganisms
- Microbiologic barriers- commensal microorganisms (gut, vagina, etc.)
8
Q
What is systemic defense? What are the two examples?
A
Systemic defense – involved in the destruction and elimination of foreign agents that have made it through the external barrier or altered self cells
* Cellular component – cells of innate immunity (phagocytosis), cells of acquired immunity (specialized cells such as T cells)
* Humoral component–antibodies,complement proteins, antimicrobial proteins
9
Q
All epithelial surfaces secrete antimicrobial peptides called _
A
defensins
10
Q
What does defensins do?
A
Defensins kill bacteria, fungi and enveloped viruses by disrupting their membranes
11
Q
To prevent defensins from disrupting human cells they do what?
A
To prevent defensins from disrupting human cells they are synthesized as part of a longer, inactive polypeptide and function poorly unless they are in lower ionic concentrations of sweat, tears, or the lumen of the gut to become active
12
Q
Most epithelia is coated with a flora of what?
A
Most epithelia is coated with a flora of nonpathogenic microorganisms that compete with pathogens
13
Q
How many microbial species live in healthy human gut? What is this called?
A
- More than 500 microbial species live in the healthy human gut- called commensal species
14
Q
What does the commensal species do? (3)
A
- inhibit colonization by pathogens
- enhance human nutrition by further processing digested food
- making vitamins
15
Q
What happens when a patient takes antibiotics?
A
- When a patient takes antibiotics, the nonpathogenic flora is killed together with the pathogens that caused the disease
- The body is recolonized by microorganisms – can be bad or good!
16
Q
What is the innate immunity?
A
- The immunity we were born with, includes the barriers, it’s fast, no memory
17
Q
What is the adaptive (acquired) immunity?
A
specific, diverse, slow, can develop immunologic memory. Can be passive or active
18
Q
What is passive immunity or active immunity?
A
- Passive immunity- refers to the situation when the person receives the antibodies from another source. Includes transfer of antibodies through placenta, colostrum (breast feeding), genetically engineered antibodies (vaccine)
- Active Immunity- refers to the situation when the individual is exposed to an antigen (naturally or through immunization). The individual builds up their own defense (antibodies) against the antigen
19
Q
What is c.diff?
A
20
Q
The innate mechanisms are determined entirely by what?
A
the genes a person inherits from their parents
21
Q
Innate fast or slow? What does it cause?
A
- Works fast, within minutes, responsible for causing fevers!
22
Q
How does an innate immune response to pathogen every time?
A
- Keeps no memory of specific pathogens, responds the same way every time to a pathogen
23
Q
Innate immune response:
* Recognition of pathogen causes what?
* WHat is activated?
A
- Recognition of a pathogen, recruitment of effector cells that engulf bacteria, kill virus infected cells, or attack protozoan parasites and a battery of serum proteins called compliment (mark pathogens with molecular flags)
- Serum proteins of the complement system are activated in the presence of a pathogen to form a covalent bond between a fragment of complement protein and the pathogen, the pathogen gets marked as dangerous.
24
Q
Innate immune response:
1. The soluble complement fragment summons what?
1. Effector cell has what?
1. The receptor and bound ligand are what?
A
- The soluble complement fragment summons a phagocytic WBC to the site of the complement activation
- Effector cell has a surface receptor that binds to the complement fragment attached to the pathogen
- The receptor and bound ligand are taken into the cell by endocytosis and further to the phagosome where it is destroyed
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What are the different components of the complement system?
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Where does all cells of the innate system originate from? What are they?
Originate from the pluripotent hematopoietic stem cell
* These stem cells derive leukocytes, erythrocytes, and megakaryocytes
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What is hematopoiesis?
the development by which hematopoietic stem cells give rise to hematopoietic cells
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Where are the different sites of hematopoiesis?
* **Early embryo**- blood cells are produced in the yolk sac->liver.
* **3rd-7th week of fetal life** the spleen is the major site of hematopoiesis
* As the bones develop during the **4th-5th month**, hematopoiesis starts to shift toward the bone marrow and by birth it is all in the bone marrow
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In adults, where does hematopoiesis occur?
occurs mainly in the bone marrow of the skull, ribs, sternum, vertebral column, pelvis, and femurs
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Hematopoietic stem cells can also become cells that commit to one of two cell lineages: What are they? Why are they different?
myeloid or lymphoid
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What are granulocytes?
prominent cytoplasmic granules, which contain reactive substances that kill microorganisms and enhance inflammation
* Neutophil, Eosinophil, basophil
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What are Neutrophils and what do they do?
* most abundant (95% of circulating granulocytes) and lethal granulocyte – specializes in capture, engulfment, and killing of microorganisms AKA **phagocytes**.
* Rapidly mobilize to enter sites of infection, first cells to arrive. They can work in anaerobic situations.
* 6hr half life, release granules causing damage to host tissue, die at the site of infection, forming **pus**
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What are eosinophil? What do they defend in? When do they increase in?
Second most abundant granulocyte – defend against helminth worms and other intestinal parasites.
*Abundant in the mucosa of the gastrointestinal tract where they defend against parasites, and in the mucosa of the respiratory and urinary tracts.
* Circulating eosinophils are increased in allergic diseases such as asthma and in various other respiratory and gastrointestinal diseases
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What are basophil? What do they release and when?
least abundant (0.2%), release histamine and other inflammatory mediators when activated by binding of specific antigens to IgE molecules - participate in immediate-type hypersensitivity (allergic) reactions
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Mast cell:
* Where does it live?
* What does it do?
* What is it part of?
* lives in all connective tissue
* activation and degranulation of this cell at sites of infection is a major contributor to inflammation, release granules (including histamine)
* large part of allergic response
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What are monocytes?
leukocytes that circulate in the blood, bigger than granulocytes, distinctive indented nucleus. All cells look the same, thus “mono”cytes. They travel in the blood to tissues where they mature to macrophages
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What are macrophages?
well equipped for phagocytosis. Scavengers. Long lived commanders. Provide intelligence to other cells and orchestrate local response to infection. Secrete cytokines that recruit neutrophils and other leukocytes to the area. Usually the first phagocytic cell to sense an invading organism
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What are the functions of monocytes/macrophage?
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Dendritic cells:
* Lives where?
* What type of morphology?
* Common with what?
* What do they do?
* Lives in the body’s tissues, have distinct star shaped morphology.
* Have many properties in common with macrophages, but their unique function is to act as cellular messengers to initiate the adaptive immune response.
* They do this by leave the infected tissue with a cargo of degraded and intact pathogens to bring to one of several lymphoid organs
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Lymphocytes:
* Look like what?
* What do they do?
* Lymphocytes are practically filled with the nucleus; monocytes are the largest of the white cells and have variably shape nuclei.
* Neither stain to the same extent as basophils or eosinophils, while the neutrophil is pale by comparison and have a multilobed nucleus that helps the squeeze through the small gaps in capillaries when called upon to fight bacterial infections.
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What is the lymphoid lineage?
has both a cell of innate immunity and two cells of the adaptive immune response
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What are Large granular lymphocyte?
* Effector cells of innate immunity called Natural Killer Cells (NK cells).
* They are important in the defense against viruses.
* They enter infected tissue, kill virus infected cells, and secrete cytokines that impede viral replication in infected cells
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The innate immune response works to slow the spread of infection while it calls upon WBC’s called what
Lymphocytes
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Why it is called adaptive immune response?
because it adapts to the nuances of the infecting pathogen
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*main difference* the adaptive immunity uses what?
uses cell-surface receptors, which are used by lymphocytes
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What happens during infection with adaptive immunity?
During infection only those lymphocytes bearing receptors that recognize the pathogen are selected to participate in the adaptive response and their numbers are expanded and matured to produce large number of cells
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Which is quick and slow: adaptive and innate?
Adaptive: slow
Innate: quick
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Give an example when the innate and adaptive system works together
Example: Influenza causes debilitating symptoms 3-4 days after start of infection (when innate system is being outrun), symptoms persist for 5-7 days while adaptive immune response is being organized and put to work
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During development each lymphocyte is programmed to do what?
to make a single species of cell-surface antigen receptor
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What happens to lymphocytes on infection by a particular pathogen?
On infection by a particular pathogen, the small subsets of lymphocytes having receptors that bind to the pathogen or its components are stimulated to divide and differentiate, expanding the population of effector cells from each antigen-binding lymphocyte
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Lymphocytes expand the population of effector cells from each antigen-binding lymphocyte provides what?
* This **response provides long term immunological memory** which allows these cells to produce a stronger and faster adaptive response when they have subsequent encounters (also why its called “acquired immunity”)
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How can immunological memory vary?
* Some pathogens like measles, one full blown infection can provide immunity for decades. Influenza effect is more short lived as it changes on a yearly basis to escape the acquired immunity in human hosts
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What cells are responsible for adaptive immunity? Explain how they work?
**Small lymphocyte** – cells responsible for adaptive immunity. They are small because they circulate around in their immature form that is functionally inactive. Recognition of a pathogen drives a process of lymphocyte selection, growth, and differentiation
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Most important difference between B lymphocytes (B cells) and T lymphocytes (T cells) is what? Explain
the receptors
* **B cells** – (5-15% of circulating lymphocytes) surface receptors for pathogens are immunoglobulins, express a single type of immunoglobulin
* **T cells** – (85-95% of circulating lymphocytes)T cell receptors, express a single type of T-cell receptor
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What can t cells break down into?
* CD4+ T helper cells
* CD8+ T killer cells
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Where do lymphocytes congregate? Give examples
Lymphocytes congregate in **lymphoid tissues/lymphoid organs**
* Ex: Bone marrow, thymus, spleen, adenoids, tonsils, appendix, lymph nodes
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What are lymphoid tissues?
found lining the mucosal surfaces of the respiratory, gastrointestinal, and urogenital tracts
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Lymphoid tissues are divided into two types, list them
* **Primary/central lymphoid tissue** – where lymphocytes develop and mature to the stage at which they are able to respond to a pathogen, **ex: bone marrow, thymus**
* **Secondary/peripheral:** where mature lymphocytes become stimulated to respond to invading pathogens, ex: **lymph node, spleen** (serves as a filter for the blood to remove damaged or old red blood cells)
60
Where do B cells and T cells originate and complete maturation?
* **B cells** – Originates in the bone marrow and completes maturation in the bone marrow before entering circulation
* **T cells **– Originate in the bone marrow, but leave in their immature stage and migrate to thymus (adults in lymph nodes) to complete maturation
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What happens to the vast majority of immature lymphocytes?
vast majority of immature lymphocytes are destroyed because they fail to develop immunoglobulins of T cell receptors. The small fraction of immature B and T cells that successfully complete development depart from the primary lymphoid organs and enter the circulation
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* Pathogens are carried how and where?
* What else is the traveling along this route?
* Pathogens are carried by the lymphatics to the nearest lymph node
* Also traveling along this route are dendritic cells that have been activated by the infection and are carrying pathogens and their components
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Lymph is what? What do they have? What can it cause?
Lymph flow is sluggish (no dedicated pump), do have valves to prevent backwards flow. If it gets interrupted can develop lymphedema
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* Lymph nodes lie where?
* Lymphatics eventually return this fluid to the blood via what?
* **Lymph nodes** lie at the junction of the anastomosing network of lymphatic vessels which collect the plasma that continually leaks out of the blood vessels and forms the extracellular fluid
* Lymphatics eventually return this fluid to the blood via the **thoracic duct**, which empties into the left subclavian vein in the neck
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What can lymphocytes do?
* Mature lymphocytes leave the primary lymphoid tissue and enter the blood stream, then secondary lymph tissue, then lymphatics, and back to the blood- **recirculation of lymphocytes**
* Lymphocytes do enter and leave the spleen as well
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Within the lymph node, t cells move into where?
T cell areas where they form transient interactions with dendritic cells
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fter binding to the pathogen components displayed by the dendritic cell, the T cell is signaled to divide and **differentiate** into:
* **Helper T cells (CD4)** – stay in the lymph node and provide soluble proteins and intercellular contacts that drive the differentiation of B cells possessing immunoglobulin receptors that bind that pathogen
* **Cytotoxic T cell (CD8)** – these cells kill infected cells with viruses or other intracellular pathogens
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T cell receptors can only bind to what? What does it assemble into? What is this called?
T cell receptors can only bind short peptides that have been assembled into a complex with a membrane glycoprotein called a **major histocompatibility complex molecule (MHC)**
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What is the difference with B cell antigens and T cell antigens
B cell antigens bind directly as whole native structures, T cell antigens must be broken down into peptides
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How do you assemble the peptide?
MHC complex takes place in the cell where the antigen was formed->complex then transported to cell surface where it is accessible to T cell receptors – essentially they present antigens to T cells so the peptide(antigen): MHC complex is referred to as **antigen presenting cells**
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Cells that are expressing MHC complexes can present to who?
Cells that are expressing MHC complexes can present antigens to T helper cells or cytotoxic cells
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List the different APCs?
* Langerhans cells in skin
* Dendritic cells
* Macrophages
* B cells
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Explain the process of MHC class 1 molecules
present peptide antigens derived from pathogens that replicate intracellularly such as viruses and some bacteria and whose proteins are present in the cytosol of the infected cells
* Present peptides to **cytotoxic T cells** that function by killing infected cells and distinguished by the presence of the CD8 glycoprotein on their surfaces
* Since all nucleated cells can be infected by viruses, **MHC Class I molecules are present on almost all cell types**
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Explain the process of MHC class II molecuels
present peptides obtained from pathogens and their products that are present in the extracellular milieu and have been taken up into the endocytic vesicles of phagocytic cells
* MHC class II molecules of dendritic cells presents peptides to **helper T cells**
* Helper T cells are distinguished by the presence of the **CD4 glycoprotein** on their surface
* Since helper T cells interact only with immune system cells, **MHC class II molecules are present on only a few cells types**
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* Immunoglobulins are expressed where?
* Plasma cells screte what?
* **Immunoglobulins are expressed on the surface of B cells where they can bind pathogens**
* Plasma cells secrete soluble forms of the immunoglobulins known as **antibodies**
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* What targets pathogens for phagocytosis?
* What do binding surface of antibodies interact with?
* Antibodies bind to bacterial cells and intact viral particles in the extracellular spaces, **targeting them for phagocytosis**
* Binding surface of the antibodies interact with intact components of the pathogen surface such as glycoproteins and proteoglycans
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What is an antigen?
any molecule, macromolecule, virus particle, or cell that contains a structure recognized and bound by an immunoglobulin or T cell receptor
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What are epitopes?
the particular part of the antigen bound by the immunoglobulin or T cell receptor is know as the antigenic determinant or epitope
* Both B cells and T call receptors have specificity for the antigen they bind
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* Where are antibodies found?
* Immunoglobulins are divided into what?
* Antibodies are glycoproteins found on B- cell membranes or secreted by plasma cells
* Divided into 5 classes or isotypes which differ in their heavy-chain constant regions and have specialized effector functions when secreted as antibodies:
* IgA, IgG, IgD, IgE, IgM
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IgA:
* Where is it made? where is it transported?
* How do IgA bind
* IgA is what?
* Made in the lymphoid tissues underlying mucosa and then selectively transported across the mucosal epithelium to bind extracellular pathogens and their toxins on the mucosal surfaces
* IgA binds antigens on microbes before they invade tissues. Causes antigen aggregation.
* IgA are also first defense for mucosal surfaces such as the intestines, nose, and lungs
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IgG:
* What does it facilitate?
* What has cell surface receptors?
* What produces the greatest stimulation?
* Where can it pass through?
* What does it provide?
facilitate the engulfment and destruction of extracellular microorganisms and toxins by phagocytes
* Neutrophils and macrophages have cell surface receptors that bind to the constant regions of the IgG chains.
* **A combination of IgG antibody and complement produces the greatest simulation of phagocytosis** because both macrophage receptors for IgG and complement participate in the process
* IgG 70-75% can pass through the placenta, involved in activating the complement system
* provides long term protection because it persists for months and years after the antigen that has triggered their production – bacteria, viruses, binds antigens to enhance phagocytosis by other cells
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IgM:
* What is it?
* Best at what?
* What are cell surface IgM and IgD?
is always the first antibody to be secreted in the immune response (IgD also made, but negligible amounts), **part of the primary immune response**
* Best at activating the compliment
* Cell surface IgM and IgD are the antigen receptors on circulating B cells that have yet to
encounter antigen
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IgE:
* Bind where?
* In under developed countries IgE has large role in what?
* In developed countries, IgE is what?
bind tightly to receptors on the surface of mast cells
* In under developed countries IgE has large role in response to worms and parasites due to strong inflammatory reaction
* In developed countries, IgE is most often encountered as the antibody in unwanted allergic reactions
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After immunization or infection - naïve B cells become what?
activated and can switch from expressing IgM and IgD on their surface to expressing IgG, IgE or IgA
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What is neutralization?
antibodies neutralize pathogens or their toxic products by binding to them and thus preventing them to enter cells and subsequent their infection. This mechanism is critical for protection against bacterial toxins and also pathogens such as viruses
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What is opsonization
In opsonization, antibodies enable phagocytosis for ingesting and destroying the extracellular bacterium. The phagocytes recognize the Fc region (the base of the ”Y”) of the antibodies coating the pathogen and foreign particles
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The third effector mechanism of antibodies is activation of several plasma proteins known as what?
Complement system
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What is the first immunoglobulins for our body? What does it provide?
* IgM antibodies are the first immunoglobulins your body makes after you're exposed to germs.
* They provide short-term protection while your body makes other antibodies.
* IgM antibodies are in your blood and lymph fluid
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What is IgG important for? Where is it mostly?
* antibodies are very important for fighting infections from bacteria and viruses.
* Most of the immunoglobulins in your blood are IgG.
* You also have some IgG antibodies in all your body fluids.
* Your body keeps a "blueprint" of all the IgG antibodies you have made.
* That way, if you're exposed to the same germs again, your immune system can quickly make more antibodies.
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IgA protects what?
antibodies protect your respiratory tract and your digestive system from infections. You have IgA antibodies in your blood, saliva, and gastric juices.
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An immunoglobulins blood test measures what?
the amounts of IgM, IgG, and IgA in your blood to help diagnose different types of diseases
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Why do we test immunoglobulins in blood?
Help diagnose and monitor a variety of conditions that may cause abnormal levels of IgM, IgG, and/or IgA, such as auto immune disorders (RA or lupus), cancer, and acute and chronic infections
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What is intravenous immunoglobulins?
What does it reflect?
* is a concentrate of the pooled immunoglobulins derived from 1000 to 100000 healthy donors depending upon the manufacturer. Immunoglobulins play a pivotal role in humoral adaptive immunity
* so **IVIG reflects a collective exposure of the donor population to their environment and can be expected to contain an antibody repertoire of multiple specificities against a broad spectrum of infectious agents (bacterial, viral, and others), and self-antigens**
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The composition of IVIG products closely corresponds to what?
to that of immunoglobulins in the normal human plasma, especially IgG (along with its subclasses), IgA, traces of other Ig antibodies, cytokines, and soluble receptors
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IVIG therapy aims to do what?
replenish sufficient amounts of IgG antibodies that passively neutralize or opsonize a broad spectrum of infectious pathogens but could also elicit an active immune response via activation of various immune cells, thus conferring protection against diverse diseases
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The indications for IVIG can be classified informally into what?
a few broad categories based on the mechanism of action and the type of conditions they treat. Ex: Kawasaki disease, immune thrombocytopenic purpura, inflammatory myopathies, Guillain–Barré syndrome
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What are the different categories of IVIG?
As a replacement therapy in immunodeficiencies.
* For immunomodulatory and anti-inflammatory therapy, (a) Immunomodulation in hematological and organ-specific autoimmune disorders (b) Anti-inflammatory in rheumatic inflammatory conditions, infectious and neurological disorders.
As a hyperimmune therapy against specific infectious agents.
* Different IVIG doses (low vs. high) are administered based on the indicated medical condition because the mechanisms of action differ with different doses. Low-dose immunoglobulins serve merely as a passive replacement in immunodeficiencies. High-dose immunoglobulins take an active part and modulate the immune functions with additional anti-inflammatory activity
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What is the clonal selection theory?
This hypothesis states that each lymphocyte has a unique antigen specificity and the proliferation of that specific lymphocyte is induced by the antigen binding to that specific receptor. The interaction of antigens and lymphocyte receptors is governed by the relative affinity of the receptor for the antigen. The clonal selection hypothesis explains that subsequent responses to the same antigen are more rapid, robust, and long lasting. The proliferation of specific lymphocytes in response to antigen results in the generation of antigen-responsive clones of cells.
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Because of antigen-induced proliferation what happens?
some of the proliferating lymphocytes may commit to long-
term memory cells that persist for many years. Activated B cells may undergo isotype switching by changing from the production of IgM to IgG, IgE, or IgA thus allowing different physiological and biological properties. By these mechanisms, a maturing immune response maintains antigen specificity but establishes memory and functional diversity.
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The development of adaptive immunity based on what?
on the clonal selection of lymphocytes bearing specific receptors is critical in allowing all pathogens, no matter how novel, to be recognized and in allowing the development of immunological memory.
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What are the physical barriers, innate immunity and adaptive immunity
