Host defenses are composed of two complementary, frequently interacting systems: (1)innate...
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Transcript of Host defenses are composed of two complementary, frequently interacting systems: (1)innate...
Host defenses are composed of two complementary, frequently interacting systems:
(1)innate (nonspecific) defenses, which protect against microorganisms in general, and
(2) acquired (specific) immunity, which protects against a particular microorganism.
TWO TYPES OF IMMUNITY
Nonspecific (innate)•Physical and chemical agents•Lysozyme•Acute phase proteins•Complement system•Cytokines (chemokines)•Phagocytes (granulocytes, macrophages)•Natural killer (NK) cells•Dendritic cells•Toll-like receptors
Specific (adaptive)•Antibodies (B lymphocytes)•T lymphocytes
Present at birth
Immediate protection against variety of pathogens and foreign substances
Immunity signifies all those properties of the host that confer resistance to a specific infectious agent.
Immunity
Natural Acquired or adaptive (specific)
(Innate, nonspecific)
Passive Active
Acquired ( Adaptive) Immunity
Active Passive
Natural Artificial Natural Artificial (Infection)
(Immunizing agents)
Clinical Subclinical (Placental transfer,
colostrum)
(administration of immune sera)
First Line of Defense Epidermis Mucous membranes
Mucous Cilia Lacrimal apparatus of
eyes Saliva Urine flow Vaginal secretions Defecation and vomiting
Sebum Perspiration Lysozyme Gastric juice
Intact skin is the first line of defense against many organisms. In addition to the physical barrier presented by skin, the fatty acids secreted by sebaceous glands in the skin have antibacterial and antifungal activity.
Innate (nonspecific) defenses
Skin and Mucous Membranes
Mucous membranesMucous membranes protective covering in intestine, lungs, eyes
etc., that resists penetration and traps many microbes
antimicrobial secretions
Lysozyme Lactoferrin: macrophages and PMNs, sequesters
iron Lactoperoxidase: produces superoxide radicals mucosal-associated lymphoid tissue (MALT)
MUCOSAL MUCOSAL SURFACESSURFACES
•Gastrointestinal tract
•Respiratory tract
•Urinary tract
•Reproductive tract
Respiratory System- The mucociliary blanket of the respiratory epithelium traps microorganisms less than 10 ㎛ diameter - The bronchial-Associated Lymphoid Tissue (BALT)
Gastrointestinal Tract - In the stomach : lower pH, enzymes - In the intestine : enzymes - In the large intestine : the normal microbiota ⇒ preventing the establishment of pahtogens
⇒ destroy microorganisms
Genitourinary Tract - Urine kills some bacteria due to its low pH and the presence of urea and other metabolic end products
The Eye - Tears contain large amount of lysozyme, lactoferrin and sIgA
A second important defense
is the mucous membrane of the respiratory tract,
which is lined with cilia and covered with mucus. The
coordinated beating of the cilia drives the
mucus up to the nose and mouth,
where the trapped bacteria can be expelled.
In lacrimal fluid, sputum, saliva, blood, milk, tissues and organs lysozyme is found. It is found in some bacterial cells. Nasal mucus is bactericidal for many microbes and viruses of influenza, herpes, poliomyelitis, etc.
Second Line of Defense
Antimicrobial proteins
1. Interferons (IFNs) Antivirals that prevent replication of virus
2. Complement system Enhance immune reactions
3. Transferrins Inhibit bacterial growth by reducing available
iron
Interferons (IFNs) are antiviral proteins produced in response to viral infection.
alpha-IFN, beta-IFN, gamma-IFN.
The mode of action of -IFN and -IFN is to induce uninfected cells to produce antiviral proteins (AVPs) that prevent viral replication.
Interferons are host-cell–specific but not virus-specific. Gamma-interferon activates neutrophils and
macrophages to kill bacteria.
Interferons (IFNs)
Complement System Summary
Series of 30 plasma (serum) proteins, activated in a cascade
Three effects of complement system:
1. Enhances inflammatory response, e.g.: attracts phagocytes
2. Increases phagocytosis through opsonization or immune adherence
3. Creates Membrane Attack Complexes (MACs) Cytolysis
Classical Pathway of Complement ActivationClassical Pathway of Complement Activation
IgA and IgE cannot activate complement
Alternative Pathway of Complement ActivationAlternative Pathway of Complement Activation
Lectin Pathway of Complement ActivationLectin Pathway of Complement Activation
Late Steps of Complement Activation
Inflammation Stimulated by ComplementInflammation Stimulated by Complement
TransferrinsTransferrins
Transferrins are iron-binding proteins. Inhibit bacterial growth by reducing the amounts of available iron.
Transferrin transports iron from the small intestine, where the iron is absorbed, to the tissues, where the iron is used. Transferrin and lactoferrin bind iron, limiting the growth of pathogens in the blood.
Lactoferrin is present in tears, semen, breast milk, bile, and nasopharyngeal, bronchial, cervical, and intestinal mucosal secretions. Transferrin is present in serum and the intercellular spaces of many tissues and organs.
Innate Immunity Depends on Receptor-Recognition of Common Pathogen-Associated
Molecules Pathogen-associated molecular patterns (PAMPs)
help the innate immune system recognize pathogens
Toll-like receptors (TLRs) are signaling receptors on: macrophages dendritic cells endothelial cells
TLRs on TLRs on MPhs, MPhs, dendritic dendritic cells, cells, epithelial epithelial cellscells
Cytokines!
PAMPs recognition
Second Line of Defense Natural killer (NK) cells
~ 5 – 10% of lymphocytes In spleen, lymph nodes and red bone marrow Attack body cells displaying abnormal plasma membrane
proteins Perforin perforates cell membranes Granzymes destroy cell proteins
Phagocytes Phagocytosis
Neutrophils Macrophages
Develop from monocytes Wandering Fixed
Figure 21.8a
Phagocytosis
Killing mechanisms of phagocytes
SEM of macrophage engulfing E. coli cells on the surface of a blood vessel
PhagocytosisPhagocytes recognize the enemy
either directly, by binding to components on
the surface of the organism or
indirectly, by binding to a foreign entity that has antibody bound to it.
Inhibit adherence: M protein, capsules
Streptococcus pyogenes, S. pneumoniae
Kill phagocytes: Leukocidins
Staphylococcus aureus
Lyse phagocytes: Membrane attack complex
Listeriamonocytogenes
Escape phagosome Shigella
Prevent phagosome-lysosome fusion
HIV
Survive in phagolysosome Coxiella burnetti
Microbial Evasion of Phagocytosis
Natural Killer Cells Recognize and Kill Abnormal Cells NK cells are formed in the bone marrow, and
migrate to: tonsils lymph nodes spleen
When activated, they produce cytokines that trigger response by macrophages and other cells
Then they move into blood and lymph where they kill: cancer cells virus-infected cells
When an NK cell recognizes a cell as “non-self” it releases cytotoxic perforins and granzymes
ADCC by NK Cells
Destruction of Virus-Infected Cells by NK Cells through Antibody-Dependent Cellular Cytotoxicity
(ADCC)
Tissue damage triggers the inflammatory response
The inflammatory response mobilizes nonspecific defense forces
Tissue injury; release ofchemical signals such ashistamine
1 2 3Dilation and increased leakinessof local blood vessels; migrationof phagocytes to the area
Phagocytes (macrophages andneutrophils) consume bacteriaand cell debris; tissue heals
Pin
Skin surface
Bacteria
Chemicalsignals
Whiteblood cell
Swelling
Phagocytes andfluid moveinto area
Phagocytes
Red, swell, warm
Non-specific defense system
The inflammatory response can disinfect tissues limit further infection
CytokinesCytokines
•“Cytokines” are soluble protein mediators secreted by immune cells (mostly) that act on other cells to regulate their activity; many are called “interleukins” (IL-1, IL-2, etc.)
•Cytokines have many functions, we’ll focus on a few central functions of a few key cytokines
•A subfamily of cytokines primarily functions in directing migration of cells, these are called “chemotactic cytokines” or “chemokines”
- monokines, lymphokines, interleukines
colony stimulating factors, chemokines,
interferon - The four cytokine families
Function : • autocrine • paracrine • endocrine
A summary of innate and acquired immunity
INNATE IMMUNITY Rapid responses to a
broad range of microbes
ACQUIRED IMMUNITYSlower responses to
specific microbes
External defenses Internal defenses
Skin
Mucous membranes
Secretions
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells
Humoral response(antibodies)
Cell-mediated response(cytotoxic lymphocytes)
Invadingmicrobes
(pathogens)
Break !