born with; defenses against any pathogen; general

first and second line of defense

Innate Immunity: Physical First line Defense

skin

Innate Immunity: Physical First line Defense

Mucus Membranes

Membrane: also epitheal layer

Mucus: Viscous glycoprotein material keeps membrane from drying

Lacrimal apparatus: tear ducts; tears

Cilia: sweep microbes up from lower respiratory tract

Others: hair, urine flow, vaginal secretions, defication, vomiting, peristalsis

Innate Immunity: Chemical First line Defense

Sebum: fatty acids inhibits microbial growth; secreted by sebacious glands

Lysozymes: break down petidoglycan; tears, urine, sweat

Gastric Juice: very low pH is inhibitory; Helicobacter pylori-stomach ulcers

Innate Immunity: Chemical First line Defense

Urine: low pH; lysozymes

Vaginal Secretions: low pH is inhibitory

Normal Flora: use nutrients; produce inhibitory compounds;

#bacterial cells > #human cells

Innate Immunity: Second line Defense

Innate Immunity: Second line Defense

Leukocytes

Neutrophils: phagocytosis

Basophiles: Histamine; allergic reactions

Eosinophils: selective for parasites

Monocytes (Macrophages): best phagocytes

Innate Immunity: Second line Defense

Leukocytes

Dendritic cells: phagocytosis

Natural Killer cells: Destroy target cells

*=3rd line defense

Innate Immunity: Second line Defense

Lymphatic System

Lymph: Fluid

Lymphoid Tissue: ex. tonsils

Red Bone Marrow: blood cell origin

Lymphatic Vessels: carry lymph and blood

Innate Immunity: Second line Defense

Phagocytosis

Ability to ingest microorganisms

capsule

toxins

biofilm formation: extracellular matrix

hide inside phagocyte

Second Line Defense

Inflammation

Cytokines released; recruit phagocytes

Redness/Heat: increased permeability and vasodilation; cells can leave vessel and enter tissue

Pain/Swelling: increased blood and pressure; nerve damage

Second Line Defense

Fever

Cytokines travel to brain:

hormone-like molecules; reset (increase) body temp

Rate of metabolism increased; shivering

Decrease availible Iron

Decrease Doubling time of bacteria w/ increased body temp

Second Line Defense

Antimicrobial Substances

Complement System

30+ proteins complement innate and adaptive immunity

Proteins kept inactive; due to high potency

C3a C3b = activated proteins (lower case)

Cytolysis: makes holes in bacterial membrane; cell lysis

Enhance Inflammation: proteins stimulate histimines that bind to bacterial cell

Activated Complement System

Opsonization

Opsinization = Enhanced phagocytosis

Protein coats bacteria

Second Line Defense

Antimicrobial Subtances

Interferons

Antiviral properties; interfere with viral replication

Infected cell releases interferons that bind to healthy cells "paul revere"

Healthy cells produce antiviral proteins

Second Line Defense

Antimicrobial Subtances

Iron Binding Proteins (IBP)

IBP keep Fe from siderophores

Transferrin: blood in tissue

Lactoferrin: milk, saliva, mucus

Ferritin: liver, spleen, bone marrow

Hemoglobin: RBCs

Second Line Defense

Antimicrobial Substances

Antimicrobial Peptides

Peptides (NOT proteins) produced by host cells

Synthesis is triggered by proteins or sugars on a pathogen’s surface

broad spectrum

Second Line Defense

Antimicrobial Substances

Antimicrobial Peptides:

Modes of Action

Inhibit cell synthesis

form pores in pathogen's membrane

destroys pathogen's DNA/RNA

No bacteria resistant

stem cell splits

Humoral: differentiates in bone marrow; B-cell

Cell mediated: differentiates in Thymus; T-cell

received from donor;

breast milk, placental transfer

Immune serum; anitivenom

capsule

peptidoglycan

flagella

bacterial toxins

pollen

transplanted tissue/blood

portion of ag that reacts with antibody;

aka antigenic determinant

Antibiotic Classes

IgM

Antibiotic Classes

IgG

follows IgM; most common in serums

Functions:
–Enhance phagocytosis by opsonization
–Neutralize toxins and viruses
–Binds complement

Protects fetus/newborn; passive immunity

Antibiotic Classes

IgA

Found in secretions

Function:
–Newborn protection against GI pathogens by colostrum (first breast milk)
–Neutralizes/inhibits entry of pathogens through mucous membranes

Antibiotic Classes

IgD

Found on surface of some lymphocytes

Function:

helps activation of lymphocytes

Antibiotic Classes

IgE

Found on mast and basophil cells

Function:

Allergic Reactions

Parasitic worm infections

Ag/Ab binding

Agglutination

Enhances Phagocytosis (reducing #infectious units);

Ag bind 2-3 bacterial cells together

Ag/Ab binding

Opsonization

enhances phagocytosis;

Coats bacteria with antibodies

Ag/Ab binding

complement activation/fixation

Antibodies act like flags;

inflammation and cell lysis

Ag/Ab binding

Antibody-dependent cell-mediated immunity

attaches to larger target cells (parasites);

destruction by:

eosinophils: release perforic/lytic enzymes

 macrophages

NK cells

Antibody Production

B-cells

origin: bone marrow

contains specific ab on surface thats binds to specific epitope

B-cell Activation

T-cell independent

less common

polysaccharide (T-independent ag) has multiple binding sites

B-cell activation

T-cell dependent

more common

B-cell "chews" up antigen

MHC class II molecule displays antigen fragments on b-cell surface

T-cell confirms antigen and releases cytokines

Clonal selection: b-cells from expansion formed into plasma or memory cells; preventative measure - quicker response

T-cells

Cell-mediated immunity

fight intracellular pathogens

enhanced phahocytosis

respond to tumor cells

transplant rejection

oringinate in bone marrow; mature in thymus

T-cell receptors recognize specific antigen

Activated by "Antigen presenting cells" (b-cell displaying antigen)

T-cell Classes

T-helper (T_H) cells

release cytokines that activate b-cells against extracellular pathogens;

antigen interaction: MHC Class II

T-cell Classes

Cytotoxic (T_C) cells

 Antigen interaction: MHC Class I; marks cell as "self"

ags tag infected cells; non-self

Controlled destruction of infected cells; shrivel

T-cell Classes

T-Suppressor (T_S) cells

recognize "self" antigens

Immune Tolerance:

T-cell Classes

T memory (T_M) cells

Recognize previous T-dependent antigens (extracellular)

Results in fast secondary immune response

Non- T/B immune cells

Natural Killer cells

Non-phagocytic lymphocytes; induce apoptosis (controlled cell death)

Additional help: virus infected cells/tumor cells

Blood cell count: # WBC, RBC, platlets

Antibody Count: Titer test (#abs)

Cytokine Levels

Agglutination Reaction: blood typing, prego

Hypersensitivity: allergen skin test

Vaccines

ID of microbes

Immunoblotting

Immune System problems

Autoimmunity

immune reaction against self; sees host cells as pathogenic

ex. MS, Rheumatoid arthritis, Type I diabetes

Immune System problems

Ineffectiveness

occurs when some pathogens are not killed; hide inside host

ex. mycobacteria "TB", legionella, listeria

Biofilms also resistant

Immune System problems

loss-all/part

AIDS

Genetic disorders = reduced life expectancy (often before 5)

Severe combined immunodeficiency (low B and T cell levels)

Diagnosis: appearance of second infection; antibody titer against HIV

Retrovirus HIV infects (T_H) cells; specific immunity

adapted immunity wiped out

susceptibility of secondary infection is main COD

Immune System problems

Hypersensitivity

excessive immunological response to antigen

Allergy: immune response to allergen

Type I

Immediate/anaphylactic Hypersensitivity

fast; 5-30 min

ex. hay fever/bee sting allergies

Type II

Antibody Dependent cytotoxic Hypersensitivity

antibody combines with cell

ex. blood group incompatibilty

Rh factor

Type III

Immune-complex hypersensitivity

Type IV

Delayed or Cell-mediated hypersensitivity

1-3 days after exposure

ex. TB skin test, poison ivy

1. Same pathogen must be present in every case of the disease
2. Pathogen must be isolated from the diseased host and grown in pure culture

3. The pathogen from the pure culture must cause the disease when it is inoculated into a healthy, susceptible lab animal
4. The pathogen must be isolated from the inoculated animal and must be shown to be the original organism.

ability of an organism to cause disease

possess weapons aka virulence factors

short/severe

ex. strep throat

Prolonged

ex. TB

sudden/intense

ex. meningitis

initial infection

Flu/HIV

occurs after primary by oppurtunisitic pathogens

ex. pneumoniae following flu

presence of bacteria in blood

Septicemia: bacteria growing in blood

Steps to cause disease

Entry

Portal of Entry

Membranes/skin

Parenteral: direct deposition beneath skin or mucous membranes

*most pathogens have preferred POE

Steps to cause disease

Entry

Adherence

Adhesins (Ligands): bind pathogen to specific receptors in host

Steps to cause disease

Entry

Penetration

Active: pathogen has own mechanism for penetration

Passive penetration: organism penetrates tissue due to wound, burn, insect bite, animal bite, etc.

Host:

Immune recognition of epitopes on pathogen surface

Pathogen:

capsule hides cell surface; resist phagocytosis 

eleminates unnecessary components 

Antigenic phase variation: bacteria changes ags

Molecular Mimicry: pathogens decorate surface that mimic host cell surfaces

Bacterial Pathogens

Penetration into Cytoskeleton

bacteria use Actin for movement in cytoskeleton

Pathogens secrete protease to digest antibodies

ex. Ig protease

Host:

Low Nutrient Level

Pathogens:

produce siderophores; "Fe boomerang"

Select best habitat for colonization; richer nutrient area

Host:

Protection from tissue surface or mucus layer

pathogen:

secrete enzymes to break down surface

pathogen:

competes for nutrients

adapts to less favorable nutrients

Damage to Host Cells by Bacterial Pathogens

Direct Damage

Exoto

Exotoxins: produced by bacteria; secreted proteins- small amount needed

ex. tetanus, botulism

Endotoxins: within LPS released upon death; GRAM NEGATIVE

ex. Typhoid fever and N. meningitidis

 Source: Gram +

Relation to microbe: by-products of cell

Chemistry: Protein

Fever? No

Neutralized by Antitoxin? Yes

Lethal Dose: small

Source: Gram –

Relation to microbe: outer membrane

Chemistry: Lipid A

Fever? Yes

Neutralized by Antitoxin? No

Lethal Dose: ~large