Name the five major components of the innate immune system.
- Epithelial barriers
- Phayocytic cells (neutrophils, macrophages)
- Dendritic cells
- NK cells
- Plasma proteins (complement)
What are the four types of hypersensitivity reactions? Briefly describe each one.
Type 1 (allergic hypersensitivity - IgE) Type 2 (abnormal Abs) Type 3 (immune complex) Type 4 (delayed, T cell mediated)
Allergens activate TH2 CD4+ T cells, which secrete cytokines ______ and ______, activating plasma cells to secrete Ig__ and IgG4.
IL-4 and IL-13 activates plasma cells to make IgE and IgG4
Mast cells become _______ by binding Fc portions of IgE to their surface receptors.
sensitized
Describe the two phases of a Type 1 hypersensitivity reaction.
Initial rapid response (from 5 min to 60 min after exposure) results in vasodilation, increased vascular permeability, and smooth muscle spasm.
Late phase (delayed - from 2-8 hours after exposure) involves inflammation and tissue destruction with infiltration of neutrophils, eosinophils, and T cells with secretion of lipid mediators and cytokines.
Systemic anaphylaxis is an example of Type __ hypersensitivity that involves pruritus (itching), urticaria (hives), erythema, bronchoconstriction followed by laryngeal edema that may escalate to laryngeal obstruction and hypotensive shock. Can be fatal in minutes to hours.
Type 1 hypersensitivity
What causes Type 2 hypersensitivity reactions? Name the three mechanisms of tissue destruction.
Abnormal antibodies that bind to cellular antigens, causing one of three things:
- Opsonization and phagocytosis
- Inflammation
- Antibody-mediated cellular dysfunction
What causes inflammation during a Type 2 hypersensitivity reaction?
Complement activation products recruits polymorphs, monocytes, and phagocytic cells.
Myasthenia gravis and Grave’s disease are examples of what type of destructive mechanism of Type 2 hypersensitivity reactions?
Ab-mediated cellular dysfunction.
How do Type 3 hypersensitivity reactions cause inflammation?
Antibody-antigen complexes get trapped in small vessels of the body, bind complement, and cause vessel wall damage.
Which antibody subtypes are involved in Type 3 hypersensitivity reactions?
IgG and IgM
Name five symptoms of a Type 3 hypersensitivity reaction.
- Fever
- Urticaria
- Arthralgias (joint pain)
- Lymph node enlargement
- Proteinuria
What is an Arthus reaction?
A local immune complex (Type 3) reaction. Localized reaction with tissue vasculitis and necrosis that peaks at 4-10 hours after Ag exposure.
What causes Type 4 hypersensitivity reactions?
Overreaction of T cells
Type 1 diabetes mellitus, MS, RA, peripheral neuropathies like Guillan-Barre syndrome, IBD, and contact dermatitis are all examples of Type __ hypersensitivity.
4
Which T cell subtype is involved in cytokine secretion during a delayed-type hypersensitivity reaction?
Th1 CD4+ cells
Granuloma formation during a delayed hypersensitivity reaction occurs due to a ________ antigen. In this process, initial perivascular CD4+ T cells are progressively replaced by ________ over 2-3 weeks, which then turn into epitheloid cells and may later turn into multinucleated giant cells.
occurs due to a persistent antigen. T cells replaced by macrophages that can turn into epitheloid, then multinucleated giant cells
T-cell mediated cytotoxicity is a subtype of Type ___ hypersensitivity that involves the generation of ____ T cells in response to viral infections, tumor cells, or allografts.
subtype of Type 4, generates CD8+ killer T cells
How do CD8+ T cells inflict injury during T cell-mediated cytotoxicity?
Direct killing by perforin-granzyme or Fas-FasL
Are autoimmune diseases more common in women than in men?
Yeah
How do “susceptibility genes” relate to autoimmune diseases?
The susceptibility genes predispose people to generating self-reactive T cells involved in autoimmune diseases.
Name four non-organ specific autoimmune diseases.
- Systemic Lupus Erythematosus
- Progressive systemic sclerosis
- Polymyotosis and dermatomyotosis
- Rheumatoid disease
Name six organ-specific autoimmune diseases.
- Vitiligo - anti-tyrosine Abs
- Grave’s
- Hashimoto disease - anti-thyroid Abs
- Addison’s disease - anti-adrenal cortex Abs
- Type 1 DM - anti-islet cell Abs
- Myasthenia gravis
What plasma components are involved in Systemic Lupus Erythematosus?
Immune complexes and antibodies
Which population is most heavily affected by Systemic Lupus Erythematosus?
young women
Name the disease: Antinuclear antibodies deposit in many tissues, causing pleural effusions, nephritis, arthritis, Reynaud’s phenomenon (numb fingertips), and butterfly rash (in 50% of patients).
Systemic Lupus Erythematosus
At what age do primary immunodeficiency syndromes manifest?
6 months to 2 years when maternal Abs are lost.
What causes secondary immunodeficiency?
Infection, malnutrition, aging, immunosuppression, irradiation, chemotherapy, or autoimmunity.
Bruton’s X-linked Agammaglobulinemia is characterized by deficiency of __ cell maturation which predisposes the patient to recurrent _______ infections.
No B cell maturation predisposes patients to recurrent bacterial infections.
What is the genetic defect in Bruton’s X-linked Agammaglobulinemia?
BTK (tyrosine kinase associated with the pre-B cell receptor) on the X chromosome. Results in inability to form Ig light chains.
What is DiGeorge Syndrome?
Absence or underdevelopment of the thymus and parathyroid –> no T cells.
What causes hypocalcemic tetany in patients with DiGeorge Syndrome?
No PTH –> abnormal calcium metabolism causing involuntary muscle contraction.
What type of infections are patients with DiGeorge Syndrome susceptible to?
Viral, fungal, protozoal, and intracellular bacterial infections.
What is SCID? Name two specific mutations that cause it.
Severe combined immunodeficiency - lack of B and T cells. ADA and IL-2 receptor gene mutations are two examples.
Transplantation often triggers T and B cell reactions that target ____ molecules on the graft cells.
MHC
Name the three types of rejection.
- Hyperacute
- Acute
- Chronic
What causes hyperacute rejection and how fast does it happen?
Happens in minutes to hours due to pre-formed, circulating antibodies
Describe the morphological changes that occur during hyperacute graft rejection.
Abs attack graft endothelial cells causing acute fibrinoid necrosis with lumen accumulation of fibrin and cellular debris.
Which pharyngeal pouches develop into the thymus and parathyroid?
3rd and 4th
What is responsible for acute graft rejection? How long does it take to occur? What are the morphological changes?
Due to T cells, but some Abs can be involved. Happens 10-14 days after transplantation. Morphological changes: interstitial mononuclear cell infiltration with mild edema and parenchymal injury. Ab response can cause obliterative vasculitis.
How long does chronic graft rejection take? What are the morphological changes?
Months to years. Vascular changes, interstitial obliterative fibrosis
What is primarily responsible for chronic rejection?
T cells and cytokines
Is vascular obliteration more or less severe in chronic rejection (vs acute rejection)
less severe in chronic
Graft vs. host disease can happen after _____ ______ transplantation.
Bone marrow
What is amyloidosis?
Aggregation of amyloid in tissues.
What is amyloid?
A heterogenous group of fibrillar proteins that accumulate within tissues and organs due to excess synthesis or resistance to descruction.
How does amyloid stain with Congo Red stain in cross-polarizing light?
Apple green - that is how it is differentiated from other stuff that stains red.
Are amyloid proteins deposited intra, or extracellularly?
extracellularly
Can accumulation of amyloid produce pressure atrophy of adjacent parenchyma?
Yeah
What are the four forms of amyloidosis?
Primary, secondary, familial, Alzheimer’s
What is primary amyloidosis?
Typically found in multiple myeloma, amyloid is made up of Ig light chains (AL protein). Deposits found in kidneys, blood vessels, heart.
What is secondary amyloidosis?
Amyloid derived from serum amyloid-associated protein (AA protein) produced by the liver. Deposits found in kidneys, liver, spleen.
What is familial amyloidosis?
Amyloid made up of abnormal transthyretin. Deposits in nerves.
Which amyloid is involved in Alzheimer’s? Where do they deposit?
Beta amyloid, deposits in neurons.