Week 3 Allergies & Autoimmune Diseases

Question 1

Type 1 Hypersensitivity

Answer 1

IgE - mediated
Onset = 1 hour
Ex. anaphylaxis

Question 2

Type 2 hypersensitivity

Answer 2

IgG or IgM Cytotoxic
onset = hours to days
ex. hemolytic anemia

Question 3

Type 3 hypersensitivity

Answer 3

Immune Complex Mediated
onset = 1-3 weeks
ex. serum sickness SLE

Question 4

type 4 hypersensitivity

Answer 4

T-cell mediated
onset = days to weeks
ex. Rash SJS

Question 5

why type of hypersensitivity do contacted materials cause

Answer 5

type 4
t-cell mediated

Question 6

Most Common Atopic Conditions Are?

Answer 6

atopic asthma, allergic eczema, hay fever = allergic disease

People with one atopic condition are more likely to develop another

Question 7

Allergic March

Answer 7

IgE- clinical symptoms that appear early in life persist over years or decades and often remit spontaneously with age

Question 8

Type 1 Hypersensitivity Reactions

Answer 8

Sensitization: First exposure to allergen → produce IgE antibodies.

Re-exposure: Allergen binds IgE Abs → activates mast cells.

Mast cells release histamine and cytokines, causing allergic reaction.

Normal process:
Phagocytic cell ingests allergen, presents antigen.

Cascade: B cell produces IgE.

Sensitization:
IgE binds to mast cells during first exposure.

Initial symptoms mild or negligible.

Re-exposure: Immediate memory response triggers mast cell degranulation.

Release of histamine and cytokines leads to atopic symptoms.

Question 9

Anaphylaxis

Answer 9

Characterized by widespread edema, vascular shock, and dyspnea.

Severity:
Depends on previous sensitization.
Even small amounts of antigen can trigger.

Symptoms:
Itching, hives, skin erythema.
Bronchospasm, respiratory distress.

Complications:
Laryngeal edema, obstruction.
Shock, potential death within hours.

Treatment:
Epinephrine injection (EpiPen).
Epinephrine increases blood pressure and relaxes smooth muscles.

Question 10

Desensitization Therapy

Answer 10

• Allergy shots
• Principle = divert immune response from IgE to IgG (less symptoms)

Question 11

How does Hypersensitivity II Reactions destroy the antigen?

Answer 11

Opsonization and Phagocytosis:
Cells coated (opsonized) to attract phagocytes.

Antibody-Dependent Cellular Toxicity (ADCC):
IgG binds to surface antigen.
NK cell recognizes and kills antibody-coated cell.

Complement Activation:
IgG binding activates complement system.
Causes lysis by membrane attack complex or phagocytosis.
Recruitment of neutrophils and monocytes.
Release of injurious substances, leading to inflammation and tissue damage.

Question 12

Hypersensitivity II reactions

Answer 12

• Type II antibody-mediated hypersensitivity reactions are mediated by IgG or IgM antibodies directed against target antigens on cell surfaces
• The antigens may be endogenous antigens that are present on the membranes of body cells, or exogenous antigens that are absorbed on the membrane surface

Question 13

Rh Incompatibility

Answer 13

Rh Incompatibility:
Occurs when mother is Rh-negative and baby is Rh-positive.
Rh factor is a protein on red blood cells.
Inherited trait.

During Pregnancy:
Baby’s Rh-positive blood can cross into mother’s bloodstream.
The mother’s body reacts, creating antibodies against the baby’s blood.
Usually not problematic in first pregnancy.

Subsequent Pregnancies:
Antibodies remain in mother’s body.
Can cause problems in later pregnancies with Rh-positive babies.

Complications:
Antibodies attack baby’s red blood cells, causing hemolytic anemia.

Prevention:
Rhogam (immunoglobulin) given to Rh-negative pregnant women to prevent antibody formation against baby’s Rh-positive blood

Question 14

Hypersensitivity III Reactions

Answer 14

Type III Hypersensitivity: Immune complex-mediated

• Formation of insoluble antigen-antibody complexes.
• Activates complement system, leading to localized inflammation.
• Immune complexes in circulation can damage vessel linings or tissues.
• Trigger inflammatory response by recruiting neutrophils.

Examples:
Vasculitis in autoimmune disorders like SLE (lupus).
Kidney damage in acute glomerulonephritis (post-strep infections).

Question 15

Post Streptococcal Glomerulonephritis

Answer 15

Poststreptococcal Glomerulonephritis (PSGN):
- Rapid kidney function deterioration due to inflammatory response.
- Follows streptococcal infection, often group A beta-hemolytic streptococci.
- Affects glomeruli and small kidney blood vessels.
- Usually seen in children after sore throat or skin infection.

Mechanism:
- Formation of immune complexes containing streptococcal antigen and human antibody.
- Deposited in kidney glomeruli.
- Activation of alternate complement pathway.
- Leukocyte infiltration, cell proliferation, impaired capillary perfusion, and glomerular filtration rate (GFR).

Complications:
Reduction in GFR leading to renal failure, oliguria, anuria, acid-base imbalance, electrolyte abnormalities, volume overload, edema, and hypertension.

Classic Triad:
Hematuria, edema, and hypertension

Question 16

Hypersensitivity IV Reactions

Answer 16

Type IV Hypersensitivity: Cell-Mediated
- Delayed-Type Hypersensitivity (DTH).
- Involves immune response mediated by T cells.
- Requires previous exposure to antigen for response.

Example: Contact dermatitis from poison ivy.
- Initial exposure may not cause reaction; subsequent exposures trigger immune response due to sensitization.

Question 17

Type IV hypersensitivity DTH (delayed-type)

Answer 17

1. antigen is introduced into subcut tissue
2. TH1 effector cell recognizes antigen and releases cytokines which act on vascular endothelium
3. recruitment of t cells, phagocytes, fluid, and protein to site of antigen injection causes visible lesion

example: TB skin test - Characterized by perivascular accumulation of CD4 T cells and macrophages.
Local secretion of cytokines increases microvascular permeability, causing redness and swelling.

Question 18

Normal Immune Response:

Answer 18

1. an invader (virus) enters the body
2. lymphocytes create antibodies to fight invader

Question 19

Autoimmune disease

Answer 19

• Autoimmune disorders represent a group of disorders that are caused by a breakdown in the ability of the immune system to differentiate between self and non-self antigens. Caused by an inappropriate B cell (antibody) and/or T cell immune responses
• Results in destruction of your own cells/organs.

Question 20

Self antigen/Autoantigen

Answer 20

an antigen expressed on your own cells

Question 21

Autoreactive cells

Answer 21

T or B cells that bind to a self antigen

Question 22

Autoantibody

Answer 22

antibody that binds to a self antigen

Question 23

Self-tolerance

Answer 23

o To function properly the immune system must be able to differentiate foreign antigens from self-antigens: this is called self tolerance
o It results from central and peripheral mechanism that delete self-reactive immune cells that cause autoimmunity or render their response ineffective in destroying self-cells and self tissue

Question 24

Central tolerance

Answer 24

Deletion or inactivation of self-reactive T and B cells.

Occurs in thymus (T cells) and bone marrow (B cells).

Mechanisms: receptor editing, absence of costimulatory signals, immunologic ignorance.

Question 25

Peripheral Tolerance

Answer 25

Maintains tolerance in secondary lymphoid tissues.

Processes: deletion or killing of autoreactive cells, anergy, suppression of effector T cell activation

Question 26

Central vs. Peripheral:

Answer 26

Central: Eliminates self-reactive cells.

Peripheral: Deals with escaped autoreactive cells.

Importance:
Prevents immune reactions against self-antigens.
Failure of these tolerances leads to autoimmune reactions.

Question 27

Autoimmunity

Answer 27

Autoimmunity:
Results from loss of self-tolerance.
Genetic and environmental factors contribute.

Gender:
More autoimmune diseases occur in women (5:1 ratio).

Genetic Factors:
Familial clustering indicates genetic predisposition.
Human Leukocyte Antigen (HLA) genes play a strong role.

Trigger Events:
Infections, chemicals, or other factors can precipitate altered immune state.

Molecular Mimicry:
Microbes share epitopes with host, leading to immune response.

Example:
Group A strep infection triggers antibodies targeting heart or kidney tissue due to similarity with streptococcal antigens.

Question 28

Organ-specific Autoimmune Diseases

Answer 28

autoimmune response targets an antigen present in a specific organ

Examples:
Insulin-Dependent Diabetes Mellitus (pancreas - beta cells)

Graves Disease (thyroid – thyroid-stimulating hormone receptors)

Question 29

Systemic Autoimmune Diseases:

Answer 29

autoimmune response targets an antigen present at many different sites; can involve multiple organs

Examples:
Systemic Lupus Erythematosis (many cell types)

Question 30

Graves Disease

Answer 30

• an autoimmune disorder that causes hyperthyroidism
• the immune system attacks the thyroid and causes it to make more thyroid hormone than your body needs.

Immune system produces thyroid-stimulating immunoglobulin (TSI).
TSI attaches to thyroid cells.
Acts like thyroid-stimulating hormone (TSH).
Causes thyroid to overproduce T3 & T4

Question 31

Insulin- Dependent Diabetes Mellitus

Answer 31

Chronic autoimmune destruction of insulin-producing pancreatic beta cells.
- Autoreactive T cells target and kill beta cells in the islets of Langerhans.
Reduced insulin production leads to hyperglycemia.

Autoimmune Process:
Autoreactive cytotoxic T lymphocytes (CTLs) kill insulin-producing beta cells.

Result:
Reduced insulin production → hyperglycemia.

Question 32

Multiple Sclerosis

Answer 32

Multiple Sclerosis (MS):
- Autoimmune destruction of myelin sheath in brain and spinal cord by T cells.
- Disruption of electrical signals leads to paralysis.
- Trigger for myelin damage and CNS inflammation unclear.

Mechanism:
- Immune system attacks protective myelin sheath covering nerve fibers.
- Causes communication problems between brain and body.

Consequences:
Can lead to permanent nerve damage.

Core Process:
Inflammatory, involving T cells and mediators.
T-cell-mediated inflammation triggers injury to axons and myelin sheaths.
Autoimmune process can lead to degenerative phase independent of immune activity.

Question 33

Treatments for Autoimmune Diseases

Answer 33

Immunosuppression:
NSAIDs, prednisone, cyclosporin A.

Plasmapheresis: Temporary removal of antibodies.
Block MHC: Mimic similar peptides to block major histocompatibility complex.

Block B and/or T cells: Use antibodies to block their function.

Disease-Specific Treatments: Insulin for T1D, joint replacements for rheumatoid arthritis.

Treatment Approach:
Based on involved tissue/organ, effector mechanism, and chronicity.
Corticosteroids and immunosuppressive drugs may be used.

Plasmapheresis purges autoreactive cells from immune system in severe cases.