1
Q
Immune system provides resistance to disease
Not an
A
organ system! Functional system!
2
Q
immune system Made up of two intrinsic systems
A
- Innate (nonspecific) defense system
- -Constitutes first and second lines of defense
- –First line of defense: external body membranes (skin and mucosae)
- –Second line of defense: antimicrobial proteins, phagocytes, and other cells (inhibit spread of invaders; inflammation most important mechanism)
- Adaptive (specific) defense system
- -Third line of defense attacks particular foreign substances (takes longer to react than innate)
- Adaptive and innate work together!
3
Q
inate defenses surface barriers
A
skin
mucous membranes
4
Q
irate defenses internal defenses
A
phagocytes natural killer cells inflammation antimicrobial proteins fever
5
Q
adaptive defenses humoral immunity
A
B cells
6
Q
adaptive defenses cellular immunity
A
T cells
7
Q
Surface barriers are
along with their secretions
A
skin and mucous membranes, along with their secretions
- Physical barrier to most microorganisms
- Keratin is resistant to weak acids and bases, bacterial enzymes, and toxins
- Mucosae provide similar mechanical barriers
8
Q
Skin and mucous membranes produce protective
A
chemicals that inhibit or destroy microorganisms
Acid: acidity of skin and some mucous secretions inhibits growth
-called acid mantle
Enzymes:
- lysozyme of saliva
- respiratory mucus
- lacrimal fluid
- in stomach kill
Mucin
- sticky mucus
- digestive and respiratory tracts
- traps microorganisms
Defensins: antimicrobial peptides that inhibit microbial growth
Other chemicals: lipids in sebum and dermicidin in sweat are toxic to some bacteria
9
Q
Respiratory system also has modifications to stop pathogens
A
- Mucus-coated hairs in nose trap inhaled particles
- Cilia of upper respiratory tract sweep dust- and bacteria-laden mucus toward mouth
10
Q
Surface barriers breached by nicks or cuts trigger the internal
A
second line of defense that protects deeper tissues
11
Q
Innate system necessary if microorganisms invade deeper tissues; includes:
A
- Phagocytes
- Natural killer (NK) cells
- Inflammatory response (macrophages, mast cells, WBCs, and inflammatory chemicals)
- Antimicrobial proteins (interferons and complement proteins)
- Fever
12
Q
Phagocytes:
Free macrophages:
-Fixed macrophages
A
Phagocytes:
-white blood cells that ingest and digest (eat) foreign invaders
Neutrophils:
- most abundant phagocytes, but die fighting;
- become phagocytic on exposure to infectious material
Macrophages:
- develop from monocytes
- most robust phagocytic cell
- Free macrophages: wander through tissue spaces
- Fixed macrophages: permanent residents of some organs
13
Q
Phagocytosis process
A
- Phagocyte recognizes and adheres to pathogen’s carbohydrate “signature”
- Some microorganisms have external capsules that hide their surface carbohydrates, helping them evade phagocytosis
- Opsonization
- -immune system uses antibodies or complement proteins as opsonins that coat pathogens
- -“handles” for phagocytes to grab on to
- -enhance phagocytosis - Cytoplasmic extensions (pseudopods) bind to and engulf particle in vesicle called phagosome
- Phagosome fuses with lysosome, forming phagolysosome
- Phagolysosome is acidified, and lysosomal enzymes digest particles
- Indigestible and residual waste put out by exocytosis
14
Q
Pathogens that are not killed
A
Some pathogens are not killed with acidified lysosomal enzymes
- i.e. tuberculosis bacteria
- Helper T cells trigger macrophage to produce “respiratory burst”
- kills pathogens resistant to lysosomal enzymes
- HOW?
- –release cell-killing free radicals
- -produce oxidizing chemicals (e.g., Peroxide-H2O2 )
- -increasing pH and osmolarity of phagolysosome
-Defensins (in neutrophils) also help by piercing membrane of pathogen
15
Q
Natural Killer (NK) Cells
A
- Large granular lymphocytes that police blood and lymph
- -Nonphagocytic
- -Can kill cancer and virus-infected cells
- HOW?
- Attack cells that lack “self” cell-surface receptors
- Cause apoptosis in cancer cells and virus-infected cells
- –“programmed cell death”
- Enhance inflammatory response
16
Q
Inflammation
Triggered by
and benefits
A
tissue injury
i.e. trauma, heat, irritating chemicals, or infections
Benefits:
- Prevents spread of damaging agents
- Disposes of cell debris and pathogens
- Alerts adaptive immune system
- Sets the stage for repair
17
Q
Four cardinal signs of acute inflammation:
A
- Redness
- Heat
- Swelling
- Pain
Sometimes a fifth sign, impairment of function, is seen if movement or use of area is hampered
18
Q
Stages of inflammation
A
- Inflammatory chemical release
- Vasodilation and increased vascular permeability
- Phagocyte mobilization
19
Q
Inflammatory chemical release
A
- Chemicals are released into ECF by injured tissues or immune cells
- –Example: histamine released by mast cells is key inflammatory chemical
20
Q
Other inflammatory mediators besides histamine
A
- Kinins, prostaglandins (PGs), cytokines and if pathogens are involved, complement
- –All cause vasodilation of local arterioles
- –All make capillaries leaky
- –Many attract phagocytes to area
21
Q
Vasodilation and increased vascular permeability
Vasodilation causes
A
- Vasodilation causes hyperemia
- -congestion with blood
- -leads to redness and heat
- Increased capillary permeability causes exudate
- -fluid containing clotting factors and antibodies
- -leaks into tissue
- -Local swelling (edema)
- —-Pushes on nerve endings, resulting in pain
22
Q
Pain can also be due to
A
Can also be due to toxins from bacteria or released prostaglandins and kinins
23
Q
benefits of edema
A
Benefits of edema
- Fluid in tissue sweeps foreign material into lymphatic vessels
- – filtered in the lymph nodes
- Delivers clotting proteins and complement to area
- -Fibrin mesh forms
- —–Acts as scaffold for repair
- —-Isolates injured area so invaders cannot spread
24
Q
Phagocyte mobilization
four steps
A
- Neutrophils flood area first; macrophages follow
- If inflammation is due to pathogens, complement is activated; adaptive immunity elements arrive
Four Steps:
- Leukocytosis
- Margination
- Diapedesis
- Chemotaxis
25
1. Leukocytosis:
- Release of neutrophils from bone marrow in response
| - Due to leukocytosis-inducing factors from injured cells
26
2. Margination:
endothelial cells of capillaries in inflamed area project cell adhesion molecules (CAMs) into vessel lumen that grab onto passing neutrophils, causing them to slow and roll along, clinging to vessel wall
27
3. Diapedesis:
neutrophils flatten and squeeze between endothelial cells, moving into interstitial spaces
28
4. Chemotaxis:
inflammatory chemicals act as chemotactic agents that promote positive chemotaxis of neutrophils toward injured area
29
Monocytes arrive
later
- Transformed into macrophages
- --About 12 hours after the got out of the blood
- Replace dying neutrophils
- Cleanup so tissue repair can happen
30
Pus
- creamy yellow
- mixture of dead neutrophils, tissue/cells, and living/dead pathogens
Abscess:
- collagen fibers wall off sac of pus
- may need to be surgically drained
31
Granulomas
- Tumorlike growths
- Protect the body from bacteria macrophages can’t digest
- Example: tuberculosis bacilli
- Bacteria may remain inactive forever, or if person’s immunity decreases, may break free, become activated, and cause disease
32
Antimicrobial proteins
| Most important antimicrobial proteins
- Enhance innate defense
- Some attack microorganisms directly
- Some stop microorganisms from reproducing
- Interferons
- Complement proteins
33
Interferons
| -IFNs enter neighboring cells, stimulating production of
-family of immune proteins
- Cells infected with viruses can secrete IFNs
- “warn” healthy neighboring cells
- IFNs enter neighboring cells, stimulating production of proteins that block viral reproduction and degrade viral RNA
34
Complement System
- ~20 blood proteins that circulate in blood in inactive form
- Includes proteins C1–C9, factors B, D, and P, and regulatory proteins
- Provides major mechanism for destroying foreign substances
- Activation enhances inflammation and directly destroys bacteria
- --Enhances both innate and adaptive defenses
35
Complement Activation
Complement system can be activated by three different pathways:
1. Classical pathway
- Antibodies first bind to invading organisms and then bind to complement components, activating them
- --Double binding called complement fixation
- Once initial complement proteins are activated,
an activation cascade is triggered
2. Lectin pathway
- Lectins are produced by innate system to recognize foreign invaders
- When lectin is bound to specific sugars on foreign invaders, it can also bind and activate complement
3. Alternative pathway
- Complement cascade is activated spontaneously when certain complement factors bind directly to foreign invader
- --Lack of inhibitors on microorganism’s surface allows process to proceed
36
Fever
| benefits of moderate fever
- Abnormally high body temperature
- Systemic response to invading microorganisms
- Pyrogens
- --Secreted by leukocytes and macrophages when they are exposed to foreign substances
- ---Act on body’s thermostat in hypothalamus
- -------Raise body temperature
Benefits of moderate fever
- Causes liver and spleen to sequester iron and zinc
- -needed by microorganisms
- Increases metabolic rate
- ---increases rate of repair
37
Adaptive immune system
specific defensive system
- eliminates almost any pathogen or abnormal cell in body
- Amplifies inflammatory response
- Activates complement
Must be primed by first exposure
-Takes time ☹
38
Characteristics of adaptive immunity
Specific
-recognizes and targets specific antigens
Systemic
-not restricted to initial site
Memory
-mounts an even stronger attack to “known” antigens (second and subsequent exposures)
39
Two branches of adaptive system
1. Humoral (antibody-mediated) immunity
| 2. Cellular (cell-mediated) immunity
40
Humoral immunity
Antibodies
- -produced by lymphocytes
- -circulate in body fluids
Bind temporarily to target cell
- -Mark for destruction by phagocytes or complement
- -Humoral immunity has extracellular targets
41
Cellular Immunity
Lymphocytes act against target cell
Directly
---kill infected cells
Indirectly
- release chemicals that enhance inflammatory response
- or activating other lymphocytes or macrophages
-Cellular immunity has cellular targets
42
Antigens
- Provoke an immune response
- Targets of adaptive immune responses
-Most are large, complex molecules not normally found in body (nonself)
43
Characteristics of antigens
- Can be a complete antigen or hapten (incomplete)
- Contain antigentic determinants
- Can be a self-antigen
44
Two properties of Complete antigens
Immunogenicity:
--stimulate proliferation of specific lymphocytes
Reactivity
--react with activated lymphocytes and antibodies released by immunogenic reactions
-Examples: foreign proteins, polysaccharides, lipids, and nucleic acids; seen on many foreign invaders such as pollen and microorganisms
45
Incomplete antigens (AKA haptens)
- small molecules
- not immunogenic by themselves
- Examples: small peptides, nucleotides, some hormones
- May become immunogenic if hapten attaches to body’s own proteins
- -Combination of protein and hapten is then seen as foreign
- Causes immune system to attack self-proteins as well as hapten
-Examples: poison ivy, animal dander, detergents, and cosmetics
46
Antigenic determinants:
-parts of antigen that antibodies or lymphocyte receptors bind to
-Most naturally occurring antigens have more than one kind of antigenic determinants
So
--Mobilize several different lymphocyte populations
--Form different kinds of antibodies against them
47
Self-antigens
proteins located on the surface of your cells
are not antigenic to self
but may be antigenic to others in transfusions or grafts
48
MHC proteins
- Important self-proteins
- Group of glycoproteins
- Genetic and unique to each individual
- Hold a piece of self-antigen or foreign antigen
- -T lymphocytes can recognize only antigens that are presented on MHC proteins so without MHC T cells cannot function!
49
Adaptive immune system involves three crucial types of cells
```
Two types of lymphocytes
B lymphocytes (B cells)—humoral immunity
```
T lymphocytes (T cells)—cellular immunity
Antigen-presenting cells (APCs)
- Do not respond to specific antigens
- Play important auxiliary (helper) roles in immuni
50
Lymphocyte development, maturation, and activation
T and B lymphocytes share common development and steps in their life cycles
Five general steps:
- origin
- maturation
- Seeding secondary lymphoid organs and circulation
- Antigen encounter and activation
- Proliferation and differentiation
51
origin
Origin: both lymphocytes originate in red bone marrow
52
Maturation
Maturation
-Lymphocytes are “educated” in a 2-3 day process and mature in primary lymphoid organs (B cells in bone marrow and thymus)
1. Immunocompetence
- must be able to recognize 1 specific antigen
- B or T cells display only one unique type of antigen receptor on surface when mature so bind only one specific antigen
2. Self-tolerance
- Unresponsive to own antigens
53
Seeding secondary lymphoid organs and circulation
- Immunocompetent B and T cells not yet exposed to antigen are called naive
- Exported from primary lymphoid organs to “seed” (colonize) secondary lymphoid organs (lymph nodes, spleen, etc.)
- -Increases chance of encounter with antigen
54
Antigen encounter and activation
- Naive lymphocyte’s first encounter with antigen triggers lymphocyte to develop further
- Lymphocyte is selected to differentiate into active cell by binding to its specific antigen
- --Referred to as clonal selection
- If correct signals are present, lymphocyte will complete its differentiation into active cell
55
Proliferation and differentiation
Once selected and activated, lymphocyte proliferates
- Clones
- -exact copies of itself
- -Most become effector cells that fight infections
- A few remain as memory cells
- --Able to respond to same antigen more quickly second time it is encountered
-B and T memory cells and effector T cells circulate continuously
56
Antigen receptor diversity
-Genes determine which foreign substances the immune system will recognize
- ∼25,000 different genes codes for up to a billion different types of lymphocyte antigen receptors
- -Huge variety of receptors
- ---gene segments are shuffled around, resulting in many combinations
57
Positive selection process occurs
in thymus
- Selects T cells capable of recognizing self-MHC proteins
- If they can’t they undergo apoptosis
58
negative selection occurs
thymus
- Apoptosis of T cells that bind to self-antigens displayed by self-MHC
- Called clonal deletion
- ensures self-tolerance
59
Antigen-Presenting Cells (APCs)
| major types
Engulf antigens and present fragments of antigens to T cells for recognition
Major types
Dendritic cells
Macrophages
B cells
60
Dendritic cells
- Found in connective tissues and epidermis
- -Act as mobile sentinels
- Phagocytize pathogens
- Enter lymphatics to present antigens to T cells in lymph node
- --Most effective antigen presenter known
- --Key link between innate and adaptive immunity
61
Macrophages
| B lymphocytes
- Widely distributed in connective tissues and lymphoid organs
- Present antigens to T cells,
- activates T cell
- further activates macrophage
- --Activated macrophage becomes voracious phagocytic killer
- Trigger powerful inflammatory responses
- Recruit additional defenses
B lymphocytes
- -Do not activate naive T cells
- -Present antigens to helper T cell to assist their own activation
62
Humoral Immune Response
| starts when
Starts when a B cell encounters its antigen and is activated
| Antibodies specific for that particular antigen are then produced
63
Plasma cells
- Most
- antibody-secreting cells
- 2000 molecules per second for 4 to 5 days, then die
- Antibodies circulate in blood or lymph, binding to free antigens, marking them for destruction by innate or other adaptive mechanisms
64
memory cells
- Provide immunological memory
| - Mount an immediate response to future exposures to same antigen
65
Primary immune response
Primary immune response
- cell proliferation and differentiation after exposure to antigen for the first time
- Lag period: 3 to 6 days
- Peak levels of plasma antibody are reached in 10 days
- Antibody levels then decline
66
Secondary immune response
Re-exposure to same antigen gives faster, more prolonged, more effective response
- -Sensitized memory cells provide immunological memory
- -Respond within hours, not days
- -Antibody levels peak in 2 to 3 days at much higher levels
- -Antibodies bind with greater affinity
- -Antibody level can remain high for weeks to months
67
Active humoral immunity
- Earned!
- B cells encounter antigens and produce specific antibodies against them
- Two types of active humoral immunity
1. Naturally acquired
- --actual bacterial or viral infection
2. Artificially acquired:
- vaccine of dead or attenuated pathogens
- -Provide antigenic determinants that are immunogenic and reactive
- -Spare us symptoms of primary response
68
Passive humoral immunity
- Not earned-borrowed
- antibodies are introduced into body
- B cells are not challenged by antigens
- Immunological memory does not occur
- Protection ends when antibodies degrade
- Two types of passive humoral immunity
1. Naturally acquired
- -via placenta or through milk
2. Artificially acquired
- -injection of serum, such as gamma globulin
- -Protection immediate but ends when antibodies naturally degrade in body
A+P 2
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