immunology and microbiology
DESCRIPTION
Immunology and Microbiology. Host-Microbe Interactions. Non-specific (Innate) Immunity. First line of defense (Non-specific resistance) Physical and Chemical Defenses Normal Flora Second line of defense (Non-specific resistance) Phagocytosis Inflammation Fever - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/1.jpg)
Immunology and Microbiology
![Page 2: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/2.jpg)
Host-Microbe Interactions
Non-specific (Innate) Immunity
![Page 3: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/3.jpg)
First line of defense (Non-specific resistance)• Physical and Chemical Defenses• Normal FloraSecond line of defense (Non-specific resistance)• Phagocytosis• Inflammation• Fever• Antimicrobial substances: Complement,
InterferonThird line of defense (Specific Resistance)• Antibodies• B cells and T cells
![Page 4: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/4.jpg)
• Detect enemy
• Immobilize/kill enemy• Send out alarm• Recruit help• Make environment
unpalatable for enemy/prevent spread
• (process repeats)
• Toll-like receptors on macrophages; complement (3 ways)
• Phagocytosis; lysis• Cytokine release
• Inflammation; fever
![Page 5: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/5.jpg)
Toll-like receptors: What are some evolutionarily conserved features of microbes that our immune cells could recognize?
Step 2.
![Page 6: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/6.jpg)
Steps in phagocytosis
http://www.cellsalive.com/mac.htm
![Page 7: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/7.jpg)
Clinical and laboratory features of patients with an inherited deficiency of neutrophil membrane complement receptor type 3 (CR3) and the related membrane antigens LFA-1 and p150,95. Ross GD.
Over the last 3 years a group of more than 20 patients has been described worldwide who have a similar history of recurrent bacterial infections and an inherited deficiency of three related leukocyte membrane surface antigens known as CR3, LFA-1 and p150,95 (function unknown). It is believed that the patients with this disease have a reduced or absent expression of all three antigen family members on different WBC types. Neutrophils have a reduced phagocytic response to bacteria and yeast as well as a reduced ability to migrate into sites of infection.
• Adapted from J Clin Immunol. 1986 Mar;6(2):107-13.
![Page 8: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/8.jpg)
The Complement System
• Activated in 3 ways– Antibody-antigen (augments specific defense)– Molecules that recognize bacterial sugar polymer
(mannan)– “Random binding” to cell surfaces (C3b)
• Triggers a cascade• 3 effects
![Page 9: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/9.jpg)
Effects of complement system
1. Opsonization
![Page 10: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/10.jpg)
2. Membrane Attack Complex (Lysis)
Are G+ or G-ve cells more susceptible to killing by MAC? Why?
![Page 11: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/11.jpg)
Bacterial cell wall structure
Gram-negative and gram-positive bacteria
http://www.blackwellpublishing.com/trun/artwork/Animations/Overview/overview.html
![Page 12: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/12.jpg)
3. Inflammation
• What else triggers inflammation? Tissue damage
• What are features of inflammation?
• What is the inflammatory process?
![Page 13: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/13.jpg)
Which of the following statements about inflammation is false?
A. Vasodilation results in leakage of blood components
B. The process can cause damage to host tissueC. It is always accompanied by a feverD. The signs of inflammation are redness, swelling,
heat and painE. It can be triggered by activating toll-like
receptors (macrophages produce cytokines)
![Page 14: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/14.jpg)
INFLAMMATORY PROCESS
trauma or infectionvasodilation
chemotaxis and diapedesis
![Page 15: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/15.jpg)
Is that pus?
Is inflammation a good thing?
![Page 16: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/16.jpg)
![Page 17: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/17.jpg)
The movement of phagocytes in the direction of an infection, due to attraction by complement, chemicals released by microorganisms, and the remnants of damaged cell membranes is a process called
A) phagocytosis.B) chemotaxis.C) diapedesis.D) cytoadherence.
![Page 18: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/18.jpg)
• Hypothalamus controls body temp
• Pyrogens resets temp set point
• Pyrogens: cytokines; LPS
• Unfavourable for bacterial replication
• Favourable for immune response--phagocytosis; lymphocyte replication etc
FEVER
![Page 19: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/19.jpg)
Interferon and viral infections: a protective alerting system
![Page 20: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/20.jpg)
Complement and immunoglobulins can coat the outer surface of a microorganism, enhancing phagocytosis. This process is called
A) chemotaxis.B) fixation.C) opsonization.D) endotoxicity.E) membrane attack complexing.
![Page 21: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/21.jpg)
Host-Microbe Interactions
1. Innate (Non-specific) Defensesa. Chemical and Physical;
(Biological)b. Normal Flora
![Page 22: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/22.jpg)
Host-Microbe Interactions
1. Contact with microbe
a. colonization(normal flora)
b. defense breached c. Loss d. Allergy
2. Infection
a. cure, immunity b. establishment c. carrier
3. Disease
![Page 23: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/23.jpg)
All of the following statements are true with regard innate immunity EXCEPT:
A)These responses are not directed specifically to the infectious agent.
B)These responses are not affected by prior exposure to the agent.
C)These responses are inborn.D)These responses are operating constantly to
prevent the establishment of any infection.E)All of the above are true with regard to
innate immunity.
![Page 24: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/24.jpg)
First line of defense Barriers
Physical Chemical
![Page 25: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/25.jpg)
An enzyme found in our tears, saliva, serum, and mucus that degrades the peptidoglycan of the cell wall of Gram-positive bacteria is called
A) amylaseB) lysozyme.C) keratinase.D) streptokinase.E) peptidase.
![Page 26: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/26.jpg)
First line of defense-Chemical & Physical Barriers
![Page 27: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/27.jpg)
Which of the following substances is produced by the cells in our body and interferes with the multiplication of viruses by stimulating the production of antiviral proteins?
A) antivirase.B) interferon.C) inhibitase.D) complement.E) multiplicase.
![Page 28: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/28.jpg)
Which of the following are mechanisms that protect the respiratory system from infection?
1. mucus 2. mucociliary escalator 3. normal flora 4. lysozyme 5. acidic environment
A)1,2,5.B)1,3.C)1,2,3.D)2,4.E)1,2,3,4.
![Page 29: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/29.jpg)
Normal Flora of Humans
![Page 30: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/30.jpg)
• A normal human has approximately 1013 body cells and 1014 individual normal flora!
• microbes that grow on external and internal surfaces of the body without producing obvious harmful effects
• Transient microbial flora : only occasionally inhabit the body.
• Symbiotic relationships: Commensal, Mutualistic, Parasitic
What normal flora?
![Page 31: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/31.jpg)
Body sites that harbor normal flora
![Page 32: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/32.jpg)
Importance of the normal flora
• Prevent attachment of invading organisms• Produce antimicrobial substances against
other microbes that are pathogens• Stimulate immune system
– Cause the production of cross-reacting antibodies• Significant nutritional source of vitamins• Cause dental caries and gum disease
![Page 33: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/33.jpg)
How do we acquire microflora?
• During birth & within first 12 hours after delivery
• Breast-fed v bottle-fed• Contact with people, environment, food.• Eruption of teeth & introduction of solid food.
![Page 34: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/34.jpg)
What leads to changes in the normal flora?
• Antibiotic treatment• Immunosuppression• Diet• Changes in physiology , e.g. estrogen-glycogen
effect
![Page 35: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/35.jpg)
![Page 36: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/36.jpg)
Normal Skin Flora
• 1000 to >1 million/ cm2
• Diphtheroids: G+ rods & cocci, e.g. Corynebacterium & Proprionobacterium , e.g. P.acnes (acne)
• facultatively anaerobic, coagulase negative Staphylococci [carriers of coagulase positive S. aureus in population]
• Yeasts
![Page 37: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/37.jpg)
First line of defense (Non-specific resistance)• Physical and Chemical Defenses• Normal FloraSecond line of defense (Non-specific resistance)• Phagocytosis• Inflammation• Fever• Antimicrobial substances: Complement, InterferonThird line of defense (Specific Resistance)• B cells and T cells• Antibodies and Humoral Response• Cellular Mediated Immunity
![Page 38: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/38.jpg)
Genetic Immunodeficiencies
Common Variable Hypogammaglobulinemia: Affecting both males and females and occurring at any age, this disease is manifest by repeated pyrogenic infections. The B cells fail to mature to plasma cells. Passive Ig is the common treatment.
Chronic Candidiasis: Fungal infection by nonpathogenic yeast is the manifestation of a number of afflictions where few mature T cells are present. These patients often have B cells that respond to T-independent antigens, but Candida albicans (yeast) stimulates a poor antibody response.
1) What immune component fails to be made in CVH?2) How come a defect in T cells affects antibody response in chronic candidiasis?
![Page 39: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/39.jpg)
The two arms of the adaptive immune system
![Page 40: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/40.jpg)
Antigen: a molecule (or parts of one) that causes antibody generation
The specific region on an antigen recognized by an antibody
(Immunoglobulin)
![Page 41: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/41.jpg)
Antibody StructureDiversity in antibodies due to variable region
An infinitely large number of possible immunoglobulins;5 different classes: IgG, IgM, IgA, IgD & IgEMade by V(D)J recombination http://en.wikipedia.org/wiki/V%28D%29J_reco
mbination
![Page 42: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/42.jpg)
Fig. 16.06Effects of Antigen-Antibody Interactions
![Page 43: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/43.jpg)
Effects of Antigen-Antibody Interactions-2
Parasites; virally – infected host cellsNK cells release perforinsand proteases (16.8)
![Page 44: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/44.jpg)
How is the antibody response triggered?1. T-cell dependent antigens 2. T-cell independent Ags
e.g. polysaccharides, LPS
response of young children to these antigens is poor
Result: Clonal selection and expansion of B-cells
![Page 45: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/45.jpg)
A plasma cell
Clonal Expansion
Memory
Result:
Why is the RER in plasma cells so extensive?
1. Negative selection
2. Affinity maturation
3. Class switching: IgM – IgG—IgG / IgA
4. Formation of memory cells
![Page 46: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/46.jpg)
Fig. 16.11Memory Cells mediate secondary response and lifelong immunity
![Page 47: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/47.jpg)
Cellular Immunity
1. Cytotoxic T cells (CD8+)• Eliminates cells infected with virus, intracellular parasite
2. Helper T cells (CD4+)• Mediates B-cell proliferation; macrophage activation
Both stimulated by dendritic cells (cells of innate immunity)Both produce cytokines that stimulate own proliferation
![Page 48: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/48.jpg)
T cells activated by dendritic cells
A
B
C
![Page 49: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/49.jpg)
A. Recognition of virally-infected cell by cytotoxic T cell results in apoptosis
![Page 50: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/50.jpg)
B: Helper T-cell activation and interaction with B-cells
![Page 51: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/51.jpg)
Fig. 16.19C. Helper T- cells can also activate macrophages
![Page 52: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/52.jpg)
Activated macrophage: a hungry beast!
•enlarged•membrane becomes irregular•increased number of _lysosomes, containing antimicrobial substances________•produce nitric oxide
![Page 53: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/53.jpg)
Applications of Principles of Immunity
![Page 54: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/54.jpg)
54
![Page 55: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/55.jpg)
55
IgG levels in fetus vs infant
What is passive and what is active?
![Page 56: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/56.jpg)
56
Principles of Immunization
• Natural or artificial • Passive or active• Natural passive , e.g. IgG across the placenta • Artificial passive, use of immune serum
globulin e.g. IgG fraction of donor blood.• Active involves lymphocytes and confers
lasting protection due to memory
![Page 57: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/57.jpg)
57
Can you put the types of vaccines listed into categories?
![Page 58: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/58.jpg)
58
![Page 59: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/59.jpg)
59
Vaccines
• Induce artificial active immunity• Preparation of living or inactivated microbe or
virus or their components.• Adjuvants help to induce better response• Effective vaccines should be safe, few side
effects, lasting protection, low cost, stable, easy to administer
• Should induce appropriate specific response
![Page 60: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/60.jpg)
60
Attenuated immunizing vaccines• Use modified live microbe/virus• Induce infection & mild disease and solid long lasting immunity.• Single dose can induce immunity• Potential for spread to other people helps to develop HERD IMMUNITY• Disadvantages: may cause disease, cannot use in pregnancy, require
refrigeration• Examples: measles, mumps, rubella, Sabin polio vaccine, (Vaccinia ( for
smallpox))
![Page 61: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/61.jpg)
61
Inactivated Immunization
• Inactivated by chemical treatment but still antigenic• Cannot cause infection• Disadvantages: require several boosters, may cause side
effects
• Whole agent--Use inactivated bacteria or virus – Examples : Salk polio vaccine, diphtheria & tetanus toxoids
![Page 62: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/62.jpg)
62
Inactivated Immunization: Subunit vaccines
• Use isolated antigens or antigen fragments: a subunit of the total agent– bacterial toxin (toxoid), protein subunit,
polysaccharide – e.g vaccines against meningococci, pneumococci,
pertussis, H. influenza– Recombinant vaccine, e.g. Hepatitis B. Require
several doses.
![Page 63: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/63.jpg)
63
![Page 64: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/64.jpg)
64
![Page 65: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/65.jpg)
65
Future developments & information
• HIV/AIDS, Malaria, cancer• Use of DNA alone• Further information: www.immunizationinfo.org vaccine.chop.edu (Children’s Hospital of Philadelphia) • Developing New Smallpox Vaccines, in EID, vol7, #6, 2001. On
line at www.cdc.gov/eid
![Page 66: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/66.jpg)
66
Serology
• Testing for the presence of a specific antigen using specific antibody (antiserum)
• Examples: ELISA blood test for HIV, home pregnancy testhttp://www.sumanasinc.com/webcontent/animations/content/ELISA.html
![Page 67: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/67.jpg)
Mechanisms of Pathogenicity
Attachment and ColonizationAvoidance of Immune System
Toxin Production
![Page 68: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/68.jpg)
• Washwater containing Pseudomonas was sterilized and used to wash cardiac catheters. Three patients undergoing cardiac catherization developed fever, chills, and hypotension. The water and catheters were sterile. Why did the patients show these reactions?
![Page 69: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/69.jpg)
Host-Parasite Dynamics
1. Reservoirs2. Modes of transmission3. Adherence and invasion of host4. Growth in/on host5. Evade host defense6. Damage host7. Leave host for reservoir or new host
![Page 70: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/70.jpg)
How do bacterial pathogens overcome host defenses?
VIRULENCE FACTORS
bacterial products or structural components that contribute to pathogenicity or disease
A. promote bacterial colonization of the host(infectivity and invasiveness)
B. obtain nutrients, especially ironC. evade immune systemD. actively harm the host (toxins)
![Page 71: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/71.jpg)
![Page 72: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/72.jpg)
1. Motility
Swim through mucus and towards epithelial cells of mucus membranes (chemotaxis) Most microbes that colonize bladder, intestinesare motile (need to reach epithelial cells before flushed out)
Non-motile Vibrio cholerae mutants are less virulent
A1. Adherence Factors: Attachment and Colonization
![Page 73: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/73.jpg)
2. Pili and fimbrae with adhesins
![Page 74: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/74.jpg)
Pili allow uropathogenic bacteria to resist flushing and colonize the urethra.
![Page 75: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/75.jpg)
Once bacteria attach, some remain on cell surfacelike E. coli and biofilm bacteria.
Others INVADE host cells.
![Page 76: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/76.jpg)
2a. Capsule
Polysaccharide coat is sticky and aids attachmentAlso protects cell from inflammatory responseReduced complement fixation and phagocytosis.
![Page 77: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/77.jpg)
3b. Biofilm: community of encapsulated bacteria
Aid attachment of other bacteria; evade host immunesystem
![Page 78: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/78.jpg)
A2. Invasion
Proteins that induce phagocytosis in non-phagocytic cells
Advantage of living in host cell:
Ready supply of nutrientsProtected environment
Bacterium escapes fromvacuole and lives in cytoplasm
![Page 79: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/79.jpg)
Mechanism of Invasion: Type III secretion system
Pore formed through bacterial membrane and walland human cell membrane.
Deliver proteins directly from bacterial cytoplasmto human cell cytoplasm that polymerizeactin filaments.
![Page 80: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/80.jpg)
Invasion virulence factors that damage tissueor dissolve materials
e.g. Collagenase breaks down connective tissueClostridium perfringens: gangrene
Invasion of tissues possible too.
![Page 81: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/81.jpg)
C. Virulence Factors that help evade immune system.
i. Avoid or escape phagocytosis
![Page 82: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/82.jpg)
• destroy phagocytes or signals for recruitment• capsule• type III secretion of proteins that directly inhibit phagocytosis: Yersinia pestis
![Page 83: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/83.jpg)
•prevent opsonization (Protein A and Fc receptor)
![Page 84: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/84.jpg)
Antigenic variability (phase variation):alter genes that encode surface proteins like adhesins
Low immunogenicity: ‘Teflon’ pathogens (spirochaetes) few surface proteins
IgA protease
ii) evade specific immune response (antibodies)
![Page 85: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/85.jpg)
Viral evasion of cytotoxic T cell and NK cell attack
![Page 86: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/86.jpg)
D. TOXINS: Virulence factors that damage the host.
Endotoxin is only released upon death (lysis) of bacterium
What causes lysis?
![Page 87: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/87.jpg)
LPS, especially when in the blood, can cause a number of pathophysiological changes such as:
a. fever production b. inflammation c. tissue destructiond. respiratory distresse. capillary damage (leading to petechial rash, capillary leakage, and hypovolemia f. intravascular coagulation g. hypotension h. decreased cardiac outputi. Septic shock j. wasting of the body k. diarrhea (from endotoxin in intestines)
![Page 88: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/88.jpg)
![Page 89: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/89.jpg)
Exotoxins
Released from viable bacteriaGram-negative and gram-positive cellsMost potent toxic substances known
1 ng of botulinum toxin kills 1000 peopleBind to specific receptors on host cells(more localized effect than endotoxin)
•Neurotoxins (nervous tissue)•Cytotoxins (general tissue)•Enterotoxins (GI tract)
Effect depends on cell type the toxin binds
![Page 90: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/90.jpg)
Examples of bacterial exotoxins
Botulinum toxin (neurotoxin)Blocks release of neurotransmitterParalysis results
Cholera toxin (enterotoxin)Fluid loss results
![Page 91: Immunology and Microbiology](https://reader035.vdocuments.site/reader035/viewer/2022081421/56813a07550346895da1d2ff/html5/thumbnails/91.jpg)
Genetics of Pathogenicity
can involve many genes, complex.
chromosomal, plasmids, bacteriophage
Transfer of virulence genes via transformation, transduction, and conjugation.
Virulence factor genes often transferred as groups called pathogenicity islands: type III secretion system