Immuno

Atopic Dermatitis (Eczema)

• Presents with intermittent dry, pruritic, erythematous patches, papules, or vesicles.
• Commonly found on flexural regions like inside the elbows and knees.
• It's a type I hypersensitivity, mediated by IgE.
• Activated through Th2 cells releasing IL-4, 5, 6, 10, and 13.
• IL-4 and IL-13 prompt B cells to become IgE-producing cells.

Morbilliform Drug Eruption

• Classified as a Type IV hypersensitivity reaction to drugs.
• Presents as erythematous macules or papules, resembling measles.
• Occurs 5-21 days after starting the triggering drug.

Thymic Shadow Absence

• Not reliable for distinguishing between Severe Combined Immunodeficiency (SCID) and DiGeorge syndrome.
• Both conditions can exhibit thymic shadow absence.

Severe Combined Immunodeficiency (SCID)

• Can result from an enzyme deficiency, specifically Adenosine Deaminase (ADA) deficiency.

Chediak-Higashi Syndrome

• A primary immunodeficiency stemming from a mutation in the lysosomal trafficking regulator gene (LYST).
• Inherited in an autosomal recessive pattern.
• Presentation includes recurrent bacterial infections and albinism (white hair, pale skin, blue eyes).
• Blood smears show giant granules in neutrophils and platelets.

Complement System Activation

• Classical pathway activation indicated by low C3 and C4 levels, with normal Factor B/D.
• Alternative pathway activation indicated by low Factor B/D levels.

Complement Deficiency

• Deficiency in terminal components C3, C5-9 Increases risk of recurrent Neisseria meningitidis infections in children.

C1 Esterase Inhibitor Deficiency

• C1 esterase inhibitor normally initiates the classical complement pathway
• Deficiency leads to uncontrolled complement activity.
• Increased inflammation and kallikrein production, increasing bradykinin.
• Elevated bradykinin causes blood vessel leakage and angioedema.

Vaccines

• Infection can still occur if it's due to a serotype not included in the vaccine.

Hyper IgE Syndrome (Job Syndrome)

• Characterized by chronic atopic dermatitis, abscesses, and recurrent sinopulmonary infections.
• Caused by impaired Th17 T cells due to issues with JAK-STAT signaling.
• Neutrophils are unable to migrate to infection sites.
• Leads to elevated IgE antibodies as a secondary response, while other antibodies remain normal.

Systemic Lupus Erythematosus (SLE)

• More common in women, presents with arthralgias (bilateral), and pancytopenia (low RBCs, WBCs, platelets).
• Can cause glomerulonephritis, resulting in proteinuria and RBC casts.
• Type III hypersensitivity (immune complex-mediated).
• Similar to serum sickness.
• Rash may be present

SLE Lab Findings

• Thrombocytopenia occurs due to immune thrombocytopenic purpura.
• Elevated CRP, synthesized in the liver, indicates inflammation.

Antiphospholipid Syndrome

• Autoimmune condition linked to SLE.
• Characteristically involves a history of pregnancy loss and embolism.
• Testing reveals a false positive RPR and prolonged PTT.
• Complications include recurrent pregnancy loss.

Transplant Rejection

• Has three stages: hyperacute, acute, and chronic.
• Bronchiolitis obliterans, which is scarring of small airways, occurs in chronic rejection.

Acute Rejection

• Lymphocytes drive the rejection process.
• Mediated by T-cells (CD8 and CD4) and antibodies.
• CD8 cells exert direct cytotoxicity, attacking transplanted tissue, related to Class I MHC.
• CD4 cells recognize Class II MHC on dendritic cells, macrophages and B cells activating cytokine-driven inflammation.
• Antibodies lead to C4d deposition and neutrophil infiltration in capillaries.
• Histologically, there are dense interstitial lymphocytes.

Immunology Principles

Monoclonal Immunoglobulin Fragments

• Used as antibodies without the Fc region for enhanced tissue penetration due to their smaller size.

Flagellin

• It functions as a potent immune system activator for T cell-mediated immune responses.
• Increases antibody production, especially IgG.

IgA Vasculitis (Henoch-Schonlein Purpura)

• Small vessels become damaged due to IgA immune complexes activating the complement system (type III hypersensitivity), attracting neutrophils
• Presents with arthralgias and palpable purplish spots with pain during passive motion, bilaterally.
• Can follow an upper respiratory infection (URI).

Hyper IgM Syndrome

• Immunodeficiency involving both T and B cells.
• Mutation in CD40L prevents T cells from directing B cell differentiation, thus impairing antibody production.
• Lab findings include high IgM, low IgG/IgA/IgE, and absent germinal centers in lymph nodes.

Corticosteroids (Prednisone)

• Inhibits phospholipase A2.
• Increased Neutrophils: Demargination of neutrophils prevents them from attaching to vessel walls and infiltrating tissue, keeps them circulating in the blood.
• Decreased Lymphocytes/monocytes/basophils/eosinophils: Induces apoptosis and reduces proliferation to reduce the immune response.

Antihistamines

• 2nd generation antihistamines are commonly used for allergy relief.
• Examples: Loratadine, fexofenadine, desloratadine.
• Safer for older patients compared to 1st generation antihistamines.

Cromolyn (Cromoglycates)

• Inhibits the release of histamine from mast cells.

Initial Immune Response

• Histamine: An organic compound.
• Prostaglandin-E2: Lipid hormone that causes vasodilation.
• Potent bronchodilator which acts by stimulating adenylyl cyclase increasing amounts of cAMP in smooth muscle cells.
• cAMP then inhibits myosin light chain kinase allowing smooth muscle relaxation.
• Bradykinin: Nine amino acid peptide that promotes vasodilation causing cardinal signs of inflammation.

Thymomas

• Neoplasm of the thymus.
• Widened mediastinum on X-ray.
• Associated with Myasthenia gravis, superior vena cava syndrome, pure red cell aplasia, and Good Syndrome.

Random Fact

• Foreign antigens elicit stronger immune responses compared to self-antigens.

Selective IgA Deficiency

• Cause is unknown, but antibodies against IgA are present.
• Most common primary immunodeficiency.
• Blood transfusions can cause anaphylaxis due to IgA content.

Leukocyte Adhesion Deficiency

• Caused by a lack of CD18 (LFA-1 integrin).
• Impairs migration and chemotaxis of white blood cells.

Respiratory Burst

• NADPH Oxidase → Superoxide Dismutase → Myeloperoxidase is a microbicidal pathway.

Chronic Granulomatous Disease (CGD)

• Primary immunodeficiency disorder.
• Mutation in NADPH oxidase, an enzyme critical for the respiratory burst in neutrophils.
• Leads to recurrent infections, especially in the lungs and skin.
• Recurrent infections by Staph aureus, Burkholderia cepacia, Serratia marcescens, Nocardia, and Aspergillus.

CGD vs. Myeloperoxidase Deficiency

• CGD is associated with chronic infections from catalase-positive organisms.
• Myeloperoxidase deficiency results in recurrent Candida infections.

Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NF-κB) Pathway

1. NF-κB is bound to IκB, keeping it inactive.
2. A trigger binds to a receptor, activating IKK.
3. IKK phosphorylates IκB, marking it for degradation.
4. NF-κB enters the nucleus to activate genes for inflammation, immune activation, and cell survival.

Hypersensitivity Reactions

Type I Hypersensitivity

• Immediate Phase (seconds to minutes): IgE binds to antigen
• Mast cells and basophils release histamine.
• Late Phase (hours): Release of prostaglandins and leukotrienes, and Major Basic Protein synthesized by mast cells which causes tissue damage by eosinophils.

Peripheral Immune Tolerance

• Mechanisms the immune system uses to prevent T and B cells from attacking the body.

Peripheral Immune Tolerance Mechanisms

• Anergy: T/B cells don't receive a second signal.
• Suppression
• Deletion (apoptosis)

Thermal Burn

• Superficial burns lead to redness due to histamine release.
• Deeper burns (partial thickness) create blisters from fluid extravasation due to gaps in damaged venule endothelial cells.

Anaphylaxis Autopsy Findings

• Cerebral edema occurs because anaphylaxis lowers blood pressure, reducing blood flow to the brain, which causes swelling.
• Laryngeal/pharyngeal edema (swelling of the throat).
• Hyperinflated lungs develop from the inability to exhale, leading to air trapping.
• Treatment: Epinephrine counteracts systemic inflammatory effects.
  • Decreases mediator release from mast cells through beta-2 receptor binding.

X-Linked Agammaglobulinemia

• Immunodeficiency with halted B cell maturation, resulting in low levels of all immunoglobulin types.
• Recurrent Giardia infections are common.
• Mutations in the BTK gene disrupt tyrosine kinase function, essential for all B cell development stages.
• Flow cytometry shows normal CD3 levels (normal T cells) but no IgM (no B cells).

Lymphadenopathy

• Formation of multiple germinal centers
• Germinal centers, where B cells undergo affinity maturation.

Congenital vs. Post-Birth Neonatal Infections

• Congenital: Baby has sufficient time to develop IgM antibodies due to gestation.
• Neonate (after birth): Baby is exposed to many new antigens, hindering comprehensive IgM production.

T-Cell Maturation in the Thymus

• Precursors enter as CD4- and CD8-, Positive selection occurs after recognition of MHC-1 leading to proliferation into double positive (CD4 and CD8) cells.
• They differentiate to single positive, and then enter the medulla.

IL-2 / IFN-Gamma Pathway

• Th1 cells secrete IL-2 and IFN-gamma to activate macrophages and cytotoxic T cells.

Interferon (IFN) Deficiency

• More susceptible to mycobacterial and salmonella infections.
• Macrophages cannot form granulomas, causing improper activation.

Natural Killer (NK) Cells

• Kill cells lacking Class I MHC expression.
• CD8 cells NEED the MHC I expression in order to be activated.

Neutrophils

• Chemotaxis is directed by C5a and IL-8.
• LFA-1 for proper endothelium adhesion.
• PECAM-1 aids in transmigration.

Serum Sickness

• Type III hypersensitivity that presents 1-2 weeks after exposure to antitoxins, monoclonal antibodies, or a vaccine.
• Symptoms appear 1-2 weeks after initial improvement.

Allergic Rhinitis

• Seasonal allergies primarily mediated by eosinophils-classified as Type I hypersensitivity.
• Characterized by sneezing, nasal stuffiness, and watery eyes during specific seasons.