Chapter 17 Innate Immunity

Innate Immunity

is non specific

3 major categories of innate immunity

1\. Physical innate defense

2\. Chemical innate defense

3\. Cellular innate defense

Innate physical defenses are

Physical barriers, mechanical defenses and microbiome

Innate chemical defenses are

Enzymes in body fluids, antimicrobial peptides, plasma protein mediators, inflammation eliciting mediators and cytokines

Innate cellular defenses are

Granulocytes and Agranulocytes

Physical barriers

prevent pathogen from reaching target tissue site

Examples of physical barriers are

Tight junctions, desmosomes, and gap junctions

Pathogens may use

enzymes to break junction

Mucous membranes

protect via tight junction

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 is in

the blood brain barrier

Chemical mediators

produced to inhibit microbial growth

Can be produced by host

(endogenous)

Can be produced resident microbiota

(exogenous)

Endogenous Example:

sebum oil produced by sebaceous gland to seal off pores

Exogenous Example:

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

Saliva (endogenous) contains

lactoperoxidase system that catalyzes the activity of hydrogen peroxide

In the digestive system stomach acid,

pancreatic and intestinal enzymes, cryptins, liver bile, Paneth cells eliminate most pathogens (endogenous)

Lactobacilli in the vagina

ferment glycogen to produce lactate, lowering pH

Tears contain

lysozyme and lactoferrin

Antimicrobial peptides (AMPs)

cell-derived mediators with broad-spectrum antimicrobial properties

Antimicrobial peptides (AMPs) can

damage membranes, destroy DNA/RNA, or cell wall synthesis

Acute phase proteins

produced in liver and secreted into blood

Alternative pathway

initiated by the spontaneous activation of C3

Complement system

antimicrobial but also connects innate with adaptive immunity

Precursor proteins float in blood

until compliment activation through 3 types of pathways:

The three pathways are

1\. Alternative 2. Classical 3. Lectin

Classical pathway

specific antibody binds to pathogen, activating C1 complex

Lectin pathway

triggered by binding of mannosebinding lectin to carbohydrates on microbe

Opsonization

coating of a pathogen by a chemical substance

Membrane attack complex (MAC)

complex of C6, C7, C8, C9; forms pores in the membranes of Gram Negative

Cytokines

communication proteins that can stimulate immune cells to produce chemical defenses

Autocrrine

Self

Paracrine

Neighbors

Endocrine

Long distance

Cytokine classes

Interleukins chemokines and 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

Histamine

to cause bronchoconstriction

Leukotrienes

to induce coughing, vomiting, diarrhea

Prostaglandins

to induce fever

Bradykinin

induce permeability in capillaries; contributing to edema

Hematopoiesis

differentiation of blood cells from bone marrow stem cells

Granulocytes

innate WBCs

Agranulocytes

Natural killer cells B cells and T cells;

The three granulocytes are

Neutrophils, eosinophils, Basophils

Neutrophil extracellular traps (NETs)

mesh of chromatin with AMPs to trap pathogens

Pus

formation visible at site of infection (buildup of leukocytes, cellular debris, and bacteria)

Neutrophils

Produce defensins & hydrolytic enzymes

Eosinophils

contain histamine, degradative enzymes, and major basic protein (MBP)

Basophils

Important in allergic reactions and inflammatory responses, granules contain histamine & cytokines

Mast Cells

Similar function to basophils, Associated with blood vessels and nerves or found close to surface structures, Derived from the same source cell as neutrophils, eosinophils, and basophils, and Leave blood; reside is surrounding tissues

Monocytes differentiate into

macrophages and dendritic cells

Natural killer cells

Use perforin and granzymes to induce apoptosis in target cells

macrophage

macrophage – specialized in tissues

dendritic cell

skin and mucous membranes

Diapedesis or extravasation

process of leukocytes passing through capillary walls to tissues

Transendothelial migration

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

Some phagocytes

auto recognition for pathogen-associated molecular patterns (PAMPs)

Pattern recognition receptors (PRRs)

structures that allow phagocytic cells to detect PAMPs

Toll-like receptors (TLRs)

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

Most PRRs are on phagocyte surface

but some are imbedded internally

PRRs on macrophages also respond

chemical distress signals from damaged or stressed cells; inflammatory response

When PAMP is recognized

phagocyte activates genes for phagocytosis, cell proliferation, interferon production, and/or cytokines

Phagocytosis Stages

1\. Pathogen engulfment (phagocytosis)

2\. Formation of phagosome

3\. Formation of phagolysosome and pathogen particle degradation

4. Expulsion of debris

Cellular barriers Examples and Functions

Skin, mucous, membranes, and endothelial cells

Deny entry to pathogens

Mechanical defenses Examples and Functions

Shedding of skin cells, muscillary sweeping, peristalsis, flushing action of urine and tears

Remove pathogens form potential sties of infection

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Microbiome Examples and Functions

Resident bacteria of the skin, upper respiratory tract, gastrointestinal tract, and genitourinary tract

Compete with pathogens for cellular binding sites and nutrients

Types of chemical defenses

1\. Body fluids

2. Antimicrobial peptides

3\. Plasma protein mediators

4. Cytokines

5. Inflammation eliciting mediators

Microbiome competition of beneficial microbes inhibits

growth of potential pathogens

Resident flora of vaginal area keeps

Candida albicans in check

Examples of removing pathogens are

Includes urine, feces, tears, but also cilia, shedding of skin cells, & mucus

AMPs are

specific to Gram (+) or Gram (-); others broad-range (bacteria fungi, protozoa, viruses)

Acute phase proteins includes

C-reactive proteins

Ferritin •Transferrin

Fibrinogen

mannose-binding lectin

After C1,

remaining classical pathway recruited and activated in a cascade

C1 complex is

multipart protein complex; each component required for full activation overall

Lectins are

upregulated due to inflammatory response

MACs cant

penetrate thick peptidoglycan of G+

MACs poke holes in the membrane causing

water, ions, etc. to move through pores leading to cell lysis and death

Inflammation is nesacary for

• Recruitment of immune cells

• Additional elimination tactic of dead/damaged cells

• Initiate repair of host damage

Acute inflammation

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

Chronic inflamation

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

Pyrogens

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

Crisis phase

fever breaks; vasodilation and sweating

Exogenous pyrogen

LPS

Endogenous pyrogen

interleukins from leukocytes

Sometimes immune response is too strong causing

tissue and organ damage; e.g. superantigens

Fever is

Systemic inflammatory response that raises overall body temperature

Fever Enhances

innate immune defenses and can inhibit mesophile pathogen growth