ImmunoSero Lec (Midterms - Immune Response) Flashcards by CHENNEDETTE RESYL MAGLANGIT

Chemicals measured in the lab to determine whether a patient has a certain inflammaotry condition or not. It is produced in response to inflammation

Acute Phase Reactants

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The body’s overall reaction to injury or invasion by an infectious agent.

Inflammation

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These mechanisms are involved in a complex when pathogens breach the outer barriers of innate immunity.

Cellular and humoral mechanisms

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Its primary objective is to localize and irradicate the irritant and repair the surrounding tissue.

Inflammation

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A prolonged inflammatory response in chronic inflammation will affect surrounding tissue due to the release of …

Cytokines, Chemokines, and action of Macrophages in the area

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A condition where the body’s defense system inappropriately tiggers an inflammatory response when no foreign substances are present. In this disorder, the immune system causes damage to its own tissues

Autoimmune disorders

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Precursor of inflammation

Tissue damage

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In acute inflammation, the first thing that happens is the ________________ to the affected area. By doing so, we also increase our hold on to the ________________ blood cells.

increase of blood supply; white

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Major stages in inflammatory response

Dilation of capillaries to increase blood flow
Increased capillary permeability
Leukocyte transmigration through endothelium and accumulation at the site of injury
Phagocytosis

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Causes the release of chemical mediators such as histamine from injured mast cells.

Vasodilation of blood vessels

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This cardinal sign of inflammation results from the additonal blood flow of mediators or in other words due to increase blood supply and vasodilation.

Rubor (redness)

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This cardinal sign of inflammation is due to the release of histamine and other chemical mediators brought upon by the dilation of blood vessels.

Calor (heat)

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This allows the WBC to easily pass through.

Increased capillary permeability

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This cardinal sign of inflammation is due to the increased permeability of the blood vessels allowing the fluids and the plasma to leak into the tissues

Swelling (tumor)

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This cardinal sign of inflammation comes together with the swelling due to the release of chemical mediators.

Dolor (pain)

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Among the first cells to arrive at the scene of an infection and are important contributors to the acute inflammatory response.

Neutrophils

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Migration of WBCs, mainly neutrophils, from the capillaries to the surrounding tissue

Diapedesis

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Soluble mediators that act as chemoattractant to initiate and control the response.

Acute Phase Reactants
Chemokines
Cytokines

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Neutrophils are mobilized within how many minutes after the injury? How long will its emigration last?

Mobilized within 30-60 minutes
Lasts 24 to 48 hours

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Prior to diapedesis, the neutrophils move inside the blood vessels in the process known as ________________________. And they connect to the endothelial cells through the receptor ____________________.

Process: rolling
Receptor: L-selectin

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Carbohydrate structure which binds L-selectin on the endothelial cells

Sialyl-Lewis X

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Cell surface adhesion molecule that replaces L-selectin as neutrophil becomes activated.

integrins

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Migration of macrophages and dendritic cells from surrounding tissue peaks at

16 to 48 hours

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These cells attempt to clear the area through phagocytosis

Macrophages, neutrophils, and dendritic cells

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Stimulate phagocytosis

Acute-phase Reactants

Decrease in oxygen

Hypoxia

Decrease in oxygen and nutrients

Ischemia

Prolonged inflammation that happens when the acute inflammatory response went on a longer period of time.

Chronic inflammation

This is diagnosed when inflammation overwhelms the whole body.

Systemic Inflammatory Response Syndrome (SIRS)

Criteria for SIRS in terms of body temperature, heart rate, respiratory rate, and total leukocyte count.

1. Alteration of body temperature (**> 38C or < 36C**) 2. Increased heart rate 3. Increased respiratory rate 4. Total leukocyte count of **>12.0 x 109 /L** (or >10% immature forms

Stages of SIRS (3)

1. Sepsis (SIRS + infection) 2. Severe Sepsis (Sepsis + organ dysfunction) 3. Septic Shock (fatal; low blood pressure resulting to death)

Begins when the innate immune system response aggresively to the presence of bacteria.

Sepsis

Receptors from macrophages that cause the antigen presenting cell (APC) to produce proinflammatory cytokines

Toll-like receptors (TLR)

Proinflammatory cytokines

Tumor Necrosis Factor (TNF) Interleukin 1 Interleukin 6

Activate the PMN cells, platelet activating factor, leukotrienes, arachidonic acid, and plasminogen activator inhibitor.

Proinflammatory cytokines (TNF, IL-1, IL-6)

APCs involve the adaptive immune system by presenting bacterial antigen to T-cell receptor using this major histocompatibility complex (MHC) protein and co-stimulation of CD28

Class II major histocompatibility complex

Proteins produced in response to infection or inflammation

1. TNF-a 2. IL-1 and IL-6 3. Procalcitonin 4. Chemokines

A very effective biomarker of infection and systemic inflammation. Its level increases in response to a pro-inflammatory stimulus, especially of bacterial origin.

procalcitonin

Found to differentiate whether fever is bacterial (increase) or viral (normal)

Procalcitonin

Elimination of foreign cells or pathogens that have entered the human body

Phagocytosis

Phagocyte cells

Neutrophils Monocytes Macrophages Dendritic Cells

Phagocyte cells adhere to receptors on the endothelial cell wall of the blood vessels and **penetrate through the tissue by means of** ...

Diapedesis

6 steps of phagocytosis

1. Chemotaxis 2. Adherance (recognition & attachment) 3. Engulfment 4. Phagosome maturation 5. phagolysosome formation 6. Destruction and Digestion 7. Exocytosis

A process where chemoattractants **attract neutrophils** to the site of inflammation.

Chemotaxis

Defined as a change in the direction of movement of amotile cell in response to a concentration gradient of a specific chemical, chemotaxin.

Chemotactic response

After neutrophil have been attracted to the site, physical contact between the wbc and the foreign cells happens. This adherance is aided by ...

opsonins

Q1: Outflowing of the cytoplasm to **surround the microorganisms**. Q2: This outflowing is termed as ________________ which surrounds/encloses the pathogen forming a structure known as phagosome.

Engulfment Pseudopodia Formation

Formed when a phagosome fuses with a lysosome which would then trigger the lysosome to release its lysosomal content.

Phagolysosome

Digests organisms

Hydrolytic enzymes

A means where acid debris is released outside

Exocytosis

These function as chemoattractants

Antigens

**Enhances binding surface** which are serum proteins that **attach to a foreign cell or pathogen** and help prepare it for phagocytosis

Opsonin

Aside from opsonins, the antibody also facilitate or enhances phagocytosis or adhesion through this receptor.

FC receptor

The speed of phagocytosis can be greatly increased by recruiting these two attachment devices called ...

FC Receptor Complement Receptor (C3)

Which among the following does not enhance the binding of the phagocytes with the foreign matter: Opsonins Antibody C3 AOTC NOTC

NOTC

Contents of phagolysosome granules

Lysozyme Myeloperoxidase Other Proteolytic Enzyme

Follows ingestion of particles with the requires energy primarily provided by anaerobic glycolysis.

Digestion

Degradatory enzymes type: Azurophilic Granules containing enzymes **Lysozyme, myeloperoxidase**

Primary

Degradatory enzymes type; specific granules containing substances **lactoferrin**

Secondary

Tertiary granules contain substances such as

caspases

**Antibacaterial substances** released through the degranulation of neutrophils

Lactoferrin Lysozyme Defensin

One of the several substanes that can damage host tissues.

Elastase

An increase in oxygen consumption, known as the oxidative/respiratory burst, occurs within the cell as the pseudopodia encloses the particle within a vacuole.

Oxygen dependent pathway

The oxygen dependent pathway generates considerable energy via ...

oxidative metabolism

Used to reduce nicotinamide adenine dinucleotide phosphate (NADP) to NADPH by adding a hydrogen.

Hexose monophosphate shunt

NADPH reduces the ________________ to oxygen through NADPH oxidase complex which then assembles in the membrane of your phagolysosome.

superoxide

**Catalyze the conversion** of superoxide to hydrogen peroxide (potent antimicrobial) or the hydroxyl radical OH

Superoxide dismutase

One of the granules in lysozyme that **catalyze the formation** of hypochlorite (powerful oxidizing agent). This would also produce hydroxyl radicals (powerful oxidizing agent; formed if iron ions are present).

Myleoperoxidase (MPO)

The associated cyanide **increase in oxygen consumption**.

oxidative burst

A bactericidal agent considered as more stable than any free radicals, antimicrobial, enhanced by formation of hypochlorite ions.

Hydrogen peroxide

A powerful oxidizing agent and is highly toxic for microorganisms. It is the main component of household bleach used to disinfect surfaces.

Hypochlorite

Plays a major roles in the oxygen-independent pathway wherein it **depolarizes the membrane** when fusion with the phagosome occurs, **allowing hydrogen and potassium ions to enter** the vacuole.

NADPH

When activated contributes to microbial elimination

proteases

Small cationic proteins which are able to cleave segments of bacterial cell walls without the benefit of oxygen.

Defensins

Organisms killed by defensins

Gram positive & negative bacteria Fungi Viruses

A protein able to damage bacterial cell membranes.

Cathepsin G

Lymphocytes part of innate reponse that represent the **first line of defense** against cells that are virally infected, cells infected with other intracellular pathogens, and tumor cells.

NK Cells

Have the ability to recognize any damaged cell and to eliminate target cells **without prior exposure** and also **lacks specificity** which is essential to its function as early defenders against pathogens thus **giving the immune system time to activate** adaptive response.

NK Cells

Associated with resistance to HIV infection and delayed aids progression

NK cell activity, reflected by higher cytotoxic activity, interferon - y, and chemokine production.

Stimulates NK Cells Activity Which releases ...

Stimulates cytokines: Interleukin – 12 Interferon – αlpha Interferon – β Releases : Interferon-gamma (IFN-y) TNF-a CSF

Deliver inhibitory signals

Inhibitory receptors

Deliver signals to activate the cytotoxic mechanisms

Activating receptors

The inhibitory signal is based on recognition of this MHC class proteins which are **expressed on all healthy cells**

Class I MHC

Natural killing occurs when NK cells react with these proteins.

Class I MHC proteins

Lack of MHC antigens

missing self

Proteins that form channels (pores) in the target cell membrane.

Perforins

Packets of enzymes that my enter through the channels and mediate cell lysis

Granzymes

Recognize and lyse antibody-coated cells

Antibody-dependent cell cytoxicity

Binding of Antibody-dependent cell cytoxicity occurs through the ________________ receptor for the Fc protion of immunoglobulin G.

CD16

Any target cell coated with this immunoglobulin can be bound and destroyed.

IgG

Normal serum constituents that increase rapidly because of infection, injury, or trauma to the tissues.

Acute phase reactants

Acute phase reactants are produced primarily by ________________ within 12 to 24 hours in response to an increase in cytokines.

Hepatocytes (liver parenchymal cells)

**Acts like an antibody** because it is capable of opsonization (coating), agglutination, precipitation, and activation of complement by the classical pathway. It is also **calcium dependent-nonspecific**

C-Reactive proteins

Subtrate of C-Reactive proteins

Phosphocholine (part of microbial membrane)

A primitive, **nonspecific form of antibody** molecule that is able to act as a defense against microorganisms or foreign cells until specific antibodies can be produced.

C-Reactive Proteins (CRP)

Most widely used indicator of acute inflammation

CRP

A rise in its level may mean a **return of the malignancy** or beginning of **organ rejection** in transplantation.

CRP

Established clinical tool to evaluate subtle chronic system inflammation and predict cardiovascular or cerebrovascular disease.

Monitoring of CRP

Remember: CRP **< 1mg/L** – low risk for CVD **1 – 3mg/L** – average risk for CVD **>3mg/L** – high risk for CVD Normal adult range: **0.47 to 1.34 mg/L** HS – CRP: **0.01mg/L**

Has the **necessary lower level of detection of 0.01 mg/L**, which enables measurement of much smaller increases than the traditional latex agglutination screening test

High-sensitivity CRP Testing

Means to destory or inactivate C-reactive protein to avoid interference with some testing that detects for the presence of antibodies.

Heat serum to 56C for 30 mins.

Other major protein besides CRP whose concentration can increase almost a thousandfold in response to infection or injury. It is found in the **liver** and indicates **worse prognosis**

Serum Amyloid A (SAA)

Can be increased because of chronic inflammation, ahterosclerosis, and cancer. Becuase it has been found in atherosclerotic lesions, it is now though to contribute to **localized inflammation in coronary artery disease**

Serum Amyloid A (SAA)

A series of serum proteins that are normally present and whose overall function is **mediation of inflammation**

complement

A **general plasma inhibitor of proteases** released from leukocytes, especially elastase that acts to **"mop up"** or **counteract the effects of neutrophil invasion** during an inflammatory response.

Alpha 1- Antitrypsin

Deficiency of Alpha 1- Antitrypsin will lead to

premature emphysema

An alpha 2-globulin which **binds irreversibly to free hemoglobin** released by intravascular hemolysis. This acts as an **antioxidant** to provide protection against oxidative damage mediated by free hemoglobin.

Haptoglobin

Fold increase in haptoblin in inflammation, stress, or tissue necrosis.

2x-10x

True or False. Early in the inflammatory reponse, haptoglobin levels rise.

False. It may drop because of intravascular hemolysis

Most abundant of the coagulation factors in plasma, and it forms the fibrin clot.

Fibrinogen

Makes blood more **viscous** and serves to promote **aggregation** of RBCs and platelets.

Fibrinogen

Increased levels of fibrinogen may contribute to an increased risk for developing

coronary artery disease

This enzyme convert the toxic ferrous ion (Fe2+) to the nontoxic ferric form (Fe3+).

Ceruloplasmin

An autosomal recessive genetic disorder where **copper accumulates in the liver and subsequently in other tissues** such as the brain, corneas, kidneys, and bones. This is due to a **lack or decreased ceruloplasmin**

Wilson's disease