Intro to Infectious Diseases Exam 2

Hemacromatosis

Condition that causes too much iron in the blood

Empirical antibiotics

Non-specific therapy, “just guessing”

Innate immunity

First line of defense, i.e. skin/stomach acid

Adaptive immunity

Specific to its target, slower to activate, generates memory cells

B cells differentiate into…

Plasma cells which then produce antibodies

The nucleus of a plasma cell is…

Off-centered

Regular neutrophils have a…

High nucleus to cytoplasm ratio

Types of Polymorphonuclear leukocytes (PMNs)

Eosinophils, basophils, neutrophils

Types of lymphocytes

Natural killer cells, T cells, B cells

Neutrophils

Can engulf microbes by phagocytosis

Phagocytosis

Directed movement of cytoplasm generates protrusions (pseudopods) that engulf the pathogen in a phagosome vacuole which kills the microbes

Basophils + eosinophils

Phagocytose less efficiently, release products that are toxic to microbes, vasoactive chemical mediators important for inflammation

Mast cells

Contain many granules rich in histamine and heparin, reside in connective tissues and mucosa and do not circulate in the bloodstream

Monocytes

Differentiate into macrophages and dendritic cells, circulate in the bloodstream

Macrophages

Phagocytes, widely distributed throughout the body, “present” antigens on cell surface to T cells

Dendritic cells

Phagocytes, located in the spleen/lymph nodes/mucous membranes, “present” small antigens on their cell surface to T cells

WBC differentials

Total number of WBCs in the sample

Normal total WBC count

4,500-11,000/ul

Acute bacterial infection total WBC count

12,000-13,000/ul

Normal total neutrophil percentage

54%-62%

Normal total eosinophil percentage

1%-3%

Normal total basophil percentage

0%-0.75%

Normal total lymphocyte percentage

25%-33%

Normal total monocyte percentage

3%-7%

Primary lymphoid organs

Where immature lymphocytes mature; bone marrow and thymus

Bone marrow is where ____ mature, which ____

B cells, ultimately produce antibodies

Thymus is where ____ mature, which ____

T cells, modulate various facets of adaptive immunity

Secondary lymphoid organs

Where migrating lymphocytes stop to encounter antigens; lymph nodes, spleen, Peyer’s patches, tonsils, adenoids, appendix

Keratin

Found in the skin, made by keratinocytes

Sebum

Oily substance, covers + protects skin, acidic pH inhibits bacterial growth

Skin-associated lymphoid tissue (SALT)

Recognizes microbes that may slip past the physical barrier; includes Langerhans cells

Langerhans cells

Specialized dendritic cells that can phagocytose microbes

Competition between species…

Limits colonization by pathogens

Mucus

Coats surfaces and traps microbes; includes lysozyme and lactoperoxidase

Lysozyme

Cleaves cell wall peptidoglycan

Lactoperoxidase

Produces toxic superoxide radicals

Microbe-associated molecular patterns (MAMPs)

Recognized structures found only on microbes

M cells

Specialized cells that take up microbes from intestines

Mucous membranes contain…

Microbe-associated molecular patterns (MAMPs), mucosa-associated lymphoid tissue (MALT), gut-associated lymphoid tissue (GALT), Peyer’s patches, M cells

Mucous membranes are selectively permeable for…

Nutrients and waste products

Nasal cavity is lined with…

Cilia

Sneezing

The forceful expulsion of air from the lungs, to clear the organism from the respiratory tract

Alveolar macrophages

Ingest and kill most bacteria, send out chemical signals to attract other cells of the innate and adaptive immune systems

Enzymes (including lysozyme)

Degrade the cell walls of Gram-positive bacteria

Superoxide radicals (including lactoperoxidase)

Generated by host enzymes and kill pathogenic bacteria

Defensins

Small cationic peptides; made by a variety of cells such as skin, lung, genitourinary tract, and gastrointestinal tract; kill by destroying microbial cytoplasmic membrane; effective against both Gram-positive and Gram-negative bacteria, fungi, and some viruses

Inflammation

Critical innate defense in the war between microbial invaders and their hosts; provides a way for phagocytic cells (such as neutrophils) to enter infected areas within tissues

Extravasation

Movement of neutrophils out of blood vessels/through capillary vascular walls

Five cardinal signs of inflammation

Redness, heat, swelling, pain, loss of function

Infection

Microorganisms grow; produce cell damaging compounds

Vasoactive factors

Increase vascular permeability; include leukotrienes, platelet-activating factor, prostaglandins; stimulate local nerve endings, causing pain

Macrophages release…

Cytokines to communicate with other cells and inflammatory mediators

Vasodilation

Slows blood flow and, as a result, increases blood volume in the affected area; the more permeable vessel allows plasma to escape into the tissues

Extravasation and vasodilation cause

Localized swelling, redness, and heat

NSAIDS

Pain relievers that target prostaglandin synthesis

Chronic inflammation

May be due to the persistent presence of a foreign body, such as pathogens lingering in an unresolved infection, which may cause permanent tissue damage; caused by infection or nonliving, irritant material

Opsonization

Antibodies coat pathogen; helps phagocytes grab and engulf the invader (encapsulated organisms are harder to phagocytose)

Oxygen-independent mechanisms

Includes lysozyme which destroys bacterial cell wall

Oxygen-dependent mechanisms

Generation of oxygen radicals (such as superoxide radicals) that bind and damage lipids, proteins, DNA, and RNA

Macrophages, mast cells, and neutrophils generate…

Reactive nitrogen intermediates that serve as potent cytotoxic agents (NO, nitrite ions, nitrate ions)

Coxiella

Live within the phagosome

Shigella and Listeria

Escape from the phagosome and live in the cytoplasm

Salmonella and Mycobacterium tuberculosis

Prevent phagosome lysosome fusion by secreting proteins

Shigella

Trigger apoptosis

Interferons

Low-molecular-mass cytokines (15–20 kDa) produced by many eukaryotic cells in response to intracellular infection

Type I interferons

Antiviral; bind to specific receptors on uninfected host cells; induce the synthesis of two classes of proteins; include IFN-alpha, IFN-beta, IFN-omega

Type II interferons

Immunomodulatory; activate various white blood cells; include IFN-gamma

Type I interferons induce the synthesis of…

dsRNA-activated endoribonucleases; protein kinases (PKRs) that phosphorylate and inactivate e1F2 (required to translate viral RNA)

Type II interferons activate…

Macrophages, natural killer cells, T cells which increase the number of major histocompatibility complex (MHC) antigens on their surface

Natural killer (NK) cells

Seek out and destroy pathogenic microbe-infected host cells and cells that have been transformed into cancer cells

MHC class 1 surface molecules

Found on all host cells; if not present, the cell is destroyed;

Perforins

Inserted into the target cell membrane and form a pore

Granzymes

Pass through the pore into the target cell to induce apoptosis

Antibody Fc receptors

Include antibody-dependent cell-mediated cytotoxicity (ADCC)

Toll-like receptors (TLRs)

Found on host cells; enable the innate immune system to respond rapidly to infection; recognize MAMPs

Once bound to a MAMP, the TLR…

Sends a signal to the interior of the cell to start making interferon and pro-inflammatory cytokines that will speed up the inflammatory response

NOD-like receptor (NLR) proteins

Important intracellular sensors of MAMPs; trigger a different signaling pathway than TLRs but elicit the same result

Vasoconstriction

Tightens blood vessels when we're cold to preserve core heat at the expense of the periphery; shivering generates additional heat

Vasodilation

Increases blood flow to the periphery to release heat; sweat further cools the body through evaporation

Hypothalamus

A thermostat that controls vasoconstriction/vasodilation

Pyrogens

Substances that cause fever

External pyrogens

Induce the release of internal pyrogens; include bacterial toxins

Internal pyrogens

“Turn up the thermostat”; include interferons and cytokines

Process of internal pyrogens

Bind to receptors on neurons near the thermoregulatory center in the hypothalamus; stimulate the production of phospholipase A2 (required

to make prostaglandins); prostaglandins change the responsiveness of the thermosensitive neurons of the thermoregulatory center in the hypothalamus

Fever advantages

Places organisms outside of their “comfort zone” for growth; reduces iron availability to bacteria; stimulates the immune response (production and function of neutrophils and the trafficking of immune cells to lymph nodes)

Complement

Series of 20 proteins in the blood; help prevent blood infections, cascading event

Outcomes of triggering the complement cascade

Membrane attack complexes (MACs) cause cytoplasmic leaks that destroy membrane integrity; attracts WBCs, facilitates phagocytosis (opsonization)

Classical complement-activating pathway

Depends on antibodies (adaptive immunity)

Alternative complement-activating pathway

Does not require antibodies (innate immunity)

Lectin complement-activating pathway

Requires the synthesis of mannose-binding lectin by the liver in response to cytokine release from macrophage-pathogen interaction

Goal of the complement cascade

To insert pores into target microbial membranes to destroy membrane integrity and kill the cell

Protectin (CD59)

Prevents C9 from polymerizing on host membranes

Factor H

Binds to host cells and protects them from complement attack by inactivating C3b

C-reactive protein (CRP)

Activated by cytokines; binds to bacterial cell surfaces, not host cell membranes, and C1 to initiate the complement cascade

Basophils have ___ granules

Deep blue

Eosinophils have ___ granules

Bright orange

Vasoactive

Acting on vascular system

Histamine causes…

Smooth muscle contractions

Bacteriocins

Made of proteins that are antibiotic like; produced against closely related species

TIBC and iron levels have…

An inverse relationship