5. Immunity and Host Defense Flashcards
What is the immune system
fights off foreign material that threatens the body
- protects against disease
2 Branches of immune system- specificity, memory, respond rate
- Innate
- born with it
- non-specific
- no memory component
- responds rapidly - Adaptive
- highly specific
- memory component
- responds in a few days
Can you use both branches of the immune system at the same time
yes! not mutually exclusive
Innate immune system
- protects humans from most infectious diseases
- exists at birth and always present
- natural host resistance (microbiota)
- no memory
- can be specific for a particular tissue
- physical barrier, chemical defenses, cellular defenses, molecular defenses, physiological processes
Innate: Infection site and tissue specificity
pathogens prefer a specific body site to initiate infection
- based on nutritional and metabolic needs
- mechanism of spread (aerosols vs blood/bodily fluids)
Ex of bacteria that can be ingested into deep wounds
Clostridium tetani
Innate: natural host resistance and examples
- illness from pathogens varies from one species to another
- anthrax - causes fatal blood infection in cattle and cutaneous infection in humans
- HIV - infect human cells but not mice or guinea pig
Physical barriers to infection
- Skin
- Mucous membranes
Skin
- prevents invasion by microbes
-has protein (keratin) that is thick - slightly acidic (5)
- high NaCl - for drying
What can grow on skin surface
- Some fungal infections can grow right on the skins surface (but needs broken skin to cause infection)
Mucous membranes
- line tracts in the body - resp, digestive, reproductive, urinary
- mucus produced by goblet cells - traps microbes to prevent infection
- contains microbial secretions
Mucous membranes in resp tract
- contains the mucocilliary escalator
- mucosal epithelial cells contain cilia - serve to filter incoming air
- sweeping action of cilia allows the removal of mucous and trapped microbes from the lungs
Mucous membranes in gastrointestinal tract
- stomach
- acidic (pH = 2)
- proteases - small intestine
- pancreatic juice buffers acidity of incoming contents from stomach (pH of 7) and containes enzymes
- bile from liver - large intestine
- normal microbiota
- normal resident that live symbiotically inside of the colon
- use attachment sites to stay inside colon
- competitive exclusion - consume undigested nutrients
- microbial antagonism - produce antimicrobial compounds
Mucous membranes in genitourinary tract
- contains urine - toxins that are intolerable by bacteria
- act of urinating removes these contamianting microbes
female urinary tract
- contains normal microbiota
- glycogen secreted by vagina epithelial cells supplies nutrients for microbial growth
Ex of bacteria found in female urinary tract
lactobacillus acidophilus
- ferments glucose to lactic acid
- pH of 4.5
Lymphatic system
- Composed of organs and vessels that allow immune cells to contact foreign antigenic material
Antigen
foreign material that is able to activate cells of the immune system
Components of the lymphatic system
- lymphatic vessels
- Carry lymph from the tissues to the lymph nodes (unidirectional - away from tissues)
- Lymph is rich in leukocytes (wbc) and no erythrocytes (rbc) - Lymphoid organs
- primary and secondary
Primary lymphoid organs
- Bone marrow - where leukocytes are produced
- thymus gland - some leukocytes mature here
Secondary lymphoid organs
- lymph nodes
- spleen
- MALTS (mucosa associated lymphatic tissue - mucus membrane
**These all contain high concentration of leukocytes and incoming lymph is filtered (removing microbes)
MALT and GALT
mucosa associated lymphatic tissue
gut associated lymphatic tissue - leukocytes present here are constantly phagocytosing material in their surroundings in search of foreign content
Cellular defenses: leukocytes - location
- circulate in the blood and lymphatic system
- reside in the tissues and lymph nodes
- play a role in both innate and adaptive immunity
granulocytes - type of, what it looks like, func
- category of leukocytes
- large visible granules in the cytoplasm
- granules are reactive
2 functions:
-kill microbes
-signalling molecule for other components of the immune system
types of granulocytes
- neutrophils
- eosinophils
- basophils and mast cells
Neutrophils - function, location, stain, granules contain
- strongly phagocytic
- cytoplasmic granules contain lysozyme and defensins
- circulate in blood (exit the capillaries during periods of infection
- stain: no basic + acidic dyes
Eosinophils - function, location, stain
- non-phagocytic
- cytoplasmic granules will stain with acidic dyes
- work to destroy large parasitic cells like protozoa and parasitic worms
- secrete-extra-cellular enzymes and reactive oxygen species
- can also exit the capillaries into infected tissues
Basophils and Mast Cells - function, location, stain
- not strongly phagocytic
- cytoplasmic granules stain with basic dyes
- basophils circulate in blood
- mast cells reside in mucosal tissue
- degranulate in response to stimuli and releases histamine
what happens when histamine is released systemically and which cells do this?
causes life threatening vasodilation and bronchioconstriction
basophils and mast cells:
- important part of the allergic response
- causes vasodilation locally
agranulocytes (2nd category of leukocytes)
- contain cytoplasmic granules that are much smaller and difficult to view than granulocytes
types of agranulocytes
- monocytes
- lymphocytes
monocytes - location and function
- circulate in blood
- once in the tissues they are strongly phagocytic
- present foreign antigen to other cells of immune system
types of monocytes
- macrophages
- dendritic cells
only turn into these when they migrate into tissues and mature
macrophages
location:
- tissues
- lungs, connective tissue, spleen and liver
function:
- contain surface TLR (toll-like-receptors): recognize many pathogens like LPS, peptidoglycan, elements of the fungal cell wall
- induces phagocytosis
dendritic cells - location and function
Location:
- tissues that are often sites of entry for infectious material
- mucus membranes of the nose, lungs and intestines
Function:
- regularly sample the surroundings and phagocytose antigens
- phagocytosed antigen is carried to lymphoid organs
- presented to other cells of immune system (T/B Lymphocytes)
- activate the adaptive immune response
name of dendritic cells in skin
langerhans cell
lymphocyte
- leukocytes that are involved in the adaptive immune response
- circulate through the blood and remain in lymphoid organs
types of lymphocytes
- b-lympho
- t-lympho
- NK (natural killer)
B lymphocytes
- also called B cells or plasma cells
- antibody producing/secreting cells
- form the main component of humoral immunity
T lymphocytes
- aka T cells
- different types
- form the main component of cell mediated immunity
Natural killer cells
destroy abnormal cells in the body ( cancer and infections)
Molecular defenses
- secreted at mucosal sites:
1. lysozyme (breaks the beta 1-4 linkage)
2. defensins (puncture holes in the cell membrane
Phagocytosis
- destroy pathogens that may have never before been encountered in the body
- involves leukocytes capable of phagocytosisst
Steps in phagocytosis (innate)
- neutrophils and macrophages recognize PAMPS
(pathogen associated molecular patterns)
-LPS, lipotechoic acid, flagellin - PAMPS are recognized by TLRs located on the surface of phagocytic cells
- TLRs are also called pattern recognition receptors
- interaction of PAMP with a TLR triggers phagocytosis - Phagocyte engulf and destroy invading microbes
- cell membrane invaginates around a foreign particle
- engulfs it into a phagosome
- phagosome fuses with a lysosome to form a phagolysosome (oxygen-independent)
OR
- Activated phagocytes produce reactive oxygen compounds
- kill ingested microbes by oxidizing cell components (oxygen dependent killing)
What is phagolysozome filled with
lysozyme and defensins
proteases - degrades protein
lipases - degrade phospholipids
nuclease - degrade nucleicacids
What happens when invaders have been killed in phagocytosis (innate immune)
- neutrophils form exocytosis - fragments are expelled from the cell
- macrophages and dendritic cells become antigen presenting cells
- fragments of the intruder are presented on the cell surface to trigger an adaptive immune response
inflammation
occurs non-specifically in response to tissue damage, toxins and infectious material
5 cardinal signs of inflammation
redness, warmth, pain, swelling and loss of function
responses to infection injured tissue and leukocytes
- leukocyties release pro-inflammatory cytokines
- blood vessels dilate
- allows more leukocytes to access the area - vessel walls become more permeable
- leukocytes can squeeze into tissues (extravasation)
- attack invading pathogens - temperature increase may slow down the growth of pathogens
- promotes healing of damage tissue as well - blood leaking into tissues spaces can clot
- prevents movement of pathogens
Fever
Increase in body temp
- controlled by the hypothalamus
- triggered by toxins, LPS and chemicals produced by immune system
- all of these things reset the bodies thermostats
Results of a fever
- muscle contraction - shivering
- increased temp
- faster metabolism
- faster phagocytosis
- faster healing
- slower growth of microbes (growth slows at 40 degrees)
defense:
- against disease
- over 40 degrees
Definition of adaptive immune system: acquired
- begins as soon as a pathogen is acquired for the first time
- adaptive response will not occur until a pathogen is encountered
Definition of adaptive immune system: very specific
- very targetted to a specific feature of a given bacterium, virus or toxin
- immunity to one pathogen will not confer immunity to another
Definition of adaptive immune system: memory component
- produces a more effective response when a pathogen is encountered for the second time - faster and stronger
the 2 components of adaptive immune system
- humoral immunity - antibody mediated: b and plasma cells
- cell mediated immunity: b and t cells
antibodies
proteins produced by the immune system that bind and inactivate foreign antigens
immunogens
- any foreign material that has the ability to active the adaptive immune system
- normal protein, polysach, lipid material
are immunogens and antigens the same thing
for this course yes
epitomes
actual portion of the antigen that binds to the antibody
a single antigen will have more than one epitome
- increases the ability of an antigen to activate the immune system (immunogenicity)
- each epitome requires a distinct antibody
hapten
- low molecular weight compound that is too small on its own to activate adaptive immunity
- not immunogenic
- can bind to other molecules such as protein in blood and tissuess
- becomes strongly immunogenic
Example of haptens
penicillin!
What are antibodies (Ab) made of
glycosylated protein molecules (aka immunoglobins - lg)
4 subunits
- 2 identical heavy chains
- 2 idnetical light chains
Chains are assembled into 3 distinct regions
- 2 identical variable regions (FAB) - provide specificity of the antibody
- 1 constant region (FC) - interaction with immune cells - based on differences in the FC region
5 types of antibodies
- immunoglobin G (igG)
2 immunoglobin A (igA) - immunoglobin M (igM)
- immunoglobin E (igE)
- immunoglobin D (igD)
Immuniglobin M (igM)
Pentameric
- 5 different units
Always the first antibody to be produced in response to antigen - primary antibody response
Found on surface of B-lymph
- remains in blood and unable to enter tissue
- Low affinity for antigen
- good for agglutination (cross linking)
immunoglobulin G
- monomer
- predominant antibody in blood
- presented in tissues
- binds strongly
immunoglobulin A
Dimeric
• Secreted at mucosal sites
• Saliva, tears, mucous
• Important defense against respiratory,
reproductive, digestive tract infections
Immunoglobulin D (IgD):
Monomer
• Located on the surface of B cells
• Important in activation of B cells to begin
producing antibody against a specific antigen
Immunoglobulin E (IgE):
Monomer
• Binds to receptors located on the surface of
mast cells and basophils
• Binding of IgE-antigen complex triggers
degranulation and histamine release
• Allergy
igE
Five major antibody function
- neutralization
- opsonization
- agglutination
- anitbody mediated cytotoxicity
- complement activation
neutralization
- neutralizing the toxin
- antibodies bind to antigen blocking attachment sites
- prevents bacteria, virus and toxin entry into tissue and host cells
opsonization
- antibodies coat the surface of the bacterial cells
- attracts phagocytes
- greatly enhances the rate of phagocytosis
- phagocyte has the ability to interact with the fc region of the antibody
agglutination
- aka crosslinking
- each class of antibody can bind to a minimum of 2 identical antigen units
- clumps together many antigens
- allows phagocytosis to occur more efficiently
antibody mediated cytotoxicity
attachment of antibody to parasites recruits eosinophils
- eosinphils attach to the fc component of antibodies
- activated eosinophil releases reactive oxygen species and hydrolytic enzymes
- parasite is destroyed
complement activation
- a system consisting of a series of proteins found in the blood
- activated by antibody that is bound to a bacterial cell (classical pathway of complement activation)
- create a number of different immune responses when activated
- membrane attack complex (MAC) forms - inserts into the membrane of bacterial cell forming a pore
- contents of the cell leak and the bacterium dies
extra pics of complement activation
activation of antibody mediated immunity
- b cells are antigen presenting cells
- macrophages and dendritic cells also perform antigen presentation
- all antigen presenting cells can insert MHC II (major histo complex) into the plasma membrane
Antibodies are produced against ________
antibodies are produced against exogenous antigen
- antigen that exists outside of the cell in the surrounding extra-cellular fluid
- can be bacteria, virus, parasite, toxin
- once antibodies are secreted from B cells they can bind to and neutralize/opsonize these exogenous antigens
Steps in antibody production
- B cell phagocytoses exogenous antigen
- T helper cells bind to MHC II-Antigen complex resulting in T helper cell activation
- Some of these newly produced B cells will become plasma cells
Step 1 of antibody production in detail
B cell phagocytoses exogenous antigen
- digested content in the phagolysosome will not be exocytosed to the extracellular fluid
- instead it will be complexed together with MHC II (presented on surface) and inserted into the plasma membrane
Step 2 of antibody production in detail
T-helper cells bind to MHC II-Antigen complex resulting in T helper cell activation
- the activated T helper cell releases cytokines that bind to receptors on the B-cell resulting in B-cell proliferation (aka making more of B-cell)
Step 3 of antibody production in detail
Cells turn into either
1. B cells to plasma cells
- Actively transcribe, translate and secrete an identical antibody protein to the extra-cellular fluid (specific to exogenous antigen
2. B cells to memory cells
- Used in encounters with the same antigen
- not produce antibodies during current response
Primary antibody response
- OCCURS: the very first time a specific antigen is encountered - (can be natural encounter or an artificial encounter like a vaxx)
- PRODUCES: a weak antibody mediated response - slow production of low levels of antibody
- RESULTS: memory B cells
Secondary antibody response
- OCCURS: every additional time after the primary response when it sees a specific antigen
- PRODUCES: strong antibody mediated response - rapid production of antibodys - so rapid that the pathogen wont establish infection - no disease
explain this pic
Tolerance
- prevents immune responses against self-antigens
- any immune cells that are found to recognize self-antigens are destroyed early on in development
- helps prevent auto-immune disease (when the body turns on itself
Cell mediated immunity
- recognizes and destroys abnormal cells present in the body
- cells infected with the virus/obligate intracellular bacteria
- endogenous antigen - INSIDE HOST CELL
what cells do cell mediated immunity involve
cytotoxic T cells
How does cell mediated immunity work
- the diseased host cell will display the endogenous antigen in the plasma membrane complexed together with MHC I
- Cytotoxic T cells will bind to MHC I-antigen complex using their T cell receptor (TCR)
- This activates the cytotoxic T cell triggering it to release enzymes that cause death of the infected host cell
what enzymes do cytotoxic T cells release
perforins and granzymes
In order to clear a viral infection …
you need both antibody mediated immunity and cell mediated immunity
cytotoxic t cells bind to
CD8+
MHC 2 cells bind to
MHC 1 cells bind to
2 - all nucleated cells
1 - antigen presenting cells
