Immunological disorders Flashcards
Types of Immune System Disorders:
Hypersensitivity
Autoimmunity
Immunodeficiency
Hypersensitivity (Allergy):
An abnormal immune response to a relatively minor or harmless immune challenge.
Type I (Anaphylactic) Reactions (minutes) Type II (Cytotoxic) Reactions (hours) Type III (Immune Complex) Reactions (hours) Type IV (Cell-Mediated) Reactions (days)
Type I (Anaphylactic) Reactions…
Occur within minutes of exposure to antigen.
Antigens combine with IgE antibodies.
IgE binds to IgE-receptor on mast cells and basophils, causing them to undergo degranulation and release several mediators:
Histamine - Dilates and increases permeability of blood vessels (swelling and redness), increases mucus secretion (runny nose), smooth muscle contraction (bronchi).
Prostaglandins - Contraction of smooth muscle of respiratory system and increased mucus secretion.
Anaphylactic shock - Massive drop in blood pressure as lots of blood and cells move into the tissues. Can be fatal in minutes.
Allergy examples - food allergies (nuts, milk, shellfish, gluten, meat, eggs, fruit), medications, insect bites and environmental allergens (pollen, dust, animal hair, metals, etc.)
Type II (Cytotoxic) Reactions…
Involve activation of complement by IgG or IgM binding to an antigenic cell.
Antigenic cell is lysed.
Transfusion reactions…
ABO Blood group system - Type O is universal donor. Incompatible donor cells are lysed as they enter bloodstream.
Rh Blood Group System - 85% of population is Rh positive. Those who are Rh negative can be sensitized to destroy Rh positive blood cells.
Haemolytic disease of new-born - Foetal cells are destroyed by maternal anti-Rh antibodies that cross the placenta.
Type III (Immune Complex) Reactions…
Involve reactions against soluble antigens circulating in serum.
Usually involve IgA antibodies.
Antibody-Antigen immune complexes are deposited in organs, activate complement, and cause inflammatory damage.
Can lead to autoimmune diseases - Systemic lupus erythematosus (SLE), Rheumatoid arthritis.
Type IV (Cell-Mediated) Reactions…
Involve reactions by T memory cells.
- First contact sensitizes person.
- Subsequent contacts elicit a reaction.
Reactions are delayed by one or more days (delayed type hypersensitivity, DTH). Delay is due to migration of macrophages and T cells to site of foreign antigens.
Reactions are frequently displayed on the skin: itching, redness, swelling, pain. Examples include the tuberculosis skin test, poison ivy and metals e.g. from jewellery.
Autoimmune Diseases:
Clinical disorder produced by an immune response to a normal tissue component of a patient’s body.
Loss of self-tolerance leads to production of antibodies or T cells that react against one’s own antigens.
Can be mediated by antibodies or cells.
Two categories of autoimmune disorders…
Organ specific
Systemic
Organ specific autoimmune disorders
Grave’s Disease - Antibodies attach to receptors on thyroid gland and stimulate production of TH; Symptoms: Goiter (enlarged thyroid) and bulging eyes.
Hemolytic anemia - Antibodies to RBC in liver.
Insulin-dependent diabetes mellitus – T-cells kill insulin-producing beta cells in pancreas resulting in increased blood glucose.
Spontaneous infertility - Auto-antibodies to sperm.
Glomerulonephritis - Immune complexes deposition and inflammatory damage in kidneys.
Systemic autoimmune disorders
Rheumatic arthritis Crohn’s disease Ulcerative colitis Systemic lupus erythematosus (SLE) Multiple sclerosis
Rheumatic arthritis
Cause unknown, but microbial mimicry may be involved. Microbial infections may activate the immune system and lead to a loss of immune tolerance which could allow expansion of high avidity cross-reactive B‐ or T‐cell clones which through molecular mimicry may lead to autoimmune disease.
IgM autoantibodies (rheumatoid factors) against IgG form complexes in joint, leading to inflammation and cartilage damage. Often causes finger and joint deformities.
No cure. Symptoms treated with anti-inflammatory (aspirin) and immunosuppressive drugs. Physical therapy keeps joints movable. Surgical replacement of joints may be necessary.
Systemic lupus erythematosus (SLE)
Name derived from red skin rash on face.
Autoantibodies react against DNA.
When cells die, immune complexes form and deposit under skin, joints, in kidneys, blood vessels, and central nervous system.
No cure. Symptoms treated with anti-inflammatory and immunosuppressive drugs.
Multiple sclerosis
Auto-reactive T cells attack myelin (which serves to insulate the nerve fibers).
Neurologic dysfunctions, from mild (numbness of limbs) to severe (paralysis).
Strong genetic component.
Infection with certain viruses may predispose MS.
Immunodeficiency:
A failing of one or more of the body’s defensive mechanisms resulting in morbidity or mortality.
Any part of the immune system can be deficient cells, proteins, signalling mechanisms.
The body is susceptible to infection by organisms that meet with little or no resistance.
Immunodeficiency may be Primary or Secondary…
PRIMARY - Certain components of the immune system are not produced due to genetic or other factors.
SECONDARY - Immune system suppressed due to infection, leukaemia or lymphoma, myeloma, extremes of age, certain drug therapies (immunosuppression).
Clinical Features Associated with Immunodeficiency…
Feature frequency present and highly suspicious. Chronic infection Recurrent infection (more than expected) Unusual microbial agents Incomplete clearing of infection Incomplete response to treatment
Classification of Primary Immunodeficiencies…
Antibody deficiencies
Cellular deficiencies
Phagocytic disorders
Complement deficiencies
