Chapter 16 Innate Immunity

Antimicrobial Peptides (AMP)

Peptides produced by nearly all plant and animal cells used to destroy bacterial cells. Synthesis triggered by the microbes surface components. AMP are affective against bacteria, viruses, fungi, and eukaryotic parasites. AMPs inhibit cell wall synthesis, form pores in the plasma membrane, and destroy DNA and RNA new area of science

Inflammation (2nd Line of Defense)

is a defensive response due to local damage to the body's tissues. Damage can be caused by microbial infections, physical agents, or chemical agents. Defined by the following signs and symptoms: ex) Redness (erythema); due to vasodilation Pain due to nerve damage, irritation by toxins, or the pressure of edema Heat due to vasodilation Swelling (edema) due to fluid accumulation in tissue spaces from blood Loss of function (depends on the site and extent of damage) Function: Destroy and remove infective agent If destruction is not possible, then limit its effects by confining/walling off the agent and its by-products Repair/replace damaged tissue During inflammation there is an activation and increased concentration of acute-phase proteins (complement, cytokine, fibrinogen for clotting, and kinins for vasodilation) Notes on Diagram: -when knife hits skin, the cells die and send a signal that they are dead and need help-message via cytokines -with vasodilation the capillaries will dilate which allows the white blood cells to squeeze to the walls and get to the bacteria -first responders: neutrophils -Second: monocytes- then they mature into macrophages

Blood serum

is the straw-colored liquid remaining after the blood is allowed to clot

Innate (Non-specific) Immunity

defenses that protect against any pathogen regardless of: First Line of Defense: intact skin, mucous membranes and their secretions, and normal microbiota. Second Line of Defense: phagocytic WBCs, inflammation, fever, and antimicrobial substances

Differential WBC Count

determines leukocyte increase or decrease; which is a calculation of the percentage of each kind of WBC in a blood sample

Plasma

fluid portion of blood; contains formed elements-erythrocytes or RBCs and Leukocytes or WBCs and platelets is the liquid remaining after the formed elements are removed from the unclotted blood by centrifugation

Granulocytes

have large granules in the cytoplasm. Granulocytes are differentiated based on the staining of the granules: Neutrophils stain pale lilac with mixture of acidic and basic dyes. Highly phagocytic and motile; active in initial stages of infection; can leave the blood and enter infected tissue. Basophils stain blue-purple with the basic dye methylene blue. Produce histamine, which is important in inflammation and allergic response. Eosinophils stain red or orange with acidic dye eosin. Produce toxic proteins against certain parasites (helminths), some phagocytosis

Leukocytosis

increase of WBCs due to microbial infection; ex) meningitis, infectious mononucleosis, appendicitis, pneumococcal pneumonia, and gonorrhea

Phagocytic WBCs (2nd Line of Defense)

ingestion of microbes or particles by a phagocytic cell -phago: eat -cyte: cell Action: At the beginning of an infection, both granulocytes (especially neutrophils) and monocytes migrate to the infected area. The monocytes leave the blood and enter the infected tissue where they enlarge and develop into actively phagocytic macrophages. The number of granulocytes increases dramatically; however, as the infection progresses, the macrophages dominate which is reflected by an increase in monocytes. In viral and fungal infections, macrophages predominate in all phases of defense With increased age there is a progressive decline in the efficiency of phagocytosis. Also, recipients of heart or kidney transplants have impaired nonspecific defenses as a result of receiving drugs that prevent the rejection of the transplant

Adaptive (specific) immunity

resistance against a specific pathogen Third Line of Defense: specialized lymphocytes such as: B cells (antibody production via plasma cells) T cells (T helper cells, Cytotoxic T Lymphocytes, T regulatory cells)

Leukopenia

salmonellosis and brucellosis and some viral and rickettsial infections there is a decrease in the leukocyte count

TLRs bind to the following microbial structures

Lipoteichoic acid in g+ Lipopolysaccharide in g- Flagellin in flagella of motile bacteria DNA of bacteria DNA or RNA in viruses Various components of fungi and parasites

Cytokines

what TLRs induce cell to realize after binding with the defensive cells; they are proteins that relate the intensity and duration of the immune response (recruit more macrophages and dendritic cells and also activate T cells and B cells

Fever (2nd Line of Defense) (systemic response)

-Most frequent cause is infection from bacteria and their toxins or viruses -Hypothalamus normally set at 37ºC (98.6ºF) -Gram-negative endotoxin causes phagocytes to release the cytokine interleukin 1 (IL-1) -IL-1 causes the hypothalamus to release prostaglandins that reset the hypothalamus to a higher temperature, thereby causing fever -Up to a certain point fever is considered a defense mechanism Complications of fever: Tachycardia - rapid heart rate, which may compromise elderly persons with cardiopulmonary disease Increased metabolic rate which may produce acidosis Dehydration Electrolyte imbalances Seizures in young children Delirium and coma

Secretions (1st line of Defense); Chemical Factors

-Sebum: produced by the skin's oil glands, forms a protective film over the skin; bacteria that metabolize sebum form free fatty acids that cause the inflammatory response associated with acne -Perspiration: produced by sweat glands, helps maintain body temperature, eliminate certain wastes, and flush microorganisms. Perspiration contains lysozyme. Lysozyme is also found in tears, saliva, nasal secretions, and tissue fluids -Urine Flow: helps clear the urethra from microorganisms -Vaginal secretions: produced by vaginal epithelial cells is broken down into lactic acid by Lactobacillus acidophilus. The resultant acidic environment is antibacterial to other introduced bacteria into the vagina ex) glycogen -Earwax: provides a physical barrier and a chemical protectant by lowering the pH to between 3 and 5 and thereby inhibiting numerous pathogens -Gastric juice: produced by glands in the stomach, is comprised of hydrochloric acid, enzymes, and mucus. The very high acidity (pH 1.2 to 3) of gastric juice can destroy bacteria and most bacterial toxins, except those of Clostridium botulinum and Staphylococcus aureus. Many enteric pathogens are protected by food particles and can enter the intestines via the gastrointestinal tract. Helicobacter pylori neutralizes stomach acid, which allows it to grow resulting in ulcers and gastritis (inflammation of the lining of the stomach) -Salvia: dilutes and washes microbes off teeth and mucus membranes of the mouth; contains lysozyme an enzyme capable of breaking down the peptidoglycan of bacterial cell walls of g+ bacteria and to a lesser extent those of g- bacteria. Salvia also contains an antibody (Immunoglobulin A) that prevents attachment of microbes so that they cannot penetrate the mucous membrane.

Iron-Binding Proteins (2nd Line of Defense)

-transferrin (found in blood and tissue fluids) -ferritin (found liver, spleen and -red bone marrow) -hemoglobin (found within RBCs). These iron-binding proteins provide an antimicrobial effect by inhibiting bacterial growth by reducing the amount of available iron. Bacteria require iron for growth and reproduction. To survive in the human body bacteria secrete siderophores that compete with the host's iron binding proteins by binding iron more tightly

Normal Microbiota (1st Line of Defense)

In microbial antagonism, the normal microbiota prevent pathogens from colonizing the host by competing with them for nutrients (competitive exclusion); by producing substances that alter pH and oxygen availability, and antimicrobial substances which are harmful to pathogens Commensalisitc: what normal microbiota are typically considered; may cause disease if their environmental conditions change; includes opportunistic pathogens ( E. coli, Staphylococcus aureus, S. epidermidis, Enterococcus faecalis, Pseudomonas aeruginosa, and oral streptococci)

Physical Factors (1st Line of Defense)

Intact Skin (largest human organ in terms of surface area) - a mechanical form of defense -Epidermis (outer layer): epithelial cells known as endothelial cells that line blood and lymphatic vessels are not closely packed as those of the epidermis, thus allowing defensive cells and microbes to move into and out of the blood and lymph. ex) Common infections are due to staphylococci that normally inhabit the epidermis -Dermis: the skin's inner thicker portion, is composed of connective tissue -Mucous Membrane: a mechanical form of defense ; provides less protection than intact skin; epithelial layer secretes a glycoprotein fluid called mucus which maintains the membranes moist; lines the gastrointestinal, respiratory, and genitourinary tracts; ex) Lacrimal apparatus: washes eyes and drains tears; Ciliary escalator: microbes trapped in mucus produced by goblet cells in the lower respiratory tract are transported away from the lungs toward the throat by the synchronized beating of cilia at a rate of 1 to 3 cm/hour. Coughing and sneezing speeds up the process. Cigarette smoke impairs cilia function; Peristalsis, defecation, vomiting, and diarrhea all expel microbes from the body

Innate System Activation

The innate system is activated by protein receptors (toll-like receptors - TLR) in the plasma membranes of defensive cells such as macrophages (a phagocytic cell; a mature monocyte) and dendritic cells (a type of antigen-presenting cell characterized by long fingerlike extensions; found in lymphatic tissue and skin). These receptors bind to the Pathogen-associated molecular patterns (PAMPs) of the invading microbes and activate an immune responses directed against the invading microbes

Lymph Node Swelling

The maturation and proliferation of macrophages along with lymphocytes is one factor responsible for the swelling of lymph nodes during an infection

The Complement System (2nd Line of Defense)

a defense system consisting of over 30 proteins produced by the liver and found in circulation in the blood serum and within tissues throughout the body. Together, proteins of the complement system destroy microbes by cytolysis, inflammation, and phagocytosis and also prevent excessive damage to the host tissues Complementation Activation (3 pathways): 1. Classical Pathway Activated by contact between pathogen antigens and host antibodies forming an Ag-Ab complex that tigers the complement system; already have existing antibioses to bacteria and they will recognize the compliment proteins will activate C-3 2. Alternative Pathway Activated by contact between certain complement proteins and a pathogen that tigers the complement system; body has never seen it before but if it has a lipid carbohydrate on the membrane that attracts other proteins that are specific and activate C-3 3. Lectin Pathway Activated when macrophages ingest bacteria, viruses, and other foreign matter via phagocytosis. In turn, the macrophages release chemicals that stimulate the liver to produce lectins, which are proteins that bind to carbohydrates on the surface of the microbe that tigers the complement system; carbohydrate has a sugar in membrane if leptin sees it and binds to it, it will also activate C-3 Effects of Complement Activation: 1. Opsonization - Promotes attachment of a phagocyte to a microbe. 2. Cytolysis - Membrane attack complex (MAC) initiates cytolysis of the bacterial membrane. Gram negative bacteria are susceptible to cytolysis because they have only one or few layers of peptidoglycan to protect the plasma membrane from the effects of complement 3. Inflammation: C3a and C5a bind to mast cells, basophils, and platelets to trigger the release of histamine, which increases blood vessel permeability

Agranulocytes

also have granules in their cytoplasm but the granules are not visible under the light microscope. Monocytes are phagocytic as mature macrophages after entering tissues. Dendritic cells have long cellular extensions; abundant in the epidermis of the skin, mucous membranes, thymus and lymph nodes. They destroy microbes by phagocytosis and initiate adaptive immunity responses. Lymphocytes: Involved in specific immunity; antibody production. Natural Killer (NK) cells occur in the blood, spleen, lymph nodes and red bone marrow. NK cells destroy a variety of infected body cells and certain tumor cells via cytolysis and apoptosis. The released intact microbes are then destroyed by phagocytes. T cells initiate cell-mediated immunity B cells produces antibodies

Interferons (IFNs) (2nd Line of Defense)

antiviral proteins produced by certain animal cells after viral stimulation that interfere with viral multiplication -Host cell specific but not viral specific -Different types of cells in the animal host produce different interferons. Human interferons are of three main types: α-IFN, β-IFN, and γ-IFN with various subtypes within each group. -α-IFN and β-IFN are produced by virus infected cells and diffuse to uninfected neighboring cells inducing those cell to synthesis antiviral proteins (AVPs) that inhibit viral replication. Interferon plays a major role in short term and acute infections such colds and influenza. -γ-IFN causes neutrophils and macrophages to phagocytize bacteria. People with a condition known as chronic granulomatous disease can not kill bacteria; however, when they take γ-IFN they can kill the pathogenic bacteria. -α-IFN used to treat Kaposi's sarcoma, a cancer often associated with HIV; genital herpes; hepatitis B and C; malignant melanoma; and hairy cell leukemia. -β-IFN is used to treat the progression of multiple sclerosis