Dysregulation & Deficiency

Question 1

Ways immune system can dysfunction

Answer 1

• Normal immune response causing pathologic conditions
• Defects in immune regulation
• Autoimmune disease
• Immunodeficiency

Question 2

People affected by Tuberculosis (TB)

Answer 2

• 1/3 of world is infected panel brick walls
• Only 5-10% has lifetime risk of developing active TB

Question 3

Tuberculosis (TB) causative agent

Answer 3

• Caused by Mycobacterium tuberculosis
• Usually airborne inhaled
• Pathology created due to normal immune system function

Question 4

How TB infects person

Answer 4

1. TB modifies surface of phagosome, so it unable to fuse with lysosome within Marcophage.
2. Therefore TB can thrive/multiples in macrophage
3. Eventually TB burst out of macrophage, and contents of lysosomes are released into lungs
4. Inflammatory response is initiated

Question 5

Results of TB infection

Answer 5

• Person dies, and eventually TB dies too
• Person recovers: cytokines like INFγ hyperactivates macrophages, which eliminate TB
• Person lives with chronic infection

Question 6

Sepsis

Answer 6

• Chemicals are released into the bloodstream to fight infection
• Inflammation tirggers a cascade that can damage multiple organs –> organ failure
• Septic shock occurs, blood pressure drops, PT dies

Question 7

People at risk of Sepsis

Answer 7

MC in elderly people

Question 8

Sepsis Tx

Answer 8

IV fluids and antibiotics

Question 9

Major cytokine involved in Sepsis

Answer 9

Tumor necrosis factor (TNF)

• Increase blood vessel permeability
• Increase fluid loss
• Decrease blood pressure and volume

Question 10

Septic shock

Answer 10

Results when positive feedback loops cause overreaction to a system wide infection

Question 11

Chiropractic Tx for Sepsis

Answer 11

Vagal stimulation can decrease macrophage releasing TNF

Question 12

People affected by Allergies

Answer 12

• 54% of US Pop suffers type I hypersensitivity rxns (MC allergies)
• Incidence still rising
• Allergic people respond diff to allergens, than non-allergic people

Question 13

Allergic vs Non-allergic

Answer 13

Allergic

• STRONG response to allergens
• Produce much IgE
• Th2 bias

Non allergic

• Weak response to allergens
• Mainly produce IgG
• Th1 bias

Question 14

Cells associated with Allergies

Answer 14

Th2 bias

Question 15

Phase one of Allergies

Answer 15

1. FC end of IgE binds to mast cell
2. Fab end binds to allergen, which triggers mast cell degrandulation
3. On subsequent exposure allergen can cross link IgE. Cluster sends signal downstream promoting degranulation of mast cell, which release Histamine, Protease, heparin and other chemicals

Question 16

Phase two of Allergies

Answer 16

Immediate = degradulation of mast cells & basophil

• Mast cells basophils bind IgE
• Resulting crosslinking of Fc region –> degradulation
• Cells secrete cytokines (IL-5) which recruit eosinophils

Delayed (chronic) = prominently Eosinophils

• Delayed b/c they must be recruited from bone marrow

Question 17

Function of mast cells, basophils & eosinophils

Answer 17

provide defense against PARASTIC infections (too large for macrophage/neutrophils to phagocytize)

• IgE “guides” mast, baso, eosino to target

Question 18

Why developing fetuses have Th2 bias

Answer 18

TH1 releases cytokines (TNF, IL-2) that may consider parental genes as foreign invaders. Thus placenta produces IL-4 which causes both maternal and fetal Th2 bias

Question 19

Heredity and allergies

Answer 19

specific gene taken for allergies susceptibility have been identified.

• Allergy concordance in identical twins is 50%.
• They may have a new form of IgE receptor that sends high level of IL-4 (promotes class switching of B cells to produce IgE).

Question 20

Glucocorticoids (cortisol)

Answer 20

treatment for allergies that works by Th cell production of cytokines thereby activating fewer T cells

• blocking binding of IgE to mass cells = Xolair
• histamine blockers = Claritin, Allegra • chiropractic in homeopathy

Question 21

Specific immunotherapy to cure allergies

Answer 21

• injection of gradually increasing doses of crude allergens
• after several years of regular treatment, patient becomes tolerant to allergen
• causes the cells to class which from IgE to another class (like IgG)

Question 22

Autoimmune disease

Answer 22

results when there is a breakdown in mechanisms meant to preserve tolerance of self

• affects ~5% of Pop
• 100 known types
• incidence is rising,

Question 23

Autoimmune disease causation

Answer 23

true reason is unknown

• autoimmune disease Is an unsuccessful adaptation, THOUGHT caused by drastically changing environment in recent history

Question 24

molecular mimicry

Answer 24

A hypothesis as to why infection may lead to breakdown of self-tolerance yielding autoimmune disease: Non-self molecule are similar enough to self, thereby causing immune system to activate against self.

Question 25

Molecular mimicry mechanism

Answer 25

1. BCR and TCR have variable affinity which allows them cross react with several antigens with some similarity 2. During infection, lymphocytes recognize their Cognate antigen associated with microbe. 3. After infection enough similarity exists between Cognate antigen and Self antigen to cause an AUTO immune response 4. inflammation must occur in the same tissue that expresses self antigen, in order to activate APCs to re-stimulated self reactive T cells 5. cytokines generated by inflammation can upregulate MHC I expression on normal cells, thereby making them targets for self reactive CTLs

Question 26

The inflammatory reflex

Answer 26

A cholinergic anti-inflammatory pathway that is down regulated by the vagus nerve

Question 27

How molecular mimicry can cause autoimmune disease

Answer 27

lymphocytes have receptor that recognize their cognate antigen on a microbe. * Receptor recognize a group of antigens, with affinities ranging from high to low (cross reactivity) * receptor may cross react with self antigen causing autoimmune disease * doesn't occur prior to infection because affinity is too low, or never brought into contact

Question 28

Re-stimulation of autoimmune T cells

Answer 28

When self reactive T cells activated by microbial mimicry reach tissues where they can cross react with self antigens, they must be continually re-stimulated by APCs. * It's not continually restimulated they die via apoptosis * if they do not achieve the necessary costimulation, they die via anergized * Activation of APCs is triggered by inflammatory cytokines (TNF and IFN-γ) Which is controlled by Innate immune system (Vagus Nerve cholergenic antiseptic reflex)… Inflammation must be in place otherwise T cell would never get co-stimulation necessary to activate * Once activated APCs express MHC and co-stimulation molecules necessary for T cell re-stimulated.

Question 29

Myasthenia gravis

Answer 29

self reactive antibodies against the Ach receptor prevents Ach from binding, producing muscle weakness and autoimmune dysfunction • example of autoimmune disease

Question 30

multiple sclerosis

Answer 30

immune system attack on myelin in CNS thought to be due to self reactive T cells • Example of autoimmune disease

Question 31

Rheumatoid arthritis

Answer 31

T cells attack cartilage protein in joints. IgM-IgG antibody complexes can activate macrophages leading to chronic inflammation • example of autoimmune disease

Question 32

Lupus erythemaosis

Answer 32

A breakdown between B and T cell tolerance that may affect skin, joints, kidney, brain, and other organs leading to chronic inflammation. • Example of autoimmune disease

Question 33

Guillian-Barre

Answer 33

immune system attack on myeline in PNS • example of autoimmune disease

Question 34

transverse myelitis

Answer 34

An inflammatory process of the spinal cord, and can cause axon demyelination • example of autoimmune disease

Question 35

Autoimmune Lymphoproliferative Syndrome

Answer 35

genetic defect were T cells refuse to die when chronically stimulated by self antigen, due to genetic defect in Fas or Fas Ligand proteins • example of autoimmune disease

Question 36

criteria for autoimmune disease

Answer 36

* Pt must have MHC molecules that present itself antigen * Pt must have T and/or B lymphocyte receptors that recognize self antigen * must be environmental factors that breakdown tolerance mechanisms

Question 37

susceptible times for autoimmune disease development

Answer 37

* frequently follows bacterial/viral infection * environmental factors * chronic inflammation

Question 38

causes of immunodeficiency

Answer 38

* genetic defects: single gene mutations, severe immunodeficiency syndrome (SCIDS) * AIDS

Question 39

acquired immunodeficiency syndrome (AIDS)

Answer 39

the major cause of human immunodeficiency virus 1 (HIV-1) * incidence = 34,000,000 * Knocks out immune function by targeting T Helper cells • mortality typically due to opportunistic infection

Question 40

HIV infection

Answer 40

thought that virus gains access via rectal or vaginal mucosa and infects T Helper cells * hijacked cellular machinery to make copies of self and infect other cells * chronic phase can last for 10 years or more * during chronic phase total number of T helper cells gradually decrease and cripple immune system

Question 41

cells infected by HIV-1

Answer 41

* T helper cells * macrophages * dendritic cells * HIV docs to CD4 protein via GP 120 on Virus

Question 42

treatment for HIV

Answer 42

Highly Active Anti-– Retroviral Treatment (HAART)