The document provides an overview of the immune system, detailing its three lines of defense: non-specific innate immunity (first and second lines) involving physical barriers, phagocytosis, inflammation, and fever, and specific adaptive immunity (third line) involving T and B cells along with antibodies. It discusses the importance of normal flora in preventing infections, the complement system's role in defense, and how various factors, including antigens and virulence factors, affect host-pathogen interactions. Additionally, it covers the mechanisms of immunization, vaccine types, and the genetic basis of pathogenicity.

1. Immunology andImmunology and
MicrobiologyMicrobiology
Host-Microbe Interactions
 Non-specific (Innate) Immunity
First line of defense (Non-specificFirst line of defense (Non-specific
resistance)resistance)
Physical and Chemical Defenses
Normal Flora

2.  Second line of defense (Non-Second line of defense (Non-
specific resistance)specific resistance)
Phagocytosis
Inflammation
Fever
Antimicrobial substances: Complement,
Interferon
Third line of defense (Specific
Resistance)
Antibodies
B cells and T cells

3. 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

4. •Toll-like receptorsToll-like receptors:: What are someWhat are some
evolutionarily conserved features of microbes thatevolutionarily conserved features of microbes that
our immune cells could recognize?our immune cells could recognize?
Step 2.

5. Steps in phagocytosisSteps in phagocytosis
•The movement of phagocytes in the direction of anThe movement of phagocytes in the direction of an
infection, due to attraction by complement, chemicalsinfection, due to attraction by complement, chemicals
released by microorganisms, and the remnants ofreleased by microorganisms, and the remnants of
damaged cell membranes is a process calleddamaged cell membranes is a process called
phagocytosisphagocytosis..

6. The Complement SystemThe 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
•Effects of
complement
system

7. 1.1.OpsonizationOpsonization

8. 2. Membrane Attack Complex (Lysis)2. Membrane Attack Complex (Lysis)

9. 3.3. InflammationInflammation
A. Vasodilation results in
leakage of blood
components.
B. The process can cause
damage to host tissue
C. It is always accompanied
by a fever
D. The signs of inflammation
are redness, swelling, heat
and pain
E. It can be triggered by
activating toll-like
receptors (macrophages
produce cytokines)

10. Inflammation Process

13. 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

14. Interferon and viral infections: a protective alerting systemInterferon and viral infections: a protective alerting system

15. 1. Innate (Non-specific)1. Innate (Non-specific)
DefensesDefenses
a. Chemical anda. Chemical and
Physical;Physical; ((BiologicalBiological))
b. Normal Florab. Normal Flora

16. Host-Microbe InteractionsHost-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

17. First line of defense-First line of defense-
Chemical & Physical BarriersChemical & Physical Barriers

18. Body sites that harborBody sites that harbor
normal floranormal flora

19. Importance of the normal floraImportance 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

20. How do we acquire microflora?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.

21. What leads to changes in theWhat leads to changes in the
normal flora?normal flora?
Antibiotic treatment
Immunosuppression
Diet
Changes in physiology , e.g. estrogen-
glycogen effect

23. Normal Skin FloraNormal 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

24. First line of defense (Non-specific resistance)
• Physical and Chemical Defenses
• Normal Flora
Second line of defense (Non-specific resistance)
• Phagocytosis
• Inflammation
• Fever
• Antimicrobial substances: Complement, Interferon
Third line of defense (Specific Resistance)
• B cells and T cells
• Antibodies and Humoral Response
• Cellular Mediated Immunity

25. 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?

26. The two arms of the adaptive immune systemThe two arms of the adaptive immune system

27. Antigen: a molecule (or parts of one) that
causes antibody generation
(Immunoglobulin(Immunoglobulin) The specific region on an antigen
recognized by an antibody

28. Antibody StructureAntibody Structure
Diversity in antibodies due to variable region

29. Effects of Antigen-Antibody InteractionsEffects of Antigen-Antibody Interactions

30. Effects of Antigen-Antibody
Interactions-2

31. How is the antibody response triggered?
1. T-cell dependent antigens 2. T-cell independent Ags2. 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

32. A plasma cell
Clonal Expansion
Memory
Result:
1. Negative selection
2. Affinity maturation
3. Class switching: IgM – IgG—IgG /
IgA
4. Formation of memory cells

33. Memory Cells mediate secondary response and lifelong immunityMemory Cells mediate secondary response and lifelong immunity

34.  Cellular ImmunityCellular 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

35. T cells activated by dendritic cells

36. A. Recognition of virally-infected cell by cytotoxic T cell
results in apoptosis

37. B: Helper T-cell activation and interaction with B-cellsB: Helper T-cell activation and interaction with B-cells

38. C. Helper T- cells can also activate macrophages

39. Applications of Principles ofApplications of Principles of
ImmunityImmunity

40. 40
IgG levels inIgG levels in
fetus vs. infantfetus vs. infant
 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

41. 41

42. 42

43. 43
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.
PrinciplesPrinciples of Immunizationof Immunization

44. 44
 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))
VaccinesVaccines

45. 45
 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
Attenuated immunizing vaccinesAttenuated immunizing vaccines

46. 46
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.
Inactivated ImmunizationInactivated Immunization

47. 47

48. 48

49. 49
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
Inactivated Immunization:Inactivated Immunization:
Subunit vaccinesSubunit vaccines

50. SerologySerology
Testing for the presence of a
specific antigen using specific
antibody (antiserum)
Examples: ELISA blood test for
HIV,
home pregnancy test
http://www.sumanasinc.com/webcontent/an
50
Future developments &Future developments &
informationinformation

51. Mechanisms of PathogenicityMechanisms of Pathogenicity
• Attachment and Colonization
• Avoidance of Immune System
• Toxin Production

52. Host-Parasite DynamicsHost-Parasite Dynamics
1. Reservoirs
2. Modes of transmission
3. Adherence and invasion of host
4. Growth in/on host
5. Evade host defense
6. Damage host
7. Leave host for reservoir or new host
How do bacterial pathogens overcome host defenses?
VIRULENCE FACTORSVIRULENCE FACTORS
bacterial products or structural components that contribute tobacterial products or structural components that contribute to
pathogenicity or diseasepathogenicity or disease
A. promote bacterial colonization of the host
(infectivity and invasiveness)
B. obtain nutrients, especially iron
C. evade immune system
D. actively harm the host (toxins)

54. 1. Motility
Swim through mucus and towards epithelial cells of mucus membranes
(chemotaxis)
Most microbes that colonize bladder, intestines
are motile (need to reach epithelial cells before flushed out)
Non-motile Vibrio cholerae
mutants are less virulent
A1. Adherence Factors: Attachment and Colonization

55. 2. Pili and fimbrae with adhesins

56. Pili allow uropathogenic bacteria toPili allow uropathogenic bacteria to
resist flushing and colonize the urethraresist flushing and colonize the urethra..

57. Once bacteria attach, some remain on cell surface
like E. coli and biofilm bacteria.
Others INVADE host cells.

58. 2a. Capsule2a. Capsule
Polysaccharide coat is sticky and aids attachment
Also protects cell from inflammatory response→
Reduced complement fixation and phagocytosis.

59. 3b. Biofilm: community of encapsulated bacteria3b. Biofilm: community of encapsulated bacteria
Aid attachment of other bacteria; evade host immune
system

60. A2. InvasionA2. Invasion
Proteins that induce phagocytosis in non-phagocytic
cells
Advantage of living in host cell:
•Ready supply of nutrients
•Protected environment
Bacterium escapes from vacuole and lives in cytoplasm

61. Mechanism of Invasion: Type III secretion systemMechanism of Invasion: Type III secretion system
Pore formed through bacterial membrane and wall
and human cell membrane.
Deliver proteins directly from
Bacterial cytoplasm to human cell
cytoplasm that polymerize
actin filaments.
Invasion of tissues possible too.
Invasion virulence factors that damage
tissue or dissolve materials.
e.g. Collagenase breaks down
connective tissue
Clostridium perfringens:
gangrene

62. C. Virulence Factors that help evade immune system.
i. Avoid or escape phagocytosis

63. • destroy phagocytes or signals for
recruitment
• capsule
• type III secretion of proteins that directly
inhibit phagocytosis: Yersinia pestis
•prevent opsonization (Protein A and Fc
receptor)

64. 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)

65. Viral evasion of
cytotoxic T cell
and NK cell attack

66. LPS, especially when in the blood, can
cause a number of pathophysiological
changes such as:
a. fever production
b. inflammation
c. tissue destruction
d. respiratory distress
e. capillary damage (leading to
petechial rash, capillary leakage,
and hypovolemia
f. intravascular coagulation
g. hypotension
h. decreased cardiac output
i. Septic shock
j. wasting of the body
k. diarrhea (from endotoxin in
intestines) 00
•Endotoxin is only released upon death (lysis) of bacterium

68. ExotoxinsExotoxins
•Released from viable bacteria
•Gram-negative and gram-positive cells
•Most potent toxic substances known
•1 ng of botulinum toxin kills 1000 people
•Bind 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

69. Examples of bacterial exotoxinsExamples of bacterial exotoxins
Botulinum toxin (neurotoxin)
• Blocks release of neurotransmitter
• Paralysis results
Cholera toxin (enterotoxin)
• Fluid loss results

70. 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