MIC 205 Exam 4: 18: Immunologic Disorders

Immunologic Disorders

• Results in an overreaction or undereaction of the immune response

Over-Reaction

Allergy & Autoimmune

Undereaction

Immunodeficiency Diseases

Allergy

• Immune system reacts to an antigen it usually ignores and typically results in a hypersensitivity condition

• Any immune response against a foreign antigen exaggerated beyond the norm

• Type I, Type II, Type III, Type IV

Autoimmune

The immune system is reacting to “self” therefore, has lost the ability to distinguish self/non-self

Autoimmune affects the

blood cells, endocrine organs, nervous and connective tissue, and other major organ systems

Immunodeficiency Diseases

• No or little directed immune response

• Primary ( at birth ) or acquired immunodeficiency diseases

Type I ( Immediate Hypersensitivity)

• Exposure to allergens will cause the release of inflammatory molecules

  • histamines, kinins, proteases, leukotrienes, and prostagladins

Occurs in seconds to minutes

Examples of Allergens

Pollen-hay, cats, bee stings, foods, drugs, ragweed, dust mites

Type I ( Immediate Hypersensitivity) has a two step process that is IgE mediated, what are those two steps?

Sensitization

Degranulation

Sensitization ( Type I)

• Primary exposure to the allergen

• B cell activation will start the specific immune response

• Plasma cells will produce an IgE response against the allergen (antigen)

• IgE bind to mast cells, basophil, or eosinophil

Degranulation

• Subsequent Exposure

• Allergen binds IgE on mast cells, basophil, or eosinophil

• Release of histamines and other cytokines ( degranulation)

• Starts the inflammation response

Degranulation prompts a mild reaction ( localized), how does this happen?

• Dependent on the portal of entry

• reddening of skin, swelling, watery eyes, hives

• Small inhaled allergens may reach the lungs and cause asthma

Systemic Anaphylaxis ( Anaphylacitc Shock) ( part of Type I)

• starts localized then spreads systemic

• many mast cells may degranulate at once, releasing large amounts of histamine and inflammatory mediators

What happens during Anaphylaxis?

• drop in blood pressure

• violent contractions of the bronchial muscle

• airway constricted and fills with mucous

• death within minutes

Treatment for Type I

• Prevention of Desensitization ( staying away from allergen)

• For mild reactions: antihistamines, corticosteroids, bronchodilator for asthma

• Systemic Anaphylaxis: Immediate use of Epinephrine

3 different testing for Type 1

1. ImmunoCAP specific IgE blood test

2. Skin Test

3. Immunotherapy

ImmunoCap specific IgE blood test

• Diagnosis based on detection of high levels of IgE against specific allergen within the patient’s blood

Immunotherapy

• administer a series of injections of diluted allergen

• must be repeated every two to three years

Type II ( Cytotoxic Hypersensitivity )

Reults when cells are destroyed ( cytotoxic) by an immune response

Combined activities of complement and antibodies ( IgM and IgG)

Occurs as a component in many other autoimmune diseases

Examples of Type II ( Cytotoxic hypersensitivity)

• Destruction of blood cells following an incompatible blood transfusion

• Destruction of fetal red blood cells in hemolytic disease of the new born

• Drug inducted ( Pencillin reaction)

Blood Transfuion gone wrong ( Type II)

• Donor’s blood group antigens may stimulate the production of antibodies in the recipient that binds to the transfused cells

• Activates the complement system

• Destruction of donated blood cells can occur in hours to days

• Triggers blood clotting within vessels and circulatory failure

• Hemolytic anemia

Hemolytic Disease of the new born ( Type II)

• Rh antigen - common to EBCs of humans and rhesus monkeys

• Rh- woman carrying a Rh+ fetus may be at risk for hemolytic disase

• Usually in 2nd pregnancy: mother has rh- antibodies, but the baby has Rh+ antigens —> Rh- antibodies will diffuse into the placenta of the baby and cause a hemolytic disase

What is adminstered to prevent hemolyrtic disease of the newborn?

RhoGAm

Drug-induced cytotoxic reactions ( Type II cytotoxic hypersensitivity)

• Penicillin and most drugs are too small to trigger an immune reaspone, but they can be antigenic if they bind to larger moleculs trigerringan immune response

Pencillin and Drug-induced cytotoxic reactions example ( Type II)

1.) Penicllin binds to platelets, thus triggering an immune response

2.) Complex triggers the humoral response and recruit the complement to form MAC and lyses the cells

3.) Inhibits the ability of the blood to clot due to a decrease in platelets

4.) Causes agranulocytosis and hemolytic anemia

Type III ( Immune complex-mediated)

• Caused by the formation of immune complex

• Some of the complexes are removed by phagocytes

• Othr complexes will bind to blood vessel walls or be trapped in organs and joints

• Inflammation response will cause tissue damage

• can cause localized or systemic reactions

Type III can cause

Localized and systemic Reactions

Examples of Localized Reactions ( Type III)

1. Hypersensitivity Pneumonitis

2. Glomerulonephritis

Hypersensitivity Pneumonitis ( Localized Reaction)

• inhalation of antigens into lungs stimulates antibody production

• Subsequent inhalation of the same antigen results in the formation of immune complexes and activates comlment system

  • eg. Farmer’s lung from Hay spores, Pigeons’s lung from dust from pigeon feces

Glomerulonephritis ( localized reaction)

• immune complexes in the blood are deposited in glomeruli (kidneys)

• damage to the glomerular cells impedes blood filtration

• causes kidney failure and ultimately, death

Examples of Systemic Reaction of Type III

1. Rheumatoid Arthritis

2. Systemic Lupus

Rheumatoid Arthritus ( systemic reaction)

• immune complexes deposited in the joints result in the release of inflammatory chemicals

• Loss of the cartilage of the joint and bone loss

• Treated with anti-inflammatory drugs

• 0.5-1 percent of the U.S adult population

Systemic Lupus ( systemic reaction

• Antibodies bind to DNA to form immune complex formation

• DNA-antibody complexes are deposited in the skin

• Many other auto-antibodies can also occur

• 16,000 diagnosed yearly in the US ( 90% women)

Symptoms of Systemic Lupus

Rash, light sensitivity, joint pain, bleeding disorder, kindey damage, neurological symptoms

Treatment for Systemic Lupus

Immunosuppresive drugs and Glucocorticoids

Type IV ( Delayed or Cell-Mediated)

• Inflammation 12 to 24 hours after contact with certain antigens

  • Due to antigen, antigen-presenting cells, and T cells

  • Delays reflect the time it takes for macrophages and T cells to migrate and proliferate at the site of the antigen

3 major classes of Type IV

1.) Tuberculin Response

2.) Contact Dematitis ( poison ivy, latex, soaps)

3.) Graft Rejection ( rejection of tissues or organs that have been transplanted

Example of Type IV

Wearing gloves for a day and not getting a reaction —> Wearing gloves the next day and getting a reaction ( specifically latex gloves apply to this situation)

Contact Dermatitis ( Type IV)

• cell-mediated immune response ( T-cells)

• results in an intensely irritating skin rash

• acellular, fluid-filled blisters develop in severe cases

What is contact dermatitis triggered by ?

Chemically modified skin proteins that the body regards as foreign

What is the treatment for contact dermatitis

Glucocorticoids

Tuberculin Response ( Type IV)

An injection of tuberculin beneath the skin causes a reaction in an individual exposed to tuberculosis

Used to diagnose contact with antigens of M. tuberculosis

-24 to 73 hr post exposure

• The Immediate response is generated by memory T cells

Tuberculin Response is used to diagnose contact with antigens of M. tuberculosis, what does a “no response” results yield?

No response means that the individual is not infected or vaccinated

This is also may indicate that the individual may susceptible to micro bacterial tuberculosis

Tuberculin Response is used to diagnose contact with antigens of M. tuberculosis, what does a “red, hard swelling” results yield?

Red, hard swelling indicates that the person has been previously infected or immunized.

If a person has a “red,hard swelling” result but 2x worse on the Tuberculin Response test, what does that indicate?

A overreactive immune response which indicates that the immune system doesn’t remove it self accurately.

It can’t distinguish self from non-self

Graft Rejection ( Type IV)

Rejection of tissues or organs that have been transplanted

Grafts perceived as foreign by a recipient undergo rejection due to differences in MHC I or II molecules

Why is immune response against foreign MHC on graft cells difficult?

They are a difficult because of a high degree of variability

Example of a Graft Rejection

Organ Transplants

What type of drugs stop graft-versus-host disease?

Immunosuppressive drugs

Different causes of Development of Autoimmune disease

• Loss of recognition of self vs. non self

• Occurs more often in elderly

• More common in women than in men

• Genetic and Environmental ( Examples: Diseases)

  • Autoimmunity affecting endocrine organs

    • Type I diabetes mellitus juvenile ( T-cells destroy the insulin-secreting cells of the pancreas)

  • Autoimmunity affecting nervous tissue

    • Multiple sclerosis ( T cells destory the Myelin sheaths that surrounding neurons)

  • Autoimmunity affecting connective tissue

    • Rheumatoid arthritis

  • Autoimmunity affecting blood cells

    • Autoimmune hemolytic anemia

Why are City kids prone to autoimmune diseases instead of rural kids?

They are prone to autoimmune diseases because they are constantly inside, so when they exposed to microbes, their body produces an overresponse

Why are rural kids less prone to autoimmune diseases?

They are less prone to autoimmune diseases because they are constantly exposed to microbes because they are out playing with dirt/hay, so their body builds immunity towards an infection. Thus making them less likely to develop autoimmune diseases

What are the two types of Immunodeficiency diseases?

1.) Primary ( inborn: genetic defects)

2.) Acquired

3 Examples of Primary ( Inborn: genetic defects)

1.) Agammaglobulemia

2.) DiGeorge Syndrome

3.) Severe Combined Immunodefiency (SCID)

Agammaglobulemia

• B-cell deficiency

• Treated with mass doses of immune serum & antibiotics

• IgA deficiency is most common

DiGeorge Syndome

• Due to the lack of thymus gland

• T-cell deficiency

  • Viruses poses a greater threat

How is DiGeorge syndrome treated?

Thymic Stem Cells

Severe Combined Immunodeficiency (SCID)

Deficiency of lack of T and B-cells

Example of Severe Combined Immunodeficiency (SCID)

Bubble Boy

2 types of Acquired Immunodeficiency Diseases

1.) Infectious agents that cause these diseases leprosy, tuberculosis, AIDs

2.) Immunosuppressants that damage T and/or B cells

• Examples: Chemotherapy/Radiation Therapy

Problem in Chemotherapy?

It targets cells that are actively replicating

Examples: Loss of hair, problems are immune system ( WBCs are actively growing)

AIDS ( Acquired Immunodeficiency Syndrome)

caused by Human Immunodeficiency Virus ( HIV)

What are the target cells of AIDS ( Acquired Immunodeficiency Syndrome) ?

T-helpers and macrophages

Death isn’t caused by AIDS itself, what is it caused by?

Infections/ Cancer

AIDS Signs and Symptoms: When do you know if you have AIDS?

Less than 200 CD4+ T cells per cubic millimeter of blood, is when an AIDS diagnosis is given

AIDS Signs and Symptoms ( Picture)

What are the 3 types of transmission of HIV?

1.) Sexual

2.) Blood Products

3.) Mother to Child

Sexual Transmission of HIV ( 0.5 to 1.0% transmission)

• The majority of all HIV have been passed through unprotected sexual relations.

• Transmissions occurs when an infected person comes in contact with the genital, oral, or rectal mucous membranes of a noninfected person

Blood Products (90% transmission)

Blood present with HIV comes in contact with:

• Break in the skin

• Open wounds

• IV Drug Use

• Blood/Plasma transfusions

• Organ transplants

• Tattoos and piercing

There have been no reports of HIV transmission via Mosquitos

Mother to Child ( 30% transmission)

Transmitted to the child during pregnancy, at childbirth, and during breastfeeding at a rate of about 25%

ARV’s and C-sections can reduce HIV transmission by about 1%

Testing for HIV: Window period

The time between a person gets HIV and when a test can accurately detect it is

• It varies from person to person and also depends upon the type of HIV test

• Some tests can detect HIV sooner than others

Testing for HIV ( image)

How many people worldwide live with HIV/AIDs?

36.7 million people are living with HIV/AIDS as of 2021

• 36.7 million were adults and 1.7% million were children (<15 years old)

• 54% women and girls

• 1.5 million new infections in 2021, this is a 23% reduction since 2014

  • 1.3 million adults and 160 k children

How many people living in the United States have HIV/ AIDs?

1.2 million people living with HIV as of 2021

• The number of HIV infections in the U.S. was 34,800 in 2019

HIV incidence declined 8% from 2015 to 2019

About 13% of people don’t know their status

How many people with HIV/ AIDS live in Arizona

18,975 people with HIV as of 2021

272 deaths in 2020

About 696 new infections, 87% were linked to care

How many people with HIV/AIDS live in the Phoenix Metro Area?

13,028 people in Maricopa COunty living with HIV in 2020

About 497 new infections of HIV in Phoenix Metro Area

Worldwide HIV ( picture)

Is an HIV Vaccine/Cure possible?

No, because the virus has the ability to integrate ( provirus) and hide in cells ( reservoir)

• The virus is always creating errors and changing

• Replication of the virus occurs at a rapid rate

• Depletion of immune cells ( Immunodeficiency)

• Immune exhaustion

• Prophylaxis

However, it is important to bring awareness/ education on HIV

The HIV virus is always creating errors and changing

HIV has 1 million genetically variants

AIDS has 100 million genetically variants

10,000 defective virus partials

Why is the HIV virus always creating errors and constantly changing?

Reverse Transcriptase is sloppy and creates variations of HIV virus

Eliminate of T-helper cells = immune exhaustion

Prophylaxis (Pre/Post)

Give antiretroviral treatment and strong drugs to prevent development of virus for 6 months —> Test distributed again in 3 weeks —> Test at 6 weeks —> final test 6 months later ( to ensure if the person has been infected with HIV or not)

Pre-Exposure Prophylaxis (PREP)

• Given to people who are in a relationship the drugs

• The drugs are expensive, and the drugs are not good for you

Causes damage to liver and kindeys