Immunology: Innate & Adaptive Immunity, Cell Types, and Clinical Disorders

Comprehensive practice flashcards covering innate versus adaptive immunity, immune cell morphology and functions, cytokine signaling, complement activation pathways, lymphoid tissue histology, antigen processing, and inherited primary immunodeficiencies.

Where do hematopoietic stem cells originate, and what two main lineages do they give rise to?

Hematopoietic stem cells originate in the bone marrow and give rise to the myeloid lineage and the lymphoid lineage.

Which innate immune cell originates from the lymphoid lineage rather than the myeloid lineage?

Natural killer ($\text{NK}$) cells (as well as innate lymphoid cells, $\text{ILCs}$).

How do the innate and adaptive immune systems differ in terms of response speed, specificity, memory, and developmental genetics?

The innate immune system has a fast response speed, broad/nonspecific recognition, low/no memory, and is germline encoded. The adaptive immune system has a slow initial response speed, high antigen specificity, long-lasting immunologic memory, and develops via somatic recombination during lymphocyte development.

What downstream signaling sequence occurs following ligand binding to Toll-like receptors ($\text{TLRs}$)?

$\text{TLR}$ binding signals the recruitment of specific adaptors, which activate transcription factors $\text{NF-}\kappa\text{B}$ and $\text{IRF}$ (interferon regulatory factor) to activate the expression of inflammatory cytokines and antiviral responses.

Which Toll-like receptors are located on the plasma membrane versus within endosomes?

Plasma membrane receptors include $\text{TLR 1, 2, 4, and 5}$, whereas endosomal receptors include $\text{TLR 3, 7, 8, and 9}$.

What is the primary difference between $\text{PAMPs}$ and $\text{DAMPs}$?

$\text{PAMPs}$ (Pathogen-associated molecular patterns) are conserved structures from invading microbes (e.g., lipopolysaccharide, peptidoglycan), whereas $\text{DAMPs}$ (Damage-associated molecular patterns) are endogenous molecules released from host cells damaged by infection or sterile injury.

What is the inflammasome, and what are its major downstream actions?

The inflammasome is a caspase-1–containing enzyme complex formed in response to $\text{PAMPs}$ and $\text{DAMPs}$. It cleaves precursor molecules to produce active $\text{IL-1}$ and $\text{IL-18}$, and processes gasdermin to form membrane pores, causing pyroptosis (osmotic cell death).

What are the three main subsets of innate lymphoid cells ($\text{ILCs}$) and their primary cytokine outputs?

$\text{ILC1}$ produces $\text{IFN-}\gamma$ to defend against viruses; $\text{ILC2}$ produces $\text{IL-5}$ and $\text{IL-13}$ to defend against helminths and mediate allergic inflammation; and $\text{ILC3}$ produces $\text{IL-17}$ and $\text{IL-22}$ to maintain intestinal barrier function and lymphoid organogenesis.

Which colony-stimulating factors stimulate neutrophil production, and what chemical reaction mediated by myeloperoxidase occurs during the respiratory burst?

Neutrophil production is stimulated by $\text{G-CSF}$ and $\text{GM-CSF}$. During the respiratory burst, myeloperoxidase catalyzes the reaction: $\text{H}_2\text{O}_2 + \text{Cl}^- \rightarrow \text{HOCl}$ (hypochlorous acid/bleach) to destroy ingested microbes.

Which two chemoattractant molecules are primarily responsible for recruiting neutrophils to inflamed tissues?

$\text{IL-8}$ ($\text{CXCL8}$) and leukotriene $\text{B}_4$ ($\text{LTB}_4$).

Which phagocytic myeloid cell is depicted in this smear, functioning in tissues to ingest large microorganisms and debris (e.g., as specialized microglia in the brain)?

Macrophage

Which granulocyte is depicted in this histological image, characterized by bilobed nuclei, bright pink/red granules, and defense against helminthic parasites?

Eosinophil

Which leukocyte is depicted in this image, accounting for less than $1\%$ of circulating white blood cells and containing coarse granules of histamine and heparin?

Basophil

Which innate lymphocyte is shown in this image, functioning to kill virus-infected cells and tumor cells exhibiting absent $\text{MHC class I}$?

Natural killer ($\text{NK}$) cell

What receptor trigger induces the differentiation of mast cells from their bone marrow precursors in peripheral tissues?

The $\text{c-Kit}$ receptor (activated by stem cell factor released by tissues).

How do Natural Killer ($\text{NK}$) cells mediate antibody-dependent cell-mediated cytotoxicity ($\text{ADCC}$)?

$\text{NK}$ cells express $\text{CD16}$ (a low-affinity $\text{Fc}$ receptor for $\text{IgG}$ antibodies). When $\text{CD16}$ binds the $\text{Fc}$ region of $\text{IgG}$ bound to infected cells, it triggers the release of perforin and granzymes to induce apoptosis.

What is the difference between active and passive immunity?

Active immunity is self-produced by the host upon antigen exposure, yielding both protection and long-lasting immunologic memory. Passive immunity involves the transfer of preformed antibodies to vulnerable individuals, conferring rapid protection without immunologic memory.

What are the four sequential steps involved in leukocyte homing and transendothelial migration into tissues?

1. Rolling (mediated by selectins and their ligands)\n2. Activation (triggered by chemokines)\n3. Arrest/firm adhesion (mediated by integrins binding to ligands like $\text{ICAM-1}$)\n4. Transendothelial migration/diapedesis (following chemokine chemotactic gradients).

Which immunodeficiency is shown in this clinical image, characterized by defective respiratory burst and recurrent infections with catalase-positive organisms?

Chronic granulomatous disease ($\text{CGD}$)

What is the underlying genetic defect in Leukocyte Adhesion Deficiency type 1 ($\text{LAD-I}$), and what is its classic clinical hallmark?

$\text{LAD-I}$ is an autosomal recessive deficiency of the $\beta_2$ integrin subunit ($\text{CD18}$ / $\text{LFA-1}$), impairing firm adhesion and chemotaxis. Its hallmark presentation is delayed separation of the umbilical cord, along with neutrophilia and recurrent bacterial infections without pus.

What genetic mutation causes Chédiak-Higashi syndrome, and what are its key clinical features?

An autosomal recessive mutation in the $\text{LYST}$ (lysosomal trafficking regulator) gene, causing aberrant vesicle fusion. Features include oculocutaneous albinism, pyogenic bacterial infections, bleeding tendencies (platelet dysfunction), progressive neuropathy, and a high risk of hemophagocytic lymphohistiocytosis ($\text{HLH}$).

Which microbial genus causes recurrent, severe infections in individuals with terminal complement deficiencies ($\text{C5-C9}$)?

$\textit{Neisseria}$ species (e.g., $\textit{Neisseria meningitidis}$).

What is the molecular cause and classic clinical manifestation of Hereditary Angioedema ($\text{HAE}$)?

An autosomal dominant mutation causing deficiency or dysfunction of the $\text{C1}$ esterase inhibitor ($\text{C1-INH}$). This leads to uninhibited activation of the complement and contact systems, producing excess bradykinin and resulting in recurrent subcutaneous and submucosal non-pitting edema.

What surface protein deficiencies cause Paroxysmal Nocturnal Hemoglobinuria ($\text{PNH}$)?

Deficiency of decay-accelerating factor ($\text{CD55}$) and $\text{CD59}$ (which blocks $\text{C9}$ binding and $\text{MAC}$ formation), leaving erythrocytes and platelets vulnerable to complement-mediated lysis.

Which two proinflammatory cytokines uniquely stimulate leukocyte production in the bone marrow?

$\text{TNF}$ and $\text{IL-1}$.

What are the primary functions of Type I interferons ($\text{IFN-}\alpha$ and $\text{IFN-}\beta$)?

They act via paracrine signaling on neighboring uninfected cells to induce enzymes that inhibit viral replication, and act in an autocrine fashion to enhance host cell susceptibility to cytotoxic T-lymphocyte ($\text{CTL}$)–mediated killing.

What molecule serves as the common convergence point where the classical, lectin, and alternative pathways of complement activation merge?

$\text{C3}$ (specifically through the generation of a $\text{C3}$ convertase, which cleaves $\text{C3}$ into $\text{C3a}$ and $\text{C3b}$).

Where in the thymus do positive and negative selection of developing T cells take place?

Positive selection occurs in the thymic cortex (mediated by type 2 and type 3 epithelial reticular cells presenting $\text{MHC I and II}$), whereas negative selection occurs in the thymic medulla.

How are T cells and B cells organized within the white pulp of the spleen?

T cells localize around the central arteriole in the periarteriolar lymphoid sheath ($\text{PALS}$), while B cells localize within the lymphoid nodules/follicles and germinal centers.

What is the complete path of lymph flow through a lymph node from entrance to exit?

Afferent lymphatic vessel $\rightarrow$ Subcapsular sinus $\rightarrow$ Trabecular (cortical) sinus $\rightarrow$ Medullary sinus $\rightarrow$ Efferent lymphatic vessel.

What are the specialized epithelial cells found in the follicle-associated epithelium ($\text{FAE}$) of Peyer's patches, and what is their distinguishing feature?

$\text{M}$ cells (microfold cells), which lack a brush border and microvilli, functioning as antigen-transporting cells to deliver luminal antigens to underlying B and T cells.

How do $\text{MHC Class I}$ and $\text{MHC Class II}$ differ in cellular distribution and the type of T cells they interact with?

$\text{MHC Class I}$ is expressed on all nucleated cells (absent on RBCs) and presents endogenous antigens to $\text{CD8}^+$ cytotoxic T cells. $\text{MHC Class II}$ is expressed on professional antigen-presenting cells ($\text{APCs}$) and presents exogenous antigens to $\text{CD4}^+$ helper T cells.

What role do the invariant chain, $\text{CLIP}$, and $\text{HLA-DM}$ play in $\text{MHC Class II}$ antigen processing?

The invariant chain occupies the peptide-binding cleft of $\text{MHC Class II}$ in the ER to keep it inactive. In the endosome, it is cleaved to $\text{CLIP}$, which is subsequently removed by $\text{HLA-DM}$ to allow exogenous peptides to bind.

What are the physiological functions of the atypical MHC molecules $\text{HLA-E}$, $\text{CD1}$, and $\text{MIC-A/B}$?

$\text{HLA-E}$ displays leader peptides from other $\text{MHC I}$ molecules to signal normal processing to $\text{NK}$ cells; $\text{CD1}$ presents lipid and glycolipid antigens to $\text{NK}$ and T cells; and $\text{MIC-A/B}$ act as stress-induced molecules recognized by $\text{NK}$ cells to trigger targeted cell destruction.