Micro: Notes 17 (Innate Immunity)

What is the body's first line of defense against foreign matter in a NON-SPECIFIC manner?

innate immunity

Physical barriers

prevent pathogen from reaching target TISSUE site

What do physical barriers use to prevent pathogens from reaching target tissue site?

tight junctions, desmosomes, or gap junctions

What can invading pathogens use to break junctions in the physical innate defense?

enzymes

Hyaluronidase

an enzyme that degrades hyaluronic acid, a natural substance found in the body's tissues and fluids, "spreading factor"

What is the most prominent physical barrier?

skin

What can serve as a portal of exit for many pathogens

wounds - S. aureus infections

Keratin

resists microbial enzymes

Salt

can inhibit growth

Mucous membranes

protect via tight junctions (nose, mouth, lungs, urinary, digestive)

How are microbes shed through the mucous membrane?

through mucus produced and/or cilia

Mucus

may contain antimicrobial peptides

Mucociliary escalator

ciliated epithelial cells of the UPPER RESPIRATORY SYSTEM move debris-laden mucus out of the lungs

Peristalsis

movement of smooth muscles to move

Candida albicans

cause yeast infections

Endothelia

tightly packed epithelial cells lining BLOOD VESSELS, lymphatic vessels, urogenital track

What protects the Blood-brain barrier that protects the CNS

endothelia

Mechanical innate defense

physical removal of pathogens (urine, feces, tears, cilia, shedding of skin cells, and mucus)

Microbiome innate defense

microbiome competition of beneficial microbes inhibits growth of potential pathogens

Example of a microbiome innate defense

resident flora of vaginal area keeps candida albicans in check

Chemical mediators

produced to inhibit microbial growth

Endogenous

produced by host

Exogenous

resident microbiota produced

Can be continuously produced or in response to a stimulus and can work alone or in conjunction with other substances

chemical mediators

What does Lactobacilli ferment?

glycogen to produce lactate which lowers pH making a more acidic environment (pathogen prevention)

Sebum oil produced by sebaceous gland to seal off pores

endogenous example

Proprionibacterium acnes digest sebum to produce oleic acid and lower skin pH

exogenous example

Saliva produced in oral cavity (saliva contains lactoperoxidase system that catalyzes the activity of hydrogen peroxide)

endogenous example

In the digestive system stomach acid, pancreatic and intestinal enzymes, cryptins, liver bile, Paneth cells eliminate most pathogens

endogenous examples

Lactobacilli in the vagina ferment glycogen to produce lactate, lowering pH

exogenous example

Antimicrobial peptides (AMPs)

cell-derived mediators with broad-spectrum antimicrobial properties that damage membranes, destroy DNA/RNA, or cell wall synthesis

Bacteriocins

resident microbiota, gastrointestinal tract, bacteria, disrupts membrane

Cathelicidin

epithelial cells, macrophages, other cell types, skin, bacteria and fungi, disrupts membrane

Defensins

epithelial cells, macrophages, and neutrophilis, throughout the body, bacterial/fungi/viruses, disrupts the membrane

Dermicidin

sweat glands, skin, bacteria/fungi, disrupts the membrane and ion channles

Histatins

salivary glands, oral cavity, fungi, disrupts intracellular functions

Plasma mediators

antimicrobial compounds that are found in blood plasma

Acute phase proteins

produced in liver and secreted into blood

Acute phase proteins - C - reactive proteins and serum amyloid A

coats bacteria (opsonization), preparing them for ingestion by phagocytes

Acute phase proteins - Ferritin and Transferrin

bind and sequester iron, thereby inhibiting the growth of pathogens

Acute phase proteins - Fibrinogen

involved in the formation of blood clots that trap bacterial pathogens

Acute phase proteins - Mannose-binding lectin

activates complement cascade

Complement system

antimicrobial but also connects innate with adaptive immunity

Precursor proteins float in blood until what?

compliment activation (through 3 pathways)

Complement system - Alternative pathway

initiated by the spontaneous activation of C3

Complement system - Classical pathway

SPECIFIC ANTIBODY bind to pathogen, activating C1 complex

C1 complex

multipart protein complex; each component required for full activation overall. After C1, remaining classical pathway recruited and activated in a cascade

Cytolysis

bursting of cells

Chemotaxis

movement of immune cells

Complement system - Lectin pathway

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

Lectins (acute-phase proteins) is unregulated because of what?

inflammatory response

Lectin pathway protective outcome

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

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

Cytokine molecular messengers - Autocrine

same cell secretes and receives cytokine signal

Cytokine molecular messengers - Paracrine

cytokine signal secreted to a nearby cell

Cytokine molecular messengers - Endocrine

cytokine signal secreted to circulatory system, travels to distant cells "train"

Cytokine classes - Interleukins

help recruit immune cells to infection site

Cytokine classes - Chemokines

help recruit specific leukocytes

Cytokine classes - Interferons

released by cells with viral infection to recruit immune cells

Inflammation eliciting mediators

cytokines can induce production of various inflammatory mediators: histamine, leukotrienes, prostaglandins, bradykinin

Histamine

causes bronchoconstriction

Leukotrienes

to induce coughing, vomiting, diarrhea

Prostaglandins

induce fever

Bradykinin

induce permeability in capillaries; contributing to edema (helps immune cells get out of capillaries to get to infection)

What plays a key role in innate immuity

white blood cells

Hematopoiesis

differentiation of blood cells from bone marrow stem cells

Granulocytes

innate WBCs (neutrophils, eosinophils, basophils)

Agranulocyte exception

natural killer cells

Neutrophils characteristics

3-5 connected lobes, small purple granules

Eosinophils characteristics

2-3 lobes, large red/orange granules

Basophils characteristics

2 lobes, larger purple granules

Involved with destruction of extracellular bacteria and produces defensins and hydrolytic enzymes

Neutrophils

NETS

neutrophil extracellular traps. Mesh of chromatin with AMPS to trap pathogens

Pus formation is visible at the site of infection. What does pus contain?

leukocytes, cellular debris, and bacteria

Good protection against protozoa and helminths

Eosinophils

What do the eosinophil granules contain?

histamine, degradative enzymes, and MAJOR BASIC PROTEIN (MBP)

Activated by complement cascade and is important in allergic reactions and inflammatory responses

Basophils

Basophil granules contain what?

histamine and cytokines

Interluekins in cytokines are found in what category?

basophil category

Derived from the same source cell as neutrophils, eosinophils, and basophils. Similar function to basophils

Mast cells

Where are mast cells found?

reside in surrounding tissue and associated with blood vessels and nerves or found close to surface structures (skin and mucous membranes)

Lack visible granules in cytoplasm

Agranulocytes

What are two types of agranulocytes

lymphocytes and monocytes

Lymphocytes

natural killer cells (innate immune system) and B cells and T cells (adaptive immune system)

Natural killer cells - Agranulocytes

seek out non-self markers by recognizing the MHC PROTEIN. Can express cytokines and cytotoxic molecules stored in granules to kill non-self cells.

What does the MHC protein do?

is on host cells and tells natural killer cells not to kill them. When cells are infected they do not have it.

What do natural killer cells use to induce apoptosis?

perforin and granzymes

Largest constituent of WBCs and can differentiate into tissue-specific phagocytes

monocytes

Macrophage

specialized in tissues

Dendritic cells

skin and mucous membranes

What two cells are apart of monocytes

macrophages and dendritic cells

Tissue - brain and central nervous system

macrophage - microglial cells

Tissue - liver

macrophage - Kupffer cells

Tissue - lungs

macrophage - alveolar macrophages (dust cells)

Tissue - peritoneal cavity

macrophage - peritoneal macrophage

Phagocytes that travel to infection site. Site is entered through diapedesis, and initiated by complement factor 5a and cytokines

Leukocytes

Diapedesis or extravasation

process of leukocytes passing through capillary walls to tissues

Flattening out and squeezing through cellular junction after "rolling adhesion"

Transendothelial migration