Chapter 4 Flashcards
Hypersensitivity reactions
injurious immune reactions
inappropriate targeting or inadequate control
causes secondary tissue injury
Hypersensitivity reactions are caused by what 3 factors?
Autoimmunity, microbial reactions, environmental reactions
4 Types of Hypersensitivity reactions
ACID Type I: Allergies Type II: Cytotoxic Type III: Immune complex Type IV: Delayed
Reactions to Harmless environmental antigens
Type I Hypersensitivity
Reaction categorized by:
- activation of Helper T cells
- Increased IgE antibody productions
- Mast cell deregulation (histamine)
Type I hypersensitivity
Deregulation of mast cells releases what?
Histamine
Release of histamine causes
vasodilation (edema), increase in mucous secretion, brochoconstriction
True or False. Type I hypersensitivity produces a local reaction
False, it can produce both a local reaction or a severe anaphylaxis
Type I hypersensitivity reactions take how long to manifest?
Minutes
Examples of Type I Hypersensitivity
Hay fever, hives, eczema, asthma, anaphylaxis
Type II Hypersensitivities cause…
opsonization (phagocytosis), inflammation, various non-injurious forms of dysfunction
Examples of Type II Hypersensitivities
ABO incompatibility, Acute Rheumatic Fever, Goodpasture Syndrome, Grave’s Disease
How do you diagnose Type II hypersensitivities?
Coombs’ test
Hypersensitivity reaction characterized by immune complex formation
Type III Hypersensitivity
Characterized by:
- Antigen exposure (IgG production)
- Antigen-antibody complexes go into tissues
- Complement activation causes inflammation
Type III Hypersensitivity
Inflammation of vessel walls, kidneys, and joints
Local complement activation from Type III Hypersensitivity
Fever, Arthritis, Vasculitis, Proteinuria, Lymphadenopathy
Systemic complement activation from type III Hypersensitivity
Examples of Type III Hypersensitivities
Lupus (SLE), Polyarteritis Nodosa (PAN), Reactive Arthritis (Reiter Syndrome), Serum Sickness
Immune complexes
deposited into vessel walls
Immune complexes cause tissue damage including ___
Fibrinoid Necrosis
Amount of time after exposure that Antigen-antibody complexes deposit into tissues?
5-10 days
T-Cell mediated inflammation
AKA “delayed” antibody independent
Type IV Hypersensitivity
Two types of Type IV hypersensitivity
Cytokine-mediated
Direct Cytotoxicity
Cytokine mediated type IV hypersensitivity
Involves CD4+ T cells
activates neutrophils and macrophages
can commonly progress into chronicity
Direct cytotoxicity type IV hypersensitivity
CD8+ T cells attack antigenic cells
Protease –> damage or apoptosis
delayed reaction, possible granuloma formation
e.g. poison ivy, TB, MS, Type 1 diabetes
Failed self-tolerance = self-reactive T & B cells
Autoimmune disorder
Central tolerance
apoptosis in thymus or marrow
Peripheral tolerance
inactivation or apoptosis of T & B cells
Prime targets of autoimmune tissue damage
connective tissue & vessels
Genetic factor associated with autoimmune
HLA alleles
HLA alleles
locus on genes on chromosome 6
regulate immune system by encoding for antigen-presenting proteins
these special T cells are able to present antigens to other cells to stimulate specific antibody production
T cells that have HLA genes
If someone comes back with a positive ANA test, they most likely have _____
Lupus
lupus is most common in what demographic?
African American women of childbearing age
Autoantibody-mediated tissue injury
autoantibodies against various cells (type II)
immune complex deposition (type III)
Lupus causes vessel injury by:
increasing risk of thrombosis with
fibrinoid necrosis
acute necrotizing vasculitis
intimal thickening
Lupus causes renal failure by:
Glomerulonephritis
characterized by proteinuria, hematouria, and urinary red blood cell casts which can pass through the glomerulus if it is damaged
Lupus can only be diagnosed if the patient presents with at least _ out of 11 of the criteria
4
photosensitivity caused by lupus can present as
Malar rash (butterfly) Discoid rash (erythema, raised, scaling) dermoepidermal degeneration caused by IgG deposits
serositis caused by lupus can present as:
pluritis or pericarditis
atypical chest pain
This causes verrucous (wart-like) vegetations on the mitral valve and is a symptom of lupus
Libman-Sacks Endocarditis
Pancytopenia
decrease in red blood cells, white blood cells, and platelets
Risks for developing Lupus
sex hormones (estrogen - hormone replacement therapy), UV light, smoking, infections
most common causes of death in lupus patients are:
renal failure, coronary artery disease, infection due to pancytopenia
Having lupus puts you at an increased risk for this type of cancer
B cell lymphoma
Sjogren Syndrome
CD4+ T cells (Type IV) unknown antigen
damage ductal epithelial cells
Sjogren syndrome can cause damage in these two glands most commonly
Lacrimal and salivary
Lacrimal gland destruction
called keratoconjunctivitis sicca
dry eyes –> inflammation, erosion, ulceration
Salivary gland destrution
called xerostomia
dry mouth –> fissuring, ulcerations
Sjogren syndrome can less commonly affect
vagina, nasopharynx (laryngitis), upper airways (bronchitis), kidneys, CNS, Muscles
Diagnosis for Sjogren syndrome
+ ANA
Isolated Sjogren syndrome
Sicca syndrome
Sjogren can be secondary to what autoimmune disorder most commonly
RA
Age range for women to develop Sjogren
35-45 years
Sjogren increases risk by 40x for this cancer
B cell lymphoma
Systemic Sclerosis (scleroderma)
extensive fibrosis in multiple tissues
vascular destruction of small arteries
Systemic sclerosis most commonly is found in what demographic?
Women age 40-60
Limited Systemic sclerosis
CREST Syndrome
CREST syndrome
Calcinoisis, Raynaud, esophageal dismotility (fibrosis of lower 2/3), sclerodactyly (hard, eroded skin), telangiectasia (spider veins)
diffuse systemic sclerosis
rapid/widespread skin involvement, early visceral involvement, aggressive
Congenital immune deficiency disorders
rare, early onset
X-linked agammaglobulinemia
Bruton disease 6 months male failed B cell maturation bacterial/viral infections: otitis media, pharygitis, sinusitis treatable with IgG infusions
Common variable immunodeficiency
decreased antibody response to infection
normal B cells, no plasma cells
increased GI infections
increased risk for autoimmunity
Isolated IgA deficiency
decrease IgA production in mucous membranes
can be asymptomatic
recurrent URTIs or Diarrhea
very common in caucasians
Hyper-IgM syndrome
High or nomral IgM
Low IgG, IgA, IgE
recurrent pyogenic bacterial infections
70% are x linked (male)
severe combined immunodeficiency
bubble boy
lyphopenia (low T & B cells) & lymphoid atrophy
highly vulnerable to all microbial infections
most common among Native Americans
Examples of secondary immunodeficiency
infection, malnutrition, aging, cancer
Therapy-induced immunosuppression (MC)
Mechanisms of acquired immunodeficiency
suppression of marrow
lymphocyte dysfunction
AIDS
caused by HIV
destroys CD4+ T cells & macrophages via apoptosis or cytotoxicity
screening for HIV in blood transfusions
p24 antigen via ELISA or western blot
HIV resistance gene
CCR5
Stages of AIDS
Acute, Chronic, Crisis
Acute stage AIDS
pyrexia, pharygitis, myalgia, viremia
~3-6 weeks after infection
decreased viremia after 12 weeks
Chronic stage AIDS
2-10 years after infection
MC general lymphadenopathy
steady decline of CD4+ T cells, steady incline of viral load
infections: candidiasis, VZV
Crisis stage AIDS
1mo), diarrhea, weight loss, CNS defects
opportunistic infections & neoplasms
Cachexia
loss of lean muscle mass
common opportunistic neoplasms in crisis stage AIDS
Kaposi sarcoma, Burkitt Lymphoma, Primary CNS lymphoma, Cervical cancer
Ontogenic viruses
Kaposi sarcoma herpes virus, Epstein barr virus, HPV
Amyloidosis is caused by (2)
- many inflammatory or inherited conditions
2. failed phagocytosis
Amyloid
non-branching fibrillar proteins
Test for Amyloidosis
Congo Red Dye = apple-green birefringence
tissue biopsy, serum & urine
Three types of Amyloid protiens
- Amyloid Light (AL)
- Amyloid Associated (AA)
- β-amyloid (Aβ)
Amyloid Light (AL)
B Cell proliferation: plasma cells (multiple myeloma)
immunoglobulin light chains, Bence-Jones protiens
Amyloid-Associated (AA)
Liver: Serum-Associated Amyloid (SAA)
Chronic inflammation: TB, RA, Ankylosing spondylitis, IBD, osteomyelitis
β-Amyloid (Aβ)
amyloid precursor protein: cerebral plaques
alzheimer disease
People with Down Syndrome have a 100% chance of developing ________ by age 40, why?
Alzheimer Disease due to the multiplication of the genes that are in charge of amyloid production
Primary Systemic Amyloidosis
(MC) malignant plasma cells AL proteins (multiple myeloma)
Secondary (reactive) Systemic Amyloidosis
Chronic inflammation
AA proteins
Aging Associated Systemic Amyloidosis
Elderly Patients, Senile Systemic Amyloidosis
Localized Amyloidosis
single organ/tissue
AL proteins
Localized Amyloidosis in tongue
macroglossia
Localized Amyloidosis in kidney
enlarged, pale, firm, decreased function
most common organ associated, very severe
Localized Amyloidosis in Brain
Aβ plaques, Alzheimer Disease
Localized Amyloidosis in Spleen
Splenomegaly, firm, decreased function
Localized Amyloidosis in Liver
massive hepatomegaly, pale, decreased function
Localized Amyloidosis in Heart
Cardiomegaly, decreased function
Restrictive Cardiomyopathy
Localized Amyloidosis in Wrist Ligaments
Carpal tunnel syndrome
Seen in patients on long term dialysis since the Amyloid proteins are not completely filtered out and can accumulate in the body
Amyloidosis is most likely to be lethal if it involves
Kidney or heart
Prognosis of amyloidosis
1-3 years post diagnosis
worse if associated with multiple myeloma