PA2203 LEC HR 1-3

What is immunology?

The study of the body's defense against infection and the adverse consequences of immune responses.

What are the two major arms of the immune system?

Innate immunity and adaptive (acquired) immunity.

What does the immune system consist of?

Cells, tissues, and molecules that mediate immune responses.

When does hemopoiesis first begin?

Third week of gestation in the yolk sac.

Where do definitive hematopoietic stem cells (HSCs) arise?

Aorta-gonad-mesonephros (AGM) region of the intraembryonic mesoderm.

What is the main site of blood cell formation during mid

gestation? - Fetal liver.

Why is the fetal placenta clinically important?

It contains HSCs used for umbilical cord blood transplantation.

When do HSCs migrate to bone marrow?

By the fourth month of development.

Where does hematopoiesis occur after birth?

Red bone marrow and some lymphoid tissues.

Where does hematopoiesis occur after puberty?

Restricted to the axial skeleton.

Which immune lineage appears first during development?

Myeloid lineage.

Which macrophages originate embryonically and self

renew? - Microglia, Kupffer cells, alveolar macrophages.

Are innate immune cells functional at birth?

Present but immature.

What functional limitations do neonatal innate immune cells have?

Reduced TLR expression, cytokine production, phagocytosis, MHC expression, and antimicrobial activity.

When does the thymus begin developing?

Around week 5 of gestation.

When are thymocytes detectable in the thymus?

By week 9 of gestation.

What happens to the thymus after birth?

It involutes, especially after puberty.

What are B1 cells?

Early fetal B cells that secrete low-affinity IgM and lack memory.

What antibody do B1 cells secrete?

Low-affinity IgM (natural antibody).

Do B1 cells have immunological memory?

No.

When do conventional B2 cells appear?

After bone marrow development (approximately week 16).

Where do B1 cells primarily reside?

Spleen and body cavities such as peritoneum and pleura.

What T

cell phenotype dominates in fetal life? - Treg and Th2 bias.

Why are Th1 responses weak in early life?

Immature immune polarization and tolerance bias.

Why are neonates immunologically vulnerable?

Immature innate immunity and undeveloped adaptive immunity.

What T

helper bias do neonatal T cells show? - Th2 and Th17 bias.

Why does neonatal T

cell bias matter clinically? - Reduced defense against intracellular pathogens and weaker vaccine responses.

Which antibody crosses the placenta?

IgG.

When does maternal IgG transfer begin?

Around week 13 of gestation.

How long does maternal antibody protection last after birth?

Approximately 6-9 months.

Which antibodies are found in breast milk?

Secretory IgA, IgG, and IgM.

Why are most vaccines not given before 2 months?

Poor adaptive immune response.

Why is the influenza vaccine given at 6 months minimum?

Poor protection in younger infants.

Why vaccinate despite immune immaturity?

Risk of severe infection outweighs delayed immune maturity.

What is immunosenescence?

Age-related deterioration of immune function.

When does immune decline become significant?

Around age 60.

What causes immunosenescence?

Thymic involution and reduced naïve T-cell output.

What is inflammaging?

Chronic low-grade inflammation associated with aging.

Which cytokines are elevated in inflammaging?

IL-6, IL-1, TNF-α, CRP.

What defines innate immunity?

Rapid, non-specific, germline-encoded defense with no memory.

What are the three phases of the immune response?

Innate, early induced innate, adaptive.

What are the four types of epithelial defenses?

Physical, mechanical, chemical, microbiological.

Give examples of mechanical epithelial defenses.

Cilia movement, coughing, sneezing, peristalsis, blinking.

What is mucus made of?

Glycoproteins called mucins.

What is the function of mucus?

Traps microbes and prevents epithelial contact.

What is microbiota?

Normal nonpathogenic microorganisms on body surfaces.

How does microbiota protect against infection?

Competes with pathogens and produces antimicrobial substances.

Why can antibiotics increase infection risk?

They disrupt microbiota allowing pathogens to overgrow.

What does lysozyme do?

Breaks peptidoglycan in bacterial cell walls.

Which bacteria are more susceptible to lysozyme?

Gram-positive bacteria.

What does secretory phospholipase A2 do?

Hydrolyzes bacterial membrane phospholipids.

How do defensins kill microbes?

Insert into microbial membranes forming pores.

What is complement?

A system of plasma proteins that enhance pathogen elimination.

How many complement pathways exist?

Three.

What are the three complement pathways?

Classical, lectin, alternative.

Which complement pathway is antibody dependent?

Classical pathway.

What is the central convergence point of complement activation?

C3 convertase.

What are the products of C3 cleavage?

C3a and C3b.

What is opsonization?

Coating pathogens to enhance phagocytosis.

What forms the membrane attack complex (MAC)?

C5b through C9.

Which pathogens are most affected by complement deficiency?

Extracellular bacteria.

What are the three main phagocytic cell types?

Macrophages, neutrophils, dendritic cells.

Which innate cell encounters pathogens first in tissues?

Macrophages.

Which innate cell has the strongest phagocytic activity?

Neutrophils.

What is the main function of dendritic cells?

Antigen presentation linking innate and adaptive immunity.

What is a phagolysosome?

Fusion of phagosome with lysosome.

How are microbes killed inside phagolysosomes?

Acidification, enzymes, reactive oxygen and nitrogen species.

What are neutrophil extracellular traps (NETs)?

DNA-based extracellular structures that trap microbes.

Are NETs intracellular or extracellular?

Extracellular.

What are pattern recognition receptors (PRRs)?

Receptors that recognize infection or cell damage.

What are pathogen

associated molecular patterns (PAMPs)? - Conserved microbial structures.

Give examples of PAMPs.

LPS, dsRNA, peptidoglycan, β-glucans.

What are danger

associated molecular patterns (DAMPs)? - Endogenous molecules released from damaged cells.

Give examples of DAMPs.

Free DNA, ATP, histones, heat shock proteins.

How many toll

like receptors are expressed in humans? - Ten.

Which TLR recognizes LPS?

TLR-4.

Which TLR recognizes double

stranded RNA? - TLR-3.

Where are some TLRs located intracellularly?

Endosomal membranes.

What happens after TLR activation?

NF-κB and IRF activation leading to cytokine production.

Which cytokines are produced after TLR signaling?

TNF-α, IL-1β, IL-6, IL-8, type I interferons.

What is the induced innate response?

Amplified inflammatory response recruiting immune cells.

What is the role of M1 macrophages?

Pro-inflammatory antimicrobial activity.

What is the role of M2 macrophages?

Tissue repair and anti-inflammatory responses.

What is the primary role of NK cells?

Antiviral and anti-cancer surveillance.