Inflammation and Immunity Flashcards
Understand the purpose of inflammation and components of the inflammatory response. Differentiate between innate and adaptive immunity and understand the factors involved in immune response.
1
Q
What is involved in the body’s first line of defense?
A
- Skin
- Epithelial cells ( which lines all organs and secretes antimicrobial enzymes to help fight off pathogens)
- Mucous membranes
- Cilia (“moving”, they filter, found in our trachea, bronchi, so basically lungs, ears and respiratory tract)
2
Q
What is your body’s second line of defense?
A
Innate inflammation; it’s also non-specific
3
Q
What is your body’s third line of defense?
A
Adaptive immune system response (T and B cells); it is a specific response
4
Q
What is inflammation?
A
An innate, non-specific , rapid automatic response to cell injury
5
Q
What is the purpose of inflammation?
A
To create a response that:
- Neutralizes harmful agents
- Is vascular (move through the bloodstream)
- Depends on cellular and chemical mediators
- Removes damaged and dead tissue and generates new tissue
6
Q
What are the cells involved in inflammation?
A
- Endothelial cells (-line inner walls of blood vessels, -regulate vessel patency by secreting heparin to dissolve clots and -prevent them from forming, -allows permeability, -vasodilation, -adhesion and repair)
- Platelets/Thrombocytes (clotting)
- Granulocytes (Neutrophils, Eosinophils, Basophils, Mast cells)
- Agranulocytes ( Macrophages, dendritic cells)
- Lymphocytes (NK cells)
7
Q
What are neutrophils?
A
- First responders of inflammation
- most common WBC in our blood
- small phagocytes (they engulf bacteria)
- short lifespan, 24-48 hours
- they release chemical mediators
- they create pus cells (these are dead neutrophils that have phagocytized the pathogen)
8
Q
What are mast cells?
A
-most important activator in inflammatory response
9
Q
What do mast cells secrete?
A
- Histamine
- Chemokines
- Other Cytokines (Interleukin, TNF)
10
Q
What is histamine?
A
A biochemical mediator that releases vasoactive amines.
It Causes:
–Vasodilation (this leads to redness, swelling, or heat)
–Increased vascular permeability
–Bronchoconstriction ( *which is a parasympathetic NS response b/c vasodilation=parasympathetic NS)
11
Q
What are chemokines?
A
-They are small protein molecules that attract a specific type of WBC (neutrophils, eosinophils) to inflammation site
12
Q
What do mast cells synthesize?
A
- Leukotrienes
- Eicosanoids-Prostaglandins
- PAF (Platelet Activating Factor)
13
Q
What are Leukotrienes and their functions?
A
They are inflammatory mediators that:
-Increase vascular permeability
-Cause smooth muscle contraction (bronchoconstriction-parasympathetic)
-Cause neutrophil and eosinophil chemotaxis (these are chemical signals that summon WBC)
-Act later/last longer than histamine in response
( this means your secondary response to allergen is much stronger)
14
Q
What are Prostaglandins and their functions?
A
They are mediators that cause:
– Increase vascular permeability
– Vasodilation
– Smooth muscle contraction (bronchoconstriction)
– Induce pain
–Cause neutrophil chemotaxis
[ASA & NSAIDS block inflammatory prostaglandin synthesis-inhibit inflammation & pain]
15
Q
What are Platelet Activating Factors (PAF) and their functions?
A
They are mediators that:
- Induce platelet aggregation, clotting
- Stimulate WBC aggregation and migration, endothelial cells
- Vascular permeability
16
Q
What are Basophils?
A
Granulocytes that are:
–prominent in allergic reactions
–phagocytic
–release histamine and vasoactive agents
–activated to release granules w/ allergic immune reactions (IgE)
(1% of WBCs)
17
Q
What are Eosinophils?
A
-Arrive at injury site 2-3 hours after neutrophils
-phagocytic
-Important in allergic reactions, parasitic infections (by secreting toxins), chronic inflammation
-Long lifespan
(2-3% of WBCs)
18
Q
What are Monocytes/Macrophages?
A
- Monocytes mature to macrophages in tissues
- Produced by bone marrow
- Located in lymph nodes, spleen, lymph tissue, and lungs (lymph filters out toxins, pathogens and excess fluid)
- Largest of the leukocytes
- Lifespan is 3-4 times longer than any leukocytes
19
Q
What are the functions of Macrophages?
A
- Phagocytosis
- Scavenger cells
- Secretion of cytokines to cause inflammation ( TNF, interleukins, interferons, CSF, fibroblast GF)
- direct recognition of pathogens
- Antigen-presenting cells { they display a part of the pathogen to the helper T cells) } (making them a bridge to adaptive immunity)
- Produce cytokines and co-stimulators to stimulate innate and adaptive immune response
- –activate T cells, B cells, innate immune cells
20
Q
What are cytokines?
A
They are inflammatory mediators that:
- have a short half life
- low molecular weight proteins
- brief, self-limiting, mediate cell reactions
- pleotrophic and redundant ( meaning they act on many different kind of cells and cause calls to have similar functions—this happens b/c we want the inflammatory response to be big enough to contain what’s going on; makes the response more powerful)
21
Q
What are the types of cytokines?
A
- Tumor necrosis factor (TNF)
- Interleukins (IL)
- Interferons (IFN)
- Colony Stimulating Factor (CSF)–RBCs, WBCs, Platelets
- Chemokines (recruit/direct migration of inflammatory/immune cells)
22
Q
Describe Interleukins (IL) and their role.
A
- Produced mainly by macrophages
- Calls lymphocytes and WBCs into action
- Immunotherapy ( IL treatment b/c patients whom has gone through chemo have become immunocompromised, this helps get their WBCs and lymphocyte counts up)
- Induces fever ( which is a systemic response)
23
Q
Describe Interferons (INF) and their role.
A
- Produced by host cells invaded by viruses or cancer to prevent disease from invading healthy cells
- Interferes with DNA replication
- Inhibits cancer proliferation and viral binding
- Activates macrophages, NK cells in innate immunity
- Activate lymphocytes in adaptive immunity
- DOES NOT save cells already infected by virus
24
Q
Describe Tumor Necrosis Factor and their role.
A
-Produced mainly by macrophages and T cells
-Can cause cancer cell death
-Responds to gram-negative bacteria ( E.coli, Chlamydia), virus-infected cells, cancer cells
- Induces fever
Very high doses can be lethal
25
What are Dendritic Cells?
- Phagocytic cells of the innate immune response
- found under epithelial tissue-skin, lungs, nose, go (b/c its easy access to pathogens)
- They capture dead cells and pathogens
- Activated by pathogens
- secrete cytokines
- migrate to regional lymph nodes ( when they come into contact with the pathogen)
- Antigen-presenting cells- activate Helper T cells
26
What are Natural Killer Cells?
- They are the only lymphocytes to take part in the innate immune response
- They don't have T cell or B cell receptors
- Primary defense against tumor cells, abnormal body cells, cells infected with pathogens
- They destroy cells that are diseases but doesn't kill the pathogen itself.
- They have vesicles filled with perforin which when released punches holes in/kills the cells/.
27
Eosinophils are predominant in ______and______.
allergic reactions and parasitic infections
28
What are the 3 key plasma protein systems?
1. Complement system ( proteins produced by the liver)
2. Coagulation cascade
3. Kinin system (proteins produced by liver)
29
Describe pathogen recognition by the immune system.
???
30
Describe the function of the complement system.
- Recruit phagocytes, activates mast cells, and destroys pathogens
- Used in innate and humoral (antibody) response
- Activation of C3 and C5 proteins by pathogens or antibody-antigen complex
- --C3b=Opsonins (which marks/coats pathogen and neutralizes it)
- --C3a,C5a=Chemokines
- --C55-C9=membrane attack complexes (makes a pore in the pathogen thus killing it)
31
Describe the function of the Coagulation (clotting) System.
- Platelet Activation Factor (PAF)-aggregates platelets
- -released by most inflammatory cells
- -Has an intrinsic (blood vessel) and extrinsic factor (tissue injury)
- Fibrin (insoluble, polymerized protein) forms meshwork at the injured or inflamed site
- --This helps prevents the spread of infection, localizes the microorganisms and foreign bodies, forms a clot that stops bleeding, provides framework for repair and healing.
32
Describe the function of the Kinin System and most important type of kinin.
```
- Blood proteins activated by the coagulation system (factor xii); clots off area, stops bleeding.
Bradykinin:
-Dilation of blood vessels
-Induces pain
-Causes smooth muscle contraction
-Increases vascular permeability
```
33
State the five cardinal signs of acute inflammation and the describe the physiological mechanisms associated.
1. Rubor (redness)--increase blood flow to area
2. Tumor (swelling)--increase capillary permeability
3. Calor (Heat)-Increase blood flow to area
4. Dolor (Pain)-stretching of nerves by swelling
5. Loss of function-?
34
What are the systemic changes inflammation?
-Fever
-Leukocytosis
-Increase in circulating plasma proteins
Could lead to septic shock
35
Compare the vascular and cellular stages of inflammatory response.
Vascular Phase:
-Vasodilation [increased blood flow to injured area, redness and warmth result]
-Capillary permeability [mediators allow exudate to escape into tissues resulting in edema, swelling pain, and impaired function result]
Cellular Phase
-White blood cells travel to injured tissue[1. Margination( accumalation) 2. Tethering( adhesion) 3.Transmigration ( through blood vessels out to tissue) 4. Chemotaxis ( attracted to site of injury)
-Phagocytosis [phagocytes move in to remove microbes; Opsonization, engulfment, phagosome)
36
What are exudates? What are the types of exudates that form with acute inflammatory response?
```
Exudates are fluid, proteins, RBCs, leukocytes, cell debris that form following phagocytosis.
Include:
-Serous (clear)
-Fibrinous (thick & sticky; fibrin)
-Purulent (pus)
-Hemorrhagic/sanguineous (blood)
```
37
Acute Phase Response
- An innate body defense seen during acute illnesses and involves increased production of certain blood proteins called acute phase proteins.
- occurs hours-days from onset.
- Inflammatory mediators cause increased WBC production, elevation of fibrinogen, C-reactive proteins and SAA proteins.
- symptoms=Increased HR, anorexia, somnolence and malaise
38
What is the role of CRP during the acute phase response?
Binds to pathogen, marking it for phagocytosis. It functions as an opsonin sticking microorganisms top phagocytes .
39
What is the role of SAA (serum amyloid a proteins) during the acute phase response?
Increased HDL to macrophages; these HDLs energize macrophages making them work better
40
What is the role of Fibrinogen in the acute phase response?
-Increases erythrocyte sedimentation rate (ESR)
[ESR shows us how quickly those RBCs settle in the test tube, w/ a lot of fibrin (which are thick and sticky) sedimentation rate will be faster so RBCS settle faster. Providers will order this test as it is an indicator of inflammation]
41
Systemic Inflammatory Response-Fever
TNF and IL-1 cause fever by changing the set temp of you body.
symptoms=anorexia, myalgia, fatigue
42
What are the stages of the systemic inflammatory response?
1. Prodromal=HA, fatigue malaise, aches
2. Chill=shaking, rigors, piloerection
3. Flush=warm, red
4. Defervescence= sweating ( which then lowers temp)
43
Acute inflammation
self-limiting
| heals by itself in about a week
44
Chronic inflammation
inflammation that goes on for 2 weeks or longer; happens when you're repeatedly exposed to toxins; or inflammatory response just doesn't work; Develops when acute response is not enough.
-Dense infiltration of lymphocytes and macrophages
asymptomatic
recurrent inflammation-cancer, etc
45
What is an abcess?
-an acute inflammation reponse
-its a localized inflammation with purulent exudate
-Necrotic core with pus, surrounded by neutrophils
-Fibroblasts wall it off
-Overall, it s small area containing pus made up of apoptotic neutrophils walled off by fibroblasts.
Treatment=drain it (IND=incision in drainage) then antibiotics
46
What are the causes of chronic inflammation?
Due to low grade, persistent infections, irritants for example:
- Foreign agents (talc, asbestos)
- Viruses
- Bacteria
- Autoimmune disease
- Injured tissue around a healing fx
- Obesity
- Future site of cancer (chronic inflammation leads to cancer because of constant regeneration, injury then regeneration again, this would eventually lead to mutations, leading to cancer)
47
What is a granuloma?
- chronic inflammation leads to this
- 2-3mm lesion surrounded by macrophages, resembling epithelial cells
- cells clump in a mass to surround pathogen
- membrane of connective tissue encapsulates and isolates
- if you have a splinter or sutures left in skin, a granuloma will form
- TB and syphilis (latent TB is also a granuloma, when you inhale TB for first time it is walled off in lungs)
48
Describe your body's third line of defense.
It is specific to the pathogen. It take several days to mount a full response. it's medicated by humoral (antibody) and T cells. It is activated by antigen-presenting cells, co-stimulators and cytokines
49
T cell (T lymphocytes)
mature in thymus
cytotoxic, helper (CD8 and CD4), suppressor, and memory
thymus is active during childhood and stops being active in puberty
50
B cells
mature in bone marrow
produce antibodies-immunoglobin
bind to and neutralize antigens
differentiate into plasma cells and memory cells
51
Memory Cells
- B and T cells remember specific antigen after exposure.
| - memory cells are there to help mount a faster and stronger immune response upon re-exposure
52
NK cells (or Natural Killer Cells)
Innate response
mature in bone marrow
recognize foreign cells and engulf
they are not antigen specific
53
Organs of the immune system
-Lymph nodes
-Spleen
-Lymphoid tissue
WBCs like to hang out in these because it where they can filter/catch these pathogens
54
The Life Cycle of the T Lymphocyte
1. You start with an immature helper T cell ( the helper T cells they are the coordinators of the immune response)
2. it matures in the thymus
3. it then migrates to your lymph node and tissues
4. while it is in your lymph nodes and tissues, it gets exposed to a specific pathogen (s); APC. its exposed via the MHC
5. Then the T cell is activated once exposed to specific pathogen
6. Activated T cell releases cytokines which leads to activation of B cells and macrophages (more leukocytes)
7. Also, activated T cells starts to proliferate, so that certain T cell that is geared to that specific pathogen starts to proliferate into Helper T cells, Cytotoxic T, and Memory T cells
8. Then you're able to mount a response.
55
What are the two major classes of cell-mediated immunity?
CD4 (effector)
| CD8 (effector)
56
CD4 effector cells
- Indirectly help by controlling the adaptive immune response
- They are Helper T cells ( which activate B cells, Cytotoxic T cells)
- Regulatory T- turn off system ( cytokines inhibit macrophage and lymphocyte proliferation. stop the immune response)
57
CD8 effector cells
```
Interact directly by killing intercellular target
They are Cytotoxic T cells ( which secrete perforin causing apoptosis of diseased cell
Secrete cytokines (interferons)
```
58
Tell me about Helper T cells.
- They only recognize specific antigen peptide fragments bound to MHC molecule.
- They are activated by cytokines and co-stimulators secreted by macrophages
- produce more cytokines that activate more macrophages
59
MHC
Protein molecules on cell membrane that mark cells as "Self"
| Processes antigen and presents epitopes for T cell recognition on cell surface.
60
What are epitopes?
Epitopes are small peptide fragments recognized by the immune system
61
What is the difference between MHC 1 and MHC2?
MHC 1: produced by all nucleated cells, platelets
They are recognized by CD8 cytotoxic T cells which then destroy infected cells by secreting perforin.
MHC 2: produced by antigen presenting cells-dendritic cells, macrophages, B cells
APCs engulf or opsonize the antigen; then antigens are displayed on MHC 2 receptor
Epitope is processed and presented to CD4 T helper cells which then signal immune responses
62
B-Lymphocytes (Humoral)
B cells bind to the antigen, phagocytize it, and present it to the Helper T cells because they are APCs. The Helper T cells activate the B cell to differentiate, proliferate into Memory (display antibody on surface) and Plasma cells (effector cells; secrete antibody extracellularly/out into bloodstream).
They create antibodies in response to antigen.
63
What is the functions of antibodies?
Binds to pathogen, make it recognizable and neutralizes it, they do not kill the pathogen.
- Opsonization:
- Neutralization
- Agglutination: causes clumping and precipitation because it makes it easier to rid of them/phagotacize them.
- Complement activation-complement proteins bind to antibodies, they form a membrane attack complex (c5-c9) create a pore which then cause the cell to die.
- Mast cell degranulation
64
The Life Cycle of B lymphocytes
1. immature B cells
2. matures in the bone marrow
3. then goes out in to the lymph tissue
4. at lymph tissue, it gets exposed to the antigen.
5. then it gets activated; Helper T cells secrete cytokines and causes that B cell to become activated .
6. activated B cell then proliferates in to memory cells and plasma cells
65
What is an Antigen?
- a foreign molecule (microbe, tissue) that reacts with parts of the immune system
- the antigen fits into the binding site of the antibody like a"key into a lock"
66
What is an epitope?
it is an antigenic determinant; the area of the antigen recognized b the immune system
67
What is a paratope?
is it the antigen-binding site; the matching portion on the antibody
68
What are the different classes of antibodies?
1. IgM: Primary response
2. IgG: Most common form; crosses placenta (passive immunity to fetus)
3. IgA: secreted from mucus membranes, breast milk (colostrum); can get passive immunity from IgA
4. IgD: B cell activation; can't cross placenta
5. IgE: Histamine reactions and allergies, parasite infections; Basophils and mast cells.
69
IgM
First antibody you make on initial response to any pathogen; effective in agglutination; can't cross placenta; initiate complement
70
IgG
Most common form; complement activation; crosses blood vessels; crosses placenta (passive immunity to fetus)
71
IgA
Secreted from mucus membranes, breast milk (colostrum); Prevents attachment of bacteria to epithelial surface.
72
IgD
B cell activation; Can't cross placenta. (Don't worry too much about this antibody for exam)
73
IgE
Histamine reactions and allergies, parasite infections. Basophils and mast cells.
74
Self tolerance
our immune system does not destroy our own cells; immune system differentiates self-antigens from foreign antigens
75
Central tolerance
self-reactive B and T cells are eliminated in the bone marrow and thymus
76
Peripheral tolerance
inactivation of B and T cells that escaped
77
Acquired Immunity
immunity produced by immune system response
78
Acquired Active Immunity
Exposure to antigen (catching a disease like chicken pox); immunizations
79
Acquired Passive Immunity
- Maternal antibodies transferred through placenta and breast milk (IgG, IgA)
- Gamma Globulin (shots)- they confer passive immunity by injecting w/ antibody
80
Why is it important to receive a booster shot?
Get the first injection then go back 6 wks later for boosts shot b/c you want it to be long lasting. Second time makes it last
81
Example of Acquired Active Immunity.
DPT Vaccine (Diphthria, Pertussis, & Tetanus), produces antibodies against all 3, takes weeks-months to develop; long-lasting. Adult should receive booster every 10 years (Td)
82
Example of Acquired Passive Immunity
- Maternal antibodies
- Tetanus Immune Globulin-short acting only lasts a few months; immune globulin are preformed antibodies from another source; protects immediately; short acting
83
How is HIV transmitted?
1. Sexual transmission: via semen and cervical secretions
2. Parenteral transmission: via blood, blood products, or contaminated needles
3. Perinatal transmission: from infected mother to infant
84
Describe the pathophysiology of HIV.
-It is a retrovirus; its genetic info is in RNA.
reverse transcriptase=it transcribes RNA into DNA
-HIV targets CD4 T helper cell receptors this is bad because if you don't have helper T cells you don't have adaptive immune response, so you could die due to decrease response to pathogens.
85
How do you screen for HIV?
1. First screen using ELISA/EIA that detects both HIV 1 and
2. If positive, confirm with a Western Blot assay
3. If HIV positive, you need to monitor CD4 count and monitor the viral load
86
What do you do to screen HIV in newborns and why?
--Newborns can't do ELISA because they have passive immunity from mother so in order to distinguish the child's antibodies from the mothers antibodies you need to find the virus so we use PCR which identifies viral DNA only.
At home tests are also available.
87
Difference between HIV and AIDS.
- HIV is the disease w/ a positive HIV test
- AIDS is when CD4 count is below 200 cells/ul and the presence of an AIDS indicator condition (ex. severe viral infections, fungal, a typical bacterial, rare cancers.
88
What are the clinical stages of HIV?
1. Viral Replication
2. Seroconversoin
3. Latent Period
4. Period of more rapid virus production
5. Overt AIDs
89
Viral Replication Stage of HIV
- 0-3 weeks
- infection enters body and replicates rapidly
- undetected; no symptoms
- testing based on exposure; antigen may be detected
90
Seroconversion Stage of HIV
- 3wks-6 months after exposure
- acute "mono-like" illness- 2days-2wks
- fever, sore throat, body aches, night sweats, enlarged lymph nodes, nausea vomiting, chills, fatigue, weakness, stiff neck, irritability, rash
- antibodies detected, CD4 count decreases but its still above 400
91
Latent Period
- 3-12 years
- stable serum virus level
- virus continues to reproduce and destroy immune system
- persistent lymph node enlargement or mild symptoms
- CD4 count above 400.
92
Period of more rapid virus production
- Lasts 18 months
- decreased immune activity
- symptoms: severe viral and fungal infections, herpes, CMV, EBV, opportunistic infections
- CD4 count less than 400
93
Overt AIDS
CD4 count less than 200
1 or more opportunistic infection without antiretroviral therapy, death within 2-3 yrs.
* As CD4 count falls, symptoms increase
94
Clinical Manifestations of HIV/AIDS.
1. Gastrointestinal-diarrhea, malnutrition, wastingsyndrome
2. Pulmonary (most common site for infection)--pneumonia and TB
3. Malignancy--cervical and anal cancer, lymphoma
4. Gynecologic--vaginitis, dysplasia
5. Sexually Transmitted Co-Infections--Herpes
6. Neurologic--neurocognitive impairment
7. Medication related-endocrine-insulin resistance, metabolic=elevated cholesterol and elevated triglyceride
95
What are some pharmacologic therapy for HIV?
- Antiretroviral medication- slow down disease progression
| - highly Active antiretroviral therapy (HAART)- at least 3 classes
