Pathology & Immunology Rapid Review (USMLE Step 1)

Flashcards cover core concepts in pathology and immunology from the provided lecture notes, focusing on inflammation, immune defects, transplant/transfusion immunology, vaccines, cancer biology, HIV, and key diagnostic concepts.

What activates Toll-like receptors (TLRs) on innate immune cells, and what is the downstream effect?

Pathogen-associated molecular patterns (PAMPs) activate TLRs, triggering NF-kB signaling and upregulation of immune response genes (e.g., CD14 recognizes LPS).

Name the three pathways of complement activation.

Classical pathway (C1 binding IgG/IgM), Alternative pathway, and Lectin pathway.

Which molecules act as anaphylatoxins and what are their effects?

C3a and C5a induce mast cell degranulation and neutrophil chemotaxis; C3b opsonizes pathogens; C5-9 form the MAC to lyse microbes.

Dystrophic calcification vs metastatic calcification: what distinguishes them?

Dystrophic calcification occurs in dead/diseased tissue with normal serum Ca; metastatic calcification occurs in normal tissues due to systemic Ca dysregulation (hypercalcemia).

In dialysis-associated amyloidosis, which protein deposits extracellularly?

β2-microglobulin (beta-2 microglobulin amyloid).

What is the mechanism of free radical injury and how does reperfusion contribute?

Free radicals (ROS) cause lipid, protein, and DNA damage; antioxidants normally neutralize them. Reperfusion causes a burst of ROS, worsening injury.

What is the mechanism and clinical implication of the oxidative burst in phagocytes?

NADPH oxidase generates ROS; impaired in Chronic Granulomatous Disease (CGD). Catalase-positive organisms can worsen ROS deficiency because their own H2O2 is degraded.

List the six steps of neutrophil arrival and function in acute inflammation.

Margination → Rolling → Adhesion → Transmigration → Phagocytosis → Killing.

What is Leukocyte Adhesion Deficiency (LAD) and its genetic basis?

Autosomal recessive defect in CD18 integrin (β2 integrin) leading to impaired leukocyte migration; no pus and delayed umbilical cord separation.

What is Chediak-Higashi syndrome?

LYST gene defect causing defective lysosomal trafficking; giant azurophilic granules; neuropathy, albinism, recurrent infections.

What are the Cardinal signs of inflammation?

Rubor (redness), Calor (heat), Tumor (swelling), Dolor (pain), Functio Laesa (loss of function).

How does IL-1 cause fever?

IL-1 induces COX to produce PGE2, which raises the hypothalamic set point, causing fever.

Which cells are the primary antigen-presenting cells (APCs)?

Dendritic cells, macrophages, and B cells.

Compare MHC class I and II in terms of expression and antigen source.

MHC I: all nucleated cells; endogenous antigens; presents to CD8+ T cells. MHC II: APCs only; exogenous antigens; presents to CD4+ T cells.

What is the first antibody produced in a primary immune response?

IgM.

Which antibody class crosses the placenta?

IgG.

Which antibody is a dimer that protects mucosal surfaces and is present in breast milk?

IgA.

Which immunoglobulin is most involved in allergic responses and eosinophil activation?

IgE.

What is a common consequence of IgA deficiency?

Increased susceptibility to mucosal infections (GI/respiratory), autoimmune disease (celiac), and Giardia infections.

What is the role of the immune mediator C3b?

C3b opsonizes pathogens to enhance phagocytosis.

What happens in Type I hypersensitivity and what is a common treatment?

IgE-mediated mast cell degranulation causing immediate reactions; epinephrine is first-line treatment in anaphylaxis.

Name examples of Type II hypersensitivity.

Antibody-mediated cytotoxic reactions (e.g., autoimmune hemolytic anemia, Goodpasture syndrome).

Name examples of Type III hypersensitivity.

Immune complex-mediated reactions (e.g., Arthus reaction, serum sickness).

Name examples of Type IV hypersensitivity.

Delayed-type hypersensitivity (e.g., contact dermatitis, tuberculin skin test).

What is the role of APCs in CD4+ T-cell activation?

APCs present antigen on MHC II; co-stimulation via B7-CD28 is required; activated CD4+ T cells secrete cytokines and help other immune cells.

What is central tolerance in the thymus and where does it occur?

Positive selection in the cortex (double-positive CD4+/CD8+ thymocytes); Negative selection in the medulla (apoptosis of high-affinity self-reactive cells; AIRE mutation leads to autoimmunity).

What thymic abnormality is classic in DiGeorge syndrome?

Thymic aplasia with absence of thymus (sail sign on imaging) due to 3rd/4th pharyngeal pouch defects; T-cell deficiency.

From which pharyngeal pouch does the thymus arise?

The third pharyngeal pouch (thymus and inferior parathyroids).

Describe the spleen’s white pulp, red pulp, and marginal zone.

White pulp contains PALS (T cells) and B-cell zones; red pulp contains RBCs and macrophages; marginal zone contains specialized B and T cell zones and APCs.

Name the encapsulated organisms highlighted as requiring splenic clearance (mnemonic).

Yes Some Killer Bacteria Have Pretty Nice Capsule: Yersinia pestis, Streptococcus pneumoniae, Klebsiella pneumoniae, Bacillus anthracis, Haemophilus influenzae, Pseudomonas aeruginosa, Neisseria meningitidis, Cryptococcus neoformans.

What genetic defect causes Bruton's agammaglobulinemia and its consequence?

BTK mutation leading to absent B cells and very low immunoglobulins; X-linked; recurrent bacterial infections after 6 months.

What is Common Variable Immunodeficiency (CVID) and when is it usually diagnosed?

A humoral immunodeficiency with decreased immunoglobulins; usually diagnosed after puberty, with variable antibody responses.

Which immunoglobulin deficiency is most commonly associated with mucosal infections and Giardia?

IgA deficiency.

What is the role of Th1 cells and IFN-γ in macrophage activation?

Th1 cells secrete IFN-γ which activates macrophages to enhance phagocytosis and intracellular killing.

What HIV proteins are involved in attachment, fusion, and entry into host cells?

Gp120 mediates attachment to CD4; gp41 mediates fusion/entry; CCR5 or CXCR4 act as coreceptors.

What are the major classes of antiretroviral drugs?

NRTIs, NNRTIs, Protease inhibitors, Integrase inhibitors, Entry/fusion inhibitors (CCR5 antagonists and gp41 inhibitors).

Which HIV drug is a nucleotide reverse transcriptase inhibitor and often dosed once daily?

Tenofovir (the nucleotide NRTI).

What is the difference between hyperacute, acute, and chronic transplant rejection?

Hyperacute: minutes to hours due to preformed antibodies; Acute cellular: weeks due to T-cell–mediated; Acute humoral: weeks due to antibody-mediated rejection; Chronic: months to years due to chronic vascular injury and fibrosis.

What is Graft-Vs-Host Disease (GVHD) and when does it occur?

Donor T cells attack recipient tissues; common after allogeneic bone marrow or stem cell transplant.

What is a TRALI versus TACO transfusion reaction?

TRALI: donor antibodies activate recipient neutrophils → pulmonary edema; TACO: transfusion-associated circulatory overload (volume overload).

Which vaccine type is most associated with a higher risk of intussusception according to these notes?

Inactivated vaccines (as per the provided material’s memory cue).

What is Warburg effect in cancer metabolism?

Cancer cells preferentially use glycolysis for energy production even in the presence of oxygen (aerobic glycolysis).

Describe the TNM system for tumor staging.

T: tumor size/extent; N: regional lymph node involvement; M: distant metastasis.

What is the general difference between sarcomas and carcinomas in terms of origin?

Sarcomas originate from mesenchymal (connective) tissue; carcinomas originate from epithelial tissue.

What is the function of TP53 in tumor suppression and what syndrome is associated with TP53 mutations?

TP53 encodes p53; Li-Fraumeni syndrome (SBLA: Sarcoma, Breast, Leukemia, Adrenal cortex tumors).

Which growth factor receptor is commonly amplified in breast cancer and targeted by a monoclonal antibody?

HER-2 (ErbB2); targeted by trastuzumab.

What is the significance of the RB gene in cancer biology?

RB inhibits E2F and blocks G1 to S progression; RB mutations predispose to retinoblastoma and osteosarcoma (SBLA).

Which immunohistochemical markers help identify tissue of origin in tumors?

PSA for prostate; ER for breast; cytokeratins for epithelium; GFAP for glial; S-100 for melanoma; chromogranin for neuroendocrine.

What is the role of VEGF in cancer?

Promotes angiogenesis to supply tumors with blood and nutrients.

What matters most prognostically in solid tumors: staging or grading?

Staging (TNM) generally provides the most prognostic information; grading reflects histologic differentiation.

Which embryologic structure is implicated in DiGeorge syndrome (thymic/apparatus defects) with the sail sign on imaging?

Defects involving the third and fourth pharyngeal pouches; absent thymus and parathyroids.

Which component of the spleen contains lymphocytes and is involved in immune surveillance of encapsulated organisms?

White pulp (PALS for T cells and follicles for B cells); marginal zone surrounds white pulp.

Which organism is most classically associated with caseating granulomas in tuberculosis and fungal infections?

Tuberculosis (caseating granulomas) and certain fungal infections like histoplasmosis.

What is the role of AIRE in thymic education and what happens when it is mutated?

AIRE drives negative selection of self-reactive T cells in medulla; mutation leads to autoimmune polyendocrine syndrome (APS-1).

Which type of immune response is primarily responsible for immediate hypersensitivity reactions, and which clinical treatment is life-saving in anaphylaxis?

Type I hypersensitivity; epinephrine is the life-saving treatment.

What is the primary mechanism of action of posology for TNF inhibitors (e.g., infliximab, adalimumab) and a major precaution?

They block TNF-α signaling; risk of TB reactivation and other infections; screen for latent TB before therapy.

Which test is used to detect central tolerization defects in the thymus (AIRE-related) and what is a classic associated syndrome?

AIRE-related central tolerance defects; autoimmune polyendocrine syndrome type 1 (APS-1).

What antibody isotype is primarily involved in neutralization and opsonization and is associated with complement activation when it is IgM or IgG?

IgG and IgM mediate neutralization and activate complement; IgM is particularly effective at complement activation.

Which stage of HIV disease is defined by the CD4 count falling below 200/mm3 or an AIDS-defining condition?

Acquired immunodeficiency syndrome (AIDS) stage.