Unit 3 Exam Recall Q's Flashcards

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1
Q

What do you know about the immune system?

A
  • Immune defense mechanisms against disease consist of innate and
    adaptive immunity.
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2
Q

Explain the first attempts to induce immunity.

A
  • 15th century reports suggest that the dried crust from smallpox postules were either inhaled or inserted in small cuts in the skin (a technique called
    Variolation operated in China and Turkey).
  • In 1798 the English physician Edward Jenner observed that milk-maids that
    contracted mild disease cowpox were resistant to subsequent severe smallpox infections
  • 100 years later Pasteur created the first heat attenuated strains of bacteria that he called vaccines (from the Latin vacca, meaning cow to honor Jenner’s work)
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3
Q

What do you know about Paul Ehrlich’s work? Antigen? Receptors?

A
  • He proposed that the cells in the blood express multiple receptors and the binding between one receptor and an infection agent was like the mechanism of the key and the lock.
  • He proposed that the interaction between the receptor and the infection agent would induce the cell to produce and release more receptors with the same specificity or conformation.
  • He thought that a cell would express many receptors with different affinity for different “antigens”. Today we know that each cell makes may copy of one receptor (one specificity).
  • He coined the term antigen
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4
Q

What are invading enemies the immune system has to fight against?

What are the main layers of the immune system?

A

Cancer, fungus, parasites, viruses and bacterias

The main three layers of defense are composed of innate immunity and acquired immunity :

Innate
- Layer 1: Barriers @ body surface
Skin, mucous membranes, secretions, reflexes, etc
- Layer 2: Inflammation, phagocytes, fever, complement system, interferon

Acquired
- Layer 3: cell lymphocytes, B cell lymphocytes and antibodies

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5
Q

List three important discoveries that helped to identify the importance of the immune system and/or how “immunity” is obtained.

A
  1. Starfish larvae as a model system for recognition of the importance of phagocytes in defending against infection.
  2. White blood cells, and not antibodies alone, were important instruments of the immune system. Chase’s findings laid the groundwork for later research on T/B cells.
  3. First heat attenuated strains of bacteria called vaccine (anti-rabies)
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6
Q

Compare innate vs adaptive immunity. How do they work together?

A

Innate
- the non-inducible ability to recognize and destroy an individual pathogen or its products
- does not require previous exposure to a pathogen or its products
- composed of innate immune cells, immune activators, and biotic and abiotic anti-microbial strategies

Adaptive
- The acquired ability to recognize and destroy a particular pathogen or its products (diversity)
- dependent on previous exposure to the pathogen or its products (specificity)
- directed toward an individual molecular component of the pathogen (antigen)
- Respond faster to previously encounter pathogens (memory)

Together
- The adaptive response has co-opted many of the innate effector mechanisms to enhance its effectiveness.
- Additionally, the adaptive immune system requires innate signals for its activation.
- The innate and adaptive arms of the immune response should be viewed as complementary and cooperating.

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7
Q

Describe the epithelial barrier & its second line of defense.

A
  • Mostly one cell thick ! Separates microbe rich surface from body
  • Cells often replaced and quick healing of damage
  • Contains specialized cells that produce antimicrobial peptides (e.g. Paneth cells)
  • Other specialized cells produce mucus (goblet cells)
  • Tissue regeneration is high because tissue damage is very HIGH

Has own second line of defense
- Patrolled by macrophages that can engulf invaders
- Dendritic cell samples what is present to alert other parts of the immune response

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8
Q

What are antimicrobial peptides (defensins)?

A
  • small cysteine-rich cationic proteins
  • Found in plants, vertebrates and invertebrates
  • Kill bacteria, fungi, and viruses
  • Disrupt structure of cell membranes
  • Found in many compartments of the body
  • Secreted by innate immune cells and epithelial cells
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9
Q

The components of the second Line of Defense

A
  1. Innate immune cells
    - Macrophages, Neutrophils, eosinophils, basophils, NK cells, dendritic cells, mast cells
  2. Antimicrobial mediators
    - Cytokines e.g. Interferons, TNF, IL-6, Chemokines, Complement cascade

Processes
- phagocytosis, pattern recognition receptor activation, e.g. Toll-like receptors, inflammation

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10
Q

Macrophages eat bacteria via a process termed PHAGOCYTOSIS. Explain this process.

A
  1. Bacterium becomes attached to membrane
  2. Membrane evagination (pseudopodia) forms
  3. Bacterium is ingested in the formed phagosome. Phagosome fuse with lysosome and get redox from mitochondria and peroxisome
  4. Bacterium is killed by the redox environment and digested by lysosomal enzymes. Digestion products are released.
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11
Q

What else do you know about phagocytosis?

A
  • Phagocytosis is performed for the most part by neutrophils, dendritic cells, and macrophages, which are termed professional phagocytes.
  • Innate immune effector cells that are activated by pathogens help to shape the acquired immune response.
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12
Q

What are pattern recognition molecules?

A
  • Pattern recognition is the ability of the innate immune cells to specifically recognize classes of molecules that are unique to microbes.
  • Pattern recognition is an important property of many molecules involved in the innate immune response.
  • Toll-like receptors are one example of a pattern recognition molecule, e.g., TLR4 recognizes the lipopolysaccharide component of Gram-negative bacteria cell walls
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13
Q

Explain what you know about B lymphocytes.

A
  • Small B (bone marrow-derived) lymphocytes are the precursors of antibody-producing plasma cells
  • B cells have a B cell receptor important to recognize antigens
  • Antibodies are specific for a given antigen, therefore antibodies that bind tetanus toxoid do not react with influenza virus and vice versa. Thus, the immune system is able to differentiate between various antigens: Specificity
  • B cells that bind an antigen with high affinity are activated and become plasma cells, secreting large amounts of antibody identical to the original B cell receptor, or become long-lived memory cells
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14
Q

Explain what you know about T lymphocytes.

A
  • T lymphocytes are derived from bone marrow stem cells and mature in the thymus.
  • T cells use the T cell receptor (TCR) to recognize antigen complexes with major histocompatibility complex (MHC) molecules (class I and II).
  • T cells are divided into T helper cells, T cytotoxic cells, and T regulatory cells
  • T helper cells secrete cytokines that promote and regulate immune responses.
  • T cytotoxic cells kill target cells that express foreign antigen.
  • T regulatory cells regulate immune responses to foreign invaders and prevent the development of potentially harmful immune responses to self antigens
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15
Q

Explain antigenic specificity and immunologic memory

A
  • The first contact with the infectious agent imparts immunologic memory due to clonal expansion of reactive lynphyocytes.
  • Some of the reactive lymphocytes (T and B cells) become memory cells which persist from months to a number of years as an expanded pool of antigen-specific lymphocytes. As a result, the secondary antibody and cell-mediated immune responses are more rapid and intense than the primary response
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16
Q

What are Hematopoietic Stem Cells (HSCs)?

A
  • Hematopoietic Stem Cells (HSCs) are a type of multipotent stem cell that can differentiate into various types of blood cells.
  • They are responsible for the continuous production of blood cells throughout an individual’s life, a process known as hematopoiesis.
  • HSCs are found in the bone marrow, which is the spongy tissue located in the cavities of bones.
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17
Q

What is the primary hematopoietic tissue?

A
  • The primary hematopoietic tissue in the human body is the bone marrow.
  • Within the bone marrow, hematopoietic stem cells (HSCs) give rise to various progenitor cells, which then differentiate into red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). These mature blood cells are released into the bloodstream to perform their respective functions.
  • There are two types of bone marrow: red marrow and yellow marrow. Red marrow is actively involved in hematopoiesis, while yellow marrow consists mainly of fat cells and serves a storage function. In adults, red marrow is found in the cavities of certain bones, but its distribution can change with age
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18
Q

Explain the composition of blood?

A
  1. Leukocytes
    - Lesser part of blood
    - Includes innate and adaptive immune cells
    - These are also known as ‘white blood cells’ distinguished using various stains on blood smears
  2. Plasma and cells
    - Plasma contains proteins and other solutes.
    - Most of blood
  3. Serum
    - not cells or clotting proteins (contain antibodies).
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19
Q

What are the three cell types that originate from HSCs?

A
  1. Erythrocytes (Red Blood Cells):
    - Responsible for transporting oxygen from the lungs to the rest of the body and carbon dioxide from the body to the lungs.
  2. Leukocytes (White Blood Cells): There are two main types of leukocytes:
    - Granulocytes: This group includes neutrophils, eosinophils, and basophils. They play crucial roles in the immune response, defending the body against infections.
    - Monocytes: These cells can further differentiate into macrophages and dendritic cells, participating in immune responses, phagocytosis, and antigen presentation.
    - Lymphocytes: These cells include T cells, B cells, and natural killer (NK) cells. They play a central role in the immune system, coordinating immune responses and targeting specific pathogens.
  3. Platelets (Thrombocytes):
    - Essential for blood clotting and wound healing.
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20
Q

Define three main characteristics of HSCs.

A
  1. Multipotency
    - Ability to differentiate into multiple cell types.
    - can give rise to a variety of blood cells, including red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes).
    - allows HSCs to generate the diverse range of cell types needed for the proper functioning of the blood and immune system.
  2. Self-Renewal:
    - Can divide and produce identical stem cells.
    - continuous pool of HSCs throughout an individual’s life
    - long-term maintenance of hematopoietic function.
  3. Quiescence and Activation:
    - exist in a quiescent (inactive) state for long periods, preserving their stem cell characteristics.
    - when the body needs to replenish blood cells due to factors such as injury, infection, or normal turnover, HSCs can be activated to enter the cell cycle and undergo differentiation.
    crucial for responding to the body’s demands for blood cell production while maintaining a reservoir of stem cells for future needs.
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21
Q

What do you know about lymphocytes?

A

Lymphoid stem cells produce T cells, B cells (adaptive), NK cells and NKT cells (innate). Each (adaptive) lymphocyte produces a unique protein that interacts with a single antigen.

Note (Lymphocyte & antigen):
T cells: T cell receptors (TCRs)
B cells: antibodies or immunoglobulins (Igs)

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22
Q

Explain what the two types of Myeloid cells are and their role. Compare them to the lymphoid lineage.

A

Two types:
1. Antigen-presenting cells (APCs) engulf, process, and present antigens to lymphocytes.
Ex: monocytes, macrophages, and dendritic cells

  1. Granulocytes mediate inflammatory responses. They contain toxins or enzymes that are released to kill target cells.
    Ex: neutrophils, basophils, eosinophils, mast cells

Role (overall)
contribute to the innate immune system, which provides immediate defense against infections

Comparison:
The myeloid lineage is distinct from the lymphoid lineage, which gives rise to B cells, T cells, and natural killer (NK) cells, contributing to the adaptive immune system.

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23
Q

Myeloid Cells - Neutrophil cells

Explain what you know about Neutrophils and their function.

A

Known:
- Aka polymorphonuclear leukocyte (PMN)
- Produced in the bone marrow & released into blood.
- Circulate for 7-10 hours. Migrate into tissues (die within 48 h).
- Generally, first cells to arrive at sites of infection.

Morphology:
- Segmented nucleus (most have 3 or 4 nuclear segments) connected by tapering chromatin strands.
- Primary granules (larger, denser; lysosomal function)
- Secondary granules (smaller)
Most abundant leukocyte in blood (50-70%).

Function:
- Phagocytosis of bacteria and debris
Killing of ingested bacteria (reactive oxygen intermediates & nitrogen intermediates)
- antimicrobial peptides (Defensins) like lysozyme, hydrolytic enzymes & cytokines

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24
Q

Myeloid Cells - Eosinophils cells

What do you know about Eosinophils?

A
  • Contain granules that stain a brilliant pink in standard H&E staining protocols
    1-3% of all blood
  • Important in coordinating our defense against multicellular parasitic organisms, including helminths (parasitic worms).
  • Motile cells that migrate from the blood into the tissue spaces.
  • Abundant in the small intestines
  • Outside the intestines, they are contributors to asthma and allergy symptoms.
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25
Q

Myeloid Cells - Basophils cells

What do you know about Basophils?

A
  • < 1% of all blood
  • are non phagocytic granulocytes
  • Contain basophilic granules that stain blue in standard H&E
  • Rare in the circulation but strong responders.
  • Play a role in response to parasites, particularly helminths (parasitic worms).
  • Histamine, in basophilic granules increases blood vessel permeability and allows immune cells access to a site of infection.
  • Secrete cytokines that can recruit other immune cells,
  • Best appreciated as a cause of allergy symptoms.
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26
Q

Myeloid Cells - Mast cells

What do you know about Mast Cells? Function?

A

Known:
- Produced in the bone marrow and released into blood as immature precursors.
- Differentiate upon entering tissues, usually at the interface between the body and the environment (epidermis).
- Characteristically found surrounding blood vessels and nerves.
- 2 types: Skin and Connective tissue mast cells and mucosal mast cells
- Morphology: Heavily granulated.

Function:
- Important initiators of inflammation and responses to parasites infection.
- Also involved in allergic reactions.
- Granules contain histamine.
- Also make leukotrienes, prostaglandins and cytokines.

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27
Q

Myeloid Cells - Monocyte cells

What do you know about Monocytes?

A
  • 2-12% of all blood
  • Produced in the bone marrow.
  • Released into blood (Inflammatory monocytes and Patrolling monocytes).
  • Circulate for approximately 8 hours.
  • Migrate into tissues, differentiate into macrophages.
  • Morphology: Horseshoe nucleus, vacuolated with fine granules.
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28
Q

How do Monocytes differentiate into macrophages? What is their function?

A

Monocytes change by doing the following;
- Increase in size (5-10 fold)
- Increased numbers and complexity of organelles
- Increased phagocytic activity
- Increased levels of hydrolytic enzymes
- Becomes a professional antigen-presenting cell (APC)

Function of macrophages:
- Phagocytosis of microorganisms
- Killing of ingested microorganisms
- Recruitment of immune cells into the inflammatory site
- Secrete cytokines and chemokines
- Present antigen to T cells

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29
Q

What do you know about dendritic cells?

A
  • Dendritic cells (DCs) are a type of immune cell with a pivotal role in the initiation and regulation of immune responses.
  • Dendritic cells are immune cells that capture and process antigens, presenting them to T cells to initiate adaptive immune responses.
  • Mediators between the innate and adaptive immune systems, promoting the activation of T cells crucial for targeted defense against infections.
  • Regulate immune responses, influencing T cell differentiation and promoting the development of regulatory T cells to maintain immune tolerance.
  • Surveil tissues, detecting and capturing antigens to contribute to the early recognition of infections and abnormal cells.]
  • Dendritic cells are highly efficient antigen-presenting cells. They capture antigens, which are fragments of proteins derived from pathogens or other foreign substances.
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30
Q

What are Megakaryocytes?

A
  • Large myeloid cells, in the bone marrow
  • give rise to thousands of platelets, very small cells (or cell fragments) that circulate in the blood and participate in the formation of blood clots
  • Clots not only prevent blood loss, but when they take place at epithelial barriers, they also provide a barrier against the invasion of pathogens.
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31
Q

Lymphocytes - NK Cells

What do you know about NK Cells?

A
  • Natural Killer (NK) cells are a type of cytotoxic lymphocyte, a subset of white blood cells, and they play a critical role in the innate immune system.
  • NK cells are known for their ability to recognize and eliminate infected or abnormal cells, including cancer cells, without prior sensitization or the need for specific antigens.
  • body’s first line of defense before the adaptive immune system is fully engaged.
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32
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101
Q

What are the two subtypes of parasites? What can human parasites infect? Biggest challenge they cause?

A

Types:
- Protozoans (unicellular)
- Metazoans (helminths or worms)

Infect:
- Arthropods (act as vectors)
- Human (e.g. contact, inhalation, ingestion)
- Non-Human primates (zoonotic spread)

Challenge:
- complicated life cycle, leading to changes in: antigenic structure & location over time

102
Q

What do you generally know about parasites?

A
  • Many of the most burdensome and least treatable tropical diseases are caused by protozoan parasites
  • The only common features of this group are that all are unicellular eukaryotes, and many are motile.
    Many can be free-living and found in contaminated water (e.g., Giardia or Toxoplasma).
  • Other protozoan parasites move from their arthropod vector hosts, such as mosquitoes and flies (e.g., the parasites that cause malaria and African sleeping sickness, respectively), to their mammalian hosts
103
Q

Why do we care about parasites/what they do?

A
  • malaria kills between 2-5 million children a year
  • parasitic infection is endemic/epidemic in undeveloped countries
  • comorbidity for any disease
  • multicellular parasites influence the host immune response (ex: vaccination)
104
Q

Explain immune evasion by Trypanosomes.

A
  • They exhibit antigenic variation, constantly changing their surface coat proteins, preventing the immune system from recognizing and mounting a sustained defense.
  • Have VSGs, genes that encode surface glycoproteins.
  • Additionally, trypanosomes can reside in immune-privileged sites, such as the central nervous system, making it difficult for immune cells to reach and eliminate them. These evasion mechanisms contribute to the chronic nature of trypanosome infections and the challenges in developing effective immune responses or vaccines against them.
105
Q

Explain immune modulation by helminths (Metazoan parasites)

A
  • Influence activation and induce cell death in T cells
  • Steer the T cells response from type-1 effector (limit pathology) pathways to type-2 effectors (progressive disease)
  • Induce polyclonal B cell activation and proliferation
  • Directly induce class switch to IgE and non-protective IgG subclasses
    implications for vaccination
106
Q

What are the five main types of parasites?

A

Nematodes (roundworms)
Cestodes (tapeworms)
Trematodes (“flukes”)
Extracellular protozoa and amoeba
Intracellular protozoa

107
Q

Differ between the seven types of Nematodes.

(Hint: general lifecycle, dog worms, flies, pinworm - children, pork/bear, red cod worm, raw fish worm clear)

A

Ascaris lumbricoides
Very large (pencil size)
Eggs hatch in gut; larvae migrate via blood to lungs; burst out of blood into alveoli; coughed back into gut
Must embryonate in soil
Adults live 1-2yr, eggs live 15yr
immune response limited
restricted to migratory phase

Toxocara canis
Dog roundworm (like dog Ascaris)
Eggs infectious to humans..Life cycle same as Ascaris
pathology from migrating larva
CNS damage, retinal damage
Type 1 inflammatory response (granuloma)

Onchocerca volvulus
“river blindness”
black fly bite
microfilaria actively migrate into wound and subcutaneous tissue
form nodules below skin
microfilaria migrate to eye (blindness)

Enterobius vermicularis
Common pinworm
Develop in large intestine
Worms migrate from anus at night and lay eggs causes itch
Not very pathogenic
Treatment over the counter (Pyrantel pamoate )
Eggs are very light and can persist in house dust

Trichinella spiralis
Trichinosis
Undercooked pork (bear)
Direct life cycle
Adults live in gut but larvae migrate to muscle
Inflammatory response to larva causes damage
In heavy infections damage to other organs (brain, heart)
Limited protective immune response
Anti parasitic treatment (Mebendazole)

Anisakiases
Often called “the cod worm”
Final host is seal
Intermediate host is fish (cod, haddock, halibut most common)
Fillets routinely “candled” to remove worms
Easy to see because they are red

Anisakidae
Harder to spot because they are nearly transparent
Final host is seal
Intermediate host is fish (cod, haddock, halibut most common)
Pathology due to inflammation that leads to cancer (bile duct cancer)
Caused by eating raw fish (sushi)

108
Q

Explain the life cycle of Cestodes (tapeworms)?

A

Taenia solium = pork
Taenia saginata = beef
- Very large (up to 10m)
- Scolex (head) very small
- Feed on intestinal contents & mostly non-pathogenic
- limited immune response (some IgA)
- If we eat the eggs we develop the cysticerci–sometimes in the brain (cause adult epilepsy

109
Q

Explain Trematode life cycle/info.

A

Schistosoma mansoni
- infection by cercaria
- adults live in the portal tract in liver
- immune escape site/outer surface
- type-2 immune response due to immune modulation
- no effective anti-adult immunity
- eggs released into gut, significant immunopathology caused by eggs

110
Q

Explain what you know about three types of extracellular protozoa?

A

Trypanosoma sp.
- African and South American species..African “sleeping sickness”
Bite of “tsetse fly” (40,000 infectious organisms per bite MID is 300)
- Trypomastigotes live in blood
- Non-protective CNS immunopathology
- Surface coat (VSG) changes frequently to escape immune attack

Giardia lamblia
- Common day care parasite in Canada
- Feco-oral transmission
- simple life cycle: ingest cysts, adults live in the intestine
- GI pathology (“villus atrophy”)
- protective IgA response (block attachment)

Entamoeba histolytica
- Large single celled organisms
- Cell mediated response contributes to pathology
- significant erosive pathology in gut (somewhat like very aggressive Crohns)
- GI secondary infection common
- Very serious liver involvement, occasional CNS involvement
- Limited protective immunity
- Can be fatal when untreated

111
Q

Explain an intracellular parasite effect/life cycle? How is this diagnosed?

A

Ex: Plasmodium sp. vivax, falciparum*, malariae, ovale
- infected by sporozoites
- rapid migration to the liver, leave liver as merozoites
- Immediately infect red cells (pathology due to anemia and loss of RBC deformability)
- massive and cyclic increase in parasite numbers
- Immune system has difficulty keeping up but tries very hard
Protection by Sickle Cell anemia trait (heterozygous)

Diagnosis:
- DR malaria increasing
- Check for infected RBC (looking for “ring stage” that is characteristic of malaria)
- More than 5% of of RBC infected confirms infection with P. falciparum
- This requires immediate attention because it can be fatal fast
Fever of uncertain cause, history of travel to malaria area