MCQ 40 Set 2

3 Lines of Defence

• First lies of defence are physical and chemical barriers that are continuous.
• Second line consist of the innate immunity, which is rapid and nonspecific
• Third line consist of the acquired immunity which is slow, long lasting and highly specific antibody production.

First Line of Defence: Physical Barriers

• Skin blocks pathogens through packed epithelial cells and an outer layer of dead keratinocytes; the dermis contains immune cells.
• Skin has slightly acidic pH, high NaCl concentration, is often dry, has AMPs, varies in temperature, constantly sheds, has a thick layer of dead cells, and has immune cells.
• Mucous membranes in the nose, throat, and intestines trap bacteria using mucus and cilia
• Coughing, sneezing, and vomiting are expulsive reflexes

First Line of Defence: Chemical Barriers

• Stomach features high pH, while skin has high salt and acidic pH
• Saliva contains lysozymes that target cells by cleaving glycosidic bonds in peptidoglycans, weakening cell walls and causing cell lysis.
• AMPs (antimicrobial peptides) are found in the skin and saliva
• AMPs are cationic and hydrophobic, targeting bacteria, viruses, and fungi by disrupting charged bacterial membranes/cell walls.
• Eukaryotes are generally unaffected by AMPs due to their lower charge

Examples of AMPs

• Psoriasin: Small protein produced by keratinocytes that disrupts bacterial membranes and binds to zinc, inhibiting bacterial growth; effective against Gram-negative bacteria.
• Defensins: Positively charged peptides that kill bacteria and viruses by forming pores in membranes and causing depolarization; alpha defensins are found in immune cells, while beta defensins are found in skin and saliva.
• Lactoferricin: Found in saliva and breast milk; chelates iron and is cleaved by enzymes into the AMP lactoferricin.

Phagocytosis

• Carried out by macrophages (resident in tissues) and neutrophils (recruited from the blood).
• Steps involve chemotaxis, attachment by receptor binding, ingestion and phagosome formation, lysosome fusion, microbial killing and digestion, and release of waste.

Recognizing Microorganisms

• PAMPS (Pathogen Associated Molecular Pattern) are recognized by PRRs(Pattern Recognition Receptors) on macrophages
• TLRs (Toll-like receptors) are PRRs that detect fungi and bacteria; there are 13 different types.
• Examples of TLRs include TLR2 (recognizes peptidoglycan), TLR4 (recognizes lipopolysaccharide (LPS)), TLR5 (recognizes flagellin), TLR7 (recognizes ssRNA), TLR9 (recognizes dsDNA), and TLR10 (recognizes pili).
• PAMPS are not easily mutated.
• PAMPs include nucleic acids (ddRNA and ssRNA in viruses), proteins (flagellin, pilin), lipids (LPS, lipotechoic acid), and carbohydrates (mannan, glucans, peptidoglycan).

Opsonization

• Pathogens are coated with opsonins, such as antibodies or complement proteins, enhancing their recognition and uptake by phagocytes.
• Steps include tagging (antibodies coat the pathogen), recognition (macrophages "see" the antibody's Fc region), engulfing (macrophage binds and "eats" the pathogen), and killing (pathogen is destroyed).

Process of Phagocytosis and Cell Killing

• PAMPS on microbe surfaces bind to PRRS on immune cell surface and activate phagocytosis.
• The receptor initiates phagocytosis via signal transduction.
• Actin arrangement pushes the membrane around the target cell (pseudopodia), forming a phagosome
• Phagosome: is a large formed endosome
• The microbe is engulfed into a phagosome inside the phagocyte
• The phagosome interacts with early endosomes, which deliver proteins to initiate the maturation process, and help recruit signaling molecules and enzymes.
• Fusion with late endosomes acidifies the environment due to proton pumps (v-ATPases); this pH decrease creates a hostile environment for the microbe.
• fusion with lysosomes forms a phagolysosome.
• Lysosomes contain hydrolytic enzymes degrades microbial components.
• Reactive oxygen species (ROS) and nitrogen intermediates are toxic to microbes
• Either waste is released or processed for antigen presentation, linking innate and adaptive immune responses.

How Macrophages Kill Bacteria

• Acidification: reduction of pH to 3.5-4 via H+ ATPase Pump.
• ROS species: Hypochlorite OCL- (bleach), nitric oxide, superoxide
• AMP: defensins.
• Enzymes: lysozymes degrade peptidoglycan; Dases, RNases, and Proteases exist.
• Nutrient removal: siderophores and nutrient transporters are used.

Cell Signalling and Immune Gene Expression

• Upon binding, TLRs combine and the TIR domain signals the cell to express immune genes.
• Signal transduction ends on NF-kB.
• NF-KB promotes AMP production to kill microbes
• Enhances phagocyte capacity to kill by upregulating proteins; also induces production of cytokines and inflammatory response.

The Inflammatory Response Basics

• Cascade complex at the site of infection.
• Four cardinal signs are redness/edema, swelling, pain, and heat.
• Involves mass recruiting of immune cells.
• Acute is short term in response to infection
• Chronic is long term in response to cell damage (e.g., IBS and arthritis).

Types of Cells

• Neutrophils are polymorphonuclear and most abundant, circulating in the blood and dying after 8 hours
• Macrophages are resident cells that are first to encounter microbes; found in external barriers
• Monocytes recruited to site to differentiate.
• Dendritic cells are resident in tissue, sense danger, and release cytokines.
• Mast cells are resident in skin and mucosal tissues, activated by PAMPS, cytokines, or antibodies
• Mast cells release histamine and cytokines causing vasodilation, inc capillary permeability, and stimulation of inflammation
• They are linked allergic reactions causing inflammation

Inflammatory Response Steps

• Before infection/injury, monocytes and neutrophils circulate around the body
• Resident macrophages, dendritic cells, and mast cells wait in the tissue.
• Injury/infection causes localized tissue damage/instant pain and bacterial entry.
• PRR/PAMPS then activate innate immune cells and activate cytokine
• Then cytokines, chemokines, histamine, and bioactive lipids, like TNF, IL-8, IL-1, are realized.
• Damaged cells release chemokines/cytokines.
• Alteration of capillaries causes vasodilation activated by vasoactive substances released by mast cells, triggered by tissue damage.
• Vasoactive substances cause capillaries and venules to increase in diameters then capillaries becoming permeable (swelling/edema)
• This increases blood volume and slows flow velocity.
• Inflammatory mediators then escape into blood which causes Fluid and plasma proteins to enter tissue.
• Extravasation is the attraction of neutrophils then monocytes.
• Endothelial cells express cell adhesion molecules on luminal surface (are activated via the selectin of rolling with sugar neutrophil surface molecule and weak leukocyte attachment)
• Cytokines cause endothelial to express ICAMS/integrin interaction. ICAM interaction is very strong which leads to clusters increasing membrane avidity
• Leukocyte stops, adheres strongly, and spreads due to Chemoattractant > chemokines indicats site infection (diapedesis breaks the Juctions)
• The junction of endotheial
• Neutrophils provide the first response, followed by monocytes (turning into macrophages).
• DC/macrophages then travels lympnodes and present antigens
• Clotting occurs.

Inflammatory Mediators: Cytokines

• Leukocytes communicate using cytokines and their receptors.
• Main functions causes Changed cell adhesiveness and effects on enzyme activity
• It determines when cells dies or survives + alters gene expression.
• Inducing stimulus activates the cytokine gene and is secreted and reaches receptor.

Cytokine Family

• Acts on cytokine receptors.
• Types include IL-1, IL-8, TNF, and Interferons
• IL-1: Released by macrophages and epithelial cells, binds to IL-1 receptor which is proinflammatory
• TNF: Released by macrophages and neutrophils; binds to TNF receptor which is proinflammatory.
• IL-8 (CXCL8): Recruits and activates neutrophils.
• Chemokines are chemoattractants - affect mobilization of cells (subgroup of cytokines), is small, structurally related, and is names by conserve cysteine C residue.
• Cause effects of cell adhesiveness.
• Affect cell moment by Est concentration graduation and Relased in early infection by macrophages, and damaged cells.
• CC (2 adjacent CC residues in amino terminus) Attracts monocyte and macrophages.

The Complement System Basics

• Part of the innate system and found in the blood plasma
• Produced in the liver.
• Three roles: Killing (lysis) of foreign cells, tagging foreign material (opsonising), proinflammatory signalling and chemoattraction.
• All pathways meet and make C3 convertase and formation of MAC.

Types of Pathways

• Classical Pathway: Starts with antibody.
• C1 Complex: C1q, 2 proteases - C1r and C1s with C1q binds Fc region of the antibody.
• C1r cleaves C1s + C1s then binds with C4 cleavage into C4 and C4b.
• C4b attaches to bacteria and binds C2. C1s cleaves into C2a and C2b.
• C4b and C2a make active protease C4bC2A .
• Lectin Pathway: Starts with a lectin.
• Mannose Binding Lectin is Produced by liver
• Binds repeating mannose (bacteria and yeast) and bacterial surfaces.
• MBL-associated serine protease (MASP).
• MBL Binds to bacterial surfaces + MASP1 cleaves MASP2 .
• MASP2 cleaves plasma-located C2 and C4 - >C4b is Attached: and Combines with C2 aa giving C4bC2a.
• Alternate Pathway: Does not need antibody/microbe to start.
• C3 in blood is hydrolysed giving C3(H2O).
• C3(H2O) bind to Factor B and C3(H2O) cleavaged by Factor D + Bb >> C3(H2O)Bb is initial C3 convertase.
• High reactive C3 and Cb. Factor B binds with C3b and Factor D cleave Factor B.
• C3b bound converts to microbial surface with amplifier effects

Terminal Complement Pathway

• Alternate Pathway Forms the convertse by binding to C3b: forms C5 convertase.
• Lectin Pathway C3 convertase pathway from above also forms same C5 convertase product.
• C3b has high reactive thioester bond in C3b which Covalently attaches and Exposed-OH/NH2 groups Free C3b.
• C5 cleaved induces local inflammatory response - is Nucleoates the MAC.
• Bacterial death: results from bore holes in membrane: lets antimicrobial enzymes enter and Affects function of membranes.

Completment Functions

• Tags Microbe (opsination) to immune system with ligandfor Complement Receptor, (C4b and C3b) to bacteria.
• Alerst (inflammatory Response) - Lyse invader. Binds to specific receptors on immune cells, and acts acts on capillaries while is Cleaved.

Why Doesn’t Complement Kill Our Own Cells?

• Having receptors that inhibit complement cascade.
• CD59 have terminal deficiency that has recurrent infections.

Antibodies part 2 Recap

• Antibodies produced in B cells made in bone marrow.
• IgD class is B-cell receptors + V region
• Variable (v) region differe from different antibodies and constant region remain constant.
• Variable (v) region differe from different antibodies and constant region remain constant.
• Adaptive immune system is not inherited by made de novo.

Creating an Antibody

• b cell made in bone marrow with B cell own different antibody gene.
• Segments contain Gene variable, joining, and diversity.
• The Adaptive Immune Response is the Immune system remembers Vaccine works due to memory. by B and T (controlled memory in Lymphoctye).

2 Types

• Humoral [antibodies] cell-mediated response
• Macrophages, neutrophils, and compolement that Help whn injury happens.
• Presented Antigen present by dendritic cells and Lymph Nodes
• Lymph fluid will travel
• B-cells will prudoed
• Pathway steps: Microbes andDC.
• B and T will bind

Lymphocytes

• B, which Mature, secretes -Humoral Immunity
• T, Thymus, Mediants and cell
• Originate . Migrate

Receptors Defined

• B with carb DNA or Protiens (B-cell receptor)
• T only recognize infected cells via 2 Chains from Alpha and Beta shape

B Cell Activation Clonal

• Antigen recofnise naive by
• when find B is Replicated.
• into range/plasma that work between 5-6 days in Mass but produce LifeLong (Memory) immunity that Work with Vaccines (trick by trick)

Mature T-cells

• Kill infected and activate/activate with cytokes.
• Cells can be rego via Cell and Molecules.

presentation

• 1 class cells (MHC): Display protein for Tc cell
• 2 class is APCs
• Both require T cells

Overview/Summary

• Infection
• presented from activated releases for cell or Dc
• Memory is from
• Expansion activates. Effector Cells that the Th Stimulate as a whole

B-cell

• T cells and Migrate
• Infection
• Presented (DC/spleen)
• Antigens for activation
• Detects antigen, cells
• if deteced, it activated but if not, it Waits
• and proliferats in
• Found and Acticates

B

• stay nodel (antigen from Tc with IgD)
• Takes 7 days cell with 5 classes

Mucaso Immunity System

_ Protect via mucus single layer that

• Innate in symbtic
• Is divided and effect
• that contain GI
• GALT/NALT

Immunity

• Largest layer
• protection
• protection
• and nutritional
• detrimental
• Beneficial

Homeostassis regulalation

• DC critical with Activation leading
• To T cell disruption in the system for response

Gut Organigation

• Projection for Nutrient population
• Sites: Remove the Bacteria

Infection

• Breakdown with bacterial influx

Defence

• ILCs: Sub and Inflamation
• ILC: Parasites and Muscle expulsion
• DCs interactions

Pathways

• Inflamation cytokines
• Inflamaiton NETosis and Restoring

####### treatement and disease

• vacc
• M vaccine rapid response that contains or treat

key diesases

• Damage of cells
• IEC regulated (Ctyokine), altered

molecules

• Structues increase to Pro

Allergin source test

= Food tested at

######## aerodyanmic

Cat test testing allergy in long run

2 sensitization

• low dose response
• all symps of rash breath
• wind bone
• contact released tube response IgG

Der 1 TLR4

• Cat fel Inhale FEL 1

####### Anap

Treat

mech

Cells in hypo switch from

• patterin in DCs and Inhibit
• Epitopes in subjects
• protective

influences

Factors and cells that heter

treat

Decreas (infall and 2) for blockers

genomic

Sites are and micro

Gene

Mutiated via different types

• tolergenic increase

pathogen

• Pathogens: Bacteria, virus, bacteria and parasites
• Food; airborne

Blood WBC

• Blood test helps test abnormalities via Total + Xray + Heart + Transplant

abnormality

• Heart and face bone
• Thymus needed for cells/infection
• bruton
• immune = ebv lymph nodes from
• weak that born or allergy

genetic

Test is by weight from liver or HIIV

treatment methods

• AA+BB

• XY from and cell from

2 classes

• Alllow

structure

located with Classes from Chromosomes

lymphocyte

predict transfusions by Limiting/ consuming high for tests and vacc

• apply to
• rSso - amplification by complementary sequences (DNA)
• SBT amplify via determination test

Immune

cell and tissue damage

autoantigens

• Auto reactive
• inlymph in Autoimmune diabeates or rheuma

clinical rejection

• acute vs hyper and Cellular both reject

grafts accepted

tissue, MHC

• Medications needed from inflam, cytot and MHC

stemcells

• cells in autol for engraft, from gvH from and and proster from hormone

Test your understanding of innate immunity. These flashcards cover defensins, lactoferricin, phagocytosis, opsonization, macrophage mechanisms, PAMPs, and the role of NF-κB. Review key concepts in the body's first line of defense.