Chapter 15- innate immunity

M-cells

"microfold cells" part of Peyer's Patch Fixed cells that take up microbes from the intestine and release them into a pocket formed on opposite side of the cell, where macrophages collect the microbes

how do phagocytes recognize foreign cells

"self from non-self" When phagocyte encounters a surface of another cell, the phagocyte becomes temporarily paralyzed to evaluate self vs nonself (this makes sure it does not engulf human cells)

Polymorphonclear leukocytes (3 types, list)

(PMNs) eosinophil basophil neurophil

basophil and eosinophil

(type of PMN) both non-phagocytic WBC's release products toxic to microbes are chemical mediators that increase diameter and permeability of blood vessels

neurtrophil

(type of PMN) make up nearly all WBCs in blood can engulf/ kill microbes via phagocytosis

dendritic cells

(type of monocyte) located in lymph nodes and spleen take up and present antigens on cell surface to T-cells

macrophages

(type of monocyte) wide distribution most likely to make first contact with pathogens kill invaders directly and "present" antigens on cell surface to T-cells

MAMPs found where? describe

*Microbe-associated molecular patterns* recognized by cell surface receptors such as TLRs and CD14 found - *Mucous membranes*

Major histocompatibility complex (MHC)

Transmembrane cell proteins important for recognizing self and for presenting foreign antigens to the adaptive immune system.

Vasodilation

Widening of blood vessels.

what is complement

a series of 20 proteins in the blood that prevents infections

what are pyrogens

a substance that produces fever when introduced to blood external and internal

C-reactive protein __________

activates complement!

why are fever reducers bad?

actively repress the innate immune system. so while they make you feel better, they are not helping your body fight whatever the fever is fighting

what do macrophages directly talk to

adaptive immune system (via presenting antigens on cell surface to T-cells)

Payer's Patch

aggregations of lymphoid tissues that dot the intestinal surface

"why" inflammation

allows phagocytic cells to enter infected areas w/in tissues (extravasation)

death phase

also called decline and convalescent period (period of recovery)

stationary phase

also called illness period (this overlaps with the log phase)

lag phase

also called incubation period

log phase

also called prodromal period (usually very short)

cells in the immune system:

antibodies innate protectors b-cells innate chemical defense bacterial invaders

opsonization

antibodies will coat a pathogen, making them easier to see and distinguish, which will enhance phagocytosis

compare the cells in the immune system to a medieval castle

antibodies- like arrows that defend the castle innate protectors- like alligators in a moat b-cells- like the archers that send the arrows (antibodies) innate chemical defense- boiling oil going over the castle wall bacterial invaders- the opposer trying to climb up the castle walls

CD59 (protectin) cell surface protein bind to

any C5b-C8 complex to prevent formation and C9 polymerization

acute inflammation

begins w/in seconds to minutes following the injury of tissues damage may be purely physical, or it may involve the activation of an immune response

what function does a capsule have on microbes?

beneficial-- thick sugary coating around the cell that interfere with ability of phagocytes to engulf them

what happens when your body thinks its cold

blood vessels are constricted and heat builds up causing the fever. shivering and chills also generated.

how do external pyrogens cause fever

by inducing the release of internal cytokine pyrogens, stimulating the release of enzymes required to make prostaglandins.

what do prostaglandins do

change the responsiveness of neurons in the hypothalamus, making the body think its cold.

monocytes

circulate in blood and migrate to tissues when signaled diff. into two groups: 1. macrophages 2. dendritic cells

what are the three pathways of complement

classical, alternative, and lectin pathways

WBC differentials: do what?

count total WBC, and identify cell types (neutrophils, eosinophils, basophils, lymphocytes, monocytes)

interferons are ______

cytokines produced in response to intracellular infection

advantages of fever

denature proteins of whatever is making you sick

WHAT DO THE DIFFERENT WBC LEVELS MEAN? (very important)

elevated WBC = infection or allergy elevated neutrophil = bacterial infection elevated lymphocytes = viral infection elevated monocytes = increase w/ chronic inflammation increased eosinophils = intestinal parasite or blood parasite

explain the mechanism phagocytes use to kill engulfed cells

engulfing the bacteria lysosome fusion with phagocyte

alternative pathway of complement starts how, then does what?

happens in presence of infection. gets to "normal end" via spontaneous cleavage

activation of complement is______

highly regulated

Innate Immunity

immediate but nonspecific "buys time" operates from time of infection through incubation period- until infection ends

what is the difference between infected host cells and cancerous cells

infected host cells- hide pathogenic microbe form immune system cancerous cells- take over and kill the host

what is the glycoprotein that distinguishes human cells?

inhibitory host cell *glycoprotein CD47* binds to glycoproteins on phagocytes to say "Hey, i'm good, don't eat me!"

what does Payer's Patch *do*

keep our microbiome in check by sampling intestinal microbes to "see" what is in there

what are the phases, in order, of infection

lag phase log phase stationary phase death phase

number one way pathogens avoid the consequences of phagocytoses

living inside the cells (intracellular)

list the five cardinal signs of inflammation

localized redness swelling heat pain *loss of function*

oxygen- independent pathways use___

lysozyme lactoferrin defensins

how do dendritic cells and macrophages differ

macrophages- present antigens on cell surface dendritic cells take up small soluble antigens from surroundings, and work via phagocytosis

describe defensins

made by cells in the skin, lung, GI, and GU tract kill by destroying microbial cell membrane effective against gram-positive and gram-negative bacteria, fungi, and some viruses

what is the function of a fever

maintenance of normal body temp natural response to infection or damage sweating, chills, sensation of cold pyrogens

disadvantages of fever

makes you feel gross, and if it gets high enough it can denature *host* proteins too (above 104)

WBC parts coming from *lymphoid stem cells*

natural killer cells t-cell b-cell

body cells that are infected or cancerous are dangerous to host... how are they addressed?

natural killer cells (NK cells)

how does our body end the inflammatory process

neutrophils contain destructive enzymes and signal molecules apoptosis (cell death) long lived phagocytes remove dead netrophils

lymphoid organs

organs having to do with the lymphatic system: primary and secondary organs

what does lysosome fusion with the phagocyte permit?

oxygen-dependent and oxygen-independent killing pathways

langerhans cells can do what

phagocytize found on skin

(CD59) protein factor H prevents_______

prevents complement form activation when no infection is present (inactivates C3b)

what are the primary and secondary lymphatic organs

primary= tonsils/ adenoids, lymph nodes, appendix, lymphatic vessels secondary= contact with antigens (T-cells and B-cells)

what does complement do?

protease that cleave each other in a sequence cascade -it inserts pores into microbial membranes to destroy membrane integrity

skin barrier to infection:

protective keratin shield sebum (oil) slightly acidic pH inhibits bacterial growth constant shedding of outer epithelial layers competition between micro-biome species inhibits pathogens

how do natural killer cells identify infected host cells

recognize changes in cell surface proteins of compormised cells and then degranulate and release chemicals that *kill* those (viral) cells

MAMPs can be recognized by ______, which trigger _____

recognized by toll-like receptors. these TLR's send signals to cell and start production of interferon and pro-inflammatory cytokines. these diffuse, ind to receptors on immune system cells, direct response.

mast cells

release chemical mediators granulated-histamine and heparin reside in connective tissues and mucosa *do NOT circulate in blood*

lung as barrier to infection

respiratory mucociliary elevator microbes larger than 100um trapped by haris and cilia lining nasal cavity (you sneeze and it's pushed out) have alveolar macrophages for things under 100um

chronic inflammation

result from the persistence of a foreign body *permanent tissue damage despite repair*

mucous membranes as barrier to infection

selective permeability mucus coats surfaces and traps pathogens lysozyme and lactoperoxidase kill microbes trapped in mucus

list the physical barriers to infection

skin mucous membranes lungs

SALT

skin associated lymphoid tissue recognizes microbes that may invade past physical barrier

lectin pathway of complement starts how, then does what?

starts in liver, where lectin binds to mannose, splits into C2 and C4, then converges into C3 convertase. then normal end.

oxygen- dependent pathways use ___

superoxide ion hydrogen peroxide hydroxyl radicals myeloperoxidase

how do you maintain normal body temp

-heat sensors in skin and large organs -hypothalamus controls blood flow -vasoconstriction or vasodialation

adaptive immunity

takes longer time to respond- but it is highly specific provides antigens and antibodies onset during end of prodromal phase and is maintained long after infection clears

outline the process of inflammation

1. bacteria infect tissue 2. macrophages engulf bacteria and release chemical mediators 3. cytokines induce selectins on capillary endothelia that bind to neutrophils 4. vasoactive factors induce integrins on neutrophils, which bind ICAM and VCAM 5. bradykinin loosens junctions to allow extravasation and triggers prostaglandin synthesis 6. peptides from the bacteria and chemical signals form the infected tissues are released and attract neutrophils

what are the steps of phagocytosis

1. bacterium binds to the surface of phagocytic cell 2. phagocyte pseudopods extend and engulf the organism 3. invagination of phagocyte membrane traps the organism w/in a phagosome 4. a lysosome fuses and deposits enzymes into the phagosome. enzymes cleave macromolecules and generate reactive oxygen, destroying the organism.

Vasoactive factor

A cell signaling molecule that increases capillary permeability.

Bradykinin

A cell signaling molecule that promotes extravasation, activates mast cells, and stimulates pain perception.

Mononuclear phagocyte system (MPS)

A collection of cells that can phagocytose and sequester extracellular material.

Antigen

A compound, recognized as foreign by the cell, that elicits an adaptive immune response. See also immunogen.

Tumor necrosis factor alpha (TNF-α )

A cytokine involved in systemic inflammation.

Interleukin 1 (IL-1)

A cytokine released by macrophages.

Perforin

A cytotoxic protein, secreted by cytotoxic T cells and natural killer cells, that forms pores in target cell membranes.

NOD-like receptor (NLR)

A eukaryotic cytoplasmic protein that recognizes particular MAMPs present on microorganisms.

Interferon

A family of cytokines that inhibit viral replication.

Phagocytosis

A form of endocytosis in which a large extracellular particle is brought into the cell.

Polymorphonuclear leukocyte (PMN)

A granulocyte; a white blood cell with a multilobed nucleus and cytoplasmic granules. PMNs are classified as neutrophils, basophils, and eosinophils.

Lysozyme

A hydrolytic enzyme secreted by eukaryotic cells that degrades bacterial cell wall peptidoglycan.

White blood cell (WBC) differential

A laboratory test that counts the types of white blood cells in a patient's blood.

Oxidative burst

A large increase in the oxygen consumption of immune cells during phagocytosis of pathogens as the immune cells produce oxygen radicals to kill the pathogen.

Phagosome

A large intracellular vesicle that forms as a result of phagocytosis.

Natural killer (NK) cell

A lymphocyte that kills some tumor cells and cells infected with a virus or bacteria; an important component of innate immunity.

Toll-like receptor (TLR)

A member of a eukaryotic transmembrane glycoprotein family that recognizes a particular microbe-associated molecular pattern (MAMP) present on pathogenic microorganisms.

Macrophage

A mononuclear, phagocytic, antigenpresenting cell of the immune system found in tissues.

Factor H

A normal serum protein that prevents the inadvertent activation of complement in the absence of infection.

Chemokine

A protein produced by damaged or infected tissues that stimulates the migration of white blood cells toward the site of infection.

C-reactive protein

A protein that stimulates the complement cascade; it is induced in the liver by cytokines. Elevated levels in the blood are associated with inflammation of any kind, including infection.

Lymph node

A secondary lymphatic organ, formed by the convergence of lymphatic vessels, where antigen-presenting cells and lymphocytes interact.

Langerhans cell

A specialized, phagocytic dendritic cell that is the predominant cell type in skin-associated lymphatic tissue.

Sepsis

A systemic inflammatory response, triggered by an infection, that is so extreme it can kill the patient.

Granuloma

A thick lesion formed around a site of infection.

Alveolar macrophage

A type of macrophage, located in the lung alveoli, that phagocytoses foreign material.

Defensin

A type of small, positively charged peptide, produced by animal tissues, that destroys the cell membranes of invading microbes.

Neutrophil

A white blood cell of the innate immune system that can phagocytose and kill microbes.

Mast cell

A white blood cell that secretes proteins that aid innate immunity. Mast cells reside in connective tissues and mucosa and do not circulate in the bloodstream.

Basophil

A white blood cell that stains with basic dyes and secretes compounds that aid innate immunity.

Monocyte

A white blood cell with a single nucleus that can differentiate into a macrophage or a dendritic cell.

chemical barriers employed by cells of the innate immune system

Acidic pH of stomach Lysozyme in tears Superoxide radicals generated by lactoperoxidase Defensins

Peyer's patch

Aggregates of lymphoid tissue found in the lower small intestine.

Pathogen-associated molecular pattern (PAMP)

Also called microbe-associated molecular pattern (MAMP). Molecules associated with groups of microbes, both pathogenic and nonpathogenic, that are recognized by cells of the innate immune system.

Innate immunity

Also called nonadaptive immunity. The system of nonspecific mechanisms the body uses for protecting against pathogens.

Eosinophil

An abnormally large number of eosinophils in the blood.

T cell

An adaptive immune cell that develops in the thymus and can give rise to antigen-specific helper cells and cytotoxic T cells.

B cell

An adaptive immune lymphocyte that gives rise to antibody-producing plasma cells. Along with T cells, they are antigen-specific cells responsible for the adaptive immune response.

Dendritic cell

An antigen-presenting white blood cell that primarily takes up small soluble antigens from its surroundings.

Antigen-presenting cell (APC)

An immune cell that can process antigens into epitopes and display those epitopes on the cell surface for recognition by naive T cells.

Immune system

An organism's cellular defense system against pathogens.

Pyrogen

Any substance that induces fever.

B-cells = ? T-cells= ?

B-cells = antibodies T-cells = modulate adaptive immunity

what is this "normal end" of complement

C3 cleaves into C3a and C3b -C3a is used to attract neutrophils to the scene -C3b can directly coat pathogens, causing Opsonization, and/or form a membrane attack complex (which punches holes in cell membrane)

how do membrane attack complexes form

C3b binds bacterial membrane, forming C5, which divides into C5a (helps C3a) and C5b. -C5b is mixed with C6, C7, C8 and C9 to form membrane attack complex.

what types of pathogens live intracellularly

Cosiella- lives within the toxic phagolysosome Shigella and listeria- escape from the phagosome Shigella- trigger apoptosis Salmonella- prevent phagosome fusion with lysosome

toll-like receptors

FIGURE IN NOTES

Microbe-associated molecular pattern (MAMP)

Formerly called pathogen-associated molecular pattern (PAMP). Molecules associated with groups of microbes, both pathogenic and nonpathogenic, that are recognized by cells of the innate immune system.

GALT and MALT

GALT- Gut-associated lymphoid tissue MALT- Mucosa-associate lymphoid tissue * both scattered along mucosal linings, populated with B cells, T cells, Plasma cells, and Macrophages

REGARDLESS OF THE WAY IT STARTS....

IT ALWAYS ENDS THE SAME WAY

Skin-associated lymphoid tissue (SALT)

Immune cells, such as dendritic cells, located under the skin that help eliminate bacteria that have breached the skin's surface.

Adaptive immunity

Immune responses activated by a specific antigen and mediated by B cells and T cells.

Complement

Innate immunity proteins in the blood that form holes in bacterial membranes, killing the bacteria. Some components attract phagocytes; others can coat bacteria and promote phagocytosis.

Gut-associated lymphoid tissue (GALT)

Lymphatic tissues such as tonsils and adenoids that are found in conjunction with the gastrointestinal tract and contain immune cells.

interferons have what on their cell surface?

MHC (Major Histocompatibility Complex) important for antigen presentation

types of MHC cells and their function

MHC1- immune system MHC2- cell surfaces

Integrin

Member of a family of host cell membrane proteins involved in adhesion of cells to one another and to the extracellular matrix.

WBC: come from two locations, what are they

Myeloid stem cell Lymphoid stem cell

Selectin

One of a family of cell adhesion molecules.

what are the purposes of Granulomas

to "wall off" an infection

what two things serve as "harbors for innate immune system cells" and act as phagocytic filters

Peyer's patch and M-cells

two classes of interferons

type 1- antiviral. include alpha, beta, and omega interferons type 2- immunomodulatory. include gamma interferons

WBC parts coming from *myeloid stem cell*

Polymorphoneuclear leukocytes (PMNs) Monocytes Mast Cells

roles of vasoactive factors

vasodilation: slows blood flow and increases blood volume escape of plasma into tissue vasoactive factors stimulate local nerve endings leading to pain

Apoptosis

Programmed cell death of eukaryotic cells.

Pattern recognition receptor (PRR)

Receptor on a cell of the innate immune system that recognizes common molecular patterns on microbial surfaces.

where does the killing via nutrophil occur?

via phagocytosis in phagosomes

M cell

Specialized epithelial cell (microfold cell) within Peyer's patches lining the intestine; transports antigens and microbes from the intestines across the epithelial barrier to macrophages.

Mucosa-associated lymphoid tissue (MALT)

System of concentrated sites of lymphoid tissue closely associated with mucosal surfaces, whose function includes surveying the antigens and pathogens that pass through the mucosae.

classical pathway of complement starts how, then does what?

with antibody bound to bacterial cell. binds to C1, which cleaves into C2 and C4, which converges into C3 convertase. (then normal end)

where are T-cells and B-cells made?

T-cells = *T*hymus B-cells = *B*one marrow

causes of chronic inflammation

TB, Actinomyces bovis, and protists can avoid/resist host defences and persist at infection site surgical implants asbestos particles Granulomas

Extravasation

The movement of white blood cells out of blood vessels and into surrounding infected tissue.

Antibody-dependent cell-mediated cytotoxicity (ADCC)

The process by which natural killer cells destroy viral protein-expressing, antibody-coated host cells.

Opsonization

The process by which phagocytosis is aided by coating pathogens with IgG antibodies or complement.