Immune System Dysregulation and Deficiency Flashcards Preview

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Flashcards in Immune System Dysregulation and Deficiency Deck (85)
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1
Q

Name 4 ways that the immune system can dysfunction.

A

1) Pathologic conditions caused by normal immune response
2) Conditions caused by defects in immune regulation
3) Autoimmune disease
4) Immunodeficiency

2
Q

How many people are infected with Mycobacterium tuberculosis?What percentage of the population has a risk of developing TB?

A

1/3 of the world population

5-10%

3
Q

When TB is active, how is the pathology created?

A

By normal immune system function

4
Q

What happens when an individual inhales the TB organism from an infected individual?

A

The organism is engulfed by alveolar macrophages/dust cells into a phagosome which should fuse with a lysosome to destroy the organism, but this is where it can go wrong

5
Q

In TB, when the organism is engulfed, what can go wrong?

A

The TB organism modifies the surface of the phagosome so it’s unable to fuse with the lysosome, so the organism can thrive and multiply in the macrophage. Eventually, it busts out of the macrophage, killing it and as it dies by necrosis, the contents of its lysosome are released into the lung tissue.

6
Q

In TB, what happens when the contents of the lysosome are released into the lung tissue?

A

It initiates an inflammatory response which recruits other immune cells to the battle site. This causes more inflammation.

7
Q

What are the results of the inflammatory battle site in the lung tissue in a person with TB?

A

1) The person dies
2) The person recovers
3) The person lives with chronic infection

8
Q

How can a person recover from a TB organism causing a battle site in the lung tissue?

A

1) The battle causes release of cytokines like INF-y that hyperactivates macrophages.
2) Macrophages and other cells (neutrophils) eliminate the invader
3) Adaptive immune system response also comes into play (T cells)
4) Vitamin D simulates the release of cathelicidins

9
Q

When does sepsis occur?

A

Sepsis occurs when chemical released into the bloodstream to fight the infection trigger inflammation throughout the body which can trigger a cascade of events that can damage multiple organ systems, causing them to fail

10
Q

What happens when sepsis progresses to septic shock?

A

Blood pressure drops dramatically which may lead to death

11
Q

What population is sepsis most common in?

A

Elderly people or those with weakened immune systems

12
Q

How many people die per year in the US due to sepsis?

A

250,000

13
Q

Is gene mutation that has never been observed in human lethal?

A

Yes! (I have this written that it will be on the exam in my notes)

14
Q

What cytokine is involved in sepsis?

A

TNF

15
Q

How is TNF involved in sepsis?

A

TNF that is secreted by macrophages systemwide can increase vascular permeability causing large amounts of fluid loss, decreased blood volume and decreased blood pressure causing septic shock and heart failure

16
Q

How are positive feedback loops of the innate immune system linked with sepsis?

A

Sepsis and shock can result when positive feedback loops cause an overreaction to a system wide infection

17
Q

What nerve can decrease macrophage release of TNF?

A

Vagus

18
Q

What percentage of the US suffers from type I hypersensitivity reactions which include most common allergies?

A

54%

19
Q

Is allergy associated with Th2 or Th1 bias?

A

Th2

20
Q

What causes allergies?

A

The overproduction of IgE antibodies in response to otherwise innocuous environmental antigens that causes allergies

21
Q

What immunoglobulin is overproduced in allergies?

A

IgE

22
Q

Are non allergic reaction Th1 or Th2 bias?

A

Th1

23
Q

What immunoglobulin is associated with non- allergic reactions?

A

IgG Ab

24
Q

In allergies, the Fc end of the IgE binds to what cells?

A

Mast cells

25
Q

In allergies, the Fab end of IgE binds to the allergen which triggers what?

A

It triggers the mast cell to degranulate

26
Q

What happens on subsequent exposures to an allergen?

A

The allergen can cross link IgE.. This clustering sends a signal downstream promoting degranulation of mast cells releasing histamine, proteases, heparin, and other chemicals causing familiar symptoms

27
Q

What are the two phases of allergies?

A

1) Immediate

2) Delayed

28
Q

What happens in the immediate phase of allergies?

A

Associated with degranulation of mast cells which are stationed out in the tissues and degranulation of basophils are recruited from the blood by signals given off by mast cells.

29
Q

What causes the degranulation in the immediate phase of allergies?

A

Both bind IgE and resulting cross linking of Fc receptors

30
Q

In the immediate phase of an allergic reaction, what do the Th cells secrete?

A

They secrete cytokines like IL-5 which can recruit many eosinophils from bone marrow

31
Q

What happens in the delayed (chronic) phase of allergies?

A

Eosinophils play a prominent role and add to the response but their effect is delayed because the majority of them must be recruited from the bone marrow (this takes time)

32
Q

What is the normal function of mast cells, basophils, and eosinophils?

A

Geared to provide a defense against parasitic infections that are too large to be phagocytized by macrophages and neutrophils

33
Q

What immunoglobulin acts as a guidance system for mast cells, basophils, and eosinophils?

A

IgE by targeting their chemistry at the parasite to destroy it

34
Q

Can mast cells, basophils, and eosinophils degranulate to any other immunoglobulin?

A

No, they should only be able to degranulate in response to IgE binding to parasite, limiting collateral damage

35
Q

Is a fetus supposed to be more of a Th1 bias or Th2 bias? Why?

A

Its more of an advantage for the fetus to have a Th2 bias because the 1/2 of the genetic material is paternal and could be considered foreign by the mother

36
Q

What cytokines are involved in a Th1 bias?

A

TNF which helps activate NK cells and IL-2 which causes proliferation of NK cells and CTLs

37
Q

What is the role of the placenta in Th2 bias?

A

The placenta produces large quantities of IL-4 which causes both maternal and fetal helper T cell to become Th2

38
Q

What is thought to shift newborn’s back to Th1 bias after birth?

A

Contact with microbes, especially those found in soil

39
Q

Besides contact with microbes what other things may prevent allergies or asthma from forming?

A

1) Early childhood infections
2) Children who grow up on farms
3) Children with older siblings
4) Children who grow up with dogs

40
Q

What is the percentage of allergy concordance in identical twins?

A

50%

41
Q

What type of gene is inherited in people who are atopic?

A

Class II MHC genes- they code for MHC proteins that may be especially proficient at presenting antigen/allergies

42
Q

What promotes class switching of B cells to produce IgE?

A

Mutant forms of IgE receptor that sent an unusually strong signal when cross linked resulting in high levels of IL-4

43
Q

What are some common treatments for allergies?

A

1) Glucocorticoids (cortisol)- blocks cytokine production by Th cells activating fewer B cells
2) Xolair- block binding of IgE to mast cells
3) Claritin- histamine blocker
4) Chiropractic and other homeopathic alternatives

44
Q

What is the down side to using glucocorticoids?

A

Increased susceptibility to infectious disease as you generally suppress immune system function

45
Q

How does immunotherapy work to cure allergies?

A

Injections of gradually increasing doses of allergens until tolerant. Takes several years. If it works the B cells class switch from IgE to another antibody class like IgG.

46
Q

What are allergen-specific Th cells polarized to?

A

A Th2 cytokine profile (IL-4, IL-5, and IL-13)

47
Q

When does autoimmune disease result?

A

When a breakdown in the mechanisms meant to preserve tolerance of self is severe enough to cause a pathological condition.

48
Q

What percent of people in the US do autoimmune diseases affect?

A

5-7.5%, more common in women than men

49
Q

How can infections lead to autoimmune disease?

A

Lymphocytes have receptors that recognize their cognate antigen on the microbe. The receptor may cross react with a self antigen causing an autoimmune disease (MOLECULAR MIMICRY)

50
Q

What happens when self reactive T cells that are activated by microbial mimics reach the tissues?

A

They might cross react with self antigens and must be continually re-stimulated

51
Q

What happens to the self reactive T cells if they are not continually re-stimulated in the tissues?

A

They die by apoptosis

52
Q

What happens to the self reactive T cells if they encounter self antigens that do not provide adequate co-stimulation?

A

They are anergized or deleted

53
Q

Does the innate immune system or the adaptive immune system function during autoimmune diseases?

A

The innate system gives the adaptive immune system permission to function

54
Q

What cells are activated during autoimmune diseases?

A

The APC’s are activated by inflammatory cytokines (TNF and IFN-y) from innate immune cells. Once activated the APCs express MHC and co-stimulatory molecules required to re-stimulate T cells in that tissue

55
Q

What has to happen before T cells can be re-stimulated?

A

Inflammation, otherwise the T cell would never get the co-stimulation necessary to activate

56
Q

Sill in autoimmune diseases… What can cytokines up-regulate on normal cells in the tissue?

A

MHC I, which makes these cells better targets for destruction by self reactive CTL’s

57
Q

What reflexes control inflammation?

A

Neural reflexes (vagus)

58
Q

What is insulin dependent diabetes mellitus?

A

Autoimmune destruction of pancreatic beta cells mediated by CTLs possibly with help from Ab from self reactive B cells (insidious onset)

59
Q

What is Myasthenia gravis?

A

Self reactive antibodies against the Ach receptor presents Ach from binding producing muscle weakness and autonomic dysfunction

60
Q

What is multiple sclerosis?

A

Immune system attack on myelin in CNS. Thought to be due to self-reactive T cells

61
Q

What is rheumatoid arthritis?

A

T cell attach on cartilage protein in joints. IgM and IgG antibody complexes can activate macrophages leading to chronic inflammation

62
Q

What is lupus erythematosis?

A

Long-term autoimmune disease that may affect skin, joints, kidneys, brain and other organs leading to chronic inflammation. Breakdown in B and T cell tolerance

63
Q

What is Guillain-barre?

A

Immune system attack on myeline in PNS

64
Q

What is transverse myelitis?

A

An inflammatory process of the spinal cord, and can cause axon demyelination

65
Q

What is autoimmune lymphoproliferative syndrome?

A

Genetic defect where T cells refuse to die when chronically stimulated by self antigens

66
Q

What are the conditions for autoimmune disease?

A

1) Person must have MHC molecules that can present self antigen
2) Person must have T lymphocytes and sometimes B lymphocytes with receptors that can recognize the self antigen
3) Must be environmental factors that lead to the breakdown of the tolerance mechanisms which are designed to eliminate self reactive lymphocytes

67
Q

What do autoimmune diseases typically follow?

A

Bacterial or viral infections, microbial attack, and chronic inflammation

68
Q

What is the hypothesis as to why infections may lead to breakdown of self tolerance leading to immune disease?

A

Molecular Mimicry

69
Q

What cells recognize the cognate antigen?

A

BCR and TCR

70
Q

Is it enough for a microbe to activate self reactive T cells by mimicry?

A

No, there must also be an inflammatory reaction going on in the same tissues that express self antigen, otherwise it is unlikely that the self reactive lymphocytes would exit the blood into the tissues

71
Q

What is the result of inflammation?

A

APCs are activated that can re-stimulate self reactive T cells

72
Q

How can inflammation be down regulated?

A

By the vagus!! “the inflammatory reflex” which is a cholinergic anti-inflammatory pathway

73
Q

What are 2 causes of immunodeficiency?

A

Genetic defects and AIDS

74
Q

What cells aren’t functioning properly in single gene mutations?

A

Non functional CD40 (B cell) or CD40L (Th cell)

75
Q

What organ do the single gene mutations affect?

A

Affect the formation and function of the thymus like in DiGeorge Syndrome

76
Q

What cells aren’t functioning properly in severe immunodeficiency syndrome (SCIDS)?

A

Neither B cells not T cells function

77
Q

What do you think about a genetic mutation that has never been observed in human? (**he said this would be a question!!)

A

It’s lethal!

78
Q

What is the incidence of AIDS?

A

About 34 million people worldwide

79
Q

How does AIDS knock out immune function?

A

By targeting Th cells

80
Q

When do people usually die of AIDS?

A

They usually die due to opportunistic infections like Pneumocytis carnii and Kaposi sarcoma

81
Q

What happens to Th cells during the chronic phase of HIV?

A

The total number of Th cells gradually decreases eventually crippling the immune system

82
Q

How can HIV-1 defeat the immune system?

A

1) It is a slowly replicating lentivirus
2) Uses a viral enzyme to make a copy DNA that can be inserted into host DNA and here it can sit in a latent state which cannot be detected by CTLs
3) High mutation rate allows virus to evade immune system

83
Q

What cells are infected by HIV-1?

A

Helper T cells, macrophages, dendritic cells, docks to CD4 protein via GP120 on virus

84
Q

What is the treatment for HIV-1?

A

HAART

85
Q

What do innate immune cells secrete more of when infected with HIV-1?

A

IFN- alpha and IFN-beta