Immunology Exam 1

Identification of immune response

heat, swelling, pain, redness, inflammation

Edward Jenner

Father of immunology; observed milkmaids that got cowpox did not get smallpox, so inoculated individuals with samples of cowpox so they would not get smallpox

Louis Pasteur

in the 1880s developed vaccine against rabies virus and cholera in chickens

Emily von Behring and Shibasaburo Kitasato

(1890s) discovered that serum of animals immune to diphtheria or tetanus contained specific "antitoxic activity" that could confer short term protection against disease when injected into animals/people

Elie Metchnikoff

(1900s) discovered bacteria-engulfing, phagocytic cells in blood

evidence for cellular immunity

Phagocytes

a type of white blood cell within the body capable of engulfing and absorbing bacteria and other small cells and particles.

Lysosomes

cell organelle filled with enzymes needed to break down certain materials in the cell; contain antimicrobial enzymes

phagolysosome formation

When microbes go inti a liquid membrane, the phagosome then fuses with lysosomes and granules forming this

innate immunity

germ-line, rapid response (hrs), fixed, general, constant response; Immunity that is present before exposure and effective from birth; Responds to a broad range of pathogens.

adaptive immunity

has memory; slow response (days-weeks), variable, highly selective, improve during response (B&T cells), the ability to recognize and remember specific antigens and mount an attack on them

hematopoietic stem cells

in bone marrow; can become any other type of cell under right conditions; can become lymphoid cells (B & T), can become myeloid (rise to RBC, platelets)

Granulocytes

A group of leukocytes containing granules in their cytoplasm; neutrophils, eosinophils, basophils; the cytoplasm of the cell has granules or vesicles; lipid membrane bound small compartments containing molecules (enzymes) that work in the cell or are stored & can work outside of cell

blood

A connective tissue with a fluid matrix called plasma in which red blood cells, white blood cells, and cell fragments called platelets are suspended.

white blood cells

leukocytes; any immune cell in blood stream that is not a RBC

Lymphocytes

A type of white blood cell that make antibodies to fight off infections (B and T cells); can find in blood; have the ability to go into lymphatic system

lymphatic vessels

the circulating system of the immune system; located throughout the body in almost all of the tissues that have blood vessels

Primary lympoid tissues

tissues where stem cells can differentiate into immune cells, bone marrow, thymus

secondary lymphoid tissues

tissues where adaptive immune responses are initiated, spleen and lymph nodes; pathogens (and byproducts) are brought into these tissues via other cells circulating in lymph

inflammation

a localized physical condition in which part of the body becomes reddened, swollen, hot, and often painful, especially as a reaction to injury or infection.

Cytokinesis

hormones of immune system, proteins secreted by immune cells that affect the behavior of nearby cells bearing the appropriate receptors; soluble

chemokine

a type of cytokine; proteins that act as chemoattractant; attracts cells bearing the appropriate receptors out of the blood/lymph and into the surrounding tissue when concertation is highest

Chemotaxis

movement by a cell or organism in reaction to a chemical stimulus

Chemokine concentration gradient

chemotaxis moves from low concentration to high concentration of chemokines; concentration is highest at site of inflammation

How do cytokines & chemokines function?

-a surface wound introduces pathogen, which activates resident effector cells to secrete cytokines and chemokines

-vasodilatation and increased vascular permeability allow fluid, protein, and inflammatory cells to leave blood and enter tissue

-infected tissue becomes inflamed causing redness, heat, swelling. and pain

what are the three functions of inflammation

1. recruit additional effector cells to site (vessel dilation and permeability)

2. limit spread of pathogen (ex: localized blood clotting)

3. begin process of tissue healing

B cells

lymphocytes, "humoral immunity", Cells manufactured in the bone marrow that create antibodies for isolating and destroying invading bacteria and viruses.

T cells

lymphocytes, "cell mediated immunity", Cells created in the thymus that produce substances that attack infected cells in the body.

Neutrophils

A type of white blood cell that engulfs invading microbes and contributes to the nonspecific defenses of the body against disease, 3 lobed nucleus, also referred to as polymorphonuclear cells (PMNs); have receptors for chemokines; major WBC that is recruited in immune response

peripheral blood mononuclear cells (PBMCs)

give selective responses to the immune system and are the major cells in the human body immunity. They contain several types of cells such as lymphocytes, monocytes or macrophages; in opposition to red blood cells (no nucleus

serum

plasma fluid after the blood cells and the clotting proteins have been removed; antibodies

plasma

Fluid portion of blood; serum + clotting factors

lymphatic system

Composed of a network of vessels, ducts, nodes, and organs. Provides defense against infection; b & t cells (adaptive=lymph node immune response)

movement of lymph

being squeezed through lymph vessels by the contraction of skeletal muscles

why have lymph nodes around the body ?

helps with response tome at site of issue; issues do not have to circulate

naive lymphocytes

have receptors; have not yet encountered appropriate antigen

lymphocytes

A type of white blood cell that make antibodies to fight off infections; always circulating to increase chance of seeing pathogen faster

why do cells become leaky?

endothelial cells separate so fluid from blood leaks out, blood flow decreases because vessels become dilated; lets immune cells leave vessels easier

Macrophages

controlling tissues and looking for microbe; act as scouts responsible for recognizing foreign invaders; effector cells of the innate immune system that phagocytose bacteria and secrete both pro-inflammatory and antimicrobial mediators.

goblet cells

a column-shaped cell found in the respiratory and intestinal tracts, which secretes the main component of mucus; protects against pathogens and particulate matter; player in mechanical immunity

Cilia

The hairlike projections on the outside of cells that move in a wavelike manner; helps to prevent infectious organisms from colonizing in the airway

lysozome

enzyme that can destroy bacterial cell walls and some viral capsules (present in saliva; tears; mucous); goes into peptidoglycan and breaks it down; destabilizes cell wall

antimicrobial peptides

short amino acid chains about 2-40; amphipathic, catatonic and show a direct interaction with target cell membranes; bact. & fungal cell walls contain - charge lipids so these lead to the lysis of bacterial membranes through insertion and formation of pores = lysis; while eukaryotic plasma membranes remain unaffected

amphipathic

A molecule that has both a hydrophilic region and a hydrophobic region; + charge (attracted to - charge bacteria cell walls)

Defensin

another term for antimicrobial peptide; A type of protein made by phagocytes that kills bacteria and enveloped viruses by insertion into their plasma membranes.

cellular response of the innate immune system

phagocytosis- macrophages and neutrophils engulf and digest recognized "foreign" cells and molecules

inflammatory response- localized tissue response to injury producing swelling, redness, heat, pain

natural killer cells- special class of lymphocyte-like cells that destroy virus infected cells and cancer cells

Components of neutrophils

it is a phagocyte, granulocyte (contain many granules), typically more potent and better at killing organisms than macrophages; granules contain many antimicrobial compounds including defensin

the complement system

A group of about 30 blood proteins that may amplify the inflammatory response, enhance phagocytosis, or directly lyse extracellular pathogens; composed of the alternative pathway, lectin pathway, and classical pathway

alternative pathway

First to act; Pathogen surface creates local environment conducive to complement activation; C3 convertase, opsonization, receptors recognize C3b when it has been cleaved, membrane attack complex, C3a and C5a float away and act as a chemokine, immune recruitment and leaky vessels; can act on blood vessels to increase vascular permeability and cause dilation

lectin pathway

second to act; Mannose-binding lectin binds to pathogen surface

classical pathway

third to act; C-reactive protein or antibody binds to specific antigen in pathogen surface

How does the complement system work?

alternative, lectin, and classical pathways lead to compliment activation, then C3 cleaves into C3a and C3b; C3b covalently bonds to the surface components of the pathogen (formed by the = sharing of electrons); then a recruitment of inflammatory immune cells, opsonization of pathogen facilitating uptake and killing by phagocytes, perforation(poke holes) of pathogen cell membrane, then death of pathogen

C3

made by the liver and is released into the bloodstream at high levels (always floating around), the most critical component of the complement cascade; enters circulation in an inactive form (zymogen) and is then cleaved which exposes a highly reactive bond thioester that can attach to the surface of a pathogen; will not react with own cells

C3a

inflammation; recruits phagocytes

C3b

tags bacterium for destruction

C3 convertase of alternative pathway

an assembly of proteins that deposit thousands if C3b, like a flag/tag, positive feedback; makes more C3b

Opsonization

enhances phagocytosis if bacterium is coated with C3b, receptors recognize C3b when it has been cleaved; compliment activation leads to deposition of C3b on the microbe cell wall

C5 convertase

Enzyme complex that cleaves C5 to C5a and C5b.

membrane attack complex (MAC)

C5b attracts compliment proteins and forms a pore, this compromises the membrane and leads to cell lysis

how does immune response start?

macrophages underneath epithelium start the response, recognize pathogen, and can attract mote macrophages or neutrophils, can start T or B cell response

Monocytes

a type of white blood cell; immature macrophages, in the blood stream- when it leaves to go into tissue it can mature into macrophage; have receptors for chemokines

adhesion molecules

help WBCs stick to the endothelium; only present when introduced to invaders; sticky, signaled by cytokine; increases phagocytosis

complement proteins

proteins that lyse the cell wall of an antigen; part of the nonspecific defense mechanisms of the immune system; spontaneous cleavage event

effector mechanisms of neutrophils

phagocytosis where it swallows an invader whole, one inside it gets digested and broken down

degranulation

neutrophils spew toxins to kill a pathogen from afar; release effector molecules; can be from a distance

NETosis

neutrophils disgorge their own DNA and ensnare microbes in the strands (release of DNA); neutrophil extracellular traps; can be from distance

Trogocytosis

several neutrophils surround and nibble a parasite to death; must be in contact

Phagocytosis

process in which neutrophils/ extensions of cytoplasm surround and engulf large particles and take them into the cell; must be in contact

what is the difference between macrophages and neutrophils?

macrophages are long lived and have less effector mechanisms; neutrophils have more effector mechanisms (toxic), and are short lived (hrs.)

Pathogen-associated molecular patterns (PAMPs)

Molecules associated with groups of pathogens that are recognized by cells of the innate immune system; the "stuff" that gets recognized as as foreign/non-self

How are PAMPs recognized?

structures, patterns and or molecules unique to invading microbes; in bacteria: components of the cell wall (LPS), flagellin protein, cytoplasmic DNA. In viruses: uncapped ssRNA in cytoplasm, dsRNA, cytoplasmic DNA

Pattern Recognition Receptors (PRRs)

proteins on or in cells that recognize specific compounds unique to microbes or tissue damage, allowing the cells to sense the presence of invading microbes or damage; Found on phagocytes, dendritic cells, endothelial cells, and lymphocytes; Recognize and bind PAMPs

Outcomes of PAMP recognition

1. phagocytosis- if the bacteria is recognized as foreign & there is a neutrophil or macrophage around, it could lead to engulfment

2. secretion of inflammatory cytokines

3 Major types of phagocytes

macrophages, granulocytes (neutrophils), dendritic cells

dendritic cells

(DCs) found in tissues, take microbes or fragments of microbes and shuttle them into lymph nodes; act as a bridge b/w the innate and adaptive immune system; immature reside in tissue, they migrate via lymphatic vessels to regional lymph nodes, then are matured and activate naive T cells; always sampling their surroundings, important in initiation of B & T cell responses

Mannose receptor

(PRR)cell-surface receptor on dendritic cells, macrophages, and other leukocytes that binds to mannose residues on the surfaces of pathogens, PAMP. LPS, CPs

Complement receptors

(PRR) bind to and ingest complement C3b coated microbes

Scavenger receptors

PRRs that recognizes and binds to negatively charged lipids found on microbes, lipoproteins common to bacterial cell walls

local effects of PAMP recognition

microbe is recognized by tissue macrophage which then starts to release cytokines

IL-I beta & TNF- alpha

cytokines that induce blood vessels to become more permeable, enabling effector cells and fluid containing soluble effector molecules to enter the infected tissue

IL- 6

cytokine that induces fat and muscle cells to metabolize, make heat and raise body temp in the infected tissue; trying to make a less hospitable environment for the microbe

CXCL8

chemokine, recruits neutrophils from the blood and guides them to the infected tissue

IL-12

cytokine that recruits and activates natural killer cells that in turn secrete cytokines that strengthen the macrophages in response to infection

endogeneous pyrogens

IL-I beta, IL-6, TNF alpha often referred to as this because they can induce fever

Systemic effects of PAMP recognition

(IL-1, IL-6, TNF-alpha) in the liver, acute phase proteins (C-reactive protein, mannose binding lectin) activation of complement opsonization. in bone marrow, endothelium -neutrophil mobilization-phagocytosis. in hypothalamus an increased body temp. in fat/muscle protein & energy mobilization to generate increased body temp, decreased viral and bacterial replication

PAMP recognition events

recognition of PAMP(signaling cascade)- causes signaling event - changes gene transcription - production of inflammatory cytokines

Toll-like receptors (TLRs)

-A type of PRR, Recognize PAMPs

-Set in motion a cascade of events inside the cell that amplifies and orchestrates a defense response to the pathogen(downstream signaling)

-initiates inflammation

-found at plasma membrane (Bacterial/fungal PAMPS) or within endosome (viral PAMPs)

Endosomes

intracellular compartment that transport molecules between Golgi apparatus, lysosomes, and plasma membrane

respiratory burst

oxygen uptake burst, O2 to H2O2

Reactive Oxygen Species (ROS)

a group of extremely reactive peroxides and oxygen-containing radicals that may contribute to cellular damage; hydrogen peroxide, superoxide

Chronic Granulomatous Disease (CGD)

defect in NADPH oxidase → ↑ susceptibility to infections with catalase + organisms (S. aureus, Aspergillus, etc...); genetic deficiency in NADPH oxidase (ability to kill microbe is effected if this lacks); highly susceptible to bacterial and fungal infections especially in early life

MyD88

Adaptor protein that binds to TLR4 and activates IRAK

Antibodies

B-cell receptors; Protein that is produced by lymphocytes and that attaches to a specific antigen; begin life attached to B cell plasma membrane; when b cell activates, it will start to release

Antigen

a toxin or other foreign substance that induces an immune response in the body, especially the production of antibodies; the entire molecule

epitope

A small, accessible region of an antigen to which an antigen receptor or antibody binds; also called an antigenic determinant; one antigen could have many

antibody binding

the process by which an antibody identifies and attaches to a specific antigen; always through non-covalent binding

Immunoglobulin (Ig)

antibody, structurally composed of heavy and light chains, variable region, constant region, and hinge region; most variability in the ends of the arms in the Y shaped structure

heavy chain

One of the two types of polypeptide chains that make up an antibody molecule and B cell receptor; consists of a variable region, which contributes to the antigen-binding site, and a constant region.(V, D, J, C exons)

light chain

One of the two types of polypeptide chains that make up an antibody molecule and B cell receptor; consists of a variable region, which contributes to the antigen-binding site, and a constant region. (V,J,C exons)

constant region

portion of an antibody molecule that is not variable and participates in the binding of other immune modulators

variable region

The region of antibodies that makes contact with the epitopes/antigen; variability in amino acid sequence; varies from one antibody to another even within one class