N245: Disorders of Immune Response

Nonspecific immune response

Innate, general reaction of immune system; phagocytosis and inflammation

Specific immune response

Acquired, targeted reaction of immune system; specific antibodies are created

Antigens

Proteins on the surface of cells that identify them

Self antigens

The proteins and carbohydrates present on the surface of every cell of the hosts body--> the immune system ignores these

Non-self antigens

Foreign substances found on the surface of pathogens --> the immune system is triggered and responds to these

Humoral immunity

B cells produce antibodies to deactivate pathogens

Cell mediated immunity

Lymphocytes (T cells) attack non-self cells

IgG

Most common in blood

IgG is the OG

IgM

The first antibody produced in response to antigen

IgMICHIGAN is always #1

IgA

Found in secretions --> tears, saliva, mucus, breast milk

IgE

Antibody produced during allergic reactions

allErgic

IgD

Antigen receptor on B-cells

HLA

Human leukocyte antigen (on the surface of host cells) AKA MHC

MHC

Major histocompatibility complex

What is the major histocompatibility complex/human leukocyte antigen?

The set of genes that controls the expression of self antigens --> each person has a unique MHC

MHC Type I

Codes for the antigens that are presented to cytotoxic T cells (CD8)

MHC Type II

Codes for the antigens that are presented to helper T cells (CD4)

Graft

Part of all of a tissue is removed from one person and placed into another

Allogeneic graft

A transplant in which the donor and recipient are two genetically different individuals of the same species

Syngeneic graft

A transplant in which the donor and recipient are identical twins

Autologous graft

A transplant in which the donor and recipient are the same person

Stem cell transplantation

Stem cells from a matched donor are collected and given to the recipient; the diseased stem cells of the host must first be destroyed by chemotherapy

Hyperacute Transplant Rejection

A transplantation reaction that occurs immediately after transplant --> the host's antibodies attack the graft tissue antigens --> organ failure

Acute Transplant Rejection

A transplantation reaction that occurs within the first few months after transplant --> after immunosuppression has worn off --> the host's T cells attack the graft tissue antigens

Chronic Transplant Rejection

A transplantation reaction that occurs years after transplant

After immunosuppression has worn off --> fibrosis --> loss of function --> organ failure

GVHD

Graft-versus-host disease

What is graft-versus-host disease?

A condition in which the donor T-cells recognize the HLA as foreign --> the donor organ cells attack the body of its new host --> systemic reaction

Acute GVHD

Occurs within the first 100 days after bone marrow transplant

Chronic GVHD

Occurs after 100 days following the bone marrow transplant

Type I Hypersensitivity

An overactive immune response; antigen binds to IgE antibodies on basophils/mast cells

AKA classic allergic reaction

What are allergies?

An abnormal/excessive reaction of a host's immune system to a normally harmless substance

Mechanism of allergy reaction

Exposure to allergen --> development of IgEs --> mast cells activated

Atopic reactions

A reaction that is genetic and is confined to a specific organ

Nonatopic disorders

An allergic reaction that is not genetic or specific to a certain organ

Sensitization Phase (Type 1 Hypersensitivity)

Naive B-cell encounters antigen for the first time --> formation of IgE --> IgE attaches to the receptors on mast cells or basophil

Effect Phase (Type 1 Hypersensitivity)

The "effect" phase --> the sensitized basophils RE-encounter antigen --> release histamine --> allergic reaction

Immediate Response (Type 1 hypersensitivity)

Occurs immediately after re-exposure to the antigen

S+S: Vasodilation, bronchiole smooth muscle constriction, histamine release

Secondary Response (Type 1 hypersensitivity)

Occurs a few hours after re-exposure to the antigen

S+S: More intense inflammation with invasion of eosinophils

Urticaria

Hives

Anaphylaxis

Life threatening allergic reaction characterized by hypotension, airway obstruction and hypoxia

S+S of anaphylaxis

Hives, itching, wheezing, low blood pressure

What causes vasodilation during anaphylaxis?

The release of histamine, acetylcholine, kinins, leukotrienes, and prostaglandins

What causes bronchiole constriction during anaphylaxis?

The release of acetylcholine, kinins, leukotrienes, and prostaglandins

What is the treatment for anaphylaxis?

1. Administer epinephrine --> will cause vasoconstriction and bronchiole dilation

2. Administer oxygen

Type II Hypersensitivity

Antibody mediated cytotoxic reaction

IgG or IgM antibodies bind to antigens on host cells --> triggers cytotoxic response --> targeted cells are destroyed

Myasthenia gravis

A type II hypersensitivity autoimmune disease that affects the neuromuscular junction --> produces weakness of voluntary muscles

Hemolytic anemia

A type II hypersensitivity reaction against RBCs --> anemia caused by the destruction of red blood cells

Type III hypersensitivity reaction

Immune complex mediated reaction

Insoluble antigen-antibody complexes float around in the vessels --> they land in blood vessel wall --> trigger the inflammatory response --> produce damage

Serum sickness

A systemic immune complex disorder

After taking antibiotics --> antigen-antibody complexes circulate in the blood --> systemic injury

Arthus reaction

A localized immune complex reaction

Vaccine/antigen injection --> antibody-antigen complexes form --> pain, redness, swelling, necrosis

Type IV hypersensitivity reaction

Cell mediated, delayed reaction; sensitized helper T cells recognize antigens directly (WITHOUT HELP FROM ANTIBODIES)

Example: TB skin test

Contact dermatitis

A type IV hypersensitivity reaction --> inflammation of the skin caused by contact with certain chemicals or substances (ex: poison ivy)

Autoimmune Disorders

Develop when the immune response mistakenly targets normal body cells and tissues

Autoantibodies

Antibodies produced against self-antigens

Are autoimmune diseases genetic?

Yes, certain HLA types are linked to autoimmune diseases

Are autoimmune diseases more common in men or women?

Women!

Why? --> HLA is coded in the X-chromosome

What are the two types of autoimmune diseases?

Systemic and organ specific

Multiple sclerosis: systemic or organ specific?

Organ specific, CNS

Myasthenia gravis: systemic or organ specific?

Organ specific, muscle

Hashimoto's thyroiditis: systemic or organ specific?

Organ specific, thyroid

Rheumatic fever: systemic or organ specific?

Systemic

Grave's disease: systemic or organ specific?

Organ specific, thyroid

Rheumatoid arthritis: systemic or organ specific?

Systemic

Systemic sclerosis: systemic or organ specific?

Systemic... duh

Autoimmune hemolytic anemia: systemic or organ specific?

Organ specific, blood

Polyarteritis nodosa: systemic or organ specific?

Systemic

Pemphigus vulgaris: systemic or organ specific?

Organ specific, skin

Systemic Lupus Erythematosus

Chronic, inflammatory, autoimmune disease of collagen in skin, joints, and internal organs

S+S of Lupus

Butterfly rash, vasculitis, arthralgia, fatigue, cardiovascular problems

What demographics are most affected by lupus?

Young women (higher incidence in African Americans and Hispanics)

What type of hypersensitivity reaction is lupus?

Type III (antibody-antigen complex)

What is the criteria for diagnosing an autoimmune disorder?

The rheumatologist must determine that the inflammation/immune reactions are not due to an outside source

What are the treatments for autoimmune disorders?

1. Depression of immune system

2. Prevent immune system from producing autoantibodies

3. Treating inflammation

Immunodeficiency

Failure of one or more of the immune system components --> increases the risk for infections and cancer

Primary immunodeficiencies

Genetic or developmental failure of the immune system --> immune system didn't form properly

Secondary immunodeficiencies

Acquired failure of the immune system due to infections, immunosuppressant drugs, radiation/chemo

How does immunodeficiency relate to opportunistic pathogens?

Immunodeficient people are more likely to develop opportunistic infections --> normal flora grow out of control and immune system is not strong enough to regulate them

AIDS

Acquired immunodeficiency syndrome

Pathogenesis of AIDS

HIV destroys helper T cells --> T cells can no longer trigger immune response --> increased risk for secondary infections

HIV-positive individual

Virus is known to be in the body --> however there is no S+S of immunosuppression yet

HIV

Human immunodeficiency virus

Retrovirus (RNA virus)

HIV-1

Major cause of AIDS in US and Europe

HIV-2

Major cause of AIDS in central Africa

How is HIV spread?

Unprotected sex, sharing needles with infected people, contaminated blood, mother to fetus

S+S of AIDS

Fatigue, enlargement of lymph nodes, headache, encephalopathy

How does AIDS relate to cancer?

AIDS increases the risk of all cancers --> specifically Kaposi Sarcoma and Non-Hodgkin lymphoma

How is AIDS treated?

Antiviral drugs that prevent the replication of the HIV virus