Immunology Flashcards
1
Q
Reason for various immune responses
A
protective to be infected with another worm
nutrition
treatment
immune response
anatomical location of infection
2
Q
Parts of the Innate branch
A
physical barriers
chemical barriers
microbial barriers - commensals
cellular components - phagocytes and lymphatics
3
Q
commensal
A
typically does not cause disease
4
Q
pathogen
A
primary - disease causing
opportunistic - typically commensal but will cause disease in a weakened host
- also cause disease when relocated to a site that it is not usually found
5
Q
infection
A
microbe gains access to a host
6
Q
disease
A
microbe causes symptoms
7
Q
pathology
A
damage that a microbe directly causes to the host
8
Q
immunopathology
A
unwanted side effect of immune system
9
Q
parasite
A
- organism that feeds off of another organism that provides a host and is damaged in the process
- ectoparasite - live on the outside
- endoparasite - lives inside
10
Q
Latent
A
not replication active and not detectable by culture
-example is EBV and some viruses
11
Q
Contact infection
A
vector transmitted - typically transmitted via a bite
fomites - inanimate object that can transmit pathogens
12
Q
Job of the immune system
A
protect you from foreign intruders
distinguish and protect against foreign organisms
detect and protext against foreign organisms
distinguish between self and nonself
13
Q
About the Innate system
A
- born with it - innate receptors and germline encoded
- nonspecific response and receptors
- Pattern Recognition Receptors recognize PAMPs
- first line of defense
- reacts almost immediately
- NO memory - same response (speed, strength) everytime
- Components
- physical
- chemical - lysozyme
- microbial - commensals
- phagocytes engulf pathogens
14
Q
PAMPs
A
Pathogen Associated Molecular Pattern
-recognized by PRR pattern recognizing receptors
- Gram + have LTA and PGN
- Gram - have LPS
- Fungi - zymosan
- Viruses - dsRNA
- helminth - CHO
PAMPs should never be expressed on host cells
15
Q
About the Adaptive arm
A
- must be activated by innate signals
- 5 - 10 day response time
- has memory
- second response is faster and stronger
- very specific receptors that can be tailored
- recognize antigens
- Cellular Component
- T cells - Helper and Killer
- Humoral Component
- antibody producing B cells
16
Q
Physical and Chemical Barriers
A
- defensins (on the skin, imbed into membrane - lysis), lysozyme (in the tears to degrade PGN), AMPs (antimicrobial peptides), low pH
- goblet cells - produce mucus. Important in the lungs
- cilia - wavy motion moves foreign bodies that are trapped in the mucus
- tight junctions - no gap between epithelial cells
- vili - intestines, valleys are crypts with high defensin conc.
17
Q
Cryptosporidium parvum
A
pathogen that evades destruction by stomach acid
parasite eggs are activated by stomach acid
helps time release of parasite into the intestine
-protozoan parasite
18
Q
microbial barriers
A
- nutrition competition
- take up space
- disrupting commensals can cause opportunistic infections
- immunosuppression
- change in site of microbe
- broad spectrum antibiotic
- yeast side effect
19
Q
Lymphoid organs
A
- primary - where immune cells are made and mature. bone marrow and thymus
- secondary - mature cells encounter pathogens and antigens
- nodes - lymphatic merge, immune cells filter and detect pathogens
- where the immune response starts
20
Q
lymph
A
- fluid, oxygen, nutrients, collect waste
- vessels - can transport pathogens, cancer cells, dead cells
- muscles contract to circulate lymph
- detect pathogens when in the nodes
- W. bancrofti causes elephatitis and blocks lymphatics
21
Q
7 innate immune cells
A
- neutrophils - most abundant WBC
- dendritic cells - can present antigen, phagocytic
- macrophage - v. large, presents antigen, phagocytic
- basophils, eosinophils, mast cells - allergic response and release histamine
- natural killer cell - directly kill infected host cell
22
Q
PRRs detect PAMPs
A
- PRRs are PAMP specific
- different receptors for different patterns
- extracellular PRRs - on surface of cell, none for viruses because those enter the cell
- endosome - has PRRs for extracellular detection
- for dsRNA but also for typical PAMPs
23
Q
Families of PRRs
A
- Toll like recptors (TLRs) - first discovered and best studied
- C-type lectin receptors (CLRs) - recognize CHO
- NOD like receptors (NLRs) - free floating in the cytoplasm
24
Q
Phagocytosis
A
- PRR detects PAMP
- pseudopods extend to engulf the pathogen
- pathogen trapped in the phagosome
- phagosome fuses with the lysosomes and granules
- pathogen degraded in the phagolysosome
- uses lysozyme, defensins, low pH, ROS
- parts of pathogen are exocytosed
- can amplify response and activate other immune cells
25
killing in the phagolysosome
* oxygen dependent - ROS
* oxidative burst to make ROS
* pathogens with superoxide dismutase and catalase can convert ROS to H2O2 then water and O2. Avoid killing
* Oxygen independent - low pH, defensins, enzymes
26
opsonins
* complement - small proteins
* bind to conserved pathogen components (cell wall)
* Antibodies - bind to specific antigens
* anti capsule antibodies
* opsonins make the pathogen larger and easier to detect
* receptors on phagocytes recognize opsonins and leads to phagocytosis
* opsonophagocytosis
* harder to opsonize a capsuled bacteria
* back up system if PRRs dont work
27
Evasion from phagocytosis
* capsule - hides PAMPs from PRRs, blocks opsonins
* catalase and superoxide dismutase to quench ROS
* prevent formation of phagolysosome to prevent merging
* avoid low pH by blocking the H+ pumped into phagosome
* inhibit degradative enzymes - lysozyme and defensins
* flagella - chemotax away
* mutate PAMPs
* coat in host protein to look like "self"
* produce enzymes that degrade opsonins
* Listeria moves from one cell to another using actin
28
When neutrophil cant phagocytose
* NETosis
* Neutrophil Extracellular Trap
* Antimicrobial peptides
* degrading enzymes
* kill or sequester pathogen
* Web of DNA traps the pathogen
* used for large microbes
29
DAMP
danger associated molecular pattern
30
NK cells
* can kill infected host cells
* all nucleated cells express MHC I protein
* major histocompatibility complex
* healthy cells express MHC I loaded with self protein
* signal from healthy cell prevents NK cell from being activated
* loss MHC I from cancer and viral infections - no MHC to activate the inhibitory receptor
* use granzyme and perforin
* activated from inhibitory receptor is not stimulated
* detects missing MHC I
* also has a NKR that binds to a ligand on the host cell
31
Evade NK cells
force host cell to produce fake MHC
mock inhibitory receptor
32
Cytokines
autocrine - produce cytokine to activate itself
paracrine - stimulates near by cells
endocrine - circulated befoer stimulation of other cells
chemokine - subtype that enduces cell movement
33
Tissue Damage - Inflammation
* dead cells release cytokines
* resident immune cells respond
* mast cells - histimine, vasodilator
* macs and DCs - phagocytosis
* bradykinin - pain
* chemokines - recruit neutrophils
* capillaries more permeable and cells can enter tissue
* redness, pain, heat, swelling
34
Extravasation
neutrophils from blood into tissues and move to highest IL-8 concentration
follow chemokine gradient
neutrophils destroy pathogen
innate cells communicate to adaptive cells that a pathogen was detected
35
Innate to adaptive communication
* DC and mac cells are APC (antigen presenting cells)
* phagocytosis then present antigen on MHC II via the MHCII-antigen complex
* produe cytokines (paracrine)
* Helper T cell - T cell receptor (TCR) binds the antigen on the APC _and_ activated by cytokines from phagocytic cell
* Helper T cell activated
* this bridge occurs in the lymph nodes
36
Helper T cell
* Activated by APC and cytokines
* autocrine to stimulate clonal expansion of T helper cell
* T helper effector - kill the pathogen now
* T helper memory - remember pathogen for later. vaccinations
* swollen lymph nodes
* paracrine to B cells and killer T cells
37
B cells
made in the bone marrow
only cells that produce antibody
antibodies are opsonins
effector and memory B cells - memory used in vaccines
each has one specific receptor (BCR)
regognizes a unique antigen
can directly bind to free floating antigens - then activated
38
Killer T cells
aka cytotoxic T cells (CTC)
kill infected host cells
perforin and granzyme
adaptive cells
have a T cell receptor
have memory - vaccines
39
Functions of B cells
* neutralization - make incapable of binding to the target cell. then phagocytosis
* agglutination of microbes - easier to detect large cluster. phagocytosis
* Opsonization - antibodies are opsonins, leads to phagocytosis
* antibodies can lead to holes in the membrane - lysis
* precipitation of dissolved antigens and deactivates them
40
HIV
infects and destroys T helper cells
lose entire adaptive immune system
41
B cell activation
* Need cytokines from T helper AND antigen binding to BCR to be activated
* specific surface receptors
* clonal expansion - new cells have the same BCR
* BCR becomes antibody when not attached to the B cell
* small size for dissemination
* effector B cells aka plasma cells - secrete Abs
* memory cells - for later response
42
Cytotoxic T cell (CTL)
-killer T cell
* recognize viral antigen on host cell
* does not recognize Self protein
* amplified by parachrine cytokines from helper T cell
* adaptive arm
* TCR recognizes viral Ag on host cell MHCI
* host cell is NOT an APC
* uses perforin and granzyme
43
NK vs CTL
* NK recognizes absence of MHCI self Ag
* NK no memory, CTL has memory
* both use perforin and granzyme
* CTL stimulated by TH cytokines. NK no cytokines
* TCR vs PRR
* NK innate and CTL adaptive
* NK responds to absence of self Ag, CTL responds to presence of viral Ag
44
how to get microbiome
* breast milk
* vaginal and C section birth
* f
* f
* f
* f
45
What does the microbiome do?
* Co aggregation - clump pathogen so they cant bind
* Produce biosurfactants
* produce H2O2 and bacteriocins - kill pathogens
* inhibitory signals
* competitive exclusion - take up space
* immunomodulation (alter response to the appropriate level) - immune education
* modulate tight juctions
46
anaerobes on skin
aerobic bacteria can consume the oxygen to a great enough extend where anaerobes can persist
47
Perturb the microbiota
* sexual intercourse
* diet
* antibiotics
* hand sanitizer
* age/hormones
* fecal transplants
* prebiotics - food for microbes
* probiotics - good microbes
* environment and living conditions
* pregnancy
* stress
* infection
* smoking
* travel
* other medication
48
Site specific diversity
microbe diversity changes based on area of the body
49
Effect of antibiotics and travel on microbiota
* Antibiotics kill good and bad microbes. Very low diversity while antibiotics are in use. Then few grow back, but may develop a different diveristy/population
* Travel - can kill of some bacteria. Different bacteria may become predominant
50
Autoimmune disease
* not caused by a pathogen
* immune system targets self components and attacks the host
51
Autoimmune diseases and development and helminths
* helminths are most common in underdeveloped countries
* autoimmune diseases are most prevalent in developed countries
* suggest that lack of exposure to helminths increases risk of autoimmune diseases
52
Hygiene Hypothesis
* lack of early childhood exposure to infectious agents, microbes, and parasites increases susceptibility to allergic and autoimmune diseases by modulating immune system developent.
* exposure to commensals not pathogens
* effected by imprinting events
53
Imprinting events
* events exposed to commensals before age 2
* educate the immune system
* farm animals
* sterility of environment - food and water
* breast feeding
* less antibiotics
* siblings
* day care
* vaginal and c section
* helminths
54
Nonimprinting events
frequent Dr visits - antibiotics
only child
urban lifestyle
sterile and clean environment
55
Purpose of imprinting
* imprinting on innate and adaptive cells
* educate immune system
* dampened and dont respond
* lower likelihood of autoimmune disease
* higher diversity of immune cells
* non imprinted systems are hyperactive
56
Effect of nonimprinting on adaptive arm
* nonimprinted system will have more active innate cells
* leads to more active adaptive cells
* increase cytokines from APC to helper T cells
57
T helper cell
* naive or virgin until activated by an Ag
* cytokine dictates what type of T cell it becomes
* Th 1, Th 2, Th17, T regulators
58
Th 1
needed for killing intracellular pathogens
activate CTLs and NK cells
59
Th 2
helps kill extracellular pathogens, specifically helminths
activate goblet cells to make mucus
stimulate peristalsis to move helminth out
60
Th 17
induce inflammation
recruit neutrophils (short life to limit inflammation)
strongly linked to autoimmune disease
MS, UC, psorisis have high Th 17
61
T regulators
regulate
dampen or turn down the response after pathogen is gone
out compete other cells for cytokines to weaken response
62
parasitic worm therapy
* use pig pathogen that has a short immune response and no worm colonization
* stimulate Th2 to increase mucus secretion
* worm increase T reg to increase host survival and weaken immune response
* decrease Th 17 to supress immune response
* try to modify the molecule that causes the immune response
63
ulcerative Colitits
* lack finger like projections
* mass amount of neutrophils
* diminish mucus
* not elastic
* bleeds easily - weight loss, bloody and mucus stool
* Imbalance of Th cells
* high Th 17 - high neutrophils
* low Th2 and T reg
* hyperactive neutrophils
* inflammation
* low mucus - immune cells have more access to commendal and can increase inflammation
64
Fecal microbiota transplant
* used to treat C. diff - forms spores and antibiotics kill when metabolically active
* take broad spectrum anitbiotic - lower commensals
* C. diff spores germinate and have more spae and nutrients
* vegetative growth
* gut dyxbiosis - microbiome disruption
* abdominal pain adn GI distress
* Abx kill veg bactaria but leave spores
* FMT may re-establish hemostasis
