IMMU2011 - Weeks 1-3

What is the immune system?

the immune system is the body's defence mechanism that senses danger, alerts the system, and destroys threats like pathogens

What is the difference between innate and adaptive immunity?

innate = non-specific first line of defence, adaptive = specific, develops memory, and responds more effectively upon re-exposure to the same pathogen

What are the hallmarks of the innate immune system?

rapid response, short duration, repetitive responses, interaction with adaptive immunity, non-reactivity to self

Why do we need vaccines?

they train the immune system to recognise and combat pathogens by mimicking infection, helping to prevent infectious diseases

What are cytokines?

small proteins secreted by immune cells that regulate immune and inflammatory responses through specific receptors

What are chemokines?

chemokines are a type of cytokine that guide the movement of immune cells (chemotaxis) and regulate adhesion molecule expression

What are the key innate immune cells?

neutrophils, macrophages, dendritic cells, eosinophils, basophils, mast cells, NK cells, and innate lymphoid cells (ILCs)

How are immune cells identified?

by their origin, morphology, staining properties, and expression of surface markers such as CD (Cluster of Differentiation) molecules

What are granulocytes?

innate immune cells containing cytoplasmic granules filled with inflammatory mediators (e.g., mast cells, basophils, eosinophils)

What are phagocytes?

they engulf and digest pathogens and debris through phagocytosis (e.g., neutrophils, macrophages, dendritic cells)

Where do immune cells originate?

from hematopoietic stem cells in the bone marrow

What are myeloid cells?

immature immune cells from the bone marrow that differentiate into granulocytes, monocytes, and macrophages

What are mast cells and their functions?

they mature in tissues exposed to the environment and release histamine and cytokines to mediate inflammation and allergy

What do eosinophils do?

they combat parasites and contribute to allergic reactions by releasing granules with toxic enzymes

What are basophils and where are they found?

basophils are blood granulocytes similar to mast cells, involved in allergic and humoral immune responses, usually recruited to tissues during inflammation

What are neutrophils and their role in immunity?

short-lived phagocytes that quickly respond to infection, engulf pathogens, and release inflammatory cytokines and NETs

What are monocytes and macrophages?

monocytes circulate in blood and become macrophages in tissues, where they perform phagocytosis, secrete cytokines, and act as antigen-presenting cells

What is phagocytosis?

where cells like neutrophils and macrophages ingest and destroy microbes, often using ROS, NO, and enzymes in phagolysosomes

What are antigen-presenting cells (APCs)?

cells that process antigens and present them on MHC molecules to activate T cells (e.g., dendritic cells, macrophages, and B cells)

Why are dendritic cells important?

they are key APCs that detect pathogens using PRRs, initiate inflammation, and activate naive T cells, linking innate and adaptive immunity

What are Pattern Recognition Receptors (PRRs)?

PRRs are receptors on innate immune cells that detect pathogen-associated (PAMPs) and damage-associated (DAMPs) molecular patterns

Where are PRRs found?

on cell surfaces, in endosomes, and in the cytosol of innate immune cells

What are PAMPs and DAMPs?

PAMPs = microbial patterns recognized by PRRs; DAMPs = host molecules released from damaged cells that also trigger immune responses

What are Toll-like receptors (TLRs)?

a type of PRR that detect microbial components; some are on the surface (e.g., TLR4), others in endosomes (e.g., TLR3).

How does the lymphatic system function in immunity?

it drains fluid (lymph) from tissues, carries antigens and APCs to lymph nodes, and returns filtered fluid to the bloodstream

What are primary lymphoid organs?

bone marrow and thymus - they generate and mature lymphocytes

What are secondary lymphoid organs?

lymph nodes, spleen, and mucosa-associated lymphoid tissues (MALT) - where immune responses are initiated

Where do T cells mature?

in the thymus, where they acquire antigen receptors and undergo central tolerance through interaction with AIRE-expressing epithelial cells

Where do B cells mature?

in the bone marrow, where they acquire antigen-specific receptors

What is the function of the spleen in immunity?

it filters blood, removes old red blood cells in red pulp, and initiates immune responses in white pulp

Where are B cells and T cells located in lymph nodes?

B cells are in the cortex (outer layer), T cells are in the paracortex (inner region)

What are HEVs in lymph nodes?

High Endothelial Venules (HEVs) = allow T cells to enter lymph nodes and interact with antigens

What is the role of mucosa-associated lymphoid tissues (MALT)?

it defends mucosal surfaces like the gut and airways by sampling and responding to inhaled or ingested antigens

What are innate lymphoid cells (ILCs)?

they are lymphocyte-like cells that produce cytokines and contribute to early immune responses and tissue homeostasis

What are Natural Killer (NK) cells and what do they do?

they detect and kill infected or stressed cells with low MHC-I expression and secrete cytokines for antiviral defence

How are neutrophils recruited to peripheral sites?

cytokines and chemokines induce expression of adhesion molecules on endothelial cells, allowing neutrophils to adhere and migrate to the site of infection

Why is the innate immune system limited?

it lacks memory and specificity, meaning it responds the same way to repeated infections and cannot adapt over time

What is antigen processing?

the breakdown of proteins into peptides for loading onto MHC molecules, enabling T cell recognition

What happens during dendritic cell maturation and migration?

dendritic cells upregulate molecules for T cell activation and migrate from tissues to lymph nodes to present antigens to naive T cells

What triggers inflammation?

binding of PAMPs and DAMPs to PRRs leads to cytokine release, vascular changes, and recruitment of immune cells to the infection site

What is the difference between central and peripheral lymphoid organs?

central organs (bone marrow, thymus) are where lymphocytes develop and mature; peripheral organs (lymph nodes, spleen, MALT) are where immune responses occur

What are the defence mechanisms at epithelial barriers?

physical stratification (e.g., skin), keratinisation, mucus secretion, cilia movement, tight junctions, acidic pH

How does mucus contribute to barrier defence?

it traps pathogens and particles, then is moved out by cilia (especially in the lungs).

How does acidic pH act as a defence mechanism?

creates an inhospitable environment for microbes (e.g., stomach pH ~2, vaginal pH ~4)

What are defensins and what do they do?

defensins are cationic antimicrobial peptides that disrupt microbial membranes and can activate immune cells

What are alpha-defensins and where are they produced?

produced by professional immune cells (e.g., leukocytes, Paneth cells); involved in microbial killing or maintaining gut barrier

What are beta-defensins and where are they expressed?

constitutively expressed by mucosal epithelial cells; part of baseline barrier immunity

What are the two mechanisms of action for antimicrobial peptides?

membrane disruption (lysis) and internal disruption of microbial function

Where are TLRs located and what do they recognise?

located on cell surfaces or endosomes; they recognise extracellular and endosomal PAMPs

Where are NOD-like receptors located and what do they detect?

cytoplasmic; detect intracellular PAMPs and DAMPs

Which TLRs recognize specific microbial components (TLR1/1, TLR4, TLR3)?

TLR1/2: bacterial lipopeptides; TLR4: LPS (Gram-negative); TLR3: viral dsRNA

What are the key structural components of TLRs?

LRR domain (ligand binding), transmembrane domain, and TIR domain (signalling)

What adaptor proteins are used by TLRs?

MyD88 (most TLRs) and TRIF (TLR3, TLR4) for distinct downstream responses

What are the outcomes of TLR signalling?

NF-κB activation, cytokine production, AMP production, lysosome activation, and oxidative burst

What is the function of TRIF signalling?

activates IRF3, promoting type I interferon (IFN-α/β) production (antiviral)

What do NOD1 and NOD2 recognise?

NOD1: meso-DAP (Gram-negative); NOD2: muramyl dipeptide (Gram + and -)

What is the downstream signalling pathway for NOD receptors?

CARD domain activates RIPK2 → NF-κB activation → inflammatory gene expression

What is the role of NF-κB in innate immune signalling?

master transcription factor for inflammation; drives cytokine and AMP production

What are DAMPs and how do they activate the immune system?

Damage-associated molecular patterns released by necrotic cells; detected by PRRs (e.g., TLR9 detects host DNA)

How do DAMPs differ in necrosis vs apoptosis?

necrosis releases strong pro-inflammatory signals; apoptosis releases fewer, less inflammatory DAMPs

What is the role of stromal cells in DAMP response?

stromal cells propagate chronic inflammation by releasing inflammatory mediators

What is the complement system?

a group of plasma and membrane proteins that enhance microbial killing and antibody function

What are the three pathways of complement activation?

alternative (microbes), Classical (antibody-antigen), Lectin (mannose-binding lectin)

What protein is central to all complement pathways?

C3 - all pathways converge at the step of C3 cleavage into C3a and C3b

What are the functions of C3b and C3a?

C3b: opsonisation; C3a: anaphylatoxin (inflammation)

What activates the classical pathway?

antigen-bound IgG or IgM antibodies bind C1 complex

What activates the lectin pathway?

MBL binds mannose on microbial surfaces, triggering MASP1/2-mediated cleavage of C4/C2

How is the alternative pathway initiated?

spontaneous C3 tick-over; C3b binds microbes, recruits Factor B, cleaved by Factor D

What is the function of C5 convertase?

cleaves C5 into C5a (inflammatory) and C5b (initiates MAC formation)

How is the membrane attack complex (MAC) formed?

C5b recruits C6-C9, which assemble into a pore that lyses cells

What are the roles of C5a and C5b?

C5a: chemotactic and inflammatory; C5b: initiates MAC assembly

What are the functions of complement?

cell lysis, opsonisation, inflammation

How is complement activation regulated on host cells?

DAF and MCP prevent uncontrolled activation; CD59 blocks MAC formation on host membranes

What is the role of C1 inhibitor (C1-INH)?

blocks classical pathway by preventing C1 complex assembly

What diseases are caused by complement deficiencies?

C3 deficiency → infections; C2 deficiency → lupus-like disease; C1-INH deficiency → hereditary angioedema; DAF deficiency → haemolytic anaemia

What antigens do B cells recognise?

whole proteins, lipids, carbohydrates, and nucleic acids in solution or on surfaces

What antigens do T cells recognise?

only peptides presented on MHC molecules (MHC-restricted)

What is MHC restriction?

T cells only recognise peptides when bound to specific MHC molecules

What is the structure of MHC Class I?

α1 and α2 domains form a closed peptide-binding cleft; β2-microglobulin is non-covalently attached

Where is MHC Class I expressed and what does it present to?

all nucleated cells; presents cytosolic peptides to CD8+ T cells

What is the structure of MHC Class II?

α1 and β1 domains form an open peptide-binding cleft; α2 and β2 anchor it to the membrane

Where is MHC Class II expressed and what does it present to?

APCs only (DCs, macrophages, B cells); presents vesicular peptides to CD4+ T cells

How do dendritic cells acquire antigens?

phagocytosis or endocytosis in peripheral tissues; then migrate to lymph nodes to present to naive T cells

What are the steps in MHC Class I antigen processing?

cytosolic proteins degraded by proteasome → peptides transported via TAP → loaded onto MHC I in ER → presented to CD8+ T cells

What are the steps in MHC Class II antigen processing?

extracellular antigens phagocytosed → degraded in phagolysosome → MHC II from ER meets peptide in vesicle → CLIP exchanged for peptide → presented to CD4+ T cells

What is the function of the invariant chain (Ii) in MHC Class II?

blocks premature peptide binding; CLIP fragment occupies the peptide groove

How is CLIP removed and peptides loaded onto MHC II?

HLA-DM catalyzes exchange of CLIP for higher-affinity peptide in the late endosome

What is cross-presentation?

DCs present extracellular antigens on MHC I to activate CD8+ T cells

Why is MHC polymorphism important?

ensures population-wide immune diversity against a broad range of pathogens

How do naive T cells encounter antigen?

through recirculation in lymph nodes where APCs present processed antigen