07 - Innate Immunity Flashcards
What is immunology
study of the immune system and immune response (study of the body’s defense against infection)
What is the function of the immune system
prevent infection and eradicate established infections (maintain homeostasis)
What is immunity
resistance to disease
What is the immune system
functional system (rather than organ system)
- array of molecules and trillions of immune cells that inhibit lymphoid tissues and circulate in body fluids
What are primary lymphoid organs
where pluripotent stem cells divide and become immunocompetent (able to protect)
(where immune cells are born and develop)
red bone marrow and thymus
What are secondary lymphoid organs/tissues
sites where immune cells continue their maturation and can connect with one another to initiate adaptive immune responses
(where immune responses occur)
lymph nodes, spleen, lymphatic nodules/follicles
Describe red bone marrow
What does it do
in flat bones. epiphyses of long bones, bodies of vertebrae
pluripotent stem cells give rise to mature, immunocompetent B cells and immature (pre) T cells
Describe the thymus
What does it do
bilobed organ located in the anterior mediastinum
between the sternum and the aorta
where immature T cells go to develop into mature T cells
(early in life lots of T cells but then gland gets smaller and smaller – protection of new T cells reduce)
Describe the lymph nodes
small organs distributed throughout the body
along the lymphatic vessels - filters for lymph
places where cells of the adaptive immune system “meet up”
- site where innate immune cell that encountered a pathogen goes to alert adaptive immune system
Describe the spleen
largest secondary lymphoid organ
one of its important functions is the removal of damaged/defective RBC (contains phagocytes)
sequester platelets (releases)
lymphoid organ: has WBC will detect if there are any pathogens/toxins floating in the blood
Describe the lymphatic nodules
organized masses of lymphatic tissue
- aggregations of immune cells sitting right under the epithelial barrier waiting for something to come in
not surrounded by a capsule
- embedded in the walls of organs
commonly associated with mucosal surfaces (MALT)
Describe the innate immune system
non specific - responds to anything that injured tissue
1st and 2nd line of defence
- 1. skin and mucous membranes
(continuity, fluids/secretions/ microbiome)
- 2. internal defenses (antimicrobial proteins, NK cells/phagocytes, inflammation, fever)
Describe the adaptive immune system
highly specific (identifies a specific antigen)
3rd line of defence
specific cell types and/or proteins are generated that attack foreign substances
- has memory (conferring lifelong protection)
- humoral immunity (plasma cells)
- cellular immunity (T cells)
Describe the first layer of defense
skin and mucous membranes (intrinsic barriers)
- physical (b/c continuity), chemical, biological
What are the barriers of the first line of defense
skin
eye
- blinking, tears, lysozme
respiratory tract
- coughing, sneezing, mucus, haris, ciliary action, lysozyme
gastrointestinal tract
- stomach acid, peristalsis, normal flora (B - commensal bacteria that take up space on the epithelium that prevent nasties from attatching)
urogenital tract
- flushing action of urine (P), acidity of urine (C), lysozyme, normal flora, vaginal lactic acid
skin
- sloughing (generating new cells and getting rid of the old), structural barrier, sweat/sebum, lysozyme, normal flora
Describe the second layer of defense
What are the cells and factors
non specific line of defense when pathogens penetrate the surface barriers
cells & factors:
- antimicrobiral proteins
- natural killer cells
- phagocytes
- imflammation
What are antimicrobial proteins
enhance innate defence by attacking microorganisms directly or hindering their ability to reproduce
- interferons (small secreted proteins that interfere with viral replication –> secreted by host cells)
- complement system (cascade (already present) of interacting plasma proteins that
1. promote phagocytosis of phathogens
2. cause cytolysis of bacteria (poke holes)
3. enhance inflammation (vascular response – allows WBC to go out)) - iron-binding proteins (inhibit bacterial growth by binding iron
- antimicrobial proteins (short peptides with broad spectrum antimicrobial activity)
What are natural killer cells
unique group of defensive cells
large, grandular lymphocytees
found in blood and tissues
can kill tumour and virally infected cells and dock with the cell and tell it to die using:
- perforin (make a hole in the cell)
- granzyme (promotes break down of DNA in the cell –> apoptosis)
attack cells that display activation receptors that lack inhibition receptors
from the same lineage as adaptive cells (lymphocytes) but part of the innate response
- no immunological memory, doesn’t get better every time
What do phagocytes do
What are the phases
engulf foreign microbes and/or debris
phases:
1. chemotaxis: follow chemical trail to site of damage/infection
2. adherance: attachment to pathogen/debris
3. Ingestion: phagosome interalizes pathogen/debris
4. Digestion: phagosome fuses with lysosome that contains enzymes to break down proteins, lipids,… (H2O2, O2-, OCl-)
5. Killing/elimination
washed away by lymphatics
What are the types of phagocytes
neutrophils
- most abundant leukocyte (WBC) in blood
- major component of pus (short life span)
- 1st phagocyte to move from blood to tissue during an inflammatory response (not present in healthy tissues - normally in blood sleeping, only activates when needed) –> do collateral damage
macrophages
- begin as monocytes in the blood
- move into tissues and mature into macrophages (big eaters)
- long life span
- reside in tissues, wander tissues looking for debris/invaders –> release cytocines to signal other things to come in or tell adaptive tissues to help)
dendritic cells
- tissue-resident (long lifespan)
- antigen-presenting cell (take whatever they encounter and take it to t-cells and b-cells to tell to kill)
- bridge gap between innate and adaptive immunity)
How do phagocytes recognize the pathogens they need to kill
- use pattern recognition receptors (PRRs) to “see” pathogen-associated molecular patterns (PAMPs) –> encoded in our DNA
- PRR binds to PAMP –> generates a signal that stimulates the phagocyte
- signals through some receptors causes the secretion of pro-inflammatory cytokins (talk to other immune cells, blood vessels, endothelial cells…)
What is inflammation
non-sepcific, defensive response to any tissue damage (Doesn’t have to be a pathogen)
delivers effector molecules and cells to the site of infection to assist in killing microbes
- stimulates and assists the immune systen
- prepare site for tissue repare
- very localized
What are the three stages of inflammation
- vasodilation and increased permeability of blood vessels (vascular response)
- emigration of phagocytes from blood to the infected site (cellular response)
- tissue repair (healing)
What is the intial response of inflammation
damaged cells signal that something is wrong “chemical alarm”
- inflammatory mediators released into the extracellular fluid
resident macrophages become activated (PRRs)
- phagocytose pathogens
- release cytokines and chemokins –> signal the kind of help needed as well as directions
resident mast cells release potent inflammatory mediators
- histamine (major product)
- contribute to many aspects of the inflammatory response (vasodilation and increased vascular permeability)
within the first hour, see an influx of neutrophils and monocytes (immature macrophages)
What are the signs and symptoms of inflammation
inflmmation usually localized and self-limiting (turn off by itself)
- redness (rubor/erythema) - due to increased blood flow
- heat (calor) - due to increased localized blood flow and cellular activity
- swelling (tumor/edema) - due to increased vascular permeability - cells/fluids/prtoeins collect in the tissue
- pain (dolor) - due to the swelling (stretching) and the release of neurotramitters and other chemical mediators (bradycardin..)
- loss of fucntion (funcio laesa) - due to swelling and the release of neurotransmitteres and other chemical mediators
What happens to blood vessels during inflammation
released mediators change local blood vessels
- increased vascular diameter: increased local blood flow
- reduction in blood flow velocity: gives cells a change to bind
- increased vascular permeability: cells leave blood and enter site of injury
- blood and fluid exit into the tissues: cause of edema
- immune cells emigrate/migrate/extravasate from the blood vessels to the tissue to help eliminate injurious agents
clotting of micro-vessels prevents spread of infection (trapping)
What is fever
What is the cause
abnormally high body temperature
- systemic response to invading microorganisms
body’s response to infection is more widespread
many cytokines (pyrogens) that they spill into the blood and get to hypothalamus and signals massive infection
- hypothalamus raises set point for temperature
How does fever help
mild to moderate fevers are useful adaptation to infection
- immune cells work harder and faster
- sequestration of iron and zinc by the liver and spleen
- bacteria need these minerals to multiply
pathogens and viruses can’t replicate in conditions
(excess heat denatures proteisn and enzymes can lead to brain lesions)
