BIOL 2460 - chapter 17 - PARKS - MICROBIOLOGY

Physical barriers

prevent pathogen from reaching target tissue site - Cells create tight junctions, desmosomes, or gap junctions

gap junctions

selective access to certain molecules

Shedding of _________ cells help shed microbes

epidermis

Mucous membranes

protect via tight junction - Nose, mouth, lungs, urinary, and digestive

Mucus

may also contain antimicrobial peptides

Mucociliary escalator

ciliated epithelial cells of the upper respiratory system move debris-laden mucus out of the lungs

Endothelia

tightly packed epithelial cells lining blood vessels, lymphatic vessels, urogenital track and others * Endothelia of blood-brain barrier protects CNS (tight junctions)

Mechanical Innate Defense

physically remove; urine, feces, blinking, cilia, shedding, and mucus

Microbiome Innate Defense

microbiome competition of beneficial microbes inhibits growth of potential pathogens; secrete own defenses; EX: resident flora of vaginal area keeps C. albicans in check

Chemical Mediators

produced to inhibit microbial growth; can be produced by host (endogenous) or resident microbiota (exogenous)

chemical defenses

1. Body fluids

2. Antimicrobial peptides

3. Plasma protein mediators

4. Cytokines

5. Inflammation eliciting mediators

endogenous examples

• sebum oil produced by sebaceous gland to seal off pores

• saliva produced in oral cavity

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

• tear production

exogenous examples

• Propionibacterium acnes digest sebum to produce oleic acid (olay) and lower skin pH

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

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)

EX: Bacteriocins and Defensins

Plasma Mediators

Acute phase proteins (liver -> blood) Complement proteins (lectin, alt, classical, opsonization (phagocytized later), MAC) Cytokines (chem messengers for long distance, interleukins, chemokines, interferons)

Mannose-binding lectin

activates complete cascade

Precursor proteins float in blood until _________ ________.

complement activation

Classical

antibody-antigen complex C1

Lectin

Acute-Phase Proteins (APPs); inflammatory response; mannose-binding lectin C4-->Carbohydrates

Alternative

Spontaneous Activation; C3b and C3a

Though complement activation initiation is __________, protective outcomes are the __________

different; same

Opsonization

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

Membrane Attack Complex (MAC)

complex 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

Autocrine

same cell secretes and receives cytokine signals (positive-feedback loop)

Paracrine

cytokine signal secreted to a nearby cell (neighbor)

Endocrine

cytokine signal secreted to circulatory system; travels to distant cells (roundtrip)

Cytokine classes

Interleukins, Chemokines, Interferons

Interleukins

help recruit immune cells to infection site

Chemokines

help recruit specific leukocytes

Interferons

released by cells with viral infection to recruit immune cells

Cytokine Inflammatory Mediators

Histamine, Leukotrienes, Prostaglandins, Bradykinin

Histamine

to cause bronchoconstriction (coughing)

Leukotrienes

to induce coughing, vomiting, diarrhea

Prostaglandins

to induce fever

Bradykinin

induce permeability in capillaries; contributing to edema (acute) (swelling)

Hematopoiesis

differentiation of blood cells from bone marrow stem cells

Granulocytes – innate WBCs

• Neutrophils

• Eosinophils

• Basophils

Agranulocyte exception: Natural killer cells

• Lymphocytes (adaptive)

• Monocytes (adaptive)

Neutrophils

most abundant, pus formation, NET (mesh of chromatin w/ AMPs to trap pathogens), defensins & hydrolytic enzyme

Eosinophils

protection against protozoa & helminths, histamine, MBP, degradative enzymes

Basophils

complement cascade degranulation, allergies and edema, histamine and cytokines

Lymphocytes

B & T cells, seek out and find abnormalities to kill

Monocytes

largest constituent; macrophages (tissues) and dendritic cells (skin and mucus) (mononuclear phagocyte system); adaptive immunity

Mast Cells

same source as neutrophils and eosinophils; same function as basophils; leave blood and reside in surrounding tissue; associated w/ blood vessels and nerves or found close to surface structures (i.e. skin and mucus membranes)

Natural Killer Cells

Seek out non-selfmarkers (i.e. tumors and viral infectedhost cells); Can express cytokines & cytotoxic molecules stored in granules to kill non-self cell ** Use perforin (punches a hole into the cell) and granzymes to induce apoptosis in target cells

Leukocytes

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

Diapedesis or extravasation

process of leukocytes passing through capillary walls to tissues

• cannot go through arterioles/arteries or venioles/veins bc these are thick and the process occurs in thin capillaries

Transendothelial migration

flattening out and squeezing through cellular junction after “rolling adhesion”

PAMPs

auto recognition for pathogen-associated molecular patterns Peptidoglycan LPS Flagellin Microbial DNA/RNA lipopeptides

Pattern recognition receptors (PRRs)

structures that allow phagocytic cells to detect PAMPs (external surface of leukocytes); phagocyte surface or embedded internally -PRRs on macrophages also respond to chemical distress signals from damaged or stressed cells; inflammatory response

Toll-like receptors (TLRs)

bind to PAMPs and communicate with phagocyte nucleus to elicit a response

Phagocytosis Stages

1. Pathogen engulfment (phagocytosis)

2. Formation of phagosome (digestion)

3. Formation of phagolysosome and pathogen particle degradation

4. Expulsion of debris

Pathogen Recognition

When PAMP is recognized, phagocyte activates genes for phagocytosis, cell proliferation, interferon production, and/or cytokines

Inflammation

• Recruitment of immune cells

• Additional elimination tactic of dead/damaged cells

• Initiate repair of host damage

Acute

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

Chronic

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

Fever

Systemic inflammatory response that raises overall body temperature

• Enhances innate immune defenses; mesophiles are inhibited and increases WBC

• Vasoconstriction and shivering

Pyrogens

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

• exogenous (LPS) or endogenous (interleukins)

Crisis phase

fever breaks; vasodilation and sweating