Class 3 - Alterations in Immune Response Flashcards
Adaptive / Acquired Immunity
- Third line of defence
Characteristics
- Specificity: pathogen specific response
- Memory: long term protection
- Inducible: by vaccinations
- Self-tolerance: identifies substances that are self and non-self
Humoral B cells
- Produces antibodies
- Bacteria and viruses
Cellular T cells
- Reacts directly with antigen on cell surfaces
- Viruses and cancer cells
- Helper T cells stimulate B cels
Hypersensitivty
- Excessive or inappropriate immune response to an antigen that results in disease or damage to the host
- Includes allergy, autoimmunity and alloimmunity
- May be either antibody mediated B cells or cell mediated T cells
Allergy
- An immune response to an environmental antigen
Autoimmunity
- Disturbances in the immunological tolerance of self antigens
- The body recognizes self-antigens as foreign
- Cause not clearly understood: heredity, gender, infection, and drugs?
- More common in females
Allotimmunity
- Immune reaction to tissues of another individual
- Transplant / graft rejection
Mechanisms of Hypersensitivity
Type I - IgE mediated - Mast cells degranulate Type II - IgM and IgG mediated - Antigen-antibody complex forms on the cell surface Type III - IgM and IgG mediated - Antigen-antibody complexes formed during circulation and is later deposited in different tissues - Antigen and antibody are bound together Type IV - Cell mediated by T cells
- Types I, II and III are mediated by B cells
Type I Allergy
- Against environmental antigens. Takes at least 2 exposures
- IgE mediated.
- IgE binds to receptors on the surface of mast cells. The host is sensitized.
- Subsequent exposure: the allergen binds directly to IgE on the mast cell
1. The mast cell degranulates (dissolves) and releases histamines
2. Histamine binds with H1 receptors that cause symptoms
3. Histamine causes vasodilation and increased permeability of capillaries
Systems most affected:
- skin, respiratory, GI tract
Manifestations of Type I Allergy
- Itching
- Urticarial (hives)
- Conjunctivitis
- Rhinitis (inflammation of the mucous membrane in the nose)
- GI cramps and malabsorption
Anaphylactic Reaction - Type I Allergy
- Genetic predisposition (atopic)
- Life threatening allergic reactions
Manifestations
- Wheezing and difficulty breathing
- Hypotension and tachycardia
- GI - nausea, vomiting, diarrhea
- Systemic, not local
Medication / Reaction
- First line: epinephrine
- Others: corticosteroids, antihistamines. These won’t be helpful in preserving and maintaining ABC’s
Type II Hypersensitivity Reaction
- IgG and IgM mediated
- Tissue specific. Immune response to proteins only on certain cell membranes
- Cells are lysed or phagocytize: thrombocytopenia (low blood platelet count), and transfusion reactions
Hemolytic Disease of the Newborn
Type II Hypersensitivity Reaction
- Occurs with a mom who is Rh- and baby is Rh+
- Begins to occur in the 36-37 week of pregnancy with the first baby, mom is exposed to Rh factors
- Mom produced antibodies to Rh factors
- With subsequent pregnancies, the antibodies cause hemolysis (breakdown of RBC’s) in the fetus
- Mild outcomes: jaundice. To help get rid of jaundice, put under UV “bilirubin lights” to help break down bilirubin faster
- Severe outcomes: multiple miscarriages
Prevention:
- Prevent the formation of antibodies in the first pregnancy
- Uses injection of RH immune globulin (rhogam)
- Used for Rh- moms on their first pregnancy
Identification for at risk babies
- Use fetal Rh testing
- Intrauterine transfusion
- Exchange transfusion after the baby is born to remove most of the hemolyzed RBC’s
Type III Hypersensitivity Reaction
- IgG and IgM mediated
- Antigen-antibody complexes are formed in circulation and are later deposited in vessel walls or extravascular tissues
Systemic Lupus Erythematous (Lupus)
Type III Autoimmunity
- Antigen-antibody complexes form and circulate in plasma then deposited in various tissues and organs
- Skin, muscle and bone, heart, kidneys, lungs, reproductive organs, nerves
Clinical Manifestations
- Arthralgia or arthritis 90%
- Vasculitis and rash 70-80%
- Renal Disease 40-50%
- Hematologic changes 50%
- Cardiovascular disease 30-50%
Diagnostic: must have 4 of 11 cardinal
- Facial rash - butterfly pattern, can also occur on neck and upper shoulders
- Discoid rash (raised, scaling)
- Photosensitivity
- Oral or nasopharyngeal ulcers
- Arthritis
- Inflammation of lung or heart membranes
- Renal disorder
- Neurologic disorder
- Immune disorder
- Presence of antibodies
Type IV Hypersensitivity Reaction
- Does not involve B cells / antigen-antibody
- Involves T cells
- Contact dermatitis, skin test for tuberculosis, poison ivy, acute organ rejection
Acute organ rejection:
- Uses T cells
- T cell response to unmatched HLA antigens
- Occurs within days to months after transplantation
Preventing Organ Rejection
- Tissue typing HLA: human leukocyte antigen matching
- Immunosuppressive techniques:
1. Corticosteroids: suppresses immune response, will slow healing after transplant, but still necessary, higher risk for infections - Cytotoxic drugs: destroy lymphoid tissue
- Anti-lymphoserum: specific to T cells
Immune Deficiencies
- Failure of immune mechanisms of self defence
- Primary (congenital) immunodeficiency
- Secondary acquired immunodeficiency (more common)
- Clinical hallmark is the development of unusual or recurrent, severe infections
- B cell deficiencies (humoral): recurrent and life-threatening bacterial infections
- T cell deficiencies (cellular): viral, fungal, yeast, atypical microorganisms, and cancers
DiGeorge Syndrome
Primary T-lymphocyte Deficiency - Due to a partial lack of thymus CATCH - Cardiac and aortic defects - Abnormal facial features - Thymic aplasia/hypoplasia - Cleft palate - Hypocalcemia/hypoparathyroidism
Secondary (Acquired) Deficiencies
- More common than primary deficiencies
- Normal physiology conditions aging
Complications of other conditions:
- Infancy, aging and pregnancy
- Stress
- Dietary insufficiencies
- Malignancies
- Medical treatments (chemotherapy, corticosteroids)
- Trauma, like burns
- Other diseases (diabetes, SLE)
AIDS
Secondary Acquired Deficiencies
- Caused by HIV
- Depletes the body’s CD4 T-helper cells
- CD4 T cells needed for development of both plasma cells (antibodies) and cytotoxic T cells
- Incidence of HIV infection:
1. In Canada, 20% don’t know they have HIV
2. Globally, 50% don’t know
Diagnosis:
- Opportunistic and severe infections and cancers
- CD4 T-helper cells <200 cells/mm3
HIV
- Effective antiviral therapies have made HIV a chronic disease
Epidemiology:
- Blood born pathogen is transmitted through sexual contact, blood to blood contact, through the placenta, contact with blood at birth, or through breastfeeding
- Increasing faster in women than in men
- Globally, most important mode fo transmission is heterosexual contact
Stages:
- Acute Infection:
- Within 2-4 weeks of infection
- Flu like symptoms
- Antibodies usually appear within 4-7 weeks of exposure
- Can remain sero-negative for 6-14 months - Clinical Latency:
- Asymptomatic
- With treatment, may last several decades - AIDS
- Vulnerable to infections and cancers
Diagnosis:
- Presence of the virus
- Decreased CD4 T-helper cells
General Treatment for Immunodeficiency’s
- Place missing component of the immune system
- Gamma globulin therapy
- Transplantation: bone marrow, thymus transplant (DiGeorge), stem cell
- Gene therapy
Immune Response and Stress
- Direct innervation from ANS to: Thymus, spleen, lymph nodes, lymphoid tissue, bone marrow
- Receptors on immune cells for stress hormones and neurotransmitters
- Increased cortisol, norepinephrine and epinephrine during stress:
1. Cause atrophy of the thymus (fewer T cells). This creates less resistance to infections, cancer, and more chronic sustained stress
2. Increases antibody response (B cells). Causes increased allergies and autoimmune reponses
3. May enhance or suppress inflammatory response
Stress and Disease known links to:
- Coronary disease
- Cancers
- Infections
- Type 2 Diabetes Mellitus
- Asthma
- Psychological disorders: depression, PTSD, Anxiety
- Accelerated aging