Infection and Altered Immunity Chapter 8 Hypersensitivity “Heightened state of immune responsiveness” Excessive reaction to an antigen that results.

Infection and Altered Immunity

Chapter 8

Hypersensitivity

“Heightened state of immune responsiveness” Excessive reaction to an antigen that results in a

pathologic response when re-exposed to the same antigen.

In other words, the immune system has responded in such a way that it is not beneficial to the host.

Examples: allergy, autoimmunity, and alloimmunity Examples: tissue damage, allergies, rashes, breathing

problems, etc.

Hypersensitivity

The different types of hypersensitivity are classified in “Types”. Type I Type II Type III Type IV

Some of the types will overlap in certain diseases.

Type I Hypersensitivity

Mast cell-bound IgE antibody reacts with antigen to release physically active substances (histamine, chemotactic factors, etc.).

Individuals have an inherited tendency to respond to naturally occurring inhaled and ingested allergens with continual production of IgE.

Symptoms: allergic rhinitis, asthma, urticaria, food allergies, anaphylactic shock, diarrhea, and/or vomiting

Type I Hypersensitivity

Type I Hypersensitivity

Type I Hypersensitivity

Type I Hypersensitivity

Treatment Depends on severity

Antihistamines (Benedryl, Sudafed)Bronchodilators (Albuterol)CorticosteroidsEpinephrine

Hyposensitization (Building up of IgG “blocking” antibodies)

Type II Hypersensitivity

“Cytotoxic, Tissue-specific Hypersensitivity”

Free antibody (IgG or IgM) reacts with antigenic determinants on cell membranes Phagocytosis Complement Activation (Which pathway?)

Examples: Immediate drug reactions, autoimmunity, alloimmunity

Type II Hypersensitivity

Types of Type II Hypersensitivity Transfusion Reactions Hemolytic Disease of the Newborn Autoimmune Hemolytic Anemia

Type II Hypersensitivity

Type III Hypersensitivity

Antibody reacts with soluble antigen to form complexes that precipitate in the tissues.

When soluble antigen combines with antibody, complexes precipitate out of the serum and deposit in tissues, bind/activate complement, and cause tissue damage.

Type III Hypersensitivity

Examples: Serum Sickness (Result of passive immunization with

animal serum to treat disease) Autoimmune diseases (Lupus and RA) Glomerulonephritis

Type IV Hypersensitivity

“Delayed Hypersensitivity” Sensitized T cells release lymphokines that recruit

macrophages, neutrophils, produce edema, and enhance the inflammatory response

Antibody and Complement are not directly involved

Symptoms take several hours to develop

Type IV Hypersensitivity

Contact Dermatitis Poison Ivy, Poison Oak, topical anesthetics, antiseptics,

and antibiotics Process takes days but effects last for years (blisters,

peeling, weeping) TB Test and Graft Rejection

Type IV Hypersensitivity

Autoimmunity

Autoimmunity is a breakdown of tolerance in which the body’s immune system begins to recognize self-antigens as foreign.

Theories Exposure to a previously sequestered antigen Development of a neoantigen (tumor antigen) Complications of an infectious disease Alteration of suppressor T cells

Autoimmunity

Previously sequestered antigen Some antigens are hidden from the immune

system and never come into contact with antigen-presenting cells, lymphoid organs, etc.

These sequestered antigens can be released from damaged tissue and enter the lymphatics.

Neoantigen Usually haptens that become immunogenic

after binding to host proteins

Autoimmunity

Antigens from infectious diseases Closely resemble host antigens Form antigen-antibody complexes that initiate the

immune response (hypersensitivity type III)

Alterations of suppressor T cells If a specific cell-line of T suppressor cells is affected, a

tissue specific autoimmune disease could result A general autoimmune reaction could occur if many

cell populations were dysfunctional

Autoimmunity

Autoimmune diseases will commonly follow family lines (HLA antigens)

Common autoimmune diseases Lupus

Photosensitive facial rash Worsens with sun exposure “Lupus” (wolf-like)

Common Laboratory Tests

Fluorescent Antinuclear Antibody Test Animal cells

are fixed to the slide

Rheumatoid Arthritis

Systemic autoimmune disorder affecting the synovial membrane of multiple joints.

Rheumatoid Arthritis Progression

Malaise, fever, weight loss, and joint pain Joint pain lasting longer into the day Progression from small joints to large joints

in a symmetric fashion Muscle spasms leading to joint deformity Nodules (necrotic areas) on the bones

Other Autoimmune Related Diseases

Hashimotos Thyroiditis & Graves Disease (thyroid) Insulin-dependent Diabetes (pancreas) Multiple Sclerosis (myelin sheath) Myasthenia Gravis (muscles in the face) Goodpasture’s Syndrome (kidney) Autoimmune thrombocytopenia Pernicious anemia Ulcerative colitis

Alloimmune Graft Rejection

Alloimmunity occurs when an individual’s immune system reacts against antigen of the tissue of other members of the same species.

Transplants are complicated by an alloimmune response to donor HLA antigens.

Classified as hyperacute, acute, or chronic depending on activation time.

Alloimmune Graft Rejection

Hyperacute Patient has preexisting IgG or IgM antibody to

the tissue. Antibody binds to the tissue and activates an

inflammatory response. This results in the cessation of blood flow to the

graft.

Alloimmune Graft Rejection

Acute The rejection is a cell-mediated immune response

that occurs approximately 2 weeks after the transplant.

Chronic Can occur after months or years of normal

function Signs and Symptoms: slow progressive organ

failure and damage to endothelial cells of the blood vessels

Infectious Agents

Symbiosis – two organisms living together in close association Commensalism – neither organism is harmed Mutualism – association is beneficial to both Parasitism (pathogenicity) – one benefits and the

other is harmed

Infectious Agents

Pathogens cause cellular injury because they circumvent defensive barriers.

Pathogens directly damage cells, interfere with cellular metabolism, and limit the functionality of the cell.

Virulence Ability of a pathogen to cause disease Presence of enzymes, toxins, number, capsules,

intracellular invasion

Modes of Disease Transmission

Contact Transmission Direct (touching, kissing, intercourse, etc.) Indirect (fomites - shared objects) Droplet (distance < 1 meter)

Common Vehicle Transmission Contaminated food, water, blood, vector, etc.

Carrier People who are carrying the pathogen but do not appear

to be ill.

Size Comparison

Bacteria

Unicellular Aerobic Anaerobic Bacteria can live as opportunists,

commensals, and intracellular and extracellular parasites.

Bacterial Shapes

Bacteria are characterized by their shape and size.

Before specific culture information is available, physicians use location and appearance characteristics to begin antibiotic therapy

Bacterial Shapes

Cocci Spherical, non-

motile bacteria Subcategories

Diplo (pair)Strepto (chain)Staphylo (irregular

cluster)Tetra (group of

four)

Bacterial Shapes

Bacilli Rod-shaped bacteria

Spirillia Rod-shaped, rigid, spiral

organisms Spirochetes

Non-rigid, spiral rods Pleomorpic

Cells that do not fit in any of the above categories (no defined shape)

Bacteria

Cell Wall The cell wall is composed of peptidoglycan Peptidoglycan is a large molecular network of

glucose and amino acids. Based on cell wall characteristics, bacteria are

classified as gram (+) or gram (-).

Gram Positive

Gram Negative

Identifying a Specific Bacterium

Gram Stain

Bacterial Toxins

Gram + bacteria produce exotoxins Exotoxins are released from the bacterium during

it’s life cycle.Exotoxins cause symptoms specific to the disease.Examples: Botulism, tetanus, staph food poisoning,

Toxic Shock Syndrome

Gram – bacteria produce endotoxins Endotoxins are released from the cell when it diesProduce generalized symptomsExample: Salmonella food poisoning

Sporulation

Sporulation is the formation of endospores.

When nutrients become scarce and conditions are unfavorable, certain bacteria (Bacillus, Clostridium, etc.) will form endospores.

Endopores help the DNA of the bacteria survive extreme temperatures, radiation, and chemicals.

Viruses

A virus is not technically living. It can not perform any metabolic activity.

A virus must replicate inside a host cell.

The virus provides the RNA and DNA to replicate, and the host cells provide the energy and resources.

Components Nucleic acid, capsid, and an

envelope (optional)

Viruses

Viral replication depends on absorption, penetration, uncoating, replication, assembly, and ability to release new virons.

Effects Cell protein synthesis cessation, release the cell’s own

lysosomal enzymes causing cell death, fusion of host cells, alteration of antigenic properties causing the immune system to attack the host cell, and transformation of host cells into cancerous cells.

Fungi

Fungi are important for the decomposition and recycling of organic material.

Fungi are divided into two groups, yeasts and molds

Examples: Candida Albicans (yeast infection) and Tenia Corporis (ringworm)

Fungi

Fungi release mycotoxins and enzymes that damage connective tissues

Diseased caused by fungi are called mycoses.

Fungi can cause superficial and deep infections

Some fungi are part of the normal body flora and act as opportunists

Ascaris

Ascaris lumbricoides

Pinworms

Life cycle Fecal/oral

Diagnosis: Use of

pinworm paddles

Immunodeficiencies

Immune deficiencies occur because of the impairment of one or more components of the immune or inflammatory response.

Usually manifested by the tendency to develop unusual or recurrent infections.

Can be unsafe to administer immunizing agents. At risk for graft-versus-host disease

White cells in transfused blood can are immunologically active, but the host cells aren’t.

Graft-Versus-Host Disease

Immunodeficiencies

Primary Immune Deficiency (Congenital) Occurs during leukocyte development in the

fetus or embryo. Can affect one or more white cell lines If the T and B cell lines are affect, the patient

will have normal number of the other leukocytes, but they will have low number of T cells, and diminished levels of antibodies.

Immunodeficiencies

Di George Syndrome Lack or partial lack of the thymus Lymphopenia and decreased T cell function

Bruton agammaglobulinemia syndrome Failure of B cell precursors to become mature B

cells.

Immunodeficiencies

Wiskott-Aldrich Syndrome X-linked recessive disorder IgM production is depressed

Selective IgA deficiency Produce other types of antibody but not IgA Can cause chronic intestinal candidiasis and

increased allergen uptake, and more severe allergen responses

Acquired or Secondary Immune Deficiencies

Develop after birth and not related to genetic defects Nutritional deficits

T cell number and function Enzyme cofactor deficiency

Chemotherapeutic agents Corticosteroids Burn victims Emotional stress

HIV

In 1981, a cluster of young men, with no known immune dysfunction, developed opportunistic infections with Pneumocystis carinii.

The only link was that they were homosexual. In 1982, it was discovered in hemophiliacs. The virus HIV-1 was identified in 1983 HIV-2 was discovered in 1986

HIV

HIV is a retrovirus Retroviruses infect cells by binding to a surface

receptor and inserting their RNA into the target cell A viral enzyme reverse transcriptase converts the

RNA to DNA and inserts the viral genetic material into the host cell.

The genetic material can begin replicating immediately or remain latent for a period of time (up to 10 years).

HIV

HIV

HIV is of course spread primarily through contact with blood or body fluids containing the virus. It is also speculated that ulcerations from other sexually transmitted diseases provide opportunities for the virus to enter the host.

Concentrations of HIV High: blood and semen Low: vaginal fluid, tears, sweat, breast milk

Has also been transmitted through infected tissue

HIV

Pathology Latent period may last up to 10 years Virus infects cells utilizing the CD4 antigen receptor The virus replicates in the T4 cell until the cell dies. Other cells have CD4 receptors (monocytes,

macrophages, and some brain and skin cells) The number of T4 cells continues to diminish until the

patient is prone to opportunistic infections.

Testing for HIV

Presentation at time of diagnosis Serologically negative, serologically positive

but asymptomatic, early stages of HIV, or AIDS

Window Period Laboratory Tests

Antigen Tests Antibody Tests (most common)

Testing for HIV

FYI Western Blot

ConfirmationAntigen must

be pure

Testing for HIV

Treatment (antiviral agents) Interferons Azidothymidine (AZT), Dideoxycytidine (ddC),

and Dideoxyinosine (ddI) “HIV Cocktail”Reverse transcriptase and protease inhibitors

New AIDS vaccineHow to test?Genetic variants

Treatment of Immune Deficiencies

Administration of gamma globulin Administration of fresh-frozen plasma

Antibodies and complement

Bone marrow transplants Graft-versus-host, and HLA antigens

Gene therapy