Exam 3- Chapter 15 Flashcards
What do defense mechanisms protect against?
Protect against disease-causing agents called pathogens
What do defense mechanisms make up?
Immune system
How many types of defense mechanisms are there? Name them.
- Innate (nonspecific) immunity
2. Adaptive (specific) immunity
What is another name for innate immunity?
nonspecific immunity
What is another name for adaptive immunity?
specific immunity
Are there strict “borders” for innate/adaptive immunity, or is there some overlap?
There are some areas of overlap between the two
Which type of immunity serves as as a first line of defense against pathogens?
Innate (nonspecific) immunity
Which type of immunity is inherited?
Innate (nonspecific) immunity
Name 4 examples of Innate (nonspecific) immunity?
- Epithelial membranes
- High acidity in stomach
- Cells that can engulf/kill pathogens
- Fever
When discussing the activation of innate (nonspecific) immunity, how do cells distinguish “self” from “nonself”?
pathogen-associated molecular patterns (PAMPs) unique to the pathogens
Immune cells have toll-like receptors for PAMPs on their _____.
surface
How many types of toll-like receptors have been identified?
10
How do toll-like receptors respond to pathogens?
These cells respond by secreting cytokines to recruit more immune cells or activate specific immune cells
Are lipopolysaccharides gram +, or gram -?
gram -
Is peptidoglycan gram +, or gram -?
gram +
How many types of phagocytic cells are there?
3
Name the 3 types of phagocytic cells.
- Neurotrophils
- Mononuclear phagocytic cells
- Organ-specific phagocytes
In phagocytosis, which cells are the first to arrive at an infection? What cells arrive later?
- Neutrophils
2. Mononuclear phagocytic cells
What are the two types of Mononuclear phagocytic cells , and where are they located?
- monocytes in the blood
2. macrophages in the tissues
Where are organ specific phagocytes found?
liver, spleen, lymph nodes, lungs, and brain
Some of the organ-speicifc phagocytes are called fixed phagocytes. What does this mean?
They are immobile in the walls of these organs
Organ-specific phagocytes can be considered part of what other type of phagocytic cells?
Mononuclear phagocytic cells
Neurotrophils and monocytes participate in a process called extravasation/diapedesis. What does this mean?
Neutrophils and monocytes squeeze through gaps in venule walls to enter tissue in a process called extravasation, or diapedesis
What are Neurotrophils, and monocytes attached to the site by?
Attracted to site by cytokines
Summarize phagocytosis in 3 steps.
- The pathogen becomes engulfed by pseudopods.
- The vacuole containing the pathogen fuses with a lysosome.
- The pathogen is digested.
What is fever regulated by?
hypothalamus
What chemical sets the body temperature higher?
endogenous pyrogen
Why is endogenous pyrogen produced, and by what?
- Toxins from some bacteria stimulate leukocytes to produce these cytokine
- Produced as a cytokine by leukocytes
Along with a fever, what does endogenous pyrogen induce?
Along with fever, they also induce sleepiness and a fall in plasma iron concentration (which limits bacterial activity).
What are interferons?
Antiviral polypeptides produced by infected cells
How many types of interferons are there? Name them.
3 types:
- Alpha
- Beta
- Gamma
New antiviral drugs are being developed using what?
interferons
Unlike innate (nonspecific) immunity which is inherited, how is adaptive (specific) immunity acquired?
The acquired ability to defend against specific pathogens after exposure to these pathogens
What is adaptive (specific) immunity mediated by?
Mediated by antigens and antibodies
What are antigens?
Cell surface molecules that stimulate the production of specific antibodies
What do foreign antigens illicit?
Foreign antigens illicit an immune response. The immune system can distinguish “self” from “nonself.”
What do antibodies bind to?
Antibodies bind to their specific antigens
Large molecules can have several antigenic determinant sites. What do these stimulate?
Large molecules can have several antigenic determinant sites that stimulate the production of and binding to antibodies.
What are haptens?
Smaller, nonantigenic molecules that can become antigens when bound to other proteins
What are haptens useful for?
These are useful for creating antigens for research and diagnosis.
What are immunoassays?
Tests that use specific antibodies to identify specific antigens
What are immunoassays used for?
Used to determine blood type and detect pregnancy
In immunoassays, what does binding cause?
Binding causes agglutination, which can be seen.
What are lymphocytes derived from?
Derived from stem cells in the bone marrow
The stem cells in the bone marrow in which lymphocytes are derived from seed what organs?
These stem cells seed the thymus, spleen, and lymph nodes
Through late childhood, what is the site of new T lymphocytes? What happens in late adulthood?
- The thymus is the site of new T lymphocytes through late childhood.
- It degenerates in adulthood, and new T lymphocytes are made through mitosis in secondary lymphoid organs.
What are considered primary lymphoid organs?
- Bone marrow
2. Thymus
Lymphocytes that seed the thymus become what? What do these then seed?
- T lymphocytes
- These then seed the blood, lymph nodes, and spleen
What do T lymphocytes attack?
- Host cells that have become infected with a virus or fungus
- Transplanted human cells
- Cancer cells
Do T lymphocytes produce antibodies?
NO
Where must T lymphocytes be in proximity to the victim cell in order to destroy them? What is this called?
- They must be in close proximity to the victim cell in order to destroy it.
- Cell-mediated immunity
Lymphocytes that come directly from bone marrow to seed other organs (not the thymus) are called what?
B lymphocytes
What do B lymphocytes combat?
They combat bacterial and some viral infections
Do B lymphocytes produce antibodies?
YES
Where must b lymphocytes be in proximity to the victim cell in order to destroy them? What is this called?
- They secrete antibodies into blood and lymph so can be far from the victim
- humoral immunity or antibody-mediated immunity.
Where do B lymphocytes secrete antibodies?
They secrete antibodies into blood and lymph
Name the 4 secondary lymphoid organs?
- Lymph nodes
- Spleen
- Tonsils
- Peyer’s patches (in mucosa of intestines)
What is the function of the secondary lymphoid organs?
Capture and present pathogens to macrophages and house lymphocytes
Lymphocytes migrate between lymphoid organs to sample what?
blood and lymph
What secondary lymphoid organ filters blood for pathogens? What secondary lymphoid organ filters lymph for pathogens?
- The spleen filters blood for pathogens
2. Other organs filter lymph for pathogens
When does local inflammation occur?
Occurs when bacteria enter a break in the skin
What is local inflammation initiated by?
Initiated by nonspecific mechanisms of phagocytosis by toll-like receptors
Local inflammation is initiated by nonspecific mechanisms of phagocytosis by toll-like receptors. What two things will happen next?
- Macrophages and mast cells release cytokines to attract phagocytic neutrophils.
- Complement proteins are activated, which also attract phagocytic cells.
In local inflammation, after complement proteins are activated (which also attract phagocytic cells), what happens as inflammation progresses?
- As inflammation progresses, B lymphocytes produce antibodies against bacterial antigens
- Formation of antigen-antibody complexes amplifies nonspecific response, a process called opsinization
What is opsinization?
Formation of antigen-antibody complexes amplifies nonspecific response (can be seen in local inflammation)
In local inflammation, after opsonization, what two things happen next?
- More phagocytic cells arrive via extravasation from nearby venules. T lymphocytes are the last to arrive.
- Neutrophils may spill protein-digesting enzymes into the surrounding tissues, causing pus
- Mast cells secrete heparin, histamine, prostaglandins, leukotrienes, cytokines, and TNF-α. They also recruit more leukocytes.
In local inflammation, mast cells secrete heparin, histamine, prostaglandins, leukotrienes, cytokines, and TNF-α. What does this produce?
These produce warmth, swelling, and pain (classic symptoms)
In local inflammation, mast cells secrete heparin, histamine, prostaglandins, leukotrienes, cytokines, and TNF-α. What do they also recruit?
They also recruit more leukocytes.
How are B lymphocytes activated?
Exposure to the specific antigen activates a B lymphocyte and causes it to undergo multiple cell divisions
After B lymphocytes are activated, what are two possible things that they can become?
- Some become memory cells, which are used in a later infection by the same pathogen
- Others become plasma cells, which produce 2,000 antibodies/second
When B lymphocytes become plasma cells, how many antibodies can they produce per second?
2,000 antibodies/second
What are antibodies also known as?
immunoglobulins
How many classes of antibodies/immunoglobulins are there?
5
Name the different classes of antibodies/immunoglobulins.
IgG, IgA, IgM, IgD, and IgE
Antibody Structure:
What is the shape of antibodies?
Y-shaped
Antibody Structure:
Specifically describe the structure of a Y-shaped antibody?
2 long, heavy (H) chains joined by 2 shorter, light (L) chains
Antibody Structure:
Which is constant across different antibodies, and which varies and allows antigen specificity? The bottom (Fc) or the top (Fab)?
- The bottom (Fc): constant across different antibodies
2. The top (Fab): varies and allows antigen specificity
Everyone has how many antibody molecules?
Everyone has 10^20 antibody molecules
How many different specificities of antibodies are there?
There are a few million different specificities
There should be an antibody for every ____ you might encounter.
antigen
Why are there so many different antibodies? (2 reasons)
- A large percentage of our genetic code is dedicated to making antibodies. Some genes code for light chains and some for heavy chains, and then these are combined in different ways to get even more.
- These genes mutate easily, making more combinations.
The Complement System:
What is a complement?
A group of plasma proteins activated by the binding of antibodies to antigens
Which type of immune system (innate/nonspecific or adaptive/specific) is the complement system part of?
Innate/nonspecific immune system
How the complement system works:
How many pathways of activation are there?
2
How the complement system works:
Name and describe the 2 activation pathways.
- Classic Pathway: Activity is triggered by binding of antibodies to antigens
- Alternative Pathway: Polysaccharides on bacterial membranes
How the complement system works:
Does the binding of antibodies to antigens destroy the pathogen?
Binding of antibodies to antigens does NOT destroy the pathogen
How the complement system works:
Since the binding of antibodies to antigens does NOT destroy the pathogen, what does it do?
This labels targets for attack by phagocytic cells and stimulates opsonization
How the complement system works:
What are the proteins designated as?
Proteins are designated C1−C9
How the complement system works:
- What does protein C1 serve as?
- What do proteins C2, C3, and C4 serve as?
- What do proteins C5-C9 serve as?
- C1 serves as a recognition protein.
- C2, C3, and C4 serve as activators.
- C5−C9 attack by attaching to a cell membrane and destroying it.
How the complement system works:
Which pathway is more rapid and efficient? (classic or alternative)?
Classic pathway is more rapid and efficient (involves antibodies binding to antigens)
How the complement system works:
Describe in detail the 6 steps of the classic pathway of the complement system.
- IgG and IgM activate C1, which splits C4 into two fragments, C4a and C4b.
- C4b binds to the cell membrane and becomes active, splitting C2 into C2a and C2b.
- C2a attaches to C4b and cleaves C3 into C3a and C3b.
- C3b converts C5 into C5a and C5b.
- C5b and C6−C9 are inserted into the bacterial cell membrane, forming the membrane attack complex.
- This creates a large pore in the membrane, causing influx of water into the cell = lysis.
What is the influx of water into the cell?
Lysis
How the complement system works: Complement Fragments:
- C3a and C5a serve what other functions? What does this in turn cause?
- What is yet another function of C5a?
- C3a and C5a stimulate mast cells to release histamine. This increases blood flow to the area.
- C5a also attracts neutrophils and monocytes to the region
What is the function of Cytotoxic T Lymphocytes?
Destroy body cells that harbor foreign antigens
Cytotoxic T Lymphocytes destroy body cells that harbor foreign antigens. What can this possibly be from?
Usually from a pathogen (virus or fungus), but can be due to a malignancy (cancer)
Do Cytotoxic T Lymphocytes us cell mediated immunity or humoral/antibody mediated immunity? What does this mean?
Cell mediated immunity; The T cells must touch the target victim
What two things do Cytotoxic T Lymphocytes secrete, and what is their function?
- Secrete perforins to create large pore in cell
2. Secrete granzymes to trigger apoptosis in cell
What is the function of Helper T Lymphocytes?
- Improve ability of B lymphocytes to become plasma cells
- Enhance ability of cytotoxic T cells to kill targets
- Secretion of lymphokines
What are Lymphokines? What is their function?
- Cytokines specific to lymphocytes
- Many stimulate B cell or cytotoxic T cell activity.
What is the function of Regulatory T Lymphocytes?
Inhibit response of B lymphocytes and cytotoxic T lymphocytes
What were regulatory T Lymphocytes previously called?
suppressor T lymphocytes
What can people with genetic deficiencies in regulatory T lymphocyte production develop?
may develop autoimmune diseases and allergies.
T cell receptor proteins.
Antigen recognition proteins on the membranes of T cells
Can T cell receptor proteins directly bind to antigens?
NO
What helps T cell receptor proteins bind to antigens?
Antigen-presenting cells, such as dendritic cells and macrophages
Where do dendritic cells originate and migrate?
Originate in the marrow and migrate to most tissues (especially where pathogens might enter body)
How do dendritic cells help T cell receptor proteins bind to antigens? What are they associated with?
- Engulf protein antigens, partially digest them, and display polypeptide fragments on surface for T cell to “see”
- Associated with histocompatibility antigens
Besides helping T cell receptor proteins bind to antigens, what is another function of dendritic cells?
Secrete cytokines to attract lymphocytes.
What are Histocompatibility Antigens also called?
human leukocyte antigens (HLAs)
Where are Histocompatibility Antigens found?
On surface of all body cells (except mature RBCs)
How are Histocompatibility Antigen coded for? What is this called?
- Coded for by four genes on chromosome 6
- Major histocompatibility complex (MHC)
Is there a lot of variability with the MHC?
Many versions of each gene are possible, so most people have different combinations.
What match does an organ transplant require?
An organ transplant requires an MHC match
MHC genes produce how many classes of cell surface molecules? What are they called?
2:
- Class 1
- Class 2
MHC: What is class 1 cell surface molecules made by?
Class 1 is made by all cells except RBCs
MHC: What is class 2 cell surface molecules made by?
Class 2 is made by antigen-presenting cells and B cells
MHC:
Class 2 MHC molecules and foreign antigens are presented together to ____ _ _____.
helper T lymphocytes
MHC:
Class 1 MHC molecules and foreign antigens are presented together to ____ ____ __ ____.
activate cytotoxic T cells.
Interactions with B Cells:
Activated helper Ts promote humoral response of B cells by binding to ____ ____ ___ ___ ___ __.
foreign antigens and MHC class 2s
Interactions with B Cells: Activated helper Ts promote humoral response of B cells by binding to foreign antigens and MHC class 2s. What does this stimulate?
This stimulates mitosis of Bs, conversion to plasma cells, and production of antibodies
Macrophages secrete interleukin-1. What is the function of this?
stimulates helper T cell mitosis
Helper T cells secrete macrophage colony-stimulating factor and gamma interferon. What is the function of this?
promote macrophage activity
T helpers secrete interleukin-2, which makes the macrophage produce ____ ____ ___ (against cancer) and activates ____ __ _____ ____/____.
- tumor necrosis factor
- cytotoxic T cell activity/mitosis
When must activated T-cells be destroyed?
Activated T cells must be destroyed when the infection is over
Describe the process of T-cells being destroyed.
- Active T cells produce a surface receptor called FAS and later a protein called FAS ligand.
- Binding of FAS to FAS ligand induces apoptosis
When exposed to foreign antigens, immune cells respond by making many _____ __ _____.
copies of themselves
When exposed to foreign antigens, immune cells respond by making many copies of themselves. What does this protect the body from? What is this protection called?
- This protects the body from future infections
2. This protection is called active immunity
Active Immunity:
- How long after infection does it take for antibodies to be detected in the blood?
- What is this response called?
- Will the patient get sick?
- After infection, it takes 5−10 days before antibodies are detected in the blood
- This is the primary response
- The patient will get sick
Active Immunity:
After infection, it takes 5−10 days before antibodies are detected in the blood. This is the primary response. The person will get sick.
- What will happen if the patient is later exposed to the same infection?
- What is this response called?
- Will the patient get sick?
- Later exposure to the same infection results in maximum antibody production in less than 2 hours.
- This is the secondary response.
- The person will likely never get sick.
What concept does the clonal selection theory explain?
Explains how the secondary immune response works
Explain the clonal selection theory.
- A person inherits lymphocytes specific to almost every pathogen, but there are few of each type
- The primary response triggers a massive production of cells that can respond to that antigen.
- These cells respond much quicker after exposure a second time.
What is the function of vaccines?
Stimulate a primary response and active immunity without making the person sick
How many ways can you accomplish the function of a vaccine?
3 ways
Describe the 3 ways to accomplish making a functional vaccine.
- Use a killed virus
- Use a live virus with attenuated virulence (i.e., the virus either cannot replicate or cannot infect target tissues (polio))
- Use a genetically engineered recombinant virus (hepatitis B)
Immunological Tolerance:
It is important to avoid attacking what cells?
“self” cells
Immunological Tolerance:
When does the immune system develop a tolerance foe “self” antigens?
The immune system develops a tolerance for “self” antigens in the fetal period
Immunological Tolerance:
In some instances, “self” cells are attacked. What are two reasons for this?
- If mutations occur in lymphocytes (usually good and adds to what the body can defend against)
- If cells in particular organs are never exposed to the immune system
Immunological Tolerance:
Lymphocytes that cause the attack of “self” cells are called what?
These lymphocytes are called autoreactive
Immunological Tolerance:
If lymphocytes do begin attacking cells, there are mechanisms to stop this. What are the two methods called?
- Clonal deletion
2. Clonal anergy
Immunological Tolerance:
If lymphocytes do begin attacking cells, there are mechanisms to stop this. What happens in clonal deletion?
In clonal deletion, these lymphocytes are destroyed (apoptosis).
Immunological Tolerance:
If lymphocytes do begin attacking cells, there are mechanisms to stop this. What happens in clonal anergy? What type of lymphocytes likely do this?
In clonal anergy, these lymphocytes are prevented from becoming active. Regulatory T lymphocytes likely do this.
What is passive immunity?
Passing of antibodies from one individual to another
What does passive immunity do?
Provides temporary protection
In what 3 ways can passive immunity provide temporary protection?
- From mother to fetus
- From mother to child (in breast milk)
- Artificially via immunization (snake anti-venom)
Essentially, what are tumors?
Tumors are abnormal clonal cells that dedifferentiate to an embryonic state.
Tumor growth and dedifferentiation reveal antigens that can stimulate the ______ __ __ ____ (by cytotoxic T cells).
destruction of the cell
Benign tumors:
Describe the growth rate, and likelihood of spreading.
Benign tumors are slow growing and limited to specific areas of the body.
Malignant tumors:
Describe the growth rate, and likelihood of spreading.
Malignant tumors are fast growing and spread to other parts of the body
When do cancers arise?
Cancers arise when the immune cells fail to stop the growth/spread of the tumors.
What are 3 different possibilities of the cause of tumor antigens?
- Dedifferentiated embryonic antigens not recognized by the immune system
- Mutations from carcinogens
- Viral antigens from the virus that caused the tumor (human papillomavirus)
Normally, over-expressed antigens may trigger what?
an immune response
What are natural killer cells related to?
Related to T lymphocytes
Natural Killer Cells are related to T lymphocytes but part of what?
innate immunity without the ability to recognize specific antigens
What can natural killer cells recognize?
Can recognize malignant cells and cells infected with a virus
How must natural killer cells be activated?
Must be activated by pro-inflammatory cytokines from dendritic cells
What is the function of natural killer cells?
Kill compromised cells in the same manner as cytotoxic T cells
Do cytokines released by natural killer cells activate innate or adaptive immune cells?
Cytokines released by natural killer cells activate both innate and adaptive immune cells.
Immunotherapy for Cancer:
What 3 things have been used to treat cancer? Do these cure cancer? What is currently being tested to fight cancer?
- Therapeutic antibodies
- Interferons
- Interleukin-2
- None of these “cure” cancer, but they do help some people.
- Other cytokines are currently being tested against cancer.
Does cancer risk increase or decrease with age?
Increase
Why might cancer risk increase with age?
This may be due to aging mutated lymphocytes
Tumors have been shown to grow faster in lab animals with what?
Stress
What does stress induce the release of? How does this affect the immune system?
Stress induces the release of cortisone, which is known to suppress the immune system
What is autoimmunity produced by?
Produced by failure of immune cells to tolerate “self” antigens
With autoimmunity, autoreactive T lymphocytes and autoantibodies are produced. What does this cause?
inflammation and organ damage
What are common autoimmune diseases? (8)
- Rheumatoid arthritis
- Type 1 diabetes
- Multiple sclerosis
- Grave’s disease
- Pernicious anemia
- Thyroiditis
- Psoriasis
- Lupus
Several factors may cause autoimmune diseases:
Name and describe 6.
- An antigen not normally exposed to the immune system becomes exposed
- A normally tolerated antigen is combined with a foreign hapten.
- Antibodies are produced aimed at other antibodies.
- Antibodies produced against foreign antigens cross-react with self antigens and begin attacking self cells
- Self antigens may be presented to T helper cells along with class 2 MHC molecules
- Inadequate regulatory T cell activity.
Several factors may cause autoimmune diseases:
- An antigen not normally exposed to the immune system becomes exposed
GIVE EXAMPLE OF A DISEASE.
Hashimoto’s thyroiditis
Several factors may cause autoimmune diseases:
- A normally tolerated antigen is combined with a foreign hapten. This may occur when a drug such as aspirin combines with platelets, resulting in the destruction of platelets
GIVE EXAMPLE OF A DISEASE. GIVE AN EXAMPLE OF WHEN THIS CAN OCCUR.
- Thrombocytopenia
2. This may occur when a drug such as aspirin combines with platelets, resulting in the destruction of platelets
Several factors may cause autoimmune diseases:
- Antibodies are produced aimed at other antibodies.
GIVE EXAMPLE OF THIS.
Cause of inflammation in rheumatoid arthritis
Several factors may cause autoimmune diseases:
- Antibodies produced against foreign antigens cross-react with self antigens and begin attacking self cells (can occur in the heart or kidneys after a strep infection)
GIVE EXAMPLE OF A DISEASE. GIVE AN EXAMPLE OF WHEN THIS CAN OCCUR
- Rheumatic fever
2. can occur in the heart or kidneys after a strep infection
Several factors may cause autoimmune diseases:
- Self antigens may be presented to T helper cells along with class 2 MHC molecules
GIVE 2 EXAMPLES OF WHERE THIS CAN OCCUR.
- May occur after viral infection of cells
2. Occurs in diabetes type I
What do Immune Complex Diseases involve?
Involve free antigen-antibody complexes that stimulate complement proteins and inflammation
Immune Complex Diseases:
Are they hard to take care of? Why?
No; Usually self-regulating because complexes are removed via phagocytosis
Immune Complex Diseases:
Complex formation may be prolonged or spread to other organs. What does this lead to?
Complex formation may be prolonged or spread to other organs, leading to prolonged inflammation.
Immune Complex Diseases:
What are two ways these diseases may be a result from? Give examples.
- May result from infections from bacteria, viruses, or parasites (Hepatitis B results in free complexes that cause damage to arteries due to inflammation)
- May also result from complexes formed by self antigens and autoantibodies (Rheumatoid arthritis and lupus)
What are allergies also called?
hypersensitivity
Physiologically, what are allergies?
Abnormal response to allergens (antigens)
What are the two types of allergies?
- Immediate hypersensitivity
2. Delayed hypersensitivity
What is immediate hypersensitivity?
Abnormal B cell response to allergen
When are the effects of immediate hypersensitivity seen?
Seconds to minutes after exposure
What can immediate hypersensitivity be caused by?
Can be caused by foods, bee stings, pollen, etc.
Summarize in 3 detailed steps how allergy symptoms are produced in immediate hypersensitivity.
- Dendritic cells stimulate a class of helper T cells to secrete interleukin-4 and interleukin-13, which stimulate B and plasma cells to secrete IgE antibodies.
- These antibodies do not circulate in the blood but attach to mast cells and basophils.
- When re-exposed to the same allergen, these antibodies bind with it and stimulate the production of histamine, leukotrienes, and prostaglandin D, producing allergy symptoms
What is delayed hypersensitivity? When are the symptoms produced?
Abnormal T cell response that produces symptoms 24−72 hours after exposure
What are the symptoms in delayed hypersensitivity produced by?
Symptoms are caused by secretion of lymphokines, NOT histamine.
Will taking antihistamines help with delayed hypersensitivity?
NO, symptoms are caused by secretion of lymphokines, NOT histamine
What is an example of delayed hypersensitivity?
contact dermatitis caused by poison oak, ivy, or sumac