Immunology Final Exam (Part 2) - Hypersensitivities & Immunopathy/Immune dysfunction

What are the 4 types of hypersensitivity reaction? What antibody is involved with each?

Type 1 --> Immediate; IgE

(HIstamine; allergies)

Type II --> Antibody mediated, cytotoxic; IgM and/or IgG

Type III --> Immune complex; IgM and/or IgG

Type IV --> Cell mediated, delayed; T cells

T/F: All forms of hypersensitivity requires prior exposure to the antigen

TRUE

What is the immune reactant involved with Type 1 hypersensitivity?

IgE

What is the antigen form of Type 1 hypersensitivity?

Soluble antigen

What is the immune reactant involved with Type II hypersensitivity?

IgG or IgM

What is the antigen form of Type II hypersensitivity?

Cell-bound antigen

What is the immune reactant involved with Type III hypersensitivity?

IgG and IgM

What is the antigen form of Type III hypersensitivity?

Soluble antigen

What is the immune reactant involved with Type IV hypersensitivity?

T cells

What is the antigen form of Type IV hypersensitivity?

Soluble or cell-bound antigen

Which hypersensitivity type has a mechanism of action where antigen-antibody complexes are deposited in tissue, and complement activation provides inflammatory mediators and recruits neutrophils while enzymes released form neutrophils damage tissue?

Type III Hypersensitivity

Which hypersensitivity type has a mechanism of action where Th1 cells secrete cytokines which activate macrophages and cytotoxic T cells?

Type IV Hypersensitivity

Which hypersensitivity type has a mechanism of action where allergen-specific IgE antibodies bind their mast cells via their Fc receptor, and when the specific allergen binds to the IgE, crossing-linking of IgE induces degranulation of mast cells?

Type I Hypersensitivity

Which hypersensitivity type has a mechanism of action where has an IgG or IgM antibody bind to cellular antigen, leading to complement activation and cell lysis, so IgG can also mediate ADCC with cytotoxic T cells, NK cells, macrophages, and neutrophils?

Type II Hypersensitivity

This is an example of what hypersensitivity reaction:

Red blood cell destruction after transfusion with mismatched blood types or during hemolytic disease of a newborn?

Type II Hypersensitivity

This is an example of what hypersensitivity reaction:

Contact dermatitis, Type I diabetes mellites, and multiple sclerosis

Type IV Hypersensitivity

This is an example of what hypersensitivity reaction:

Local and systemic anaphylaxis, seasonal hay fever, food allergies, and drug allergies?

Type I Hypersensitivity

This is an example of what hypersensitivity reaction:

Post-streptococcal glomerulonephritis, rheumatoid arthritis, and systemic lupus erythmatosus?

Type III Hypersensitivity

During initial exposure with a Type I hypersensitivity, the allergen will enter the body, and APCs will present it on __________ to T cells. This causes differentiation of the T cells into _______ subtype, which stimulates B cells specific to the antigen to make ________.

MHC II

Th2

IgE

During the sensitization Type I Hypersensitivity, IgE antibodies Fc regions will bind with high affinity to _________ cells, which are everywhere in the body, with the second exposure activating these cells.

Mast cells

When the allergen binds to IgE antibodies, there is clustering which causing what?

Degranulation

(Release of chemistry)

What 4 cells are degranulated in Type 1 hypersensitivity?

1) Mast cells

2) NK cells

3) Neutrophils

4) Macrophages

Chemistry released by the mast cell includes what 4 things?

1) Vasoactive amines (histamine)

2) Prostaglandins

3) Leukotrienes

4) Recruitment of other WBCs (neutrophils and eosinophils)

Leaky vessels, edema, smooth muscle spasms, increased mucus secretion, and drop in blood pressure are what type 1 hypersensitivity allergic reaction?

Local impact

Decrease in blood volume, dramatic decrease in blood pressure, MI, shock, contraction of smooth muscle of respiratory tract, and asphyxiation are what type 1 hypersensitivity allergic reaction?

Systemic Impact

What type of Type I hypersensitivity reaction includes itchy eyes, congestion, sneezing, pollen, pet dander, & dust mite feces? How is it treated?

Upper Respiratory (Hay fever)

-- antihistamine

What type of Type I hypersensitivity reaction includes asthma? How is it treated?

Lower respiratory

- epinephrine, albuterol

What are the 9 major food allergy groups?

1) Milk

2) Eggs

3) Fish

4) Crustacean Shellfish

5) Tree Nuts

6) Peanuts

7) Wheat

8) Soybeans

9) Sesame

T/F: Food allergy and food intolerance are the same

FALSE

What is the first symptom of a food allergy (type 1 hypersensitivity)?

Urticaria

How are type I hypersensitivity reactions treated? Short term? Long term?

Avoid contact (skin test diagnoses)

Short term = antihistamine & epinephrine

Long term = Desensitize, allergy immunotherapy, convert IgE to IgG

Type II Hypersensitivity (Cytotoxic) Reactions are antibody mediated by what two antibodies that will bind to the surface of cells or the ECM?

IgM & IgG

What are the 2 means of destruction by Type II Hypersensitivity (Cytotoxic) Reactions?

1) Antibody-dependent cell mediated cytotoxicity (ADCC)

2) Complement system

What destruction mechanism in Type II Hypersensitivity (Cytotoxic) Reactions is when WBCs with Fc receptors (monocytes, neutrophils, eosinophils, and NK cells) and they bind cells with IgG or IgM anitbodies?

Antibody-dependent cell mediated cytotoxicity (ADCC)

What destruction mechanism in Type II Hypersensitivity (Cytotoxic) Reactions is IgM and IgG good at, where they destroy the cells via MACs and products of the proteins will activate macrophages & neutrophils?

Complement

NOTE: IgM & IgG = Me Good at fixing complement

What is a clinical example of Type II Hypersensitivity (Cytotoxic) Reactions?

Hemolytic Disease of the Newborn

-- Rh+ father & Rh- mother

-- Mother carrying first Rh+ child, develops antigens, then anti-Rh antibodies

-- If become pregnant with another Rh+ child, anti-Rh antibodies will cross placenta and damage fetal red blood cells

What antibody crosses the placenta?

IgG

What accumulates & deposits in tissues (RA, SLE, glomerrulonephritis), vascular walls (vasculitis), and common in the kidneys & joints, and cause inflammation in Type III Hypersensitivity reactions?

Antibody-Antigen Complexes

NOTE: these are NORMALLY cleared, but in this case there is either a large excess, persistent complexes, or too fast of deposition in Type III

As a clinical example of Type III Hypersensitivity reactions, where do we see the Antibody-Antigen complexes deposit in RA? SLE? Vasculitis?

RA = joints, lungs, pericardium (Anti-IgG antibodies developed)

SLE = joints, skin, kidney

Vasculitis = blood vessels

In Type III Hypersensitivity reactions, IgM and IgG will recruit complement, attracking neutrophils and macrophages which bind Fc regions, and then what occurs?

Phagocytes attracted and try to eat the antigen-antibody complexes and release inflammatory chemistry

What are the two subtypes of Type IV Hypersensitivity reactions?

1) DTH (Delayed Type Hypersensitivity) -- usually CD4 (Th)

2) Cell Mediated Cytotoxicity -- usually CD8 (Tk)

Since Type IV Hypersensitivity reactions is the inappropriate or excessive immune responses from T cells, what antibody is involved?

NO ANTIBODIES

T cell mediated so involves CD4 (Th2 & Th17), CD8, Macrophages & Neutrophils

NOTE:

if you see Cell mediated it = T cells

if you see Humoral immunity = B cells

What are clinical examples of Type IV Hypersensitivity reactions?

Poison ivy

Type 1 diabetes

MS

Organ transplant Rejection

Which T cell does MHC I match with? MHC II?

MHC I = CD8

MHC II = CD4

Are Type IV Hypersensitivity reactions directed against self antigens or exogenous antigens?

BOTH; can be either or

What is a substance that on its own does not invoke an immune response but when combined with a protein, can become highly antigenic?

Hapten

In the clinical case of poison ivy (Type IV Hypersensitivity reactions), on the primary contact what occurs? What occurs in the secondary contact?

Primary = NO dermatitis

Secondary = Dermatitis

Does poison ivy involve CD4 or CD8?

BOTH, since its a combo of our own antigens and extracelluar antigens

NOTE: Its Th2 & Th17 for the CD4

What test is a form of a Type IV Hypersensitivity reactions?

Tuberculin-type sensitivity test

-- intradermal injection tuberculin from Bacillus tuberculosis

-- produces measurable local induration and swelling

What is the order of response time for each hypersensitivity reaction, from quickest to longest?

Quickest

1) Type I (<30 mins)

2) Type III (3-8 hours)

3) Type II (5-12 hours)

4) Type IV (24-48 hours)

Rheumatoid arthritis is a hypersensitivity reaction caused by?

A. autoantibody complexes

B. IgE binding mast cells

C. CD8+

D. IgM and IgG combinging for complement

A. auto-antibody complexes

TB skin test is what type of hypersensitivity?

A. I

B. II

C. III

D. IV

D. IV

T/F: All types of hypersensitivities require a previous exposure to the antigen

TRUE

Hemolytic disease of a newborn is caused by what type of hypersensitivity

A. anaphylactic

B. antibody-dependent cell-mediated cytotoxicity (ADCC)

C. immune complexes

D. delayed cell-mediated

B. ADCC

Allergies to peanuts are caused by:

A. antibody complexes attaching tissues

B. IgM binding neutrophil

C. Haptens attaching to protein

D. IgE attaching to mast cells

D. IgE w/ mast cells

Hypersensitivity Reaction SUMMARY

Type 1

- Rapid

- always involve IgE and degranulation of basophils or mast cells

- Ex: Food allergies, Hay fever, Asthma, Pollen/dander/dust mites

Type II

- Antibodies (M/G) bind to cell membranes or extracellular matrix

- antigen may be you or exogenous molecules (drugs adhering)

- Ex: Hemolytic Disease of the Newborn

Type III

- Antibodies (M/G) bind to soluble antigen and form antibody-antigen complexes

- inflammation takes place at sites of deposition

- Ex: Vasculitis, RA, SLE,

Type IV

- Direct attack by WBCs without use of antibodies

- T cells initiate inflammation

- Ex: Poison ivy, Type 1 diabetes, MS, Organ transplant Rejection, TB test

What pathology of normal immune response is when microbes are inhales and macrophages ingest, but the microbes evade death by preventing the interaction of the phagosome with the lysosome, hiding in the macrophages and multiply, then burst out of the cell and induce inflammatory reaction?

Tuberculosis (Mycobacterium tuberculosis)

What pathology of normal immune response is a systemic immune response caused by an infection, where pathogens or toxins are throughout the body, so cells respond and produce large quantities of cytokines (TNF) forming a positive feedback loop (cytokine storm), increasing blood vessel permeability, organ damage, and drops in blood pressure (shock)?

Sepsis

What disease caused by a defect in the immune regulation is the overproduction of IgE response to "harmless" molecules, with atopic individuals tending to push the Th2 response, leading to more IgE?

Allergies

What is the memory response to normal tissue with loss of tolerance (failure of tolerance processes) and may involve antibodies, T cells, or immune complexes?

Autoimmunity

What is the response to innocuous antigen causing harm?

Hypersensitivity

What % of Americans suffer form an autoimmunity? What percent of that is women?

8%

78% women

T/F: All hypersensitivity reactions are autoimmune conditions, but not all autoimmune conditions are hypersensitivity reactions

FALSE

All autoimmune conditions = hypersensitivity reactions

BUT not all hypersensitivity rxns are autoimmune conditions

What three conditions are needed in order for Autoimmunity to develop?

1) MHC present self peptide

2) T and B cells then recognize self antigen

3) Breakdown of self tolerance

What are 4 possible mechanisms for how autoimmunity may be induced?

1) Infection/molecular mimicry

2) Inflammation

3) Damage/stress events that expose sequestered Antigen

4) Altered gut microbiota

If we have a Th1 bias, what 3 cells are we activating? What is their overall purpose? If this go wrong what can happen?

CTL, NK cells, macrophages

-- take care of intracellular viruses & bacteria in tissue

-- If go wrong can cause autoimmune

If we have a Th2 bias, what 3 cells are we activating? What is their overall purpose? What happens if this goes wrong?

Mast cells, Eosinophils, B cells (IgA & IgE)

-- fight parasites, helminths, and bacteria in the gut

-- if go wrong can cause allergies

In pregnancy, we don't want mom's CTLs and NK cells to attack the placenta/baby, so placenta produces IL-4 which influences maternal helper T cells to become Th2 cells, which cause baby to be Th2 bias, preventing mom and baby from attacking each other. What can then help restore the Th1/Th2 balance in babies once born?

Early exposure to microbes at an early age can help restore (ex: pets, siblings, playing outside)

What is the hygiene hypothesis?

Early life environment rich in normal microbial flora primes immune system in Th1 direction towards clinical balance, where 'sterile' environment promotes development of pathological immune phenotypes & allergies/autoimmunity

For Example: Western countries w/ improved personal hygiene & decrease in childhood infections; exposure to certain allergens early in life is less frequent so incidence of allergies to environmental allergens has increased dramatically

Both intrinsic and extrinsic factors can favor susceptibility to autoimmune disease. What is an example of an extrinsic factor? Intrinsic factor?

Extrinsic = environmental factors favoring development of autoimmune disease (differences/geographical areas)

Intrinsic = Certain MHC genes linked to specific autoimmune disorders (HLA-B27; 90x more likely for ankylosing spondylitis)

T/F: Autoimmunity reactions are systemic, not organ specific, but may involve antibodies, T cells, or immune complexes

FALSE

Autoimmunity rxns can be systemic OR organ specific

What condition has autoantibodies and sensitized Th1 cells specific for thyroid antigen produced, with antibodies produced interfering with iodine uptake, inducing DTH (delayed type hypersensitivity) in the thyroid, and often inflammation results in a goiter which is a visible enlargement of thyroid gland?

Hashimoto's thyroiditis

What type of hypersensitivity reaction is Hashimoto's thyroiditis, in addition to the delayed type hypersensitivity?

Type II hypersensitivity

-- produces anti-TSH receptor antibody

What condition is caused by autoimmune attack against insulin-producing beta cells in the pancreas, with CTLs infiltrating the pancreas and activating macrophages, followed by cytokine release, production of autoantibodies, and DTH (delayed type hypersensitivity) responses?

Type 1 diabetes mellitus

What condition is autoantibodies that bind to nicotinic acetylcholine receptors on motor end plates of muscle, blocking the normal binding of acetylcholine, inducing complement-mediated lysis of cells, and results in a progressive weakening of skeletal muscles?

Myasthenia gravis

What type of hypersensitivity reaction is Myasthenia gravis?

Type II hypersensitivity (Cytotoxic)

What condition is an auto-antibody against DNA, histones, or other self structures, with deposition of immune complexes activating complement, and symptoms including fever, weakness, arthritis, skin rashes, and kidney dysfunction, and is more common in women?

Systemic lupus erythematosus (SLE)

What type of hypersensitivity reaction is Systemic Lupus Erythematosus (SLE)?

Type III hypersensitivity reaction

What condition is the most common cause of neurologic disability associated with disease in Western countries, which is a autoreactive T cell that form inflammatory lesions along myelin sheaths around nerve fibers in the brain and spinal cord, with breakdown leading to a range of symptoms, from numbness to paralysis and loss of vision?

Multiple sclerosis

What type of hypersensitivity reaction is Multiple sclerosis?

Type IV hypersensitivity

What condition is more frequent in women with its major symptoms being chronic inflammation, and rheumatoid factors are often produced with antigen-antibody complexes (auto-antibodies IgM and /or IgG bind to IgG) and is a complex disease?

Rheumatoid arthritis

What hypersensitivity is Rheumatoid arthritis?

Type III hypersensitivity

What is another name for CD80/86 in the CD28-CD80/86 complex?

B7

What is greatly affected when there is an autoimmune disease that someone is being treated for?

Their immune system is HIGHLY affected