Complement Activation

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1. Classical pathway: Is considered part of the adaptive immune response since it begins with the formation of Ag: Ab complexes. These complexes are soluble found in antibodies that bind to an epitope, situated for bacterial or viral cell membranes. Soluble Ag:Ab complexes are referred to as immune complexes and only these complexes are formed by IgM or certain subclasses of IgG-abs are capable of activating the classical complement pathway. Th initial stage of activation involves the components C1, C2, C3, and C4, which are present in the plasma as zymogens. 
2. Phosphatidyl serine: The phospholipid restricted to the cytoplasmic side of the membrane, and the change in its location serves to signal the immune system that the cell is undergoing apoptosis. 
3. Alternative tickover pathway: The pathway initiated when C3 at high concentration in serum undergoes spontaneous hydrolysis as its internal thioester bond, yielding the molecule C3(H20). 

Reference

• OrlandoinMiami. "Learn New Words." Orlando Espinosa. N.p., 30 Oct. 2015. Web. 08 Dec. 2016.

DICTIONARY

T-Cell Development

Positive selection: Is the selection of cells whose T-cell receptors respond to self-MHC. 

Negative selection: Is the selection against cells whose TCR react strongly to self-MHC combinations. 

Double Negative: This is when the fetal development of T-cell is TCR-independent and lacks the CD4+ and CD8+. So, the DN are CD4- & CD8-.  

Affinity Hypothesis: advanced model that is used to explain the paradox of MHC-dependent positive and negative selection. It asserts the differences in the strength of TC-mediated signals received by thymocytes undergoing the positive and negative selection indicating the result of the interaction. 

Intraepithelial lymphocytes: are mostly CD8+ cells that contain the features of the innate immune cells and patrol the mucosal surfaces. 

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DICTIONARY

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1. Endogenous (cytosolic) pathway:  the pathway involved in waste products from self-cells and Ag-recognition on the MHC Class I. Peptides that are broken down by proteolysis, and are transported from the cytosol to the rough ER (where catabolized peptides go to, to meet up with MHC I & TAP is), to the Golgi (where proteins are modified), and then the vesicles (where proteins are kept). When proteosome cuts off the protein, it diffuses into the cells by tapasin. Now, proteins arrive on MHC class I molecules.

2. ITAM: Immunoreceptor tyrosine-based activator motif sequences amino acid in the cytoplasmic tail (that contains serine) and repeats itself more than once. 

3. Invariant chain: non-MHC encoded protein interacts with the class II peptide-binding groove preventing any endogenously derived peptides from binding while the class II molecule is withing the RER. 

4. Double-negative (DN) cells: these are fetal T cells that lack both CD4 & CD8 cells. 

Reference

For more cartoons, visit: 

http://immense-immunology-insight.tumblr.com/page/6

INVESTIGATION

Transporter associated with antigen processing (TAP)

TAP is a membrane-spanning heterodimer that consists of two proteins, which are TAP1 and TAP2. The TAP1 & TAP2 each have their domains that appear in the rough endoplasmic reticulum and an ATP-binding domain appearing in the cytosol. TAP is found in the cell membranes of bacteria. They mediate ATP-dependent transport of sugars, amino acids, and peptides. These protein transport peptides that interact with MHC class I. However, there is a thing as TAP deficiency, and this is when there's a downregulation of peptide uptake and no new MHC class I molecules are produced. An example of this condition is the bare lymphocyte syndrome (BLS)--a defect in TAP1 and TAP2 gene. The lymphocytes in patients suffering from this disorder refuse to express MHC molecules, and if they do, it is below average levels. There are type1 BLS & type2 BLS. In type 1, MHC class I molecules are not being expressed while in type 2, expression of MHC class II is not being expressed. Besides peptides unable to bind to class I molecules, other abnormalities are increased NK cells and decreased levels of CD8 T-cells. I believe the reduced levels of CD8 is due to the lack of CD4 cells since they activate both B cells and cytotoxic CD8 cells. And because of this, their ability to fight off infections is significantly affected, individuals tend to get viral and bacterial infections often. Although, I think the NK cells are elevated because it just makes sense. If your other cells needed to fight off infections aren't working, the cells you have that works would be twice as active. So, If your CD4 cells required to destroy a pathogen is absent, then the ones you do have would have to work twice as much; and maybe that might fight off some viral infections if possible.
Other [visible] symptoms include chronic skin lesion, sinusitis, possibly constipation, and anemia.
Treatments: bone marrow transplant, and possibly gene therapy.

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References

•  Gadola, S. D., H. T. Moins-Teisserenc, J. Trowsdale, W. L. Gross, and V. Cerundolo. "TAP Deficiency Syndrome." Clinical and Experimental Immunology. Blackwell Science Inc, n.d. Web. 10 Nov. 2016. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1905688/>.
• https://rarediseases.info.nih.gov/diseases/8427/bare-lymphocyte-syndrome

#happybloggin' :)

Biochemistry vs. Immunology

ENCOUNTER

In Biochemistry: We are currently discussing carbohydrates and their functions in an organism. 

• Oligosaccharides are carbohydrates molecules composed of little monosaccharides unit. 
• Polysaccharides are multiple molecules of sugars. 
• Glycosphingolipid: lipids that come from ceramides that contain sugars/glucose. 

Polysaccharides contribute to the blood types, which are A, B, AB, & O. There are different kinds of polysaccharides (sugars), and the combination of these sugars determine the blood type of an individual. Human blood groups depend on the enzyme that catalyzes formation of the glycosidic bond. The O antigen contains (Lipids- Glucose-Galactose-N-acetylglucosamine-Galactose-Fucose)

Blood type A is composed of the same sugars above but rather N-acetylgalactosamine. The genes in a person's DNA encodes for a specific transferase enzyme for the addition of the blood type an individual is bound to have. So in plain terms, if a person's gene code for type A or type B transferase, the person would have blood type O. 

In immunology, blood type O has no antigens on the erythrocytes, blood type A has B-antigen, blood type B has A-antigen, and blood type AB has both antigens. This is why an individual gets a blood transfusion from another person with a similar blood type. Antibodies circulating the person's blood will attack RBCs that are a mismatched of theirs. 

Conclusion, In Immunology, it's about the antigens and biochemistry is how you get the antigens. Biochem discusses the structure and immunology talks about the effects of it; it elaborates more on what the antigen does. Biochemistry is about the structure of the proteins while Immunology is the function of the proteins. 

There are a lot of ways to relate biochemistry and immunology, but this is just a brief summary. To learn more about this topic,  here are websites: 

• http://biology.stackexchange.com/questions/26374/why-can-blood-group-o-be-given-to-all-blood-groups
• https://en.wikibooks.org/wiki/Structural_Biochemistry/Carbohydrates/Blood_Type
• https://www.quora.com/How-are-polysaccharides-helpful-in-determining-the-blood-group

#happybloggin' :)

#HAPPY HALLOWEEN

DICTIONARY

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• Recombination Signal Sequences (RSS): These are highly conserved heptamer and nonamer nucleotide sequences that serve as signals for the gene rearrangement process and flank each germline V, D, and J segment. 
• Terminal Deoxynucleotidyl Transferase (TdT): One of the three proteins implicated in V(D)J recombination that is responsible for the generation of additional diversity in the CDR3 region of the antibody heavy chain. TdT is also expressed in developing lymphocytes and adds untemplated "N" nucleotides to the free 3' termini of coding ends following their cleavage by recombination activation gene (RAG) 1 & 2 recombinases.  
• Coding joints: The nucleotide sequence at the point of union of coding sequences during V(D)J rearrangement to form rearranged antibody or T-cell receptor (TCR) genes. 
• Signal joints: The joints between the heptamers from the RSSs. 
• Palindromic Nucleotides: Nucleotide that forms at the V-D and D-J junction by asymmetric clipping of the hairpin junction formed by RAG1/2-mediated DNA cleavage.  

Work-cited

• By a Process Called Chemotaxis, They Reach Extravascular Tissue within 48 Hours Inflammatory Process. They Recognize and Eat up Just like Neutrophils. "Immense Immunology Insight." Immense Immunology Insight. N.p., n.d. Web. 28 Oct. 2016. <http://immense-immunology-insight.tumblr.com/page/10>.

REFLECTIONS

Currently, I'm learning about the classification of the Immunoglobulins. There are five isotypes in the human immunoglobulins, which are IgD, IgE, IgM, IgA, and IgG. These immunoglobulins have different structures and functions. IgA secretes antibodies in the mucosal membrane, IgG help control infections against bacteria, viruses, and parasites, IgM is the first antibody to respond to antigen exposure, IgE plays a role in response to allergens and IgD assists with the maturation of B cells. All these information are relevant to my career goal as a hematologist/oncologist. Most patients I come across with would be those with a B cell deficiency and T-cell deficiency & in most cases, it would be B cell deficiency. 

For instance, I come across a six-year-old patient with leukemia, which is excessive, uncontrolled proliferation of the B cell. Also, this course helps me in understanding more about my health. The diagrams on the powerpoint help me visualize what occurs in the body. You tend to write on the board more often that's quite helpful too. So far, I understand this chapter. Two things that are confusing are 1. The quote: "All immunogens are antigens, but not all antigens are immunogens." Can you please elaborate on what this quote means; because I wrote on the quiz that antigens bind to receptors on lymphocytes, and they induce an immune response, but not all antigens evoke an immune response, but I only got half a point. Another question I do not understand is: What advantage could there be in having an immune system that generates billions of lymphocytes that do not recognize any known infectious agent? I got this question wrong. If you can, please clarify these questions. 
This course has changed my perspective on everything. Like recently, someone was prescribed Hydroxyurea, and I automatically thought SCD, then I looked up on the internet if this drug helps with one type of sickle cell or both [anemia & thalassemia]. Then, I searched up the mechanism of Hydroxyurea in the body--production of fetal Hb in the bone marrow--as well as side effects. Even in little things, like when someone sneezes or coughs next to me, I slightly get irritated because and I sanitize my hands. 

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.....LOL

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Work cited

• "Microbiology and Microbiology Jokes to Share." Pinterest. N.p., n.d. Web. 20 Oct. 2016. <https://www.pinterest.com/pin/478648266621532976/>.

Dictionary

DICTIONARY

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1. Epitope: A specific portion of an antigen that is recognized and bound by an antibody or TCR-MHC combination, which is also called an antigenic determinant--determining piece that binds to an immunogen. 
2. Plasmacytomas: are tumors of plasma cells, the end-stage cell of B cell differentiation, and the cells from that tumor are typically located in the bone marrow. 
3. Once the tumor metastasizes into multiple bone marrow, the tumor is referred to as multiple myelomas, which secretes large amounts of monoclonal antibodies into the serum and fluids of the patients. 

Little Knowledge

B cells secrete antibodies or immunoglobulins. These antibodies are IgA, IgE, IgG, IgD, and IgM. These subclasses have different structures composed of heavy chains and light chains. There are more kappa light chains than there is a lambda.  Only IgA & IgM are comprised of J chain; contain a different number of Ig domains. 

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Works cited

1. Fyeahmedlab. "Diary of a Medical Scientist." Diary of a Medical Scientist. N.p., n.d. Web. 13 Oct. 2016. <http://fyeahmedlab.tumblr.com/post/42418326885>.

Blog #6

Encounter

So I volunteer at the Emergency Department with a friend of mine. It's a very busy place. I see different kinds of people and illnesses--people come in due to intoxication, few come in due to psychosis, and others come in due to pain. You witness a lot of different things. 

But, on a hot day, I went to volunteer there and as I was cleaning a bed, a nurse walked up to me and asked if I could go fetch water for a pt after. I responded yes and after I got done, I went to this patient and gave it to her. Then, I moved from room to room asking if they needed an extra blanket, extra pillow, water, or food including the room of the patient I had just given water. She said she wanted more water. And, of course, I went again to get her water. Then, she sat up and I asked if she was okay and she said: "yeah, just pregnant," I smirked. Two minutes later, she opened the curtains and asked for more water. At this moment, I thought this was a normal, regular routine because her body needs extra fluid since she's pregnant. So, I got her some more water. Three minutes later, she asked for some water. Now, it seemed to me like this is more than just being thirsty. And, so I went to her and asked if she needed the doctor, but she refused. I thought about telling the nurse about her excessive thirst, which is viewed as a good thing, but I thought I was getting ahead of myself. 

And, so my friend and I decided to hide upstairs [because we couldn't be seen with our phones] to use our phones in figuring out why this pt has an excessive thirst. So I looked up "excessive thirst while pregnant" and I opened the first site, and it talks about gestational diabetes. Some women develop this diabetes only during the pregnancy [hence the word "gestation" in gestational diabetes]. It happens when the hormones during pregnancy, how the body makes insulin that breaks down sugar in food & how the body utilizes it. So, one of the signs of this diabetes is excessive thirst, blurred vision, frequent urination, etc. So we assessed the symptoms: Blurred vision explains the glasses but frequent urination and excessive thirst are normal during pregnancy. So we concluded that she was suffering from gestational diabetes, and so did more research and it showed that this illness may cause premature labor. From my understanding, premature babies tend to have few RBC which is essential to carry and transport O2 throughout the body. Which means that having few RBC means having few B cells produced in the bone marrow, that leads to a premature immune system, which leads to reduced innate and adaptive immunity. So premature babies have few phagocytotic cells that are necessary to kill pathogens and lower production of chemokines which activates T cells & lowers ability to fight bacteria and viruses; making the baby immune to sepsis and respiratory infections. A few minutes later, we went back downstairs to the ED just to find out that there was nothing majorly wrong with this pt and my friend & I just over-thought the situation. Later that night, she was discharged. My friend and I just laughed it off and tidied up the room the pt got discharged from. Even though we had the wrong diagnosis, we learned something new that day. 

*pt = patient*

*RBC = red blood cells*

*O2 = oxygen*

Cartoon of the week LOL

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References

1. Biolegend. Web log post. Biolegend. N.p., n.d. Web. 04 Oct. 2016.
2. "Gestational Diabetes." Gestational Diabetes. N.p., n.d. Web. 04 Oct. 2016.
3. Melville, Jacqueline M., and Timothy J. M. Moss. "The Immune Consequences of Preterm Birth." Front. Neurosci. Frontiers in Neuroscience 7 (2013): n. pag. Web. 

Blog #5

DICTIONARY

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Words for the week:

• Pathogen-associated molecular patterns (PAMPs): can be defined as conserved molecular components on the surface of microbes, such as cell wall of fungi, parasite, virus and bacteria. They can be expressed whether or not the microbes are pathogenic.
• Pattern recognition receptors: Receptors that recognize PAMPs. They trigger phagocytosis of the specific microbe. 
• Opsonins: are phagocytosis-enhancing proteins that bind to conserved , repeating components on the surface of microbes such as sugar structures, lipopolysaccharides (LPS), and viral proteins. 
• Mucins: are glycoproteins which prevents pathogens attachment. Also, traps microbes and cilia propels microbes away. 
• Tumor Necrosis Family (TNF): can be defined as family of cytokines that regulates the production, effector function, and homeostasis of cells participating in the skeletal, neuronal, and immune systems. 

Little Knowledge

Encapsulated bacteria (bacteria with an outer covering) possess a polysaccharide coat with a unique chemical structure. Examples of E.B include--salmonella typhi, hemophilus influenzae type b, streptococcus, and many more. They are antiphagocytic and vulnerable to B cells. Therefore, patients with B cell deficiency are likely to have encapsulated bacterial infections. For instance, those who have gotten a splenectomy are more susceptible to these pathogens. In addition, children do not have the ability to create antibodies to polysaccharides and are therefore, more likely to be infected by these type of bacteria (especially kids who are not breastfed), they lack T cell independent response. Therefore, it is standard medical procedure to get vaccinations, so these vaccinations can produce an I.R in cases such as this. 

*immune response = I.R*

Works cited

• "Immunology Basics." Pinterest. N.p., n.d. Web. 26 Sept. 2016.
• Ambrosino, D. M., G. Schiffman, E. Gotschlich C., P. Schur H., G. Rosenberg A., G. Delange G., E. Loghem Van, and G. Siber R. "Correlation between G2m(n) Immunoglobulin Allotype and Human Antibody Response and Susceptibility to Polysaccharide Encapsulated Bacteria." Journal of Clinical Investigation 75.6 (1985): 1935-942. Web.

Life gives us so much to reflect on...but so little time!

Reflections

My Immunology class, so far, has been revealing. As a medical student who would like to pursue hematology/oncology, this class has been so informative on different topics on the structure and function of the immune system, innate and adaptive immunity.  

BASICS

The organs of the immune system are categorized. Primary organs include thymus and bone marrow. Secondary organs include spleen, lymph nodes, and mucosal tissues. Tertiary organs are liver, skin, lungs. First, the thymus produces what are called T cells--two types--CD4(helper t cell) and CD8(cytotoxic t cell). The helper t cells activate both the cytotoxic t cells (which are cells that kill infected target cells) and B cells (cells that secrete antibodies to destroy ingested microbes and are produced in the bone marrow). Second, the spleen is an organ that filters old RBCs & WBCs (macrophages and dendritic cells) are stored there. You may be wondering what happens when a person gets their spleen removed (splenectomy)? Well, I earned that there are other organs that can work as well as the spleen which are the liver and kidneys. These two will take over the role of a spleen. 

The diagrams and case studies make me think. It's awesome. Everything I have learned so far are important. One thing that is confusing would be placing each cell in either innate or adaptive or both category. I think a chart of both immunity would be helpful. Ex: Helper t cells are adaptive while NK cells are innate, because I confuse innate cells with adaptive cells.

As a future hematologist, I have been self-studying on various blood related disorders. It involves treating disease that affect blood and its components. But first, I would have to know the components of blood, types of blood, and blood proteins. And, comprehending these cells would truly assist me in diagnosing my patients and finding the best treatment for them. Recently, a friend of mine came down with a cold, presented with fever, headache, loss of appetite, and nausea; and as usual she bought some painkillers for her headache and 'supposedly' for the cold. During lunch, I noticed she took two pills and without any hesitation, I told her that antibiotics does not cure a common cold because a cold is a virus infection and antibiotics are antibacterial medications. I didn't expect her to believe me; and so I researched it and showed it to her then she put it away. As a medical student, it is my job to educate others.

Case Study: 

A case study of a 70 year old woman had a CC of lethargy and bronchitis. She had been treated for two months with  antibiotics for bronchitis. The patient noted increasing fatigue and a fever with night sweats. P.E showed splenomegaly and lymphadenopathy. After evidence of abnormal cells on the bone marrow examination, the patient was sent to a Cancer Institute where staging of this disease was done. Four months from diagnosis, she relapsed with CNS involvement. The spinal fluid showed 100% abnormal mononuclear cells. (www.polconsultant.com). 

I would need to know the WBC, hematocrit, Plt, Hgb, & RBC numbers by doing a laboratory examination. I would [of course] place her on chemotherapy. What is the probable diagnosis? Hint: 

WBC 12,600	Differential:
RBC 3.70	Segs 42%
Hgb 11.0	Lymphs 45%
Hct 34.5	Monos 10%
Plt 255,000	Eoso 3%
	Lymphocytes appear immature with cleaved nucleus.

a.  Hashimoto's disease
b.  Non-Hodgkin's disease
c.   Multiple Sclerosis




Happy blogging!

Works Cited

• AG, Donna. "Reflection Perfection: 60 Photos That Show You How It’s Done." Hongkiatcom. Laura Williams, n.d. Web. 22 Sept. 2016.
• "Case Studies." Hematology. Western Tennessee Healthcare, n.d. Web. 22 Sept. 2016.

Blog #3 HOUSE.MD.

House, M.D. S2:E22 "Forever" 

In this episode, a woman suffered seizures while bathing her baby and almost drowned her baby. Her husband throwing up in a separate bathroom calls for her and with no response, he goes to check on her and dials 9-1-1. 

 (In the hospital)

EMT:  Four year old infant submerged in the bathtub.
           Don't know how long. Not responsive to the scene.

            (baby continues crying)

EMT #2: Caucasian, female, 32
               Tonic-cloning seizure in the bathroom.

First (False) Diagnosis: Colic Disease: Excessive crying in babies. Causes include constipation, GERD, lactose intolerance, anal fissures, subdural hematomas, and infantile migraine. The baby showed signs of intestinal gas, and allergy to the vitamins used for treatment. The baby experienced burning feeling in the thoracic cavity, pain, and tightness, dyspnea which led the doctors to think that he had chemical pneumonitis. In addition, the mother had multiple contractions in the chest which also led them to think that whatever the baby has, he got from the mother.

Actual Diagnosis: Celiac Disease aka Gluten-sensitive Enteropathy--genetic immune disease that results in the damage of the lining of the small intestine due to a sensitive reaction to gluten proteins. Celiac can be triggered by all kinds of stress--bills, childbirth, marriage, etc. The small intestine becomes damaged, less able to absorb vitamins and minerals into her bloodstream. Her body couldn't absorb niacin which caused pellagra, her body couldn't absorb vitamin K, which caused the bleeding.

My Immunology thoughts on Celiac Disease

A.A = Amino Acid(s)

So gluten is a protein, and proteins are long chains of amino acids. There are 20 various kinds of amino acids which of course would have 20 different kinds of linked long chains. These A.A are broken down to simpler compounds in our gut cell, proteins are secreted from the pancreas into the Ileum. (enterocytes = intestinal cells) and then transferred to our bloodstream. These A.A are created into a genetic sequence (AUG, GUU, GAA...) to make them into a protein. According to gi.org, "Gluten has two large numbers of glutamine and proline. We don't have the enzymes to break these amino acids apart. Rather than breaking the long chain into peptides, it stops at a peptide, a short chain." Therefore, gluten protein breaks down into a number of various peptides. In people with celiac disease, it's like each peptide causes a problem that increases the autoimmune reaction of other peptides.  I think the gluten peptide passes through the stomach cells where they are recognized as "foreign invaders."

Comment for more questions!

Works Cited

Chawla, Anupama. "Diagnosis and Management of Celiac Disease." Clinical Nutrition INSIGHT 36.1 (2010): 1-4. Web.

Blog #2 Investigation

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When I was searching up more information about the bone marrow, a condition came up during one of my researches called Amyloidosis. Amyloidosis is a condition where abnormal proteins called amyloid builds up in the tissue or organs. These proteins are produced in the bone marrow. Due to this build up, that affects their shape and function. My sources explains the types of amyloidosis, which are: Primary (AL) amyloidosis--seen in people with blood cancer and affects the kidneys, liver, heart, and certain nerves. Secondary (AA) amyloidosis--results from another chronic diseases such as lupus, rheumatoid arthritis, Crohn's disease. Familial Amyloidosis--this is passed down from families. It is caused by abnormal amyloid transthyretin (TTR) protein made in the liver. Dialysis-related amyloidosis--mostly occurs in the elderly that have been in dialysis for more than 5 years.
Although, some types of amyloid proteins have been linked to Alzheimer's disease but the brain is rarely involved in systemic amyloidosis. I have a lot of questions involving this disorder. Since it's produced in the bone marrow, why isn't it autoimmune? People with this condition, do they make enough CD4 cells & B cells? What is/are the main purpose(s) of amyloid proteins? What are they intended for? So many questions! I'm still researching on this topic...Amyloidosis Pt. 2 coming soon! :)

Works Cited

• "Amyloidosis: Symptoms, Treatments, Prognosis, Causes." WebMD. WebMD, 16 Apr. 2005. Web. 09 Sept. 2016.
• Tanzi, R. E., A. Mcclatchey I., E. Lamperti D., L. Villa-Komaroff, J. Gusella F., and R. Neve L. "Protease Inhibitor Domain Encoded by an Amyloid Protein Precursor MRNA Associated with Alzheimerʼs Disease." Alzheimer Disease & Associated Disorders 2.4 (1988): 383. Web.

...Path to Immunology...

Dictionary

VARIOLATION: The transfer of diseases from one person to another. In 1976, Edward Jenner used cow pox to protect humans against small pox, which was his first experimental vaccination.

HISTOCOMPABILITY LYMPHOCYTES ANTIGENS (HLA): These proteins helps with the regulation of the immune system. 

PHAGOCYTES: Leukocytes that engulfs microbes and foreign materials. 

TOLERANCE: The body becomes less responsive to any physiological harm.

References

• "Your Dictionary. The Way You Want It." Dictionary Definitions You Can Understand. N.p., 04 Jan. 2011. Web. 31 Aug. 2016.
•