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W 18 Immunology BI-208

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Jennifer Jezylo

on 23 February 2018

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Transcript of W 18 Immunology BI-208

Lymphatic and Immune Systems
Functions –
Remove excess tissue fluid & return it to the bloodstream
Transport of lipoproteins from the intestinal villa to the bloodstream
Defense against disease
Lymphatic System:

One-way system similar to the venous system
Valves
Lymph movement is dependent on skeletal muscle contractions
Lymph capillaries - lymph vessels - lymph ducts

Thoracic duct = Largest
Empties the lower extremities, abdomen, L arm, L side of head & neck.
Joins into the L subclavian vein
Right lymphatic duct
Empties R arm, R side of the head & neck
Joins into the R subclavian vein
Lymph Organs
Lymph nodes
Tonsils
Spleen
Thymus
Appendix
Peyer’s patches
Red bone marrow
Lymph nodes
Contains macrophages (Tissue monocytes) to clean and filter the lymph prior to emptying it back into the CV system
Located at certain points along the lymphatic vessels
* Swollen, painful lymph nodes may be a sign of infection
* Swollen, non-painful lymph nodes can be cancerous
Tonsils

First line of defense against pathogens entering the nose and mouth
Spleen
Contains lymphocytes to help in immune system function
Macrophages to filter and clean the blood by removing debris and old RBCs
Can be removed, but then immunity to infection is decreased
Appendix
Thymus gland (primary lymphatic organ)
Located in the thoracic cavity along the trachea
Large in children, but small and often absent in adults
T-lymphocytes (a type of leukocyte) mature here
Produces thymic hormones (thymosin) that help the T-lymphocyte maturation process
Red bone marrow

(primary lymphatic organ)
Site of origination of all blood cells (Hematopoietic stem cells)
B cells mature here

Immunity
= The ability of the body to defend itself against pathogens, foreign cells, and abnormal cells, such as cancer cells
Immune system
- All cells and tissues responsible for immunity
Nonspecific (innate) defenses –
Types of nonspecific defenses:
Species barriers
Barriers to entry
Inflammatory response
Natural killer cells
Protective proteins (compliment and interferon)
Fever
INNATE (non-specific) Defenses:
SKIN - physical barrier
Break in the skin will allow entry
Extensive damage may be life threatening
Ex. Burns
Some skin bacteria are beneficial, and inhibit the growth of pathogens
Sweat, oil, waxes - Released by the skin
IgA - Secretory antibody (immunoglobulin) is also found in skin secretions
Contain chemicals toxic to many bacteria/fungi.
Bacteriocidal = Cause bacterial death
Bacteriostatic = Prevent bacterial growth
Ex. Sweat contains
lysozyme
which can destroy bacterial cell walls
Signs of inflammation:
Pain
Heat
Swelling
Redness
+/- pus
+/- joint immobilization
Fever - nonspecific (innate)
A sign that the body is responding to infection
Can be triggered by some pathogens
Can be triggered by chemicals released by macrophages
Helps to stimulate the body’s defense mechanisms, suppresses the growth of some bacteria, & promotes WBC action
High fever (> 39º C, 103º F) can denature enzymes
> 41º C, 105º F are usually fatal
Specific (adaptive) defenses - When nonspecific (innate) defenses have failed
Adaptive (specific) immunity -
Antigen - A foreign substance that stimulates the immune system
Can be part of a foreign cell, cancer cell, toxins, insect venom, pollen, pathogen, etc.
Self-antigens – Antigens found on the surfaces of our body cells
*Not foreign or antigenic to us, but strongly so to others!
Adaptive immune response is
systemic
- Not restricted to the initial infection site
Antigen specific
Has “
memory
” - Recognizes previously encountered pathogens and mounts a faster and even stronger attack on them

The antigens that YOUR immune system responds to is determined largely by
GENETICS
and
environment

Antibody (humoral) mediated -
A macrophage (or other APC) engulfs and destroys a pathogen (phagocytosis)
The macrophage displays fragments of the pathogen’s antigens on its own surface
A T-helper cell (CD4) with matching receptors encounters the macrophage
The macrophage releases
interleukin-1
This triggers the T-helper (CD4) to release
interleukin-2
Interleukin-2 stimulates B-cells to become activated and divide many times, producing
plasma cells
to mass-produce antibodies specific for the antigen (monoclonal antibodies - All produced by the same B-cell and all the same type)
These antibodies bind to the antigen to inactivate it or trigger its destruction by non-specific defenses
Neutralization, agglutination, compliment fixation, precipitation
Suppressor (regulatory) T-cells shut down the immune response after an infection has been overcome
Primary Immune Response
The first time a pathogen is encountered -
Primary immune response
Some B and T cells remain forever as memory cells - A body’s long-term protection against re-infection against a specific pathogen
Response of memory cells to a subsequent infection by the same pathogen
Secondary immune response
Much faster and more powerful!
Only protect against a pathogen that the immune system has already encountered!
ACTIVE humoral immunity
-
Occurs after a person is
...
1. infected
with a pathogen, or…
2. Immunization (vaccination)
Vaccine contains modified pathogens or toxins that can no longer produce disease but can stimulate an immune response
(Attenuation)
This stimulates the production of memory cells, which function in the
secondary immune response
Gives immediate protection
Sometimes wears off = Boosters needed
***Review HERD IMMUNITY for the exam!
PASSIVE Immunity
-
Prepared antibodies (immunoglobulins) are given to fight a microbe
Immediate but temporary!
As soon as the antibodies (proteins) begin to degrade, susceptibility returns!
1.
Passive
NATURAL
immunity
- from mom to babies
across the placenta, and in breast milk
2. Passive
ARTIFICIAL
immunity -
Gamma globulins (antibodies)
taken from someone who has recovered from an illness and injected into someone who has been exposed to the same illness
Allergic response - Allergies
Inappropriate reaction (hypersensitivity) of the immune system to a harmless substance (allergin)
AUTOIMMUNE Disease -
Lymphocytes in the immune system mistakenly attack & destroy the body’s own cells
Cause unknown, but sometimes occur after recovery from an infection
No cure, but most can be controlled by drugs
Ex. Multiple Sclerosis T-cells attack & destroy the myelin sheath surrounding nerves
Ex. Rheumatoid Arthritis Synovial membranes attacked & destroyed
Ex. Fibromyalgia
ANTIBODY TYPES -
IgG - Gamma globulins
Main, most abundant antibody
Plasma protein
IgD
Antigen receptor on B cells
Important in B cell activation
IgE
Important in chemical mediation of inflammation
Secreted by plasma cells
Allergic response & parasitic infections cause ↑
IgM
Important in compliment activation
Secreted by plasma cells
IgA
Secretory immunoglobulin
Found in secretions such as sweat, milk, intestinal juices, etc.
Protects body surfaces
Lymphoid cells
Lymphocytes B and T cells
Specific (adaptive) immunity
Produced in red bone marrow and mature (become immunocompetent) in bone marrow (B cells) or thymus (T cells)
Effective against antigens
*Antigen = substances (usually surface proteins) the body
recognizes as foreign material
Macrophages and dendritic cells (APC = Antigen Presenting Cells)
Tissue monocytes = macrophages
Phagocytize foreign material
Help activate T cells

Inflammatory response –
Prevents spread of potentially dangerous agents
Disposes of pathogens/debris
Begins tissue repair
Injury occurs damaged cells release chemical messengers (inflammatory mediators)
Histamine
Cytokines to attract WBCs to the area Fluid andWBCs pass through to injured area
Prostaglandins
Complement
These chemicals increase blood flow to injury (
hyperemia = heat and redness
), Increases capillary permeability (
exudate - fluid - seeps from the blood into interstitial spaces = swelling
),
Exudate causes
pressure on free nerve endings = pain
... If blood vessels are injured, platelets are called and clotting seals off injured area
***NOTE: Hyperemia is NOT the same as fever!
Fever is a systemic response and hyperemia is LOCALIZED.
Natural killer (NK) cells – Large, agranular lymphocytes that act as guardians of the blood and lymph
Lyse, destroy viral infected body cells (or cancer cells) before adaptive immune system is activated
Destroy by attacking the cell-membrane of the target cell, and poking holes in it with chemicals called
perforins
(NOTE: they are not phagocytic) allow H2O to flow in, and the cell bursts
Unlike other lymphocytes, these are non-specific…they’ll attack anything
*Amended: 1. Possibly involved in adaptive immunity, too
2. Recent studies show promise in treatment of HIV
Fever – widespread, systemic response to invasion
Abnormally high body temperature
Reset of body thermostat (located in the hypothalamus) due to pyrogens – chemicals secreted by WBCs exposed to pathogens
Causes the liver/spleen to sequester zinc and iron (needed for bacterial replication and growth)
Bacteriostatic
Increases metabolic rate of body cells to speed repair
Innate response (continued):
Protective proteins (compliment and interferon) – antimicrobial
Enhance
innate defense
by directly attacking pathogens or their ability to grow/reproduce
Interferon (IFNs)
– a family of related proteins secreted by viral-infected body cells to protect neighboring cells
They $ near-by cells to synthesize PKR, to interfere with viral replication in these cells
Different cell types secrete different types of IFN
Ex. Fibroblasts secrete interferon - Good for reducing inflammation
Ex. Most WBCs secrete interferon (lymphocytes however, secrete “immune” interferon)
Also activate macrophages and NK cells
Good anti-virals
Protective proteins (Con't) -
Complement system
– > 20 plasma proteins (produced by the liver) act in innate body defense as well as assisting in the adaptive response, circulating in an inactive state
Factors B, D, and P and C1 – C9, and others TNTC (too numerous to count!)
Release of a variety of chemical mediators that amplify the inflammatory process
Two-pronged attack involving
lymphocytes
(leukocytes):
Cell-mediated immune response: Involves T-cells
Antibody-mediated immune response (humoral response): Involves mainly B-cells
Both parts are controlled by a type of T-cell called a helper T-cell (or CD4 cell)
***Both parts occur simultaneously
The
strength
of each response depends on the pathogen (intra or extra-cellular?)
Cells of the adaptive immune system: lymphocytes and Antigen-Presenting Cells (APC)
Lymphocytes – T or B cells
Both produced by hematopoietic cells in the red bone marrow
Become immunocompetent in the primary lymphoid organs –
Thymus (T-cells) and/or bone marrow (B-Cells)
Cells of the immune system
Antigen-Presenting Cells (APCs)
– Mobile sentinels
Engulf and destroy antigens, and present fragments on their surfaces to be recognized by T cells
Dendritic cells
– Present antigens and secrete proteins to activate T cells. Found in CT
Langerhan’s cells
– Found in epidermis
Macrophages (and
monocytes
)
– Present antigens and secrete proteins to activate T cells
Found throughout the intercellular matrix (mostly in lymphoid organs)
Activated B-cells –
Produce antibodies
ALL
LEUKOCYTES
are involved in fighting infection, somehow.
Antibodies: Form antigen-antibody complexes, and cause microbe death by…
Complement fixation and activation
– Cellular antigens, such as bacteria or mismatched blood transfusion
* Cell lysis
* Also, increase the inflammatory response and promote phagocytosis
Neutralization
– Simplest - Antibodies block sites on viral or bacterial endo/exotoxins to cause loss of toxic effect and then…
* Eventual destruction by phagocytes
Agglutination
– X-linking of cells with more than one antigen binding site
* Forms large web-like lattices and eventual clumping (agglutination)
* Especially IgM (has 10 antigen binding sites!)
Precipitation
– X-linkage of soluble molecules into large complexes
* Settle out of solution, and are more easily phagocytized
Antibodies (immunoglobulins – Igs) – Proteins secreted by activated B cells (plasma cells) in response to an antigen challenge
IgG – Gamma globulins
 Main, most abundant antibody
 Plasma protein
IgD –
 Antigen receptor on B cells
 Important in B cell activation
IgE –
 Important in chemical mediation of inflammation
 Secreted by plasma cells
 Allergic response and parasitic infections cause an increase ↑
IgM – Multiple binding sites for large pathogens
 Important in compliment activation
 Secreted by plasma cells
IgA –
 Secretory immunoglobulin
 Found in secretions such as sweat, milk, intestinal juices, etc.
 Protects body surfaces
Cell mediated immune response –
What happens if the antigen is inside a body cell?? (small, intracellular infectious microbes)
Antibodies don’t go there! Humoral response is for extracellular pathogens
**The cell-mediated response comes to the rescue!
Involves T-cells (CD4 or CD8)
CD4 (T4 cells)
= Helper T cells (Th)
Stimulate proliferation of other T cells and B cells
Release cytokines to stimulate other immune cells
CD8 (T8 cells)
= Cytotoxic T cells (Tc) ... AKA killer T cells
Directly attack and destroy body cells Infected by (SPECIFIC) pathogens
Target viral infected cells, cells infected with other intracellular pathogens, and others.
Secrete cytokines such as perforins, granzymes, lymphotoxin, and/or interferon that have variable effect on the target cells (mostly cell lysis)
Suppressor T cells (Ts or Regulatory T cells)
– Mop-up crew!
Like the antibody mediated response, The cell-mediated "arm" recognizes and responds to processed antigen fragments that are presented by APCs
Best in cell-to-cell interactions
Target body cells infected with viruses/bacteria
Abnormal or cancerous cells
Foreign tissue cells

SO ... putting it all together:

Cell mediated Immunity and Antibody mediated immunity -
APC attacks and destroys a pathogen (phagocytosis), and displays antigenic fragments on its surface
Circulating CD4 cell (helper T) comes in contact w/the APC causing it to release interleukin-1
This stimulates the CD4 cell to release interleukin-2
Interleukin-2 causes …
Rapid clonal division of cytotoxic (CD8) and regulatory T cells (Part of the cell-mediated response)
Rapid division by B cells, and differentiation into plasma cells (Antibody-mediated response)
Plasma cells secrete large amounts of antibody specific for the free antigen, aiding destruction by
compliment fixation, neutralization, agglutination,
or
precipitation
CD8s destroy infected body cells in the ways outlined above
Regulatory (suppressor) T cells shut down the immune response
Memory T and B cells are produced to function in the
SECONDARY immune response
the next time that specific pathogen is encountered
Immediate allergic response –
Occurs within seconds
Caused by IgE antibodies
Release of histamine from
basophils and eosinophils
Anaphylactic shock is possible → death
Delayed allergic response –
Initiated by memory cells
Cytokines secreted by macrophages and T-cells at the site of the allergin
 Ex. Skin test for TB
 Ex. Contact dermatitis
Phagocytosis is ...
a. An innate immune response
b. Engulfing and destroying a pathogen
c. An important job of neutrophils
d. The job of circulating macrophages
e. All of the above
Compliment proteins are ...
a. Part of the innate immune response only
b. Involved with both innate and adaptive immunity
c. Particular to viruses
d. Only considered part of adaptive immunity
e. None of the above
Systemic mycoses generally stimulate more of an antibody mediated adaptive defense in the body. Particularly...
a. Compliment fixation
b. Neutralization
c. Agglutination
d. Precipitation
e. All of the above, except b
A leukocyte is a(n) ...
a. Red blood cell
b. White blood cell
c. Platelet
d. Epithelial cell
e. None of the above

Fever ...
a. Should be immediately treated to prevent complications
b. Is a natural innate response to infection
c. Can be dangerous if too high
d. Is normally above 37 degrees C
e. All of the above, except a
Leukocytes include ...
a. Astrocytes
b. Erythrocytes
c. Eosinophils
d. Thrombocytes
e. All of the above
Phagocytosis = an innate response
Neutrophils - Most common type of phagocyte
Neutrophilia = Increase in neutrophils
First responder
Part of purulent discharge (pus)

Macrophage - (Monocytes found within the tissue) Phagocytes and help signal lymphocytes (APCs)
Eosinophils - Phagocytes
Increase = eosinophilia
Parasitic infection
Allergic reaction
eosinophil
basophil
neutrophil
Band cell (Immature neutrophil)
lymphocyte
monocyte
Natural Killer Cell
Innate immune responses include ...
a. Species barriers
b. Inflammation
c. Fever
d. Phagocytosis
e. All of the above
Phagocytic leukocytes include ...
a. B cells
b. Lymphocytes
c. T cells
d. Macrophages
e. All of the above

Basophils - Granulocytes
Release histamine and other inflammatory mediators
Increase with allergy and parasitic infection
Leukocytes:
Granulocytes:
Neutrophils
Eosinophils
Basophils (Mast cells)
Agranulocytes
Lymphocytes
Monocytes (Macrophages)
Hillary, an 18 year old Causation female, presents complaining of nausea and left flank pain. She had been having intermittent fevers and chills for about five days, which started at about the time that she noted polyuria with dysuria. Today, Hillary is worried because she has noted some hematuria and she is not currently menstruating. A urinalysis reveals TNTC Gram (-) rods which grow black colonies with a metallic sheen on EMB and reddish colonies on MacConkey's Agar.
Etiology?
a. Salmonella spp.
b. Pseudomonas aeuruginosa
c. Shigella spp.
d. Staphylococcus aureus
e. Escherichia coli

Before coming in, Hillary took some amoxicillin that had been given to her four months ago for cystitis. That infection had been successfully treated by the amoxicillin, but it didn't seem to be having an effect on this current infection.
Why?
a. It's a different strain of bacteria
b. It's a different genus of bacteria
c. Hillary has become antibiotic resistance
d. The E. coli has become antibiotic resistant
e. All of the above are possible
How will you determine what antibiotic to use for Hilary's infection?
a. Do an antibiotic sensitivity test
b. Use a broad spectrum antimicrobial
c. A bacteriostatic antibiotic should be fine
d. Call the CDC
e. Amoxicillin should work

Has “memory” - Recognizes previously encountered pathogens and mounts a faster and even stronger attack on them
The antigens that YOUR immune system responds to is determined largely by
GENETICS
and
environment
Cells of the adaptive immune system: lymphocytes and Antigen-Presenting Cells (APC) -
Usually MONOCYTES (or macrophages)
Lymphocytes – T or B cells
Both produced in the red bone marrow
Become immunocompetent in the
primary lymphoid organs –
Thymus (T-cells)
and/or bone marrow (B-Cells)
Immunocompetence

The cells "learn" to recognize and respond to specific pathogens
Once the cells become immunocompetent, they are committed – Can only react to a specific antigenic determinant - but are still immature
T cells constantly circulate to chances of encountering antigens
Most programmed lymphocytes are never called into service
Once programmed, the cells travel to the 2° lymphoid organs to encounter antigens, and complete their maturation into fully functional antigen-activated T and B cells
Antigens are delivered via lymphatic system to lymph organs, where they encounter immune cells
Lymphocyte - SPECIFIC (adaptive) immunity
NOT a direct phagocyte
Molly Moonbeam is a recovering alcoholic, and a vegetarian. She regularly takes aspirin for her arthritis, but no other medications are noted in the file. Today, her primary complaint is bloody urine of a week’s duration. She has a lack of energy, and has had a hard time getting out of bed for a few months. On initial observation, Molly appears quite pale and thin. You note that her skin has a yellow tinge, and find petechia on her sclera and gums. Large bruises are noted on her inner thighs and upper arms. Upon palpation, she is tender, and appears swollen in the right upper, abdominal quadrant. Her lungs sound normal, but you note tachycardia (HR = 113 bpm), and a slight heart murmur.
What organ(s) may be causing her abdominal discomfort?
a. Heart
b. Urinary bladder
c. Liver
d. All of the above
Both b and c
What tests might you want to do?
a. ECG to determine the cause of her heart murmur
b. Urine test for pathogens
c. Blood cultures for anemia
d. Abdominal ultrasound
e. Both b and d
Mucous membranes: Innate defense
Mucous
Bacteriocidal chemicals (HCl low pH)
+/- Cilia
What is pus?
a. Bacteria and damaged tissue
b. Neutrophils and bacteria
c. A small cat
d. Lymphocytes plus viruses
e. All of the above, except c
Skin modifications:
1. Innate immune responses include ...
a. Barriers to entry
b. Inflammatory response
c. Antibody reaction
d. Direct destruction of viral infected cells
e. Both a and b

2. The membranes covering the organs of the abdominal cavity are …
a. Parietal pleura
b. Visceral peritoneum
c. Parietal peritoneum
d. Parietal pericardium
e. Visceral pericardium

3. The radius is ___ to the ulna.
a. Dorsal
b. Medial
c. Proximal
d. Distal
e. Lateral


4. The fibula is ___ to the tibia.
a. Anterior
b. Posterior
c. Lateral
d. Medial
e. Cranial
5. The craniosacral division of the autonomic nervous system …
a. Is considered the “rest and digest” division
b. Uses nor-epinephrine as is primary neurotransmitter
c. Constricts bronchioles
d. Will cause decreased blood flow to the skeletal muscles
e. All of the above, except b


6. A mature cartilage cell is a(n)…
a. Osteoblast
b. Osteoclast
c. Chondrocyte
d. Fibrocyte
e. Chondroblast

7. Antibodies ...
a. Can directly destroy pathogens
b. Mark pathogens for phagocytic destruction
c. Remain as memory cells to protect against future infection
d. Are produced by stimulated T-cells
e. Are part of the innate immune response
8. Primary immune system organs include ...
a. The lymph nodes
b. Peyer's patches
c. Red bone marrow
d. Yellow bone marrow
e. Both c and d
9. The leukocyte responsible for specific (adaptive) immunity is a(n) ...
a. Eosinophil
b. Lymphocyte
c. Thrombocyte
d. Neutrophil
e. All of the above
10. B-lymphocytes become immunocompetent in the ...
a. Lymph nodes
b. Red bone marrow
c. Thymus
d. Spleen
e. Tonsils
11. Primary signs/symptoms of inflammation include ...
a. Pus
b. Fever
c. Stiffness
d. Redness
e. increased blood pressure

12. Eosinophilia occurs ...
a. With the adaptive immune response
b. In liver disease
c. In the case of allergy
d. When bleeding problems occur
e. With third degree heart block


13. The first branches from the aortic arch include ...
a. The cardiac veins
b. The brachiocephalic trunk
c . Veins carrying deoxygenated blood to the coronary sinus
d. The vessels entering the right atrium from the coronary sinus
e. Both c and d
14. Depolarization of the atria is ...
a. Depicted in the QRS wave of an ECG
b. Seen in the P wave of an ECG
c. Accompanied soon after by ventricular systole
d. Dependent on purkinge fiber stimulation
e. All of the above

15 In fetal circulation ...
a. Umbilical arteries carry oxygenated blood to the inferior vena cava
b. The fetal lungs are by-passed by the hepatic portal system
c. The ductus arteriosus shunts blood from the right atrium to the left atrium
d. Arteries carry deoxygenated blood and veins carry oxygenated blood
e. Nutrient-rich blood enters the liver
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