Immunology - Innate & Adaptive Immune Responses Flashcards

Question 1

MHC Class I vs. MHC Class II: Expression and Co-Receptor Specificity

Accepted Answer

**MHC Class I**:
- **Expression**: All nucleated cells.
- **Co-receptor**: Binds **CD8+** Cytotoxic T cells ($8 	imes 1 = 8$).
- **Function**: Presents endogenous antigens (e.g., viral or mutated self-proteins).

**MHC Class II**:
- **Expression**: Professional Antigen-Presenting Cells (APCs: Dendritic cells, Macrophages, B cells).
- **Co-receptor**: Binds **CD4+** Helper T cells ($4 	imes 2 = 8$).
- **Function**: Presents exogenous antigens (e.g., extracellular bacteria).

Question 2

Endogenous vs. Exogenous Antigen Processing Pathways

Accepted Answer

**Endogenous Pathway (MHC I)**:
- Cytosolic proteins are ubiquitinated and degraded by the **proteasome**.
- Peptides are transported into the ER via **TAP** (Transporter associated with Antigen Processing) and loaded onto MHC Class I.

**Exogenous Pathway (MHC II)**:
- Extracellular proteins are internalized via endocytosis/phagocytosis and degraded in endolysosomes.
- **Invariant chain (Ii)** blocks the peptide-binding groove of MHC II in the ER until cleaved to **CLIP** in the endosome, where antigen exchange occurs.

Question 3

T-Cell Development: Positive vs. Negative Selection

Accepted Answer

**Positive Selection (Thymic Cortex)**:
- Double-positive ($CD4^+CD8^+$) T-cells must recognize self-MHC molecules on thymic cortical epithelial cells with moderate affinity.
- Failure results in apoptosis by neglect. Determines CD4/CD8 lineage.

**Negative Selection (Thymic Medulla)**:
- T-cells displaying high affinity for self-MHC/self-antigen (presented via **AIRE** gene expression) undergo apoptosis.
- Prevents autoimmunity (establishes central tolerance).

Question 4

Two-Signal Requirement for T-Cell Activation

Accepted Answer

**Signal 1 (Antigen Recognition)**:
- TCR and CD4/CD8 co-receptor bind to the peptide-MHC complex on an APC.

**Signal 2 (Co-stimulation)**:
- **CD28** on the T cell binds **B7-1/B7-2 (CD80/CD86)** on the APC.

*Clinical Note*: T-cell activation without Signal 2 leads to **anergy** (functional unresponsiveness) or apoptosis.

Question 5

T-Dependent vs. T-Independent B-Cell Activation

Accepted Answer

**T-Dependent Activation**:
- Protein antigens are processed by B cells and presented via MHC II to activated CD4+ T helper cells.
- CD40 (B cell) binds **CD40L** (T cell), inducing germinal center formation, affinity maturation, memory B-cell production, and isotype switching.

**T-Independent Activation**:
- Polysaccharide or non-protein antigens cross-link multiple B-cell receptors (BCRs).
- Yields primarily **IgM** with low affinity and minimal immunological memory.

Question 6

Complement Activation Pathways: Classical, Lectin, and Alternative

Accepted Answer

**Classical Pathway**:
- Activated by **IgM or IgG** antibody-antigen complexes binding to **C1** ("GM makes classic cars").

**Lectin Pathway**:
- Activated by **Mannose-Binding Lectin (MBL)** binding microbial surface carbohydrates.

**Alternative Pathway**:
- Activated by direct spontaneous hydrolysis of **C3** ($C3 \rightarrow C3(H_2O)$) on pathogen surfaces.

Question 7

Complement Cascade: Key Convertases and the MAC

Accepted Answer

**C3 Convertases**:
- Classical/Lectin: $C4b2b$
- Alternative: $C3bBb$
- Function: Cleaves C3 into **C3a** (anaphylatoxin) and **C3b** (opsonin).

**C5 Convertases**:
- Cleave C5 into **C5a** (anaphylatoxin & neutrophil chemoattractant) and **C5b**.

**Membrane Attack Complex (MAC)**:
- Composed of **C5b-C9**; creates transmembrane pores causing osmotic cell lysis.

Question 8

Immunoglobulin Isotypes: Structural and Functional Overview

Accepted Answer

- **IgG**: Most abundant monomer in serum; crosses placenta; fixes complement; opsonizes pathogens.
- **IgA**: Monomer (serum) or dimer (secretions); present in milk, tears, saliva; protected by a secretory component.
- **IgM**: Monomer (BCR) or pentamer; first antibody produced in primary response; most efficient complement activator.
- **IgE**: Monomer; binds Fc$\epsilon$RI on mast cells and basophils; mediates Type I hypersensitivity and defense against helminths.
- **IgD**: Monomer; present on naive B-cell surfaces along with IgM.

Question 9

Somatic Hypermutation vs. Class Switch Recombination

Accepted Answer

**Somatic Hypermutation**:
- Introduces point mutations in the variable ($V_H$ and $V_L$) regions of Ig genes.
- Mediated by **AID** (Activation-Induced Cytidine Deaminase) to increase antigen-binding affinity (affinity maturation).

**Class Switch Recombination**:
- Replaces the heavy-chain constant ($C_H$) region (e.g., $IgM \rightarrow IgG$).
- Mediated by AID and T-cell cytokines (CD40-CD40L interaction required); variable region and antigen specificity remain unchanged.

Question 10

Type I Hypersensitivity: Mechanism & Clinical Features

Accepted Answer

**Mechanism**:
- Pre-formed **IgE** cross-links antigen on Fc$\epsilon$RI receptors of mast cells and basophils, triggering immediate degranulation of **histamine**, leukotrienes ($LTC_4, LTD_4, LTE_4$), and prostaglandins.

**Key Features**:
- Fast onset (minutes).
- Examples: Anaphylaxis, allergic asthma, allergic rhinitis, systemic urticaria.

Question 11

Type II Hypersensitivity: Mechanism & Clinical Features

Accepted Answer

**Mechanism**:
- **IgG or IgM** antibodies bind to cell-surface or extracellular matrix antigens, leading to cellular destruction (complement activation, phagocytosis, ADCC) or tissue damage.

**Key Features**:
- Tissue-specific antibodies.
- Examples: Autoimmune hemolytic anemia, Goodpasture syndrome, Myasthenia gravis, Rheumatic fever, Hemolytic Disease of the Newborn.

Question 12

Type III Hypersensitivity: Mechanism & Clinical Features

Accepted Answer

**Mechanism**:
- Antigen-antibody (IgG/IgM) **immune complexes** form and deposit in vessel walls and tissues, activating complement and attracting neutrophils (releasing lysosomal enzymes).

**Key Features**:
- Systemic manifestations (vasculitis, arthritis, glomerulonephritis).
- Examples: Serum sickness, Systemic Lupus Erythematosus (SLE), Post-streptococcal glomerulonephritis (PSGN), Arthus reaction.

Question 13

Type IV Hypersensitivity: Mechanism & Clinical Features

Accepted Answer

**Mechanism**:
- **Cell-mediated** (delayed-type) reaction involving sensitized **T cells** (CD4+ Th1/Th17 cells or CD8+ CTLs). No antibodies involved.

**Key Features**:
- Delayed onset (48–72 hours).
- Examples: Contact dermatitis (poison ivy, nickel), PPD tuberculin skin test, Graft-versus-host disease (GVHD), Multiple Sclerosis.

Question 14

Natural Killer (NK) Cells & Missing-Self Hypothesis

Accepted Answer

**Missing-Self Hypothesis**:
- NK cells target cells with downregulated or absent **MHC Class I** molecules (frequently caused by viral infection or malignant transformation).

**Activation Receptors**:
- Killer Inhibitory Receptors (KIRs) bind self-MHC I to prevent lysis.
- **CD16** (Fc$\gamma$RIII) binds the Fc region of IgG, inducing **Antibody-Dependent Cellular Cytotoxicity (ADCC)** via perforins and granzymes.

Question 15

Pattern Recognition Receptors (PRRs) & PAMPs

Accepted Answer

**PAMPs** (Pathogen-Associated Molecular Patterns):
- Conserved microbial structures essential for pathogen survival (e.g., LPS, peptidoglycan, flagellin, dsRNA).

**PRRs** (Pattern Recognition Receptors):
- Host receptors (e.g., **Toll-like Receptors / TLRs**, NOD-like receptors) that recognize PAMPs.
- Signal transduction activates transcription factors like **NF-\kappa B**, triggering proinflammatory cytokine synthesis ($IL-1, IL-6, TNF-\alpha$).

Question 16

CD4+ Helper T-Cell Subsets (Th1, Th2, Th17, Treg)

Accepted Answer

- **Th1**: Induced by IL-12/IFN-\gamma; secretes **IFN-\gamma**; activates macrophages and CD8+ T cells against intracellular pathogens.
- **Th2**: Induced by IL-4; secretes **IL-4, IL-5, IL-13**; promotes IgE class-switching and eosinophil activation against parasites/allergens.
- **Th17**: Induced by TGF-\beta/IL-6; secretes **IL-17**; recruits neutrophils against extracellular bacteria and fungi.
- **Treg**: Defined by **FoxP3** expression; secretes **IL-10 and TGF-\beta**; suppresses immune responses to maintain self-tolerance.

Question 17

V(D)J Recombination Mechanics

Accepted Answer

**Definition**:
- Somatic recombination of Variable (V), Diversity (D), and Joining (J) gene segments responsible for generating diversity in TCR and BCR antigen-binding domains.

**Key Enzymatic Components**:
- **RAG-1 and RAG-2**: Recognize Recombination Signal Sequences (RSS) and generate double-stranded DNA breaks.
- **TdT** (Terminal Deoxynucleotidyl Transferase): Adds non-templated (N) nucleotides at junction sites, greatly expanding junctional diversity.

Question 18

Leukocyte Extravasation Steps

Accepted Answer

1. **Margination & Rolling**: Mediated by **E-selectin / P-selectin** on endothelium binding to **Sialyl Lewis X** on leukocytes.
2. **Tight Adhesion**: **Integrins** (e.g., LFA-1, Mac-1) on leukocytes bind **ICAM-1/VCAM-1** on endothelial cells (upregulated by TNF-\alpha and IL-1).
3. **Diapedesis (Transmigration)**: Mediated by **PECAM-1 (CD31)** interactions between leukocyte and endothelial junctions.
4. **Chemotaxis**: Leukocytes migrate toward inflammatory stimuli (**C5a, IL-8, LTB4, bacterial N-formyl peptides**).

Question 19

Active vs. Passive Immunity

Accepted Answer

**Active Immunity**:
- Induced by exposure to foreign antigens (natural infection or vaccination).
- Slow onset, long-lasting protection due to immunological memory cell development.

**Passive Immunity**:
- Transfer of pre-formed antibodies (e.g., maternal IgG across placenta, IgA via breast milk, or administration of IVIG/antitoxins).
- Immediate protection, short duration (weeks/months), no memory cells generated.

Question 20

Primary vs. Secondary Lymphoid Organs

Accepted Answer

**Primary Lymphoid Organs**:
- **Bone Marrow** & **Thymus**.
- Sites of lymphocyte antigen-independent generation, maturation, and central tolerance selection.

**Secondary Lymphoid Organs**:
- **Lymph Nodes, Spleen, MALT** (Mucosa-Associated Lymphoid Tissue).
- Sites of antigen trapping, APC interaction, antigen-dependent activation, and adaptive immune response initiation.

Immunology - Innate & Adaptive Immune Responses

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