March 20 Flashcards
what is the 1st line of defence
physical & chemical surface barriers
what is the 2nd line of defence
internal cellular & chemical defense (if pathogen penetrates barriers)
what is the 3rd line of defense
immune response (if pathogen survives nonspecific, internal defenses)
what does the innate immune system consist of
- natural, not learned through experience
- 1st and 2nd line of defense
what does the adaptive immune system
- learned through experience
- 3rd line of defense
What do uncommitted stem cells in the bone marrow give rise to?
They give rise to progenitor cells for the remaining blood cells and platelets.
Where do platelets develop before entering circulation?
They develop to the megakaryocyte stage in the bone marrow before being released as platelets in circulation.
Which blood cells arise from progenitor cells in the bone marrow?
Neutrophils, monocytes, and basophils arise from progenitor cells and are found in circulation.
How are lymphocytes derived?
Lymphocytes originate from their own lineage of lymphocyte stem cells in the bone marrow, which give rise to circulating lymphocytes.
what do leukocytes divide into?
granulocytes and agranulocytes
what do granulocytes divide into
- neutrophils
- eosinophils
- basophils
what do agranulocytes divide into
- lymphocytes
- monocytes
- macrophages
How do basophils stain in hematoxylin dye?
Their cytoplasmic granules stain blue.
What is the primary function of basophils and mast cells?
They function in inflammatory reactions and allergies.
What substances do basophils and mast cells release, and what are their effects?
Heparin: Anticoagulant that slows blood clotting.
Histamine: Vasodilator that increases blood flow to tissues.
How do neutrophils stain?
Their cytoplasmic granules stain slightly pink.
What is the primary function of neutrophils?
They play a key role in immunity and are the early first responders to infections.
How do neutrophils fight infections?
They phagocytose (ingest & kill) about 5-20 bacteria during their short 1-2 day lifespan.
steps of neutrophil extravasation
- Roll along endothelial wall
- Are tethered, captured, & activated
- Crawl to exit sites
(endothelial cell junctions) - Exit sites open due to
signals between leukocytes & endothelial cells
How do eosinophils stain?
Their cytoplasmic granules stain bright red.
What is the primary function of eosinophils?
Defense against parasites.
How do eosinophils attack parasites?
They attach to large, antibody-coated parasites and release toxic substances from their granules to damage/kill them.
What is the primary function of monocytes & macrophages?
Phagocytosis – engulfing pathogens and debris.
Where are monocytes and macrophages found?
Monocytes: Found in the bloodstream.
Macrophages: Found in tissues.
How effective are macrophages compared to neutrophils?
Macrophages are larger and more effective, ingesting 100 bacteria per lifetime, while also removing old RBCs & dead neutrophils.
What was the original name for tissue macrophages?
The reticuloendothelial system (not originally associated with leukocytes).
What are the names of macrophages in different tissues?
Histiocytes – skin
Kupffer cells – liver
Osteoclasts – bone
Microglia – brain
Reticuloendothelial cells – spleen
What is the primary function of lymphocytes?
Immune response.
What are the three main types of lymphocytes?
Natural killer (NK) cells
T lymphocytes (T cells)
B lymphocytes (B cells)
What is an antigen?
A molecule (often on the surface of a pathogen) that the immune system recognizes as a specific threat.
What are MHC markers?
Proteins expressed on the surface of a cell that display both self & non-self antigens.
What are the functions of MHC markers?
They are used in the recognition of pathogens in immune responses and also in self-recognition.
Where is MHC-I found?
On the cell surface of all nucleated cells in vertebrates.
Where is MHC-II found?
Mostly on macrophages, B cells, and dendritic cells (antigen-presenting cells, APCs).
How are T cells activated?
T cells have receptors that recognize antigens presented by antigen-presenting cells (APCs).
What happens when a helper T cell (CD4) encounters an APC with a foreign antigen on MHC-II?
The helper T cell secretes cytokines that enhance the immune response.
Do all helper T cells bind to an antigen?
No, only those with receptors that recognize the specific antigen will bind.
Where does the initial “priming” of T cells to an antigen occur?
In lymph tissues such as the spleen, lymph nodes, tonsils, and gut.
What happens during Step 3 of the immune response?
The helper T cell divides and transforms into an effector helper T cell.
What happens in Step 4 (“Alarm”)?
The effector helper T cell activates:
Cell-mediated (T cell) response: Activates naïve cytotoxic T cells.
What happens in Step 5 (“Building Specific Defenses”)?
The naïve cytotoxic T cell divides into:
Effector cytotoxic T cells (Step 6: Defense).
Memory cytotoxic T cells (Step 7: Continued Surveillance).
What do effector cytotoxic T cells (CD8) do in Step 6 (“Defense”)?
They target and kill cells displaying foreign antigens, such as:
Infected tissue cells (intracellular pathogens).
Cancer cells.
Transplanted organ cells.
How do cytotoxic T cells kill infected cells?
- Bind to MHC-I on infected cells.
- Release perforin, which forms pores in the target cell.
- Granzymes enter the pores, triggering apoptosis (cell death).
What is the function of memory T cells in Step 7?
They are stored for continued surveillance, allowing for a faster immune response upon re-exposure.
Why are B cells unique at birth?
There are many different B cells, each capable of producing a unique antibody.
How do B lymphocytes acquire the ability to produce antibodies?
They inherit the ability to produce specific antibodies.
How many types of antibodies can a single B cell produce?
Each B cell can produce only one type of antibody but remains naïve until activated.
What happens when a B cell encounters its specific antigen?
It divides many times, producing a large population of genetically identical B cell clones.
How many antibodies can B cells produce per second?
Approximately 2,000 antibodies per second.
What happens during the primary immune response?
- It occurs after the first exposure to an antigen.
- The response is slower & weaker.
- It produces mostly IgM antibodies.
Why is the secondary immune response faster and stronger?
It is due to lymphocyte clones & memory cells that quickly recognize the antigen.
What type of antibodies are primarily produced during the secondary response?
IgG antibodies.
What do antibodies do to pathogenic bacteria?
Antibodies mark pathogens as targets for immunological attack but do not destroy them directly.
How may pathogens be attacked after being marked by antibodies?
- Innate immune cells (such as macrophages and neutrophils) may attack the pathogen.
- Complement proteins (part of the blood protein defense system) may also attack the pathogen.
How many complement proteins are involved in the complement pathway?
There are 9 complement proteins (C1-C9) that are inactive in the plasma.
What triggers the activation of complement proteins?
Complement proteins become activated when antibodies mark the antigens (bacteria).
What are the three pathways of the complement system?
- Classical pathway (high-level activity, triggered by antibodies).
- Alternative pathway (low-level, continuous activity).
- Lectin pathway.
How are the classical and lectin pathways similar?
The classical and lectin pathways are very similar in their activation process.
Is the complement system part of innate or adaptive immunity?
It is a type of innate humoral immunity (always ready and found in blood) but also has adaptive humoral immunity characteristics (can be specialized to a pathogen).
What happens when complement proteins are triggered?
The proteases cleave specific proteins and initiate an amplifying cascade, followed by additional cleavages.
What are the two main outcomes of the complement pathway activation?
- Massive amplification of the immune response.
- Formation of the cell-killing membrane attack complex (MAC).
What is the first step in the complement pathway?
Recognition by C1.
What proteins are involved in the activation phase?
The activation phase involves C4, C2, and C3 (in this order).
What proteins are involved in the attack phase of the complement pathway?
The attack phase involves C5, C6, C7, C8, and C9.
How does the classical pathway of the complement cascade begin?
It starts with antibodies and C1 proteins binding to the surface of the pathogen.
How does the lectin pathway of the complement cascade begin?
It starts with lectins binding to mannose residues on the surface of the pathogen.
What are lectins?
Lectins are carbohydrate-binding proteins that are highly specific for sugar moieties.
What happens during Step 1 of the complement cascade (classical pathway)?
Activation of C1 (classical pathway).
What does C1 do in Step 2 of the complement cascade?
C1 catalyzes the hydrolysis of C4 into C4a and C4b.
What happens in Step 3 of the complement cascade?
C4b binds to the plasma membrane and becomes active.
What occurs during Step 4 of the complement cascade?
C3 is cleaved into C3a and C3b due to an intermediate step involving the splitting of C2.
How does the alternative pathway differ from the classical pathway in Step 4?
The alternative pathway also results in the cleavage of C3 but through a different sequence of events. Both pathways converge at the cleavage of C3.
What happens in Step 5 of the complement cascade?
C3b converts C5 into C5a and C5b.
What is the role of C3a and C5a in Step 6?
- C3a and C5a stimulate mast cells to release histamine.
- They also act as chemokines, attracting macrophages, neutrophils, monocytes, and eosinophils.
What happens in Step 7 of the complement cascade?
C5, C6, C7, C8, and C9 are inserted into the bacterial cell membrane to form a membrane attack complex (MAC), leading to cell lysis.
what is the Membrane Attack Complex (MAC)
large pore that kills bacterial cell through osmotic influx of water
what is the defensive process - inflammation
Injured tissue releases chemical signals:
Blood vessels widen
1. Redness – blood flow carries defensive cells & chemicals to damaged tissue,
removing toxins
2. Heat – increases the metabolic rate of cells in the injured area to speed healing
Capillaries become more permeable
3. Swelling – fluid containing defensive chemicals, blood-clotting factors, oxygen,
nutrients, & defensive cells seeps into injured area
4. Pain – hampers movement, allowing the injured area to heal
how does inflammation also occur in response to tissue damage & stress
- Bruises & torn tissue (acute
inflammation) - Disease states such as
arthritis, obesity, etc.
(chronic inflammation)
What is sepsis?
Sepsis is systemic, whole-body inflammation that causes organ dysfunction and can be potentially fatal.
What are some common symptoms of sepsis?
High fever
Rapid pulse/respiratory rate
Hypotension (low blood pressure)
Hypoxemia (low oxygen levels)
Oliguria (low urine output)
Acidosis
What is the treatment for sepsis?
Antibiotics and IV fluids are commonly used to treat sepsis.
What is septic shock?
Septic shock occurs when blood pressure falls so low that organs are not adequately perfused, leading to organ failure.
What bacterial component is usually the cause of sepsis?
Bacterial lipopolysaccharide (a component of gram-negative bacteria) is often the cause of sepsis.
How does a localized infection contribute to sepsis?
A localized infection triggers the innate immune response.
What happens when large amounts of endotoxin enter circulation?
When large amounts of endotoxin enter the bloodstream, inflammatory cytokines are released, contributing to the systemic inflammation of sepsis.
How does the immune system normally function?
The immune system functions by distinguishing “self” from “non-self” to prevent attacking the body’s own cells.
What are autoimmune diseases?
Autoimmune diseases occur when the immune system fails to recognize and tolerate self-antigens, leading to the immune system attacking the body’s own tissues.
What are six possible reasons why self-tolerance may fail?
An antigen that does not normally circulate in the blood becomes exposed to the immune system.
A self-antigen may be altered by combining with a foreign hapten.
The immune system may produce antibodies directed against other antibodies.
Antibodies produced against foreign antigens may cross-react with self-antigens.
Self-antigens may be presented to helper T cells alongside MHC-II.
Autoimmune diseases may occur due to inadequate activity of regulatory (suppressor) T cells.
What causes AIDS, and what cells does it target?
AIDS is caused by human immunodeficiency virus (HIV), which infects and destroys helper T cells in the gastrointestinal mucosa.
Why does HIV weaken the immune system?
HIV decreases immunological function, making individuals more susceptible to opportunistic infections and cancer.
What type of virus is HIV?
HIV is a retrovirus, meaning its genetic code is carried in RNA.
What enzyme does HIV use to replicate?
Reverse transcriptase transcribes viral RNA into complementary DNA for viral replication.
How does antiretroviral therapy (ART) help with HIV/AIDS?
ART inhibits reverse transcriptase, suppressing HIV replication indefinitely but is not a cure.
Why does HIV return when ART is stopped?
HIV viral DNA integrates into the host DNA of memory helper T cells, allowing the virus to reappear when ART is discontinued.
What are the two types of abnormal immune responses that cause allergies?
- B cell-mediated (immediate hypersensitivity) – e.g., hay fever, asthma.
- T cell-mediated (delayed hypersensitivity) – e.g., contact dermatitis (poison ivy).
What immune response occurs in non-allergic individuals?
The allergen stimulates Th1 cells, which secrete IFNγ and IL-2, leading to a normal immune response.
What happens in IgE-mediated immediate hypersensitivity (allergic response)?
- The allergen stimulates Th2 cells to secrete IL-4 & IL-13, causing plasma cells to secrete IgE antibodies instead of IgG.
- IgE binds to mast cells & basophils, leading to the release of histamine & cytokines (causing itching, sneezing, tearing up, runny nose, etc.).
What is T cell-mediated delayed hypersensitivity?
It occurs hours to days later because the reaction is mediated by lymphokines instead of antibodies.
Example: Contact dermatitis from poison ivy.
