Lessons 1-3

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

Inflammation cycle via cytokines

-bacteria trigger macrophages to release cytokines/chemokines -macrophages recruit neutrophils to site of invasion -neutrophils and monocytes enter and produce an immune response

Examples of PRRs

-mannose and glucan receptors and the scavenger receptors (bind cell-wall carbohydrates of bacteria, yeast, and fungi) -NOD like receptors (sense intracellular bacterial invasion) -Toll-like receptors (TLRs) are an important family of pattern recognition receptors present on macrophages, dendritic cells, and other immune cells. Recognize different microbial components; for example, a heterodimer of TLR-1 and TLR-2 binds certain lipopeptides from pathogens such as Gram-positive bacteria, while TLR-4 binds both lipopolysaccharides from Gram-negative and lipoteichoic acids from Gram-positive bacteria

Steps of inflammatory response

1) Bacteria trigger macrophages to release cytokines and chemokines (direct the migration of neutrophils to the site of infection) 2)Vasodilation and increased vascular permeability cause redness, heat, and swelling 3) Inflammatory cells migrate into tissue, releasing inflammatory mediators that cause pain

Cell mediated immunity steps

1) Inflammatory inducers are chemical structures that indicate the presence of invading microbes or the cellular damage produced by them. 2) Sensor cells detect these inducers by expressing various innate recognition receptors, and in response produce a variety of mediators that act directly in defense or that further propagate the immune response. 3) Mediators include many cytokines, and they act on various target tissues, such as epithelial cells, to induce antimicrobial proteins and resist intracellular viral growth; or on other immune cells, such as ILCs that produce other cytokines that amplify the immune response.

Functions of macrophages

1) engulf and kill invading microorganisms. This phagocytic function provides a first defense in innate immunity. 2) Dispose of pathogens and infected cells targeted by an adaptive immune response. 3) orchestrate immune responses: they help induce inflammation, 4) produce many inflammatory mediators that activate other immune-system cells and recruit them into an immune response

Adaptive immunity is initiated when

1)an innate immune response fails to eliminate a new infection 2) activated antigen-presenting cells—typically dendritic cells that bear antigens from pathogens and co-stimulatory receptors—migrate to the draining lymphoid tissues.

Basophils

A circulating leukocyte that produces histamine. Promotion of allergic responses and augmentation of anti-parasitic immunity

Major histocompatibility complex (MHC)

A family of genes that encode a large set of cell surface proteins called MHC molecules. Class I and class II MHC molecules function in antigen presentation to T cells. Foreign MHC molecules on transplanted tissue can trigger T cell responses that may lead to rejection of the transplant

complement system

A group of about 30 blood proteins that may amplify the inflammatory response, enhance phagocytosis, or directly lyse extracellular pathogens. can lead to inflammation, opsonization, lysis, and neutralization

Granulocytes

A group of leukocytes containing granules in their cytoplasm; short lived mature in the bone marrow, and their production increases during immune responses neutrophils, eosinophils, basophils

Natural killer cells

A type of white blood cell that can kill tumor cells and virus-infected cells; an important component of innate immunity. especially important against intracellular infections Unlike lymphocytes, they lack antigen specific receptors Releases lytic granules that kill some virus-infected cells

Neutrophils

A type of white blood cell that engulfs invading microbes and contributes to the nonspecific defenses of the body against disease. most common WBC major phagocytic cell

opsonization

Antibodies coating an antigen render it recognizable as foreign by phagocytes (macrophages and neutrophils), which then ingest and destroy it With the antigen coated in opsonins, binding to immune cells is greatly enhanced

Peyer's patches function

Antigen is collected by specialized epithelial cells called microfold or M cells. The lymphocytes form a follicle consisting of a large central dome of B lymphocytes surrounded by smaller numbers of T lymphocytes. Dendritic cells resident within the Peyer's patch present the antigen to T lymphocytes. Effector lymphocytes generated in Peyer's patches travel through the lymphatic system and into the bloodstream, from where they are disseminated back into mucosal tissues to carry out their effector actions

Difference between antigens and epitopes

Antigens are the molecules recognized by the immune response while epitopes are the sites within the antigens to which antigen receptors bind Antigens are often much bigger and complex than the sites to which they bind. The actual portion of the antigen that is bound is known as the antigenic determinant, or epitope

Adaptive immunity relies on what two types of cells?

B cells: mature in the bone marrow and are the source of circulating antibodies. T cells: mature in the thymus and recognize peptides from pathogens presented by MHC

CD8 T cells selectively recognize peptides that are bound to _____ molecules, while CD4 T cells recognize peptides presented by ___

CD8: MHC class I CD4: MHC class II

antibody structure

Composed of two identical heavy chains and two identical light chains. Heavy and light chains each have variable and constant regions. The variable regions of a heavy chain and a light chain combine to form an antigen-binding site that determines the antigen-binding specificity of the antibody. Both heavy and light chains contribute to the antigen- binding specificity of the antibody molecule

Features of lymphocyte development that distinguish adaptive immunity from innate immunity

Each developing lymphocyte expresses only one receptor specificity. Whereas the cells of the innate immune system express many different pattern recognition receptors and recognize features shared by many pathogens, the antigen-receptor expression of lymphocytes is 'clonal,' so that each mature lymphocyte differs from others in the specificity of its antigen receptor. Because the gene rearrangement process irreversibly changes the lymphocyte's DNA, all its progeny inherit the same receptor specificity.

Process of clonal selection

Each lymphoid progenitor gives rise to a large number of lymphocytes, each bearing a distinct antigen receptor. Lymphocytes with receptors that bind ubiquitous self antigens are eliminated before they become fully mature, ensuring tolerance to such self antigens. When a foreign antigen interacts with the receptor on a mature naive lymphocyte, that cell is activated and starts to divide. It gives rise to a clone of identical progeny, all of whose receptors bind the same antigen. Antigen specificity is thus maintained as the progeny proliferate and differentiate into effector cells. Once antigen has been eliminated by these effector cells, the immune response ceases, although some lymphocytes are retained to mediate immunological memory.

Course of antibody response

First encounter with an antigen produces a primary response. Antigen A introduced at time zero encounters little specific antibody in the serum. After a lag phase (light blue), antibody against antigen A (dark blue) appears; its concentration rises to a plateau and then gradually declines, typical of a primary response. When the serum is tested for antibody against another antigen, B (yellow), there is little preset. When the animal is later challenged with a mixture of antigens A and B, a very rapid and intense antibody secondary response to A occurs, illustrating immunological memory. This is the main reason for giving booster injections after an initial vaccination. Note that the response to B resembles the primary response to A, as this is the first encounter with antigen B

mucosa-associated lymphoid tissues (MALT)

Generic term for lymphoid tissues associated with the gastrointestinal tract, bronchial tree and other mucosa.

Innate Lymphoid Cells (ILCs)

ILCs have roles in mediating immune response. Lymphoid cells are not specific to adaptive immune response. develop from the same progenitor cells in the bone marrow as NK cells, and they also lack antigen-specific receptors comprise several closely related lineages that differ in the specific cytokines that they will produce when activated

Dendritic cells initiate adaptive immune responses

Immature dendritic cells residing in a tissue take up pathogens and their antigens by macropinocytosis and by receptor-mediated endocytosis. They are stimulated by recognition of the presence of pathogens to migrate through the lymphatics to regional lymph nodes, where they arrive as fully mature nonphagocytic dendritic cells that express both antigen and the co-stimulatory molecules necessary to activate a naive T cell that recognizes the antigen. Dendritic cells stimulate lymphocyte proliferation and differentiation

Function of the spleen

Immune surveillance and response in BLOOD. Collects antigens in blood and also degrades old RBCs and damaged RBCs.

innate immunity

Immunity that is present before exposure and effective from birth. Responds to a broad range of pathogens.

Compare contrast innate vs adaptive immunity

Innate immune responses occur rapidly on exposure to an infectious organism Adaptive immune system responses take days rather than hours to develop. Is capable of eliminating infections more efficiently because of exquisite specificity

Difference between innate and adaptive immunity

Innate: bodies initial generalized defense (non specific) includes fever, pH change, monocytes, neutrophils,macrophage, inflammation. Adaptive: specific defense includes B and T cells, plasma membrane, antigen-presenting cells

How do dendritic cells link the innate immune system and the adaptive immune systems?

Like the other cells of innate immunity, dendritic cells recognize pathogens via invariant cellsurface receptors for pathogen molecules and are activated by these stimuli early in an infection. Dendritic cells in tissues are phagocytic; they are specialized to ingest a wide range of pathogens and to display their antigens at the dendritic cell surface in a form that can be recognized by T cells

gut-associated lymphoid tissues (GALT)

Lymphoid tissues closely associated with the gastrointestinal tract, including the tonsils, adenoids appendix, Peyer's patches in the intestine, and layers of intraepithelial lymphocytes.

What two types of cells are involved in phagocytosis?

Macrophages and neutrophils

Three types of phagocytes in the immune system

Macrophages, granulocytes, dendritic cells

pathogen-associated molecular patterns (PAMPs)

Molecules associated with groups of pathogens that are recognized by cells of the innate immune system.

The innate immune system relies on _______, the adaptive immune system relies on _________.

PRRs to detect common microbial structures (PAMPs) or the damage they cause a repertoire of antigen receptors to recognize structures that are specific to individual pathogens

Clonal selection theory

States that the antigen selects which lymphocyte will undergo clonal expansion and produce more lymphocytes bearing the same type of receptor.

What would happen if you only had an immune response that was in days or weeks?

The microbes would always overpower the immune system because of such a fast replication rate

clonal selection

The process by which an antigen selectively binds to and activates only those lymphocytes bearing receptors specific for the antigen. The selected lymphocytes proliferate and differentiate into a clone of effector cells and a clone of memory cells specific for the stimulating antigen.

monocytes

Type of white blood cell that differeniate into macrophages or dendritic cells circulate in the blood and continually migrate into tissues, where they differentiate

Explain the role of peripheral lymphatic organs in infection

When an infection occurs in a tissue such as the skin, free antigen and antigen bearing dendritic cells travel from the site of infection through the afferent lymphatic vessels into the draining lymph nodes —peripheral lymphoid tissues where they activate antigen-specific lymphocytes. The activated lymphocytes then undergo a period of proliferation and differentiation, after which most leave the lymph nodes as effector cells via the efferent lymphatic vessel. This eventually returns them to the bloodstream, which then carries them to the tissues where they will act

Effector T lymphocytes

When effector T cells subsequently detect antigen, they can manifest three broad classes of activity. Cytotoxic T cells kill other cells that are infected with viruses or other intracellular pathogens bearing the antigen. Helper T cells provide signals, often in the form of specific cytokines that activate the functions of other cells, such as B-cell production of antibody and macrophage killing of engulfed pathogens. Regulatory T cells suppress the activity of other lymphocytes and help to limit the possible damage of immune responses.

complement

a component of serum that acts in conjunction with antibodies to destroy pathogenic bacteria

Memory cells

a long-lived lymphocyte capable of responding to a particular antigen on its reintroduction, long after the exposure that prompted its production.

memory cells

a long-lived lymphocyte capable of responding to a particular antigen on its reintroduction, long after the exposure that prompted its production. can be reactivated much more quickly than naive lymphocytes, which ensures a more rapid and effective response on a second encounter with a pathogen and thereby usually provides lasting protective immunity.

complement activation

activation of the complement system by antibodies coating a bacterial cell. Bound antibodies form a platform that activates the first protein in the complement system, which deposits complement proteins on the surface of the bacterium. This can lead in some cases to formation of a pore that lyses the bacterium directly. More generally, complement proteins on the bacterium can be recognized by complement receptors on phagocytes; this stimulates the phagocytes to ingest and destroy the bacterium

lymphocytes = _____ immunity

adaptive

Leukocytes

all white blood cells including innate and adaptive immune cells

First line of defense

anatomic barriers skin, mucosa, intestine, respiratory epithelium

neutralization

antibodies protect against pathogens or their products is by binding to them and thereby blocking their access to cells that they might infect or destroy

Antibodies are ____ receptors

antigen

Defensins

antimicrobial peptides that inhibit microbial growth makes a pore in the lipid bilayer of microbes

Cytokine

any protein secreted by immune cells that affects the behavior of nearby cells bearing appropriate receptors

antigen

any substance recognized by the adaptive immune system that triggers the production of antibodies Typically antigens are common proteins, glycoproteins, and polysaccharides of pathogens Can include a much wider range of chemical structures, for example, metals such as nickel, drugs such as penicillin, and organic chemicals such as the urushiol (a mix of pentadecylcatechols) in the leaves of poison ivy.

What are three strategies of hosts to deal with the threat posed by microbes?

avoidance, resistance, and tolerance avoidance: prevent exposure to microbes, and include both anatomic barriers and behavior modifications tolerance: increasing growth by activating dormant meristems, the undifferentiated cells that generate new parts of the plant

Three layers of immunity

barrier, innate, adaptive

antibodies

bind specifically to toxins and neutralize their activity

Fc receptors

bind the constant region and facilitate phagocytosis of the bacterium

Most cells of the immune system arise from the

bone marrow

hematopoietic stem cells

cells in the bone marrow that give rise to all cells in the blood All the cellular elements of blood, including the red blood cells that transport oxygen, the platelets that trigger blood clotting in damaged tissues, and the white blood cells of the immune system are produced by these cells

Opsonization

coating antigen with antibody enhances phagocytosis

Spleen function

collects antigen from the blood and is involved in immune responses to blood-borne pathogens collects and disposes of senescent red blood cells

Two regions of antibodies

constant (Fc) region variable region

What cells carry pathogen antigens to peripheral lymphatic organs?

dendritic cells

antibody constant region

determines an antibody's functional properties— how it will engage with the effector mechanisms that dispose of antigen once it is recognized

Clonal deletion

developing lymphocytes that are potentially self-reactive are removed before they can mature

Adaptive immunity develops

develops during the lifetime of an individual as an adaptation to infection with that pathogen

cytotoxic t cells

effector T cells that act against cells infected with viruses.

MHC class II molecules are found on

expressed by the predominant antigen-presenting cells of the immune system: dendritic cells, macrophages, and B cells

antibody isotypes/classes

five forms of the constant region of an antibody Each class carries out its particular function by engaging a distinct set of effector mechanisms

B cell receptor (BCR)

formed by the same genes that encode antibodies, a class of proteins also known as immunoglobulins (Ig) antigen receptor of B lymphocytes is also known as membrane immunoglobulin (mIg) or surface immunoglobulin (sIg)

CD8 and CD4

glycoprotein markers that identify and distinguish various types of T cells help to determine the interactions between the T cell and other cells

Mast cell

granules contain many inflammatory mediators, such as histamine and various proteases, which play a role in protecting the internal surfaces from pathogens, including parasitic worms trigger a local inflammatory response to antigen by releasing substances that act on local blood vessels

naive lymphocytes

have receptors; have not yet encountered appropriate antigen

SLO initiate

immune system responses

humoral immunity

immunity mediated by antibodies

The immune system is activated by __________ that indicate the presence of pathogens or tissue damage.

inflammatory inducers

What happens when a lymphocyte encounters its corresponding antigen in the peripheral lymphatic tissues?

it proliferates, and its clonal progeny differentiate into effector T and B lymphocytes that can eliminate the infectious agent. A subset of these proliferating lymphocytes differentiates into memory cells, ready to respond rapidly to the same pathogen if it is encountered again.

Peyer's patches

large collections of lymphoid tissue found in the submucosa of the small intestine have no afferent lymphatics, and the antigen enters directly from the gut across a specialized epithelium made up of so-called microfold (M) cells

Secondary lymphoid organs

lymph nodes Peyer's patches spleen mucosal tissues

Main cell types seen in the initial phase of an inflammatory response are

macrophages and neutrophils

Inflammatory inducers

molecular components unique to bacteria or viruses, such as bacterial lipopolysaccharides, or molecules such as ATP, which is not normally found in the extracellular space PAMPs

Shortest lived cells of the immune system

neutrophils, basophils, eosinophils

Three types of granulocytes

neutrophils, eosinophils, and basophils

Does the innate immune response differ when exposed to the same pathogen multiple times?

no

Activation of B cells requires

not only antigen, which binds to the B-cell receptor, but also the cooperation of activated helper T cells, a type of effector T cell

MHC class I are found on

on most cells of the body, serve as an important mechanism to defend against viral infections

Each developing lymphocyte expresses_____ receptor specificity

one

Each lymphocyte carries cell-surface receptors of _____ antigen(s)

one single

Three ways antibodies can participate in host defense

opsonization neutralization complement activation

Eosinophils and basophils are thought to be important chiefly in defense against

parasites also play a role in allergic responses

Antigen and lymphocytes eventually encounter each other in

peripheral lymphoid organs the lymph nodes, spleen, and mucosal lymphoid tissues

Dendritic cell

phagocytic when they are immature and can take up pathogens; after maturing, they function as specialized cells that present pathogen antigens to T lymphocytes in a form they can recognize, thus activating T lymphocytes and initiating adaptive immune responses Function Antigen uptake in peripheral sites Antigen presentation

Primary lymphoid organs

place where immune system development occurs bone marrow and thymus

All cellular elements of the blood and the immune system arise from

pluripotent hematopoietic stem cells in the bone marrow

nasal-associated lymphoid tissue (NALT) and bronchus-associated lymphoid tissue (BALT)

present in the respiratory tract. Like the Peyer's patches, these mucosal lymphoid tissues are also overlaid by M cells, through which inhaled microbes and antigens that become trapped in the mucous covering of the respiratory tract can pass.

barrier defenses of innate immunity

protecting body from microbes entering and colonizing in the body skin, stomach (ex: stomach acid), airway, urogenital tract, mucus, microbes common features are antimicrobial peptides produced by barrier organs

pattern recognition receptors (PRR)

proteins on or in sensor cells (Macrophages, neutrophils, and dendritic cells) that recognize specific compounds unique to microbes or tissue damage, allowing the cells to sense the presence of invading microbes or damage recognize simple molecules and regular patterns of molecular structure known as pathogen-associated molecular patterns (PAMPs) that are part of many microorganisms but not of the host body's own cells.

Spleen white vs red pulp

red pulp: site of red blood cell disposal white pulp: contains lymphocytes that can stimulate an immune response.

immunological tolerance

refers to mechanisms that prevent an immune response from being mounted against the host's own tissues

Macrophages

relatively long-lived cells and have roles in both adaptive and innate immune systems Functions: Phagocytosis and activation of bactericidal mechanisms Antigen presentation

NK cells

responsible for immune surveillance has granules (small particles) with enzymes that can kill tumor cells or cells infected with a virus

Chemokines

specialized subgroup of secreted proteins that act as chemoattractants, attracting cells bearing chemokine receptors, such as neutrophils and monocytes, out of the bloodstream and into infected tissue

Dendritic cells

specialized white blood cells that patrol the body searching for antigens that produce infections a major class of sensor cells whose encounter with pathogens triggers them to produce mediators that activate other immune cells

adaptive immunity

the ability to recognize and remember specific antigens and mount an attack on them ex: a person recovered from measles is now protected from measles

plasma cells

the effector form of B lymphocytes, and they secrete antibodies that have the same antigen specificity as the plasma cell's B-cell receptor. The antigen that activates a given B cell becomes the target of the antibodies produced by that B cell's progeny.

Clonal expansion

the mass proliferation of antibody-producing cells by clonal selection clone of identical cells can now secrete clonotypic antibodies with a specificity identical to that of the surface receptor that first triggered activation and clonal expansion

common myeloid progenitor

the precursor of the macrophages, granulocytes, mast cells, and dendritic cells of the innate immune system

Questions to think about with pathogens

their replication rate One important function of innate immune responses is to keep the numbers down until the adaptive immune system can pick up

effector lymphocytes

those that have met their antigen, become activated, and have differentiated further into fully functional lymphocytes

What is the major function of the complement in complement activation?

to enable phagocytes to engulf and destroy bacteria that the phagocytes would not otherwise recognize

What is the common purpose of the spleen, lymph nodes, and mucosa associated lymph tissues?

trapping antigens and antigen-presenting cells from sites of infection in order to present antigen to migratory small lymphocytes, thus inducing adaptive immune responses

interferon gamma

type of cytokine that acts by activating phagocytes to more efficiently kill intracellular pathogens and by inducing target tissues to resist intracellular pathogens produced by some but not all subsets of innate and adaptive lymphocytes

How do T cells recognize epitopes?

usually recognize protein antigens and do so very differently from antibodies. can recognize epitopes that are buried within antigens. These antigens must first be degraded by proteases and the peptide epitope delivered to a self molecule, called an MHC molecule. It is in this form, as a complex of peptide and MHC molecule, that antigens are recognized by T-cell receptors (TCR)

Activation of B cells

usually requires not only antigen, which binds to the B-cell receptor, but also the cooperation of activated helper T cells, a type of effector T cell

How are T cells activated?

via encounters with dendritic cells that have picked up antigens at sites of infection and migrated to secondary lymphoid organs.

Eosinophil

white blood cell containing granules that stain red; associated with allergic reactions Killing of antibody-coated parasites