BIOL 2460 Chapter 17

Innate Immunity

Immunity that is present before exposure and effective from birth. Body's 1st line of defense against foreign matter in a non-specific manner

Physical barriers

prevent pathogen from reaching target tissue site

Tight junctions

Membranes of neighboring cells are pressed together, preventing leakage of extracellular fluid

Desmosomes

Anchoring junctions that prevent cells from being pulled apart

Gap junctions

(communicating junctions) provide cytoplasmic channels between adjacent cells

Mucous membranes

protect via tight junction

• Nose, mouth, lungs, urinary, and digestive

• Microbes are shed thru mucus produced and/or cilia

Mucociliary escalator

ciliated epithelial cells of the upper respiratory system move debris-laden mucus out of the lungs Ciliated epithelial cells from the human trachea

Endothelia

Tghtly packed epithelial cells lining bloodvessels, lymphatic vessels, urogenital track and others

• Endothelia of blood-brain barrier protects CNS

Mechanical Innate Defense

physically remove pathogens

• Includes urine, feces, tears, but also cilia, shedding of skin cells, & mucus

Microbiome Innate Defense

•Microbiome competition of beneficial microbes inhibits growth of potential pathogens

•Ex. Resident flora of vaginal area keeps Candida albicans in check

Chemical Innate Defens

produced to inhibit microbial growth•

Can be produced by host (endogenous) or residentmicrobiota (exogenous

Endogenous

Produced within the body

-sebum oil produced by sebaceous gland to seal off pores

Exogenous

Produced outside the body

-Propionibacterium acnes digest sebum to produce oleic acid and lower skin pH

lactoperoxidase system

Catalyzes the activity of hydrogen peroxide

Antimicrobial peptides (AMPs)

cell-derived mediators with broad-spectrum antimicrobial properties

• AMPs can damage membranes, destroy DNA/RNA, or cell wall synthesis

• Some are specific to Gram (+) or Gram (-); others broad-range (bacteria ,fungi, protozoa, viruses)

Acute phase proteins

produced in liver andsecreted into blood

Mannose-binding lectin

soluble acute-phase protein in the blood that binds to mannose residues on pathogen surfaces and, when bound, activates the complement system by the lectin pathway

Complement system

antimicrobial but also connects innate with adaptive immunity•

Precursor proteins float in blood until complement activation

Alternative pathway

initiated by the spontaneousactivation of C3

Classical pathway

specific antibody binds to pathogen, activating C1 complex

C1 complex

is a multipart protein complex; each component is required for full activation overall

• After C1, the remaining classical pathway was recruited and activated in a cascade

Lectin pathway

Triggered by binding of mannose-binding lectin to carbohydrates on microbe

• Similar to the classical pathway

• Lectins (acute-phase proteins) upregulated due to inflammatory response

Opsonization

coating of a pathogen by a chemical substance(opsonin) to be phagocytized more easily

Membrane attack complex (MAC)

complex of C6,C7, C8, C9; forms pores in the membranes of G-• water, ions, etc. move through pores leading to cell lysis and death

• Cannot penetrate thick peptidoglycan of G+

Cytokines

communication proteins that can stimulate immune cells to produce chemical defenses

Interleukins

help recruit immune cells to infection site

Chemokines

help recruit specific leukocytes

Interferons

released by cells with viral infection to recruit immune cells

Histamine

to cause bronchoconstriction

Leukotrienes

to induce coughing, vomiting,diarrhea

Prostaglandins

to induce fever

Bradykinin

induce permeability in capillaries;contributing to edema

Hematopoiesis

differentiation of blood cells from bone marrow stem cells

Granulocytes

A group of leukocytes containing granules in their cytoplasm; neutrophils, eosinophils, basophils.

Agranulocytes

A group of leukocytes without granules in their nuclei; lymphocytes, monocytes.

Neutrophils

3-5 connected lobes & small, purple granules

• Involved with the destruction of extracellular bacteria

• Produce defensins & hydrolytic enzymes

• Pus formation visible at the site of infection

•(NETs) -a mesh of chromatin with AMPs to trap pathogens

Eosinophils

2-3 lobes & large, red/orange granules

•Good protection against protozoa & helminths

•Granules contain histamine, degradative enzymes, and major basic protein (MBP)

Basophils

2 lobes & large, purple granules

•Activated complement cascade inducede granulation of basophils

•Important in allergic reactions and inflammatory responses

•Granules contain histamine & cytokines

Mast Cells

Associated with blood vessels and nerves or found close to surface structures (i.e. skin and mucous membranes); respond to injury, infection, or allergy by producing and releasing substances, including heparin and histamine

Lymphocytes

• Natural killer cells; innate immune system

• B cells and T cells; adaptive immune system

Monocytes differentiate into

macrophages and dendritic cells

Natural Killer Cells

A type of white blood cell that can kill tumor cells and virus-infected cells; an important component of innate immunity.

Use perforin and granzymes to induce apoptosis in target cells

Macrophages

They carry out various functions, including engulfing and digesting microorganisms, clearing out debris and dead cells, and stimulating other cells involved in immune function.

Dendritic cells

Antigen-presenting cells, actively that migrate to lymph nodes to stimulate T cells and initiate adaptive immune responses

Leukocytes

phagocytes that travel to infection site

Diapedesis or extravasation

Process of leukocytes passing through capillary walls to tissues

Transendothelial migration

flattening out and squeezing through cellular junction after "rolling adhesion" (occurs in capillary walls only)

Pathogen-associated molecular patterns (PAMPs)

Molecules associated with groups of pathogens that are recognized by cell receptors in white blood cells of the innate immune system

• Peptidoglycan

• LPS

• Flagellin

• Microbial DNA/RNA

• lipopeptides

Pattern recognition receptors (PRRs)

structures that allow phagocytic cells to detect PAMPs

Toll-like receptors (TLRs)

bind to PAMPs and communicate with phagocyte nucleus to elicit aresponse

Phagocytosis Stages

1. Pathogen engulfment (phagocytosis)

2. Formation of phagosome

3. Formation of phagolysosome and pathogen particle degradation

4. Expulsion of debris

Inflammation

a localized physical condition in which part of the body becomes reddened, swollen, hot, and often painful, especially as a reaction to injury or infection.

Acute inflammation

immediate response to breach in physicalbarrier. Induces erythema (redness), edema(swelling), heat, pain, and altered function

Chronic inflammation

occurs when short term (acute)inflammation is not enough. Infections sites may bewalled off with WBCs (granulomas)

Pyrogens

produced by pathogens that alter hypothalamus (regulator of body temp)

• Can be exogenous or endogenous

Crisis phase

fever breaks; vasodilation and sweating

Exogenous pyrogen

LPS

Endogenous pyrogen

interleukins from leukocytes