Immunology and Human Disease Flashcards

1
Q

Why does the human body make a great host?

A

The human body makes a great host since it provides optimal temperatures, nourishment, and protection.

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2
Q

What is the estimated number of bacteria species?

A

There are currently an estimated 10 million to a billion different species of bacteria. To make things even more complicated, there are different serotypes of species.

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3
Q

What are serotypes?

A

Serotypes are distinct antigenic variations that exist between bacteria of the same species.

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4
Q

Name an example of a bacteria with many serotypes. What does this mean for our immune response?

A

For example: there are an estimated 92 different serotypes of Streptococcus pneumonia. Therefore, there are different antigenic macromolecules (epitopes) present on the capsular surface of different strains of S. pneumonia. An individual can be infected and successfully remove one serotype of S. pneumonia, but be incapable of removing a different serotype because immunological memory would not recognize it.

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5
Q

What is antigenic drift?

A

Antigenic drift is defined as point mutation in genes causing alterations in the structure of an organism. For example: yearly influenza outbreaks. The influenza bug changes from year to year, and this is why the flu shot has to be administered yearly. The result of antigen drift within the community is an epidemic, a localized outbreak resulting in mild disease.

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6
Q

What is antigenic shift?

A

Comparatively, antigenic shift is defined as radical changes in surface antigens based on reassortments of the organisms genome. This is often the case in pandemics, which result in severe disease states and increased mortality on a global scale. For example: the Bubonic Plague.

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7
Q

What are virulence factors?

A

Virulence factors are molecules secreted or expressed by pathogens that enable them to colonize, divide, and cause damage.

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8
Q

Name some examples of toxin virulence factors, pathogen example and associated disease state.

A
  1. Neurotoxin, cytotoxin, and enterotoxin that destroys host cells.
  2. Pathogen: Escherichia coli.
  3. Disease state: Enterohemorrhagic E. coli (EHEC).
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9
Q

What pathogen uses its capsule as a virulence factor? What benefit does it give the pathogen?

A

Streptococcus pneumonia uses its capsule as resistances to phagocytosis. Pneumonia.

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10
Q

What is the virulence factor whose function is to non-specifically bind to MHC class II molecules and cause the widespread activation of T Cells?

A

Superantigens E.g. Staphylococcus aureus that results in Toxic Shock Syndrome

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11
Q

What virulence factor and pathogen that results in the disease state Toxoplasmosis?

A

Vesicle Formation - Creates its own membrane enclosed vesicle within the cell, so MHC is unable to bind and present peptides. Toxoplasma gondii uses this to cause Toxoplasmosis.

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12
Q

What virulence factor destroys polysaccharides that holds cells together?

A

Enzymes (ex. Hyaluronidase) - Destroys polysaccharide that holds cells together so that the pathogen can spread through human tissue easier. Streptococcus pyogenes uses this to cause Necrotizing fasciitis.

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13
Q

What is latency?

A

Latency occurs when a pathogen enters a dormant state. The organism has entered cells and is therefore present, but is not undergoing replication, so no disease state is apparent.

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14
Q

Give an example of an organism that is capable of latency?

A

An example of an organism that is capable of latency is herpes simplex virus 1, which is the causative agent in cold sores. During the primary infection herpes simplex virus 1 will result in an infection. When the immune system subsides the virus will go dormant within the trigeminal ganglion (which is not infiltrated by immune system cells). Once the immune system is compromised (colds, stress, flu, etc.), the virus will re-emerge.

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15
Q

Describe the HIV virus.

A

HIV, Human Immunodeficiency Virus, is an infectious agent that targets cells of the immune system. HIV is an enveloped virus that contains an RNA genome, reverse transcriptase, integrase, protease, and glycoproteins (gp41 and gp120).

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16
Q

How does HIV infect its host?

A

Gp120 on the HIV surface recognizes CD4 on the T cell surface. Gp41 then mediates fusion between the virus and the CD4 positive host cell. At this point, the RNA genome is introduced, and reverse transcription transcribes the viral RNA into cDNA (complementary DNA). The cDNA is incorporated by integrase into the helper T cells DNA genome. When the T cells normal transcription and translation process takes place, viral proteins are created. These are folded by protease and are delivered to the T cell surface where it forms a virus. The newly formed virus will then infect other neighboring T cells

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17
Q

What is the initial response of someone who contracts HIV?

A

When an individual is initially infected with HIV they exhibit flu-like symptoms. At first the immune system will respond to the viral invasion and anti-HIV is formed (antibodies to HIV).

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18
Q

What is seroconversion?

A

A detectable level of anti-HIV is referred to as seroconversion.

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19
Q

How does HIV evade the immune system if the person has anti-HIV?

A

The viral load will decrease, however, some of the virus remains within the T cells. When the immune system response subsides, the virus will slowly replicate until the viral load increases again. The T cell population will gradually decrease as the virus is increasing in numbers. This is referred to as clinical latency. T cells and viral numbers remain relatively constant and the individual is asymptomatic. Reverse transcriptase is a faulty enzyme that lacks proofreading capabilities. This means that as the HIV genome is reverse transcribed into cDNA there are inherent errors made, mutations. Therefore, HIV is highly mutable. As it increases in numbers it also mutates, which allows it to evade the host immune response.

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20
Q

When is AIDS officially diagnosed in a person with HIV?

A

When Helper T cell numbers are dwindling to very low levels. This stage is referred to as clinical AIDS, Acquired Immunodeficiency Syndrome. The immune system is incredibly compromised and the individual is extremely susceptible to opportunistic infections.

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21
Q

How many people have HIV and have died of AIDS according to the World Health Organization?

A

According to the World Health Organization there are approximately 34 million people living with HIV and approximately 35 million people that have died of AIDS (about the population of all of Canada).

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22
Q

Does genetics play a key role in a fully functioning immune system?

A

IR gene –> Stronger immune system with the gene.
Immunodeficiencies –> Can be genetically passed down from generation to generation resulting in individuals more susceptible to frequent and recurrent infections.

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23
Q

Describe the difference inheritance patterns that immunodeficiency diseases can be passed on by.

A

Immunodeficiency diseases follow predictable inheritance patterns. They can be dominant, recessive, or sex-linked. A) Dominant inheritance refers to the phenotypic expression of a trait when only one defective gene is inherited. B) Recessive inheritance requires two defective genes be inherited, one from each parent. If only one gene is inherited then the individual is an unaffected carrier. C) Finally, sex-linked inheritance refers to genes that are inherited on the X chromosome. Therefore, males are affected and females are often carriers.

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24
Q

What is the result if you have complement deficiency?

A

Deficiency in one or more of the complement proteins. Susceptible to frequent and persistent infections
What occurs if neutrophils and macrophages are unable to “stick” to epithelium to get to the site of infection?
Susceptible to frequent and persistent infections. E.g. Leukocyte Adhesion Deficiency

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25
Q

What if your body lacks receptors for IL-2, IL-4, IL-7, and IL-9?

A

Severe Combined Immunodeficiency (SCID): Susceptible to frequent and persistent infections.
Common Gamma Chain Impairment to make cytokine receptors for IL-2, IL-4, IL-7, and IL-9.

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26
Q

What occurs in ‘Wiskott Alrich’ and ‘Bare Lymphocyte’ conditions?

A
Wiskott Alrich:  Impairment of platelets and lymphocytes 
Bare Lymphocyte: Lack HLA class II molecules 
Both cause severe combined immunodeficiency (SCID): Susceptible to frequent and persistent infections
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27
Q

What are environmental factors that affect your immune system? Name examples.

A

Environmental factors are all of the other elements that contribute to an individual’s immune status which are not inherited. These factors include chemicals that an individual might encounter, ionizing radiation, UV radiation, secondary effects of a chronic disease state (such as Diabetes Mellitus) that influences a component of the immune system, infections, trauma, smoking, exercise, aging, pregnancy, stress, and diet/malnutrition.

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28
Q

What is a hypersensitivity reaction?

A

Hypersensitivity reactions are defined as the adaptive immune response to innocuous molecules. Hypersensitivity is often used synonymously with “allergic reactions”. Note: However, there are different mechanisms that result in hypersensitivity reactions that are more complicated than just “allergies”.

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29
Q

Give an example of a hypersensitive reaction.

A

The immune system is sensitive to molecules that it should not usually respond to. For example: an individual may have a reaction to cat dander. The body should typically ignore this as it is a molecule that will not cause harm to the body. The body is hypersensitive, so it attempts to remove an infection that does not exist. An individual whose body responds to the cat dander will often have breathing difficulty, itchy eyes, and a runny nose as a result of histamine being released.

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30
Q

Why is there lower concentrations of IgE, eosinophils and basophils found in circulation?

A

IgE, eosinophils, and basophils are found in low concentrations within circulation, therefore there are less molecules/cells that can be activated to innocuous substances.
reactions, examples, and the hygiene hypothesis.

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31
Q

What are the four different type of hypersensitivity reactions?

A

They differ based in the effector mechanism that recognizes and tries to attack innocuous substances.
Type I: IgE (effector molecule), Mech of Attack - Mast cell, basophil, and eosinophil activation.
Type II: IgG, Complement activation to modified cells
Type III: IgG, Immune complex deposits
Type IV: T cells, Macrophage, eosinophil, and cytotoxic T cell activation

32
Q

What type of hypersensitivity are these example conditions related to?

a) Farmer’s Lung and Serum sickness
b) Penicillin adsorption onto RBC’s
c) Allergic rhinitis, asthma, systemic anaphylaxis
d) Contact dermatitis

A

Type III - Farmer’s Lung and Serum sickness
Type II - Penicillin adsorption onto RBC’s
Type I - Allergic rhinitis, asthma, systemic anaphylaxis
Type IV - Contact dermatitis

33
Q

How can sensitization occur with IgE and the FcεRI receptor on the surface of mast cells?

A

IgE is created in response to the first exposure of an allergen, referred to as sensitization. An allergen such as pollen is inhaled and diffuses across the mucosal membranes of the upper respiratory tract. Antigen presenting cells process and present the pollen peptides to helper T cells. In turn, the helper T cells activate B cells, causing their maturation to IgE secreting plasma cells. The IgE can then attach irreversibly to the FcεRI receptor on the surface of mast cells. If the allergen is experienced again, then the pollen peptide attaches to the IgE attached to the mast cell, and the mast cell will release its granular contents into the surrounding area. In this chain of events histamine is released by the mast cells which cause vasodilation and smooth muscle constriction.

34
Q

How is the immune response different when IgE attached to a mast cell than when B and T cell receptors are activated?

A

When IgE is attached to a mast cell, eosinophil, or basophil it acts as a receptor. So, how is this different then B and T cell receptors? Well, different IgE specificities can be on one mast cell, therefore, several different allergens could activate the same cell. B and T cell can only express one specificity on their cell surface. Also, IgE on mast cells means that once IgE comes into contact with a pathogen the mast cell can immediately release its granules. There is often lag time when it comes to activating B and T cells as there needs to be differentiation and proliferation.

35
Q

How can the symptoms be different with different type I hypersensitivity locations?

A

The resulting type I hypersensitivity depends on the location of the mucous membrane breached by the allergen. Mast cells activated in the gastrointestinal tract results in vomiting and diarrhea, in the airways results in coughing and breathing difficulties, on the skin results in hives or eczema, and in the blood vessels results in edema or even systemic anaphylaxis. Chronic asthma is a unique state in which the symptoms of asthma continue even in the absence of the allergen due to the release of cytokines.

36
Q

Name some examples of type I hypersensitivities?

A

There are many substances that can cause type I hypersensitivities: wasp stings, peanuts, pollen, drugs, animal dander, etc.

37
Q

What are some treatments of type I hypersensitivities?

A

Often the treatment is avoidance of the allergen or a shot of epinephrine. Epinephrine decreases permeability in the vasculature and relaxes smooth muscle. Depending on the degree of allergic response, an individual may be desensitized to an allergen. This involves increased exposure to the allergen in order to promote antibody production from IgE to IgG, also called exhaustion.

38
Q

What is Type II Hypersensitivity?

A

IgG is created against altered components of human cells. This occurs when new epitopes are created on self cells.

39
Q

Give an example of a Type II Hypersensitivity.

A

For example: in some individuals penicillin can become adsorbed onto the surface of red cells, therefore creating new epitopes on the red cell surface. The immune system then recognizes the red cell as “non-self”, IgG attaches to the penicillin component of the red blood cell, complement is activated, and the red blood cell is destroyed (aka. drug induced hemolytic anemia).

40
Q

What is Type III Hypersensitivity?

A

Type III hypersensitivities result from the formation of IgG immune complexes. Normally, large complexes are fixed by complement and removed. However, small complexes escape complement and accumulate in the tissue until it is large enough to activate complement. The result is inflammation.

41
Q

Give an example of a Type III Hypersensitivity.

A

Some examples of type III hypersensitivities include: Nephritis, Arthritis, Arthus Reaction, and Farmer’s Lung.

42
Q

What is Type IV Hypersensitivity?

A

Type IV hypersensitivities result from effector T cells aimed at self. Typically, symptoms are not experienced until 1-3 days after contact with the innocuous substance, which is why this type of hypersensitivity is sometimes referred to as delayed-type hypersensitivity reactions (DTH).

43
Q

Give an example of a Type IV Hypersensitivity.

A

For example: an individual can have a contact sensitivity to Poison Ivy. The chemical Pentadecacatechol is left on the skin surface, dendrites present the peptide in MHC class II to TH1 cells, TH1 cells then activate macrophages and CD8 T cells which kill self epithelial cells that express the pentadecacatechol peptides. Another example is helper T cell activation of macrophages in the gastrointestinal tract when someone has a sensitivity to gluten (as seen in Celiac Disease) resulting in inflammation.

44
Q

What is the hygiene hypothesis?

A

If people are too clean, then the immune system is not challenged and the result is hypersensitivities to innocuous substances.
In Western Europe, Canada, and the United States there is a large portion of the population that suffers from allergies and asthma. Conversely, the incidence in developing countries is significantly lower. In developing countries there is much emphasis placed on hygiene, increased antibiotic use, and the availability of vaccinations. In developing countries there are increased rates of parasitic infections and often contaminated water sources.

45
Q

What is atopy?

A

Atopy is a genetic predisposition of an individual to developing allergies.

46
Q

What happens when one gets an autoimmune disease?

A

The immune system attacks healthy self cells and tissues. This can happen when there is no longer tolerance to self.

47
Q

What makes someone susceptible to developing an autoimmune disease?

A

It is a composition of genetic (they run in the family) and environmental factors (such as smoking or acquiring certain infections).

48
Q

What is an autoantigen?

A

Self antigen that provokes an immune response by that person’s own immune system.

49
Q

What is an autoantibody?

A

An anitbody produced against one’s own self antigen or autoantigen.

50
Q

What are autoimmune T cells?

A

Effector T cells targeted against self.

51
Q

What is another term for antigenic similarity and what does it mean for our immunity?

A

Molecular mimicry.
This is antigenic similarities between a pathogen and self cells which result in antibody or T cells working against the pathogen but then cross-reacting with self cells.

52
Q

What is an example of molecular mimicry with the pathogen that results in streptococcal pharyngitis?

A
  1. When a patient gets infected with streptococcus pyogenes the immune system responds by forming antibodies to antigens on the streptococcal cell wall.
  2. The adaptive immune system removes the infection but then the antibodies target cells in the heart (Ab available throughout body) as they have self antigens that RESEMBLE streptococcus pyogenes’ antigens.
  3. Those antibodies cross-react with the heart tissue. This results in the autoimmune disease RHEUMATIC FEVER.
53
Q

What are the types and effector molecules of autoimmune diseases?

A

Type II: Effector IgG; Antibody against self antigens.
Type III: Effector IgG; immune complex deposits
Type IV: Effector T cells; Macrophage and cytotoxic T cell activation.

54
Q

What component’s antigens in the human body are attacked in ‘Autoimmune Hemolytic Anemia’ (AIHA)?

A

AIHA occurs when autoantibodies attack autoantigens on the red blood cell surface.

55
Q

What part of the immune system is activated in AIHA?

A

This attachment results in the activation of the classical pathway of complement.

56
Q

What is the result of complement being activated in AIHA?

A

The red blood cells are destroyed and the patient suffers from anemia.

57
Q

What are some different kinds of AIHA?

A

There are warm AIHA (autoanti-IgG), cold AIHA (autoanti-IgM), or drug-induced AIHA based on the autoantibodies or antigens implicated in the disease process.

58
Q

What can cause Autoimmune Hemolytic Anemia (AIHA)?

A

AHIA can be brought on by other illnesses or for unknown reasons.

59
Q

What syndrome involves autoantibodies forming against type IV collagen?

A

Goodpasture’s Syndrome occurs when autoantibodies form against type IV collagen (found in the basement membrane).

60
Q

What organs are mainly targeted with Goodpasture’s Syndrome?

A

The lungs and kidneys are particularly susceptible. Attachment of the autoantibodies to the basement membrane in the kidneys leads to inflammation, impaired blood filtration, and can even become so severe the patient can die.

61
Q

What is one of the treatments for Goodpasture’s Syndrome?

A

Patients can be treated by plasma exchange. The principle being that if the autoantibody is free in circulation (within the plasma) it can be removed by removing the plasma, and replaced with plasma that is free of the autoantibody. Immunosuppressive drugs can also be prescribed.

62
Q

What is the main characteristic of Systemic Lupus Erythematosus?

A

Systemic Lupus Erythematosus (SLE or simply referred to as lupus) is characterized by a wolf like red “mask” on the face, hence lupus (Latin for wolf).

63
Q

What molecules in the body are being targeted by the autoantibodies in someone with Systemic Lupus Erythematosus and what is deposited?

A

Autoantibodies are created against intracellular macromolecules throughout the body resulting in immune complexes of autoantigen:autoantibody becoming deposited and stimulating further inflammation.

64
Q

What component of the body is attacked in Multiple Sclerosis?

A

Multiple Sclerosis is an inflammatory autoimmune disease against the myelin sheath.

65
Q

What component of the body is attacked in Multiple Sclerosis?

A

Multiple Sclerosis is an inflammatory autoimmune disease against the myelin sheath.

66
Q

What component of the immune system has gone awry in Multiple Sclerosis?

A

TH1 CD4 cells activate macrophages which secrete proteases and cytokines that cause demyelination.

67
Q

What is the result of the damage caused in Multiple Sclerosis?

A

Removal of the myelin sheath (insulating cover) on the nerve cells in the brain and spinal cord results in the nervous systems inability to communicate with cells of the body. Patients will often have mental, physical, and psychiatric issues as a result of the immune system attacking the nervous system.

68
Q

What immune system cell causes Type I Diabetes?

A

Type I Diabetes is the result of β cells in the Islet of Langerhans in the pancreas being destroyed by CD8 T cells.

69
Q

What immune system cell causes Type I Diabetes?

A

Type I Diabetes is the result of β cells in the Islet of Langerhans in the pancreas being destroyed by CD8 T cells.

70
Q

What happens if the β cells are destroyed in the Islet of Langerhans?

A

β cells are responsible for secretion of insulin. If destroyed, the body is unable to control blood glucose levels. Persistent hyperglycemic conditions or uncontrolled diabetes can result in numerous complications such as: renal failure, retinopathy, poor circulation, atherosclerosis, persistent infections, etc.

71
Q

How can type I Diabetes be controlled?

A

Diabetes can be controlled by monitoring blood glucose levels and administering insulin when appropriate.

72
Q

What is rheumatoid arthritis?

A

Rheumatoid arthritis is a debilitating chronic inflammatory autoimmune disease that primarily affects the joints.

73
Q

What immune system cell is stimulated to make autoantibodies against self in rheumatoid arthritis? What component of the body is attacked (not necessarily where systems are experienced)?

A

B cells are stimulated to make auto-IgM, auto-IgG, and auto-IgA to the Fc region of the individuals own IgG. These autoantibodies to IgG are called Rheumatoid factor. In essence, it is an autoantibody to antibody.

74
Q

Where does inflammation occur in rheumatoid arthritis?

A

This leads to inflammatory cells being recruited to the joints.

75
Q

What therapies can be used for rheumatoid arthritis?

A

Patients with rheumatoid arthritis can undergo physiotherapy and/or are prescribed anti-inflammatory medications.

76
Q

What type of tests do Doctor’s use to help diagnosis the type of arthritis in a patient?

A

Physicians will order a series of laboratory tests in order to differentiate the type of arthritis that is affecting an individual. Often, patients with rheumatoid arthritis will have a positive test for rheumatoid factor and anticyclic citrullinated peptide antibodies (anti-CCP). Since the patient is suffering from inflammation they will also have an elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).

77
Q

Why are the rheumatoid factor, anti-CCP, elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) tests not relied on for diagnosis of arthritis?

A

This is because there are patients who will have rheumatoid arthritis that will have a negative test for rheumatoid factor, a negative test for anti-CCP antibodies, a normal ESR, and/or a normal CRP. There is also 1-2% of the healthy population that has rheumatoid factor and as individual ages, this number increases even though they do not have rheumatoid arthritis.