Microbio CH17 tcc se Dr. Brookins

Three lines of defense

physical and chemical barriers then cellular defenses (innate) then adaptive immunity

Innate physical defenses

skin; mucous membranes; cellular junctions; endothelium; mechanical defenses; microbiome

Innate chemical defenses

enzymes in body fluids; antimicrobial peptides; complement; cytokines; interferons; inflammatory mediators

Innate cellular defenses

granulocytes and agranulocytes

Skin as a barrier

physical barrier with chemicals and Langerhans cells (immune cells)

Tight junctions

seal cells together so pathogens cannot pass between them

Mucous membranes

line body entry points and trap microbes with mucus

Mucociliary escalator

cilia sweep mucus and trapped microbes out of the respiratory tract

Endothelium

blood vessel lining; forms the blood-brain barrier

Mechanical defenses

coughing; sneezing; mucociliary escalator; urination; defecation; vomiting; diarrhea; eyelashes; tears

Normal microbiota (microbiome)

bacteria and fungi and protozoa and viruses that live on and in the body

Resident microbiota

microbes that live in a body site long term

Transient microbiota

microbes present for a short time

Sites with abundant microbiota

skin; external ear; external eye; upper respiratory tract; GI tract including mouth; outer urethra and genitalia and vagina

Additional sites with some microbiota

lungs; bladder; amniotic fluid and fetus

Benefits of microbiota

digest food; make vitamins; microbial antagonism; train the immune system; regulate gut development

Microbial antagonism

normal microbes block pathogens from colonizing

Altered gut microbiome risks

Crohn's disease; diabetes; heart disease; asthma; autism and mood disorders; obesity

Dysbiosis

imbalance of normal microbiota (example: after antibiotics)

Opportunistic pathogen

normal microbe that causes disease when host defenses fail or it enters an unusual place

Candida albicans

overgrowth causes thrush

Clostridioides difficile

causes pseudomembranous colitis

Pneumocystis jirovecii

opportunistic pathogen in AIDS patients

Bacteroides fragilis

can cause anaerobic gas gangrene

Catheterization

can cause urinary tract infection

Streptococcus mutans

forms oral biofilm that causes cavities and periodontitis

Dental procedure risk

bacteria enter blood (bacteremia) and can cause subacute bacterial endocarditis

Obesity and the microbiome

microbiomes from twins transplanted into germ-free mice linked obesity to gut microbes

Hygiene hypothesis

changes in human behavior have reduced microbiota diversity and raised allergy and inflammatory disease risk

Causes of lost microbiota diversity

antimicrobial overuse; diet changes; cesarean birth; no breast-feeding

Sweat and sebum

chemical skin barriers

Lysozyme

enzyme in tears and saliva and sweat that breaks down bacterial cell walls

Body pH

acidic skin and stomach and vagina inhibit microbial growth

Antimicrobial peptides (AMPs)

small proteins that kill microbes

Bacteriocins

AMP from resident microbiota in the GI tract; disrupts bacterial membranes

Cathelicidin

AMP from epithelial cells and macrophages in the skin; disrupts membranes of bacteria and fungi

Defensins

AMP from epithelial cells and macrophages and neutrophils throughout the body; disrupts membranes of bacteria and fungi and many viruses

Dermcidin

AMP from sweat glands on the skin; disrupts membranes and ion channels of bacteria and fungi

Histatins

AMP from salivary glands in the mouth; disrupts fungal function

Complement

group of plasma proteins that connect innate and adaptive immunity

Complement pathways

classical (antibody) then lectin (mannose) then alternative (factors B and D and P)

Complement functions

opsonization; inflammation; chemotaxis; cytolysis

C3b

causes opsonization leading to phagocytosis

C3a and C5a

cause inflammation

Membrane attack complex (MAC)

C5b through C9 forming a pore that lyses the microbe

Cytokines

chemical messengers between cells

Autocrine

cytokine acts on the cell that made it

Paracrine

cytokine acts on nearby cells

Endocrine

cytokine travels in blood to distant cells

Chemokines

cytokines that attract cells (chemotaxis)

Acute phase proteins

made in response to infection (example: CRP)

Interferons (IFNs)

signaling proteins that protect against viruses

Type I interferons

IFN-alpha and IFN-beta; made by virus-infected cells; make neighboring cells produce antiviral proteins

IFN-alpha

source is epithelium and leukocytes; induced by viruses

IFN-beta

source is fibroblasts; induced by viruses

Type II interferon

IFN-gamma; source is activated T cells and NK cells; activates macrophages and neutrophils

Whole blood

blood cells plus plasma

Plasma

liquid part of unclotted blood

Serum

plasma without clotting proteins

Lymph

plasma-like fluid in lymphatic vessels

Hematopoiesis

formation of blood cells from stem cells in red bone marrow (adult)

Stem cells

undifferentiated cells that become blood cells

Erythrocytes

red blood cells

Thrombocytes

platelets

Granulocytes

white cells with granules and lobed nuclei: neutrophils; basophils; eosinophils

Neutrophils

most common granulocyte; phagocytose and kill with NETs

Neutrophil extracellular traps (NETs)

extracellular killing by neutrophils

Eosinophils

kill helminths extracellularly with toxins (major basic protein)

Eosinophilia

high eosinophils; may mean helminth infection

Basophils

granulocytes involved in allergy

Mast cells

tissue cells that release inflammatory granules and cytokines

Agranulocytes

white cells without visible granules: monocytes; macrophages; lymphocytes

Monocytes

blood cells that become macrophages

Macrophages

phagocytes that live in tissues

Dendritic cells

antigen presenting cells that link innate and adaptive immunity

B lymphocytes

become plasma cells that make antibodies (humoral immunity)

T lymphocytes

cell-mediated immunity; helper T (CD4) and cytotoxic T (CD8) and Treg

Natural killer (NK) cells

innate lymphocytes that kill virus-infected and abnormal cells with perforins and granzymes

Perforins

NK cell proteins that make pores in target cells

Granzymes

NK cell enzymes that enter pores and trigger cell death

Leukocytosis

high white cell count

Leukopenia

low white cell count

Neutrophilia

high neutrophils

Neutropenia

low neutrophils

Normal WBC count

4500-11000 per microliter

Acute bacterial infection WBC

total elevated (12000-30000); more neutrophils and band cells

Viral infection WBC

total elevated; lymphocytes increased; neutrophils can be reduced

Parasitic infection WBC

total elevated; eosinophils increased

Allergy WBC

total elevated; eosinophils and basophils increased

Monocytes in chronic infection

increase (example: tuberculosis)

Lymphatic system functions

return excess fluid to the blood; carry WBC and fats and debris; immunity

Primary lymphoid organs

red bone marrow and thymus

Secondary lymphoid organs

lymph nodes; spleen; MALT; appendix

MALT

mucosa-associated lymphoid tissue: tonsils and adenoids; Peyer's patches (GALT); NALT; BALT

Phagocytes

cells that ingest microbes and debris (macrophages; neutrophils; eosinophils; monocytes)

Phagocytosis steps

chemotaxis then adherence then ingestion into phagosome then phagolysosome then killing then exocytosis or MHC-II presentation

Phagolysosome

phagosome fused with lysosome where microbes are killed

Killing agents in phagocytes

lysozyme; proteases; DNase; RNase; peroxidase; reactive oxygen (superoxide; hydrogen peroxide; hydroxyl; hypochlorite)

PRRs

pattern recognition receptors on host cells (example: TLRs and NLRs)

PAMPs

pathogen-associated molecular patterns that PRRs bind