2. Immunity
• Ability to ward off a disease/ disease causing organism/
foreign material (pollen etc)
• Susceptibility: lack of resistance to a disease
• INNATE IMMUNITY
– At birth
– First and Second line of defense
– Non-specific
– No Memory
• ADAPTIVE IMMUNITY
– Third line of defense
– Specific
– Memory response (to previous disease/ vaccination)
3. First line of defense
• Intact skin
• Mucous membranes
and their secretions
• Normal microbiota
Second line of defense Third line of defense
• Specialized lymphocytes:
T cells and B cells
• Antibodies
• Phagocytes, such as neutrophils,
eosinophils, dendritic cells, and
macrophages
• Inflammation
• Fever
• Antimicrobial substances
Figure 16.1 An overview of the body’s defenses.
4. Physical Barriers: First Line of Defense
• Skin
– Epidermis
• Outer layer – thin
• Layers of tightly packed epithelial cells
• Outermost layers dead
– Keratin (Protein)
– Sloughs off routinely
– Dermis
• Inner layer – thick
• Connective tissue
Bacteria enter through Skin ONLY when skin is
damaged
9. Chemical Factors
• Sebum: oils – protective layer on skin
– Low pH: unsatd. Fatty acids – inhibit path. Bacteria
• Sweat
– Regulates body temperature
– Flushes microbes, waste
– Lysozyme
• Gastric Juice: HCl, mucus and enzymes
– Low pH 1.5-3
– Kills most microbes and toxins (except those of S. aureus and
Botulinum)
• Some bacteria enter protected by food
• H. pylori neutralizes acid and makes a niche for itself in stomach
• Vaginal Secretions: low pH
10. Normal Flora
• Competition/ Exclusion
– Compete for nutrition
– Alter environment to prevent pathogen growth
• Commensal
– Where one benefits (normal flora), the other is
unaffected (host)
– Opportunistic pathogens
• E. coli, S. aureus, S. epidermidis
11. Second Line of Defense
• Formed Elements in the Blood
• Lymphatic System
• Phagocytes
• Inflammation
• Fever
• Antimicrobial Substances
13. Insert Table 16.1
If possible, break into multiple slides
Table 16.1 Formed Elements in Blood (Part 1 of 2)
14. Insert Table 16.1
If possible, break into multiple slides
Table 16.1 Formed Elements in Blood (Part 2 of 2)
15. • Percentage of each type of white cell in a sample
of 100 white blood cells
Neutrophils 60–70%
Basophils 0.5–1%
Eosinophils 2–4%
Monocytes 3–8%
Lymphocytes 20–25%
Differential White Cell Count
16. The Lymphatic System
• lymph : fluid
• Lymph vessels
• Lymph tissue (contain a large number of
lymphocytes T cells and B cells)
• Red bone marrow
• Lymph nodes: sites of activation for T cells and B
cells
• Tonsils/ Peyer’s patch
• Spleen: monitor blood for microbes and secreted
products (toxins)
• Thymus: T cell maturation
18. Phagocytosis
• Greek: Phagos (eat), cyte (cell)
• Ingestion of a substance/ microbe by a cell
• Phagocytes
– Cells that perform phagocytosis
– Leukocytes and/or derivatives
SEM of a neutrophil
phagocytosing
Aspergillus spores
20. Phagocytes
• Neutrophils: early during infection
– First phagocytes at site of infection
• Monocytes
– Morph into Macrophages when infection
progresses
– Fixed v/s Wandering Macrophages
• Non-motile; Specifically present in tissues/ organs
– Lymph nodes, bone marrow, spleen, liver
• Roaming through tissue, gather at site of inflammation
21. Phagocytosis: Mechanism
• Chemotaxis: attracted to site of infection
– Cytokines (released from other WBCs)
– Cell damage
– Microbial products
• Adherence: attachment to microbial surface
– Toll-like receptors (TLRs)
– Pathogen associated Molecular Patterns (PAMPs)
– Opsonins: proteins that coat microbe
• Ingestion: pseudopodia engulf microbe into phagosome
• Digestion: fusion of phagosome with lysosome
– Enzymes digest microbe
– Residual body excreted
23. PAMPs and TLRs
TLRs in the plasma membrane of phagocytes attach to
components commonly found on pathogens (PAMPs)
• LPS of gram (-) outer membrane
• Peptidoglycan of gram (+) cell wall
• DNA and RNA of viruses
• Fungal and parasite components
Shown: Pattern
Recognition
Receptor of a TLR
attaching to a
pathogen’s PAMP
25. Inflammation
• Damage to tissue: heat, infection, chemical
• Four signs of inflammation:
– Heat (calor), swelling (tumor), redness (rubor), pain
(dolor)
– Loss of function in some cases
• Acute: intense
– Infecting agent removed in short time
– S. aureus (boil)
• Chronic: less intense, more destructive
– Infecting agent cannot be removed
– TB lesion in lungs
26. Inflammation
Purpose of inflammation:
1. Destroy infectious agent
- Remove it and its byproducts from the body
2. If #1 is impossible, confine the infectious agent and
byproducts; keep from spreading
3. Repair or replace damaged tissue
Steps in the inflammatory response:
1. Vasodilation & increased blood vessel permeability
2. Phagocyte migration & phagocytosis
3. Tissue repair
27. Inflammation
Stage 1: Vasodilation & increased vessel permeability
• Histamine
• released from injured cell granules (basophils, mast cells)
• Kinins
• In plasma; attract phagocytic granulocytes to injured site
• Prostaglandins
• From damaged cells
• intensify the effects of histamine and kinins
• Leukotrienes
• Damaged basophils, mast cells
• increase vessel permeability; attach phagocytes to pathogens
• Cytokines
• activated fixed macrophages
• increase vasodilation and permeability
Clotting factors enter infection site; clot prevents spread
PUS: dead cells and body fluids; ABCESS: cavity after tissue
breakdown
28. Histamine Vasodilation, increased permeability
of blood vessels
Kinins Vasodilation, increased permeability
of blood vessels
Prostaglandins Intensify histamine and kinin effect
Leukotrienes Increased permeability of blood vessels,
phagocytic attachment
Chemicals Released by Damaged Cells
29. Inflammation
Stage 2: Phagocyte migration and phagocytosis
• Phagocytes appear on the scene within ~1 hour
Margination = cytokines alter blood vessel lining, cause
phagocytes to stick to vessel walls at inflammation site
- Traverse vessel walls to get into affected area
(= diapedesis), phagocytize invading microbes
• Granulocytes are first on scene; die off rapidly
• Macrophages enter at a later stage
- larger and more phagocytic
- Phagocytize destroyed tissue, granulocytes, remnants of
invaders
31. Inflammation
Stage 3: Tissue repair
• Dead or damaged cells are replaced in affected tissues
• Repair capacity depends on tissue type
Stroma = supportive connecting tissue
- Ex) capsule around the liver that encloses and protects it;
not involved in liver functions
Parechyma = functioning portion of tissue
- Ex) Hepatocyte cells of liver that perform the liver’s
functions
If parenchymal cells are active in repair = perfect
reonstruction; if stroma cells are more active = scar
32. Bacteria entering
on knife
Epidermis
Dermis
Subcutaneous
tissue
(a) Tissue damage
Bacteria
Blood vessel
Nerve
Figure 16.8a-b The process of inflammation.
Chemicals such as histamine, kinins,
prostaglandins, leukotrienes, and cytokines
(represented as blue
dots) are released by
damaged cells.
(b) Vasodilation and increased
permeability of blood vessels
Blood clot forms.
Abscess starts to form
(orange area).
1
2
3
33. Insert Fig 16.8d
Scab
Blood clot
Regenerated
epidermis
(parenchyma)
Regenerated
dermis
(stroma)
(d) Tissue repair
Figure 16.8d The process of inflammation.
34. Fever
Fever = abnormally high body temperature
• a systemic response
Hypothalamus = brain region that controls body temp
• Raises temp in response to cytokines by:
- blood vessel constriction
- increased metabolism
- shivering
• Maintained until cytokines (and infection) are eliminated
• Heat loss by vasodilation and sweating
Drop in body temperature
35. Fever benefits:
• Intensifies the effect of antiviral interferons
• Increases production of transferrins
- decreases iron available to microbes
• Increased speed of tissue repair
- speeds up all of the body’s reactions
Fever complications:
• Increased metabolism effects:
- Tachycardia = rapid heart rate
- Acidosis = increased acidity of blood/tissue
- Seizures, delirium, coma
- Death (temp above 112-114oF)
Fever
36. Antimicrobial Substances
Complement system = defensive system of >30 proteins
produced in the liver that circulate the blood & tissues
• “Complements” the action of immune cells
Destroy microbes by:
1. Cytolysis
2. Inflammation
3. Phagocytosis
• Act in a cascade with one reaction triggering another
Activated by one of 3 possible pathways
37. The Complement Cascade
1. C3 splits into C3a and C3b
2. C3b coats the microbe to promote phagocyte
attachment (opsonization)
3. C3b initiates formation of membrane attack complex
(MAC) on invading cell
4. MAC causes cytolysis = bursting of invading cell due to
inflow of extracellular fluid
5. C3a and C5a bind mast cells stimulate release of
histamine increase blood vessel permeability
• C5a also attracts phagocytes
39. 1. Antibodies bind antigens
antigen-antibody complexes
activate C1
2. Active C1 splits (activates) C2 and
C4 into C2a, C2b, C4a, C4b
3. C2a and C4b combine and split C3
into fragments C3a and C3b
Active fragments initiate the
complement cascade
Complement activation:
classical pathway
40. Steps:
1. C3 combines with factor B, D and P
(complement proteins) on the
surface of a microbe
2. C3 splits into C3a and C3b
complement cascade
• No antibodies involved
• Direct contact between
complement proteins
and pathogen
Complement activation:
alternative pathway
41. Lectins = proteins produced by the liver
that bind carbohydrates
Mannose binding lectin (MBL) = binds
mannose (in bacterial cell walls and
some viruses)
Steps:
1. MBL binds an invader
2. Activates C2 and C4
3. C2a and C4b combine and
activate C3
complement cascade
Complement activation:
The lectin pathway
42. Interferons
Interferons = class of cytokines produced by certain animal
cells after viral stimulation
• Interfere with viral multiplication
Three types in humans:
Alpha and Beta interferon = produced by infected host to
induce antiviral protein synthesis in neighboring cells
• Oligoadenylate synthetase = degrades viral mRNA
• Protein kinase = inhibits viral protein synthesis
Gamma interferon = produced by lymphocytes; induces
neutrophils and macrophages to kill invaders; suppresses
tumor cell proliferation
43. Interferons
Interferon complications:
• Stable for only short time periods
• Side effects of injection:
- Nausea, fatigue, vomiting, fever
• Toxic in high concentrations
- heart, kidneys, liver, red bone marrow
Medical usage:
• Limited or no effect on tumors in clinical trials
• Alpha interferon some virus-associated disorders
• Kaposi’s sarcoma
• Chronic Hepatitis B and C
44. Iron-binding proteins
Humans use iron in many ways:
• component of cytochromes in the ETC
• cofactor of many enzymes
• component of hemoglobin
Iron-binding proteins = transport and store iron
Transferrin = blood and tissue fluids
Lactoferrin = milk, saliva, mucus
Ferritin = liver, spleen, red blood marrow
Hemoglobin = red blood cells
deprives pathogens of available iron!
45. Iron-binding proteins
Siderophores = proteins released into the medium by
bacteria to capture iron from transport proteins
• Forms iron-siderophore complex, recognized by
bacterial receptors and taken into cell
• Splits iron from siderophore and utilizes it
Other mechanisms of obtaining iron:
• Release toxins when iron is low
Kills host cells, releasing their iron
Ex) Strep pyogenes
• Hemolysins lysis of red blood cells
• Hemoglobin broken down to capture iron
46. Antimicrobial Peptides
Antimicrobial peptides (AMPs) = short chains of amino acids
synthesized on ribosomes
• Synthesized by neutrophils when TLRs contact PAMPs
- Broad spectrum killing of bacteria, viruses, fungi
- Attract other phagocytes
- Sequester endotoxins
What makes them interesting?
• Work together with other antimicrobials (synergy)
• Stable over a wide range of pH
• Microbes don’t develop resistance
