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IMMUNOLOGY AND SEROLOGY

LECTURE / WEEK NO.7/ MACARUBBO L.

INNATE IMMUNITY EXTERNAL DEFENSE SYSTEM


I. External defense system  Composed of physical, chemical, and biological barriers
II. Internal defense system that work together to prevent infection from entering
a. Pathogen-recognition receptors (PRR’s) the body.
b. Acute-phase reactants o Sebaceous gland and sweat glands – act to
c. Inflammation prevent proliferation of the pathogenic
d. Phagocytosis bacteria.
e. Natural killer (NK) cells o Lysozyme – enzyme that destroys the cell wall
of the bacteria.
PHAGOCYTOSIS

 Process wherein a macrophage engulfs a bacteria.


o In the dermis layer where the capillaries and
blood vessels are located, when there is an
infection macrophages will undergo
phagocytosis.
o WBC’S are attracted to the site of infection thru
 Skin
the process called chemotaxis, the neighboring
o Physical barrier with secretions that discourage
cells will send chemokines/ chemo attractants.
microorganism growth
o Bacteria release protein that alert the
o Epidermis: Tightly packed epithelial cells coated
macrophages to their location.
in keratin
o The bacterium is engulfed and locked inside a
o Dermis: Connective tissue with blood vessels,
structure called phagosome (cell membrane of
hair follicles, sebaceous glands, sweat glands,
WBC)
and WBCs
o Special digestive enzymes shared the bacterium
o The WBCs found in the dermis include
into pieces.
macrophages, dendritic cells, and mast cells.
o The resulting harmless particle are either used
by the cell/ released out of the cell.

INNATE IMMUNE SYSTEM

 Innate immunity – natural/ inborn immunity. (Fast


reacting)
 Defenses against infection that immediately act when a
host is attacked by a pathogen
 Composed of two systems that work to promote  Skin
phagocytosis o Lactic acid and fatty acids maintain the skin at a
o External defense system—anatomical barriers pH of approximately 5.6
designed to keep microorganisms from entering o Psoriasin, a small protein produced by skin cells,
the body (e.g., skin) has antibacterial effects
o Internal defense system—includes cellular  Respiratory tract
responses that recognize specific molecular o Mucous secretions block bacteria from
components of pathogens. Phagocytosis adhering to epithelial cells
happens. (cellular level) o Coughing/sneezing moves pathogens out of
tract

IMMUNOLOGY AND SEROLOGY: INNATE IMMUNITY 1


IMMUNOLOGY AND SEROLOGY
LECTURE / WEEK NO.7/ MACARUBBO L.

 Urinary tract  Recognize molecules unique to infectious organisms


o Urine helps remove potential pathogens from  Found on:
the genitourinary tract o Macrophages and dendritic cells, neutrophils,
 Digestive tract eosinophils, monocytes, mast cells, T cells, and
o Stomach’s hydrochloric acid keeps the pH as epithelial cells
low as 1, prohibiting microorganism growth  Encoded by host’s DNA to sense extracellular infection
o Normal flora (microbiota) help to keep  Recognize pathogen-associated molecular patterns
pathogens from establishing themselves in (PAMPs) on microorganisms
these areas.  When bound to a pathogen, activate phagocytic cells
o Antibiotics – cannot discriminate good and bad  TLR detects the presence of PAMPs.
bacteria, therefore it will kill off both good and
bad bacteria.

INTERNAL DEFENSE SYSTEM

 Internal defense system


o Pathogen-recognition receptors (PRRs)
o Acute-phase reactants
o Inflammation
o Phagocytosis
o Natural killer (NK) cells

PATHOGEN-RECOGNITION RECEPTORS (PRRS) EXAMPLE OF PRRs

 Dendritic and macrophage are the first line of defense in  Toll-like receptors (TLRs)
recognizing pathogens, they have receptors to recognize o 10 types found in humans
different pathogens.  Some on cell surfaces
 PAMPs – located on the pathogen it is a signalling  Some in cytoplasm
systems, PRRs recognizes the PAMPS  When TLR detects the pathogens it will
 Toll like receptor get the information and relay it to the
o Detect certain parts of a pathogen. nucleus of the cells, the nucleus will
o Composed of multiple leucine-rich repeats decide and command the macrophage.
 Sites of receptors
o Surface of the cell membrane – use to detect
extracellular pathogens.
o Inside the cells (inside the endosome) – detect
intracellular pathogens such as virus.
o Ex. TLR5 specific for detecting flagellin (part of
the bacteria’s flagella) Dimer

IMMUNOLOGY AND SEROLOGY: INNATE IMMUNITY 2


IMMUNOLOGY AND SEROLOGY
LECTURE / WEEK NO.7/ MACARUBBO L.

CHARACTERISTICS OF TLRS PROCESS OF INFLAMMATION

 Toll-like receptors (TLRs)  The body’s overall reaction to injury or invasion by an


o Are glycoproteins that bind to particular infectious agent
substances, activating cytokine and chemokine  Cardinal signs and symptoms
production and other processes to enhance o Redness (erythema) – RUBOR
phagocytosis o Swelling (edema) – TUMOR
o Can destroy most pathogens that humans are o Heat – CALOR
exposed to before disease sets in o Pain – DOLOR
o Loss of Function – FUNCTIO LAESA
OTHER PRRs

 Other receptors
o C-type lectin receptor (CLR)
 Binds to mannan and β-glucans found
in fungal cell walls to activate cytokine
and chemokine production
 Retinoic acid–inducible gene-I-like receptor (RLR)
 Nucleotide-binding oligomerization domain (NOD)
receptor

ACUTE-PHASE REACTANTS

 Soluble factors found in serum (red/gold top)


 Detect general inflammation
 Increase rapidly in response to infection, injury, or tissue
trauma
 Facilitate contact between microbes and phagocytic cells
 Mop up and recycle important proteins after
phagocytosis

TYPES OF ACUTE-PHASE REACTANTS

PROTEIN RESPONSE TIME NORMAL INCREASE FUNCTION


(HOURS) CONCENTRATION
(MG/DL)
C-reactive protein 4–6 0.5 (BELOW IS NORMAL) 1,000X Opsonization,
complement activation
Serum amyloid A 24 5 1,000X Activates monocytes
and macrophages
Alpha1-antitrypsin 24 200-400 2–5X Protease inhibitor
Fibrinogen 24 200-400 2-5X Clot formation

Haptoglobin 24 40-290 2-10X Binds hemoglobin


Ceruloplasmin 48-72 20-40 2X Binds copper and
oxidizes iron
Complement C3 48-72 60-140 2X Opsonization, lysis

IMMUNOLOGY AND SEROLOGY: INNATE IMMUNITY 3


IMMUNOLOGY AND SEROLOGY
LECTURE / WEEK NO.7/ MACARUBBO L.

PHAGOCYTOSIS

 Cells most involved


o Neutrophils
o Monocytes
o Macrophages
o Dendritic cells

SUMMARY

 Innate immunity encompasses the body’s normally


present defense mechanisms.
 Innate immunity is characterized by:
o Lack of specificity
o No need for a prior exposure
o A similar response with each exposure
 External defenses are structural barriers and secretions
that keep microorganisms from entering the body.
NK (NATURAL KILLER) CELLS
 Internal defenses include:
 First line of defense against: o Cells capable of phagocytosis
o Cells that are virally infected o Acute-phase reactants that enhance
o Cells infected with other intracellular pathogens phagocytosis
o Tumor cells  Pathogen-Recognition Receptors (PRRs) are molecules
 Recognize any damaged cell and can eliminate it without on host cells that recognize substances found only on
prior exposure to it, giving immune system time to pathogens. Once receptors bind a pathogen,
activate adaptive response of specific T and B cells phagocytosis can take place.
 Stimulated by exposure to cytokines  PAMPs are molecules found only on pathogens, which
 When activated, produce additional cytokines and allow host cells to distinguish them from self.
colony-stimulating factors.  Acute-phase reactants are serum proteins that increase
 Influence innate and adaptive immunity rapidly in response to infection or injury.
 Inflammation is the body’s response to injury or invasion
MECHANISM OF CYTOTOXICITY by a pathogen.
 NK cells kill target cells that are infected with a virus or
other intracellular pathogen without prior exposure.
 NK cells are a link between the innate and adaptive
immune systems.

 Target cell contains MHC-I – type of substance found on


the surface of cell that communicate with the NK cell
that it is a normal body cell/ self-cell.

IMMUNOLOGY AND SEROLOGY: INNATE IMMUNITY 4

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