Elements of Innate Immune System

Primary Lymphoid Organs

Sites where lymphocytes develop and mature

Bone Marrow

Thymus

Bone Marrow

Site of blood cell production

B cells mature in the bone marrow

T-cell precursors originate here and migrate to the thymus

Thymus

Site of T-cell maturation and selection

Secondary Lymphoid Organs

Sites where mature lymphocytes encounter antigens and initiate adaptive immune responses

Lymph Nodes

Filter lymph

Major sites of lymphocyte activation

Spleen

Filters blood

Removes old/damaged RBCs

Responds to blood-borne antigens (Activates B and T cells)

MALT (Mucosa-Associated Lymphoid Tissue)

Protects mucosal surfaces

Includes tonsils, Peyer’s patches, and other mucosal lymphoid tissues

Innate Immune System

Provides immediate, non-specific defense against pathogens

Present from birth and does not require prior exposure

Major Components of Innate System

Immune cells: Neutrophils, macrophages, dendritic cells, NK cells, eosinophils, basophils, mast cells

Complement system: Blood proteins that help destroy and remove pathogens

Physical & chemical barriers

Normal microbiota

Major Functions of Innate System

Recognizes PAMPs and DAMPs

Triggers inflammation

Recruits immune cells to sites of infection

Kills and removes pathogens

Helps activate the adaptive immune response

Four Main Myeloid-Derived Cell Types

Erythrocytes (RBC)

Granulocytes

Megakaryocytes (Platelets)

Monocytes

Dendritic Cells

Professional antigen-presenting cells (APC) that capture antigens and activate naive T cells via PRRs, linking innate and adaptive immunity

Produces type 1 interferons (IFN-a/b) during viral infections

Neutrophils

Granulocyte

Rapid first responders to infection

Major cells in acute inflammation

Phagocytose and kill microbes

Kill microbes using ROS and antimicrobial/granule enzymes

Short-lived cells; abundant in pus

Eosinophils

Granulocyte

Important in defense against parasites, especially helminths

Involved in allergic disease and asthma

Release toxic granule proteins that damage parasites

Increased eosinophils (eosinophilia) may occur in parasitic infections and allergic conditions

Basophils

Rare circulating granulocytes

Involved in allergic and parasitic responses

Release histamine, IL-4, and other inflammatory mediators

Mast Cells

Reside mainly in tissues, especially near blood vessels and mucosal surfaces

Important in immediate allergic reactions

Release histamine → vasodilation and increased vascular permeability

Pattern Recognition Receptors

Recognition system for immediate response system

Recognizes PAMPs and DAMPs

Activates innate immune cells and inflammation

Pattern-Associated Molecular Patterns

Conserved structures associated with microbes

Ex: LPS, bacterial flagellin, viral RNA

Damage-Associated Molecular Patterns

Molecules released or exposed by damaged or stressed host cells

Ex: ATP, uric acid, Extracellular DNA from damaged cells

What does PRR Activation lead do?

Cytokine production (inflammation)

Enhances phagocytosis (eliminates pathogens)

Dendritic cell maturation (link to adaptive immunity)

Mature Dendritic Cells

Better presents antigens to T cells

Stronger activation of T cells

Initiates adaptive immune system

Pathway of activation of innate immune defenses

PAMP/DAMP → PRRs → activation

Macrophages

Recognizes microbes (ex: TLRs) through PRRs

Engulfs microbes into phagosomes

Phagolysosome

Phagosome + Lysosome

Components of Microbial Killing

Lysosomal enzymes (digestive)

ROS generated by NADPH oxidase

Nitric oxide generated by iNOS

IL-1

Inflammation cytokine

TNF-a

Inflammation cytokine

Antigen

Small microbial fragments displayed on surface of macrophages

MHC II molecules

Presents extracellular antigen

CD4+ T cells

Recognizes displayed antigen on macrophages and connects innate and adaptive immunity

C3b/antibodies

Coat microbes recognized by macrophages leading to more efficient phagocytosis

Chronic Granulomatous Disease

Defective NADPH oxidase causes impaired ROS production

Impaired intracellular killing

Recurrent bacterial and fungal infection

MHC I molecules

Presents intracellular antigen (viral proteins) to CD8+ cytotoxic T cells

Dendritic Cell Migration to Lymph Nodes

DC capture antigens

DC increases CCR7 receptors

CCR7 guides DC to draining lymph node via lymphatic vessels

DC presents antigen

Where do macrophages go?

THEY REMAIN IN TISSUES

Innate Lymphoid Cells

Immune cells lacking antigen-specific receptors (no TCR/BCR)

NK cells are cytotoxic ILC

Provides rapid innate immune response

Functions of Natural Killer cells

Kills infected and tumor cells

Cytokine production

Antibody-Dependent Cellular Cytotoxicity (ADCC)

Perforin

Protein that forms pores in target-cell membranes

Granzymes

Enzymes that enter cells and trigger apoptosis

Granulysin

Protein that contributes to cytotoxic and antimicrobial activity

IFN-y

Activates macrophages

CD16

Fc receptors on NK cells that bind to Fc portion of IgG on target cell

Complement system

A group of plasma proteins that work together to enhance immune defense

Circulate mainly as inactive proteins and become activated in a cascade

Classical pathway

Activated mainly by antigen–antibody complexes

Lectin pathway

MBL binds mannose and other carbohydrates on microbial surfaces

Alternative pathway

activated directly on microbial surfaces; antibody-independent

Membrane Attack Complex (MAC)

Result of convergence of all three pathways on C3 activation (C5b-C9)

C3b

Opsonization: coats pathogens enhancing phagocytosis

C3a and C5a

Promotes inflammation (especially C5a)

C5b-C9

MAC forms pores in membrane causing lysis