Chapter 15: Innate Immunity

nonspecific innate immunity

a multifaceted system of defenses that targets invading pathogens in a nonspecific manner

physical defenses

physical barriers, mechanical defenses, microbiome

chemical defenses

chemicals and enzymes in body fluids, antimicrobial peptides, plasma protein mediators, cytokines, and inflammation-eliciting mediators

cellular defenses

granulocytes and agranulocytes

physical defenses

provide the body’s most basic form of nonspecific defense

physical barriers

• barriers consist of cells that are tightly joined to prevent invaders from crossing through to deeper tissue

• ex. endothelial cells that line blood vessels have very tight cell to cell junctions

cell junctions

• composed of cell membrane proteins that may connect with the extracellular matrix or complementary proteins from neighboring cells

• tight junctions, desmosomes, and gap junctions

• invaders might try to break these down chemically using enzymes like proteases

skin barrier

composed of three layers (epidermis, dermis, and hypodermis) of closely packed cells

epidermis

• consists of cells that are packed with keratin

• dead, dense layer of protein filled husks on the surface

• fatty acids make this layer dry, salty, and acidic to inhibit the growth of some microbes

• highly resistant to breakdown by bacterial enzymes

• frequently sheds and takes the microbes with them

keratin

makes the skin’s surface mechanically tough and resistant to degradation by bacterial enzymes

mucous membranes

• lines the nose, mouth, lungs, and urinary tract to provide a nonspecific barrier

• consist of a layer of epithelial cells bound by tight junctions that secrete mucous which covers and protects the more fragile layers beneath it and traps microbes

ciliated epithelial cells

the epithelial cells lining the upper parts of the respiratory tract with cilia

mucociliary escalator

when the cilia move the mucociliary blanket out of the lungs to be swallowed, coughed up, or sneezed

goblet cells

cells that line the intestinal tract and secrete mucus

endothelia

​The epithelial cells lining the urogenital tract, blood vessels, lymphatic vessels, and certain other tissues

blood-brain barrier

protects the CNS through tight cell junctions

mechanical defenses

• physically remove pathogens from the body

• ex. flushing of urine, blinking and eyelashes,

resident microbiota

prevent the critical early steps of pathogen attachment and proliferation required for the establishment of an infection

chemical mediators

chemically inhibit microbial invaders

sebum

endogenous mediator that provides an additional layer of defense by helping seal off the pore of the hair follicle

bacterium Propionibacterium acnes and the fungus Malassezia

can use lipase enzymes to degrade sebum which produces oleic acid

oleic acid

creates a mildly acidic environment on the surface of the skin that make it inhospitable to many pathogenic microbes

saliva

contains mediators such as lactoperoxidase enzymes

esophagus mucus

contains the antibacterial enzyme lysozyme

urine

slight acidity helps it kill many microbes

lactate

inhibits microbial growth in the female reproductive system

lactoferin

chemical in tears that inhibits microbial growth by chemically binding and sequestering iron

cerumen

earwax; presence of fatty acids which makes the pH between 3-5

surfactant

lipoprotein complex in the trachea and lungs with antibacterial properties

antimicrobial peptides (AMPs)

special class of nonspecific cell-derived mediators with broad-spectrum antimicrobial properties which may or may not be routinely produced by the body

defensins

can be produced by epithelial cells throughout the body as well as by macrophages and neutrophils; disrupt the membrane

bacteriocins

produced exogenously by certain members of the resident microbiota within the gastrointestinal tract; disrupt the membrane

Antimicrobial Peptides (AMPs)

bacteriocins, cathelicidin, defensins, dermicidin, histatins

cathelicidin

on the skin; disrupts the membrane

dermicidin

disrupts membrane integrity and ion channels on the skin

histasins

disrupts intracellular function in the oral cavity

plasma

the fluid portion of blood

serum

the fluid portion left over after coagulation

acute-phase proteins

primarily produced in the lover and secreted into the blood in response to inflammatory molecules from the immune system

acute-phase protein examples

C-reactive protein, serum amyloid A, ferritin, transferrin, fibrinogen, and mannose-binding lectin

complement system

a group of plasma protein mediators that can act as innate nonspecific defense while aslo serving to connect innate and adaptive community

complement activation

the process by which circulating complement precursors become functional

alternative pathway

initiated by spontaneous activation of the complement protein C3; if invading microbes are present, C3b attaches to the surface of these microbes and will recruit other complement proteins in a cascade

classical pathway

• more efficient mechanism of activating the complement cascade

• depends upon the production of antibodies by the specific adaptive immune defenses

• must first bind to the pathogen to form an antibody-antigen complex, which activates the C1 complex then recruits the other pathways for a cascade

C1 complex

a multipart protein complex. and each component participates in the full activation of the overall complex

lectin activation pathway

• triggered by the binding of mannose-binding lectin, an acute phase protein, to carbs on the microbial surface

• produced by liver cells and are commonly upregulated in response to inflammatory signals received by the body during an infection

complement activation pathway outcomes

opsonization, inflammation, chemotaxis, and cytolysis

opsonization

the coating of a pathogen by a chemical substance (an opsonin) that allows phagocytic cells to do their job more easily

opsonins from the complement cascade

C1q, C3b, and C4b

C3a and C5a

anaphylatoxins with potent proinflammatory functions

anaphylatoxins

activate mast cells causing degranulation and the release of inflammatory chemical signals

C5a

potent chemoattractants for neutrophils and other WBCs

membrane attack complex (MAC)

complement proteins C6, C7, C8, and C9 assemble which allows C9 to polymerize into pores in the membranes of gram-neg bacteria; only effective against gram-neg bacteria

cytokines

• soluble proteins that act as communication signals between cells

• in a nonspecific immune response, may be released to stimulate production of chemical mediators or other cell functions (proliferation, cell differentiation, inhibition of cell divisions, apoptosis, and chemotaxis

chemotaxis

the movement of cells towards or aways from a chemical signal

autocrine function

the same cell that releases the cytokine is the recipient of the signal; self-stimulation by a cell

paracrine funtion

the release of cytokines from one cell to other nearby cells, stimulating some response from the recipient cells

endocrine funtion

cells release cytokines into the bloodstream to be carried to target cells much farther away

important classes of cytokines

interleukines, chemokines, and interferons

interleukins

originally thought to be produced by only leukocytes and to only stimulate them, but we now know hey are involved in modulating almost every function of the immune system; can also be unrelated to immune defenses

chemokines

chemotactic factors that recruit leukocytes to sites of infection, tissue damage, and inflammation; very specific

interferons

diverse group of immune signaling molecules and are especially important in out defense against viruses

type I interferons

• interferon-α and interferon-β

• produced and released by cells infected with virus

• stimulate nearby cells to stop production of mRNA, destroy already made RNA, and reduce protein synthesis

• also stimulate various immune cells involved in viral clearance to more aggressively attack virus-infected cells

type II interferons

• interferon-γ

• important activator of immune cells

acute-phase proteins

• cytokines stimulate this production

• i.e., c-reactive protein and mannose-binding lectin

• act as opsonins

histamine

a proinflammatory compound

mast cells and basophils

some cytokines also bind these

leukotrienes

• lipid-based proinflammatory mediators that are produced from the metabolism of arachidonic acid in the cell membrane of leukocytes and tissue cells

prostaglandins

chemical mediators that promote the inflammatory effects of kinins and histamines; help raise body temp

bradykinin

contributes to edema

formed elements

nonfluid portion of blood consisting of various types of this; all formed from the same stem cells found in bone marrow

3 major categories of formed elements

RBCs (erythrocytes), platelets (thrombocytes), WBCs (leukocytes)

red blood cells

primarily responsible for carrying oxygen to tissues

platelets

cellular fragments that participate in blood clot formation and tissue repair

hematopoietic stem cells (HSCs)

pluripotent cells in the bone marrow that all of the formed elements of blood are derived from

hematopoiesis

the process by which your body makes blood cells; hematopoietic stem cells (HSCs) receive signals from the body to become different types of blood cells, like red blood cells, white blood cells, and platelets. Think of it like a bakery where dough (HSCs) can be turned into different types of bread (blood cells) depending on the recipe (signals from the body)

majority of HSCs

erythrocytes

leukocyte division

granulocytes and agranulocytes

granulocytes

distinguished in a blood smear by the appearance of their nuclei and the contents of their granules

neutrophils (polymorphonuclear neutrophils (PMNs))

a nucleus with 3-5 lobes and small, numerous lilac-colored granules; thin strand of material attaching all of the lobes

eosinophils

2-3 lobes and larger granules that stain reddish orange

basophils

2-lobed nucleus and large granules that stain dark blue or purple

neutrophils (PMNs)

• involved in the elimination and destruction of extracellular bacteria

• can migrate through cell walls to seek out and kill infectious bacteria

• contain defensins and hydrolytic enzymes that help them destroy bacteria through phagocytosis

degranulation

when certain immune cells release small packets of toxic or helpful substances into the surrounding area

neutrophil extracellular traps (NETs)

extruded meshes of chromatin that are closely associated with antimicrobial granule proteins and components; used to mount a highly efficient and concentrated attack against nearby pathogens

chromatin

DNA with associated proteins

proteins frequently associated with NETs

lactoferrin, gelatinase, cathepsin G, and myeloperoxidase

pus (or purulent or suppurative discharge or drainage)

• visible accumulation of leukocytes, cellular debris, and bacteria at the site of an infection

• a sign that the immune defenses have been activated

eosinophils

granulocytes that protect against protozoa and helminths

granules of eosinophils

readily absorb the acid reddish dye eosin, contain histamine, degradative proteins, and a compound known as major basic protein (MBP)

major basic protein (MBP)

binds to the surface carbohydrates of parasites and this binding is associated with disruption of the cell membrane and membrane permeability

basophils

• have cytoplasmic granules of varied sizes and are named for their granules’ ability to absorb the basic dye methylene blue

• their stimulation and degranulation can result from multiple triggering events like the activation cascades of complement proteins or with the assistance of antibobies

histamine

• one of the most abundant components of basophil granules

• released with other chemical factors when the basophil is stimulated

  • these chemicals can be chemotactic and can help to open the gaps between cells in the blood vessels

mast cells

functionally similar to basophils in their role in allergic responses and other inflammatory reactions, but they are associated with blood vessels and nerves or found close to surfaces that interface with the external environment

agranulocytes

• lack visible granules in the cytoplasm

• can be lymphocytes or monocytes

lymphocytes

natural killers (nonspecific), B cells and T cells (specific)

monocytes

macrophages and dendritic cells; aka the mononuclear phagocyte system

natural killer cells (NK cells)

mononuclear lymphocytes that use nonspecific mechanism to recognize and destroy abnormal cells (ex: cancer cells and cells infected with viruses)

recognition of abnormal cells by NK cells

• involves a complex process of identifying inhibitory and activating molecular markers on the surface of the target cell

• NK cells recognize MHC and don’t attack these cells; cancer cells don’t have as many MHC markers on their surface, so they kill

• also activated by binding to activating molecular molecules on the target cells