Missed Questions

Immunology Integration Type I–IV Hypersensitivity

  • Leukotrienes:

    • Potent late-phase mediators of Type I hypersensitivity.

    • Functions:

    • Causes bronchoconstriction.

    • Responsible for mucus secretion.

  • Asphyxiation:

    • Defined as death from airway obstruction or oxygen loss.

    • Often seen in cases of laryngeal edema during anaphylaxis.

  • Urticaria:

    • Characterized by a superficial skin wheal reaction.

    • Caused by histamine release from mast cells.

  • Fibrosis:

    • Refers to chronic collagen deposition and scarring.

    • Mediated by macrophage-produced transforming growth factor beta (TGF-β).

  • Arthus vs. Serum Sickness:

    • Arthus reaction:

    • Local immune-complex reaction.

    • Typically involves injection of antigens leading to local inflammation due to antibody-antigen complexes.

    • Serum Sickness:

    • Systemic immune-complex disease.

    • Occurs following the administration of antigens, causing a more widespread immune response.

    • Both are classified as Type III hypersensitivity reactions.

  • Coombs Tests:

    • Direct Coombs Test:

    • Detects antibodies that are bound directly to red blood cells (RBCs).

    • Indirect Coombs Test:

    • Identifies free antibodies present in serum that may bind to RBCs upon transfusion.

  • DIC (Disseminated Intravascular Coagulation):

    • Characterized by widespread coagulation leading to simultaneous bleeding and the formation of microthrombi.

    • Often complicates hemolytic processes.

  • Type IV Transplant Rejection:

    • Acute rejection:

    • Primarily mediated by T-cell cytotoxicity, leading to direct damage of transplant tissue.

    • Chronic rejection:

    • Involves cytokine-mediated inflammation, resulting in fibrosis due to T-cell activity.

Autoimmunity & Tolerance

  • Central vs. Peripheral Tolerance:

    • Central Tolerance:

    • Involves the deletion of autoreactive T cells in the thymus and B cells in the bone marrow, primarily regulated by the autoimmune regulator (AIRE) gene.

    • Peripheral Tolerance:

    • Achieved by suppressive mechanisms involving regulatory T cells (Tregs), which express FOXP3.

  • Molecular Mimicry:

    • Describes how infections expose host immune cells to antigens that resemble self-antigens.

    • This leads to activation of autoreactive lymphocytes, potentially resulting in autoimmune diseases.

  • IL-6:

    • A cytokine that drives the production of acute-phase reactants.

    • Plays a significant role in promoting chronic autoimmunity by activating immune pathways.

  • SLE (Systemic Lupus Erythematosus):

    • An immune-complex disease classified as Type III hypersensitivity.

    • Characterized histologically by 'lumpy-bumpy' renal deposits, indicative of immune complex accumulation in the kidneys.

  • ESR (Erythrocyte Sedimentation Rate):

    • A marker of inflammation, reflecting the level of fibrinogen-induced stacking of RBCs.

  • Acute-Phase Reactants:

    • Changes during inflammation:

    • Increased: C-reactive protein (CRP), fibrinogen, ferritin.

    • Decreased: Albumin, transferrin.

  • Genetic Associations:

    • FOXP3 mutation leads to IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked).

    • AIRE mutation results in APS-1 (Autoimmune Polyendocrine Syndrome type 1).

    • HLA-B27 association with Ankylosing Spondylitis.

Complement & Immunodeficiencies

  • Complement Deficiency:

    • Deficiencies in complement proteins lead to various clinical syndromes:

    • C1q/C2/C4 deficiency: Associated with SLE-like symptoms.

    • C3 deficiency: Increases susceptibility to encapsulated bacteria.

    • C5–9 deficiency: Predisposes individuals to infections with Neisseria species.

  • C1 Esterase Inhibitor Deficiency:

    • Causes hereditary angioedema due to excessive bradykinin accumulation.

  • CGD (Chronic Granulomatous Disease):

    • Resulting from a defect in NADPH oxidase, leading to susceptibility to catalase-positive organisms.

    • Notable laboratory test: NBT (Nitroblue Tetrazolium) test is negative.

  • Wiskott-Aldrich Syndrome:

    • Characterized by a triad of symptoms: eczema, thrombocytopenia, and recurrent infections.

  • Ataxia-Telangiectasia:

    • Caused by mutations in the ATM gene.

    • Leads to failure in DNA repair and elevated alpha-fetoprotein (AFP) levels.

Transfusion & Hematology

  • Hydrops Fetalis:

    • Describes fetal anasarca caused by Rh-mediated hemolytic disease, classified as Type II hypersensitivity.

  • RhoGAM:

    • Administered maternal anti-D IgG that effectively clears fetal RBCs from maternal circulation before sensitization occurs.

  • Agglutination:

    • The process where antibodies cross-link cell-bound antigens, resulting in visible clumping of cells.

  • Bombay Phenotype:

    • Individuals lack the H antigen precursor and are only compatible with blood from other Bombay phenotype donors.

  • Recipient Serum:

    • Refers to patient plasma obtained during crossmatch testing, which is evaluated for the presence of antibodies.

  • TRALI (Transfusion-Related Acute Lung Injury):

    • Caused by donor anti-HLA or anti-HNA antibodies that activate neutrophils, resulting in lung capillary leak and respiratory distress.

  • Febrile Non-Hemolytic Reaction:

    • Caused by the host's antibodies targeting donor HLA proteins; symptoms include fever without evidence of hemolysis.

  • Acute Hemolytic Reaction:

    • Occurs due to ABO blood type mismatch, prompted by IgM antibodies and activation of the complement cascade leading to intravascular hemolysis.

  • Delayed Hemolytic Reaction:

    • Triggered by an antibody response (usually IgG) to minor RBC antigens, leading to extravascular hemolysis at a later time post-transfusion.

  • Allergic/Anaphylactic Transfusion Reaction:

    • Legitimized by IgE or anti-IgA mediated responses, potentially resulting in severe allergic reactions to transfused blood products.

Infection & Inflammation

  • Purulent/Pyogenic Inflammation:

    • Defined by the presence of neutrophil-rich exudate, typically seen in infections by bacteria such as Staphylococcus and Streptococcus.

  • Granulomatous Inflammation:

    • Characterized by a Th1 cellular response with macrophage activation; is notably absent in T-cell deficiency states.

  • Stages of Infection:

    • Sequence of infectious process:

    • Entry → Colonization → Invasion → Evasion → Damage → Shedding.

  • Tissue Damage:

    • Frequently mediated by the immune system through the action of cytokines and the complement system.

  • Extracellular vs. Intracellular Pathogens:

    • Extracellular pathogens are eliminated primarily via antibodies and the complement system;

    • Intracellular pathogens require intervention by T-cells for effective clearance.

Other Concepts

  • Thrombosis vs. Ischemia:

    • Thrombosis: Refers to the formation of a blood clot within a vessel.

    • Ischemia: Describes a condition of oxygen deprivation in tissues due to restricted blood flow.

  • FOXP3 & AIRE:

    • These genes are crucial for tolerance mechanisms rather than hypersensitivity; their failure can lead to autoimmunity.

  • Myasthenia Gravis (MG) vs. Multiple Sclerosis (MS):

    • MG: Due to antibodies against acetylcholine receptors (Type II hypersensitivity).

    • MS: Characterized by T-cell-mediated demyelination processes (Type IV hypersensitivity).

  • MBP & IgG in MS:

    • Myelin basic protein (MBP) acts as an antigen in MS;

    • Notable findings include the presence of intrathecal IgG bands in cerebrospinal fluid (CSF) of affected individuals.