Host defenses Flashcards
What is innate defences
properties of the normal host, non-specific defenses
What is adaptive defenses
Induced by the infection, specific to the pathogen (based on antogen)
First barrier to the pathogen is
Innate defenses
some innate defenses of our organism
- Removal of particles
- Skin
- Lysozyme ( tears and other secretions)
- Mucus and cilia lining trachea
- Blood and lymph
- Flushing urinary tract
What does innate defenses of skin and mucous membrane
Normal microbiome
Antimicrobial substances
Skin
Mucous
describe how normal microbiome in the gut acts as an innate defense
Competes for attachment sites and nutrients, secretes bacteriocin (a toxic protein secreted by
bacteria that inhibits or kills other, related
bacteria)
describe how antimicrobial substances on the skin acts as an innate defense
Fatty acids
Lysozymes
Antimicrobial peptides(AMPs)
antibodies ( if the host is immune)
How do AMPs work
Make pores in the bacterial membrane
How does skin and mucous membrane protects the host
Skin: thick layer of dead cells
Mucous membrane: mucus
Describe the innate defenses of the airways
Mucous membrane; mucus traps bacteria; ciliated cells remove mucus and trapped bacteria
What is the second line of defenses
- Complement system
- Phagocytes
- Inflammation
What is a complement system
Set of proteins that creates pores in the pathogen membrane and induces lysis
What are phagocytes
Cells that take up and digest pathogens
What is an inflammation
General nonspecific response of the innate system to toxins, pathogens and tissue damage
Why complement system is called like that
They complement the action of antibodies
Proteins of complement system
C1-C9
Two activation pathways of complement systems
- Activation by he classical pathway :antibodies
- Activation by the alternative pathway: microbial cell wall components (polysaccharide, lipopolysaccharide)
Activation of the complement results in the formation of
A membrane attack complex (MAC) that causes lysis of some Gram-negative, no effect on Gram-positive
MAC complex. What doe sit consist of and how it is formed
C5bC6789
C5b C6 and C7 come together and bind to the membrane. C8 binds to the complex and inserts into the cell membrane. Then C9 ( mutiple) comes and polymers around the complex, creating a pore-> lysis
How do you test if the pathogen can be destroyed by the complement system
Test by exposing pathogens to serum (blood without RBC)
What is the pathway of differentiation of the steam cell
Hematopoietic stem cell will develop into Myelold precursor and Lymphoid precursor
What happens after myelold precursor cells
Manocyte->dendritic cell or macrophage
Granulocytes->Neutrophill or Mast cell
What happens after Lymphoid precursor
Maturation in bone marrow-> B -cells->plasma cells
or from lymphoid to natural killer cells and T cells
What cells are in innate immunity
Dendritic cell, macrophage, neutrophile and mast cell
Natural killer cells
which cells are in adaptive immunity
T cell
Plasma cell
4 major cell types found in normal human blood
RBCs Lymphocytes (WBCs) which include: Neutrophil Monocyte Leukocytes
What are monocytes
Circulate in the blood stream, differentiate into macrophages ( and dendritic cells) in tissues, attracted to inflamed tissues, phagocytic. Macrophages are present in all tissues and take on different forms in different tissues
Granulocytes include what cells in itself
Eosinophils
Basophils
Neutrophils
Mast cells
Neurtophiles are ___, their property and the other name
They are the most abundant, phagocytic, often called polymorphonuclear leucocytes (PMNs)
Lymphocytes include in itself
B cells: antibodies
T cells: T helper cells, cytotoxic T cells
Granulocytes have____
bleach and other antimicrobial agents that are phagocytic
What are the most abundant WBCs
Neutrophiles
WBCs circulate around in
The blood and in the lymph
Lymph nodes have
Phagocytes and lymphocytes
Phagocytosis is primarily carried by
Netrophiles and macrophages
Explain the process of phagocytosis
- Attachment of the organism to the membrane of the phagocyte
- Ingestion: the organism become enclosed in a phagosome
- A) granules (endosomes, lysosomes) containing hydrolytic enzymes fuse with the phagosome, formation of the phagolysosomes
B) Oxidative burst: production of reactive oxygen species - Killing and digestion of the microorganism
Explain how generation of toxic reactive oxygen species happen
Oxidative burst: rapid increase in uptake of O2-> produces ROS (O2, H2O2, OH,OCl-)
What are important enzymes for oxidative burst
- Myeloperoxidase
- NADPH oxidase
- V-type ATPases (Pumps H+ in)
What is inflammation
A non-specific response to tissue damage or the presence or of microorganisms
Characteristics signs of inflammation
Redness, heat, swelling and pain
Why there is redness and heat during inflammation
Redness and heat are due to vasodilatation- enlargement of the blood vessels
Why there is swelling during inflammation
Swelling is due to the passage of fluid (plasma) from blood vessels to the tissues from increased vascular permeability (vasodilatation). Plasma contains antimicrobial proteins
What is the function of inflammation
It allows the recruitment of immune cells to the site of infection (vascular permeability) and an increase concentration of molecules (complement subunits and antibodies)
What role complement system plays in vasodilatation
C3a causes the release of histamine by mast cells-> acts to increase permeability of blood vessels
C5a attracts phagocytes to infected tissues
What is a diapedesis
Passage of white blood cells through the intact walls of the capillaries
What is the role of interleukin-1 in inflammation
There is an increase movement of fluid and immune cells to the infection sites. Il-1 activate cells of the immune system ( increase phagocytosis)
Il-1 acts on the thermoregulatory center of the brain , which in turn causes the body temperature to increase
What is the response to the presence of endotoxins (LPS)
Macrophages can sense endotoxins-> induce production of fever-producing (pyrogen) signaling molecules: the cytokine Interleukin-1.
What temperature is usually for the inflammation response and what of higher (precaution)
Temperature higher that 37C reduce the growth of some pathogens
Death if temperature reaches 44C
The innate defenses have
- Complement
- Antimicrobial proteins
- Phagocytes (neutrophils, macrophage)
- Inflammation (and fever)
What is happens first to the infection and what is happening after
During infection, the adaptive defenses are being primed. If the infection is prolonged, adaptive immunity will be called upon to help in the fight against the invading microorganisms
What are antigens
Molecules of the microorganisms that can be recognized by the immune system
Adaptive defenses rely on
The detection and response to foreign antigens
Cells of the adaptive immune system
B cells, T cells and antigen presenting cells (APCs: macrophages, dendritic cells; important for activation of the adaptive defense)
In Population of T cells and B cells each cell is specific for
One antigen
What will happen to T cells and B cells that were activated by the antigen
Produce copies of themselves. If activated by X antigen, then cells that are specific for it, will multiply
How antigen specificity is generated in T cells and B cells
Randomly during the development
T cells and B cells that recognize host antigen are
Destroyed
Two types of T cells
T helper cells : activate B cells and macrophages
Cytotoxic T cells: kill host cells that display foreign antigen on their surfaces
Who present antigen to T cells
APCs- macrophages, dendritic cells
WHat will happen after presenting an antigen to T cell
the T cell will become activated and produce interleukin 2 (Il-2). This induces multiplication and differentiation into effector T cells and memory T cells
Explain MHC I complex antigen presentation
If there is a foreign protein in the cytoplasm ( due to the viral infection or cancer cells), the goal is to present this protein to the surface of the cell.
Proteasome break peptide bonds in the protein. Through TAP the wrong protein gets to ER. in ER with MHCI, chaperonin and other proteins, the shady protein is carried outside of the cell for presenting
What cells have MHC I complex
All cells with nucleus, except RBCs
The difference between MHC I and MHC II
MHC I -infected target cells . Thee antigen was not present outside. It is taken from inside to outside for presentation
MHCII happens in APCs. Through the endocytosis the foreign substance is presented
MHC I recognized by Tc
MHC II recognized by Th
Explain how MHC II presentation happens
The foreign protein was taken in by endocytosis, bound to MHC II on ER. After that it was moved to phagolysosome, where it would be digested and parts of the antigen protein would be presented on the surface of the antigen presenting cell
What is MHC
The major histocompatibility complex
What cells MHC II
APCs: macrophages, Dendritic cells, B cells
What happens after MHC 1 presents an antigen
Tc releases perforins and granzymes that kill the cell through apoptosis
MHC I system and Tc are helpful against
Infection by viruses /intracellular pathogens
What happens after Th are activated by MHC II
Th cell can help activate macrophages (TNF-alpha) that are presenting antigens for which the T cell is specific.
Activated macrophages have increased phagocytic activity and produce much higher levels of hydrolytic enzymes. Often referred to as “angry killer cells”
MHCII and T helper cells are very important against
Bacterial pathogens (especially against intracellular pathogens of macrophages)
Explain the pathway from bone marrow to antibody (b cells)
Bone marrow stem cell-> B cells with different antibodies
When a specific antigen binds to antibodies, the activated B cells multiplies and differentiate into plasma B cells and memory cells
Plasma b cells-> produce antibodies
How the activation of B cells happen
The B cell displays its antibody on its surface. Acts as a receptor to pick the foreign antigen it recognizes, This antigen will be processes and displayed on its surface by MHC II
A pre-activated T cell specific for the antigen recognizes this complex (MHCII-antigen) and activates the B cell (Il-4). The T cell was previously activates by APC
The B cell multiplies and differentiates into plasma cells (produce the antibody) and memory cells (waiting for the next exposure to the antigen)
What is an antibody
Group of related proteins-immunoglobulins
Have two sites: antigen binding sites (Fab) -highly variable
AND
Constant region (Fc) binds to receptor on macrophages and activates complement (classical pathway)
Types of antibodies
IgA
IgG
IgM
IgE
IgG: where does it circulate and characteristics
Major circulating antibody, most abundant. Found in lymph, blood and extracellular fluid
IgM: characteristics, where found, what causes
First antibody to appear. Found in blood and lymph only. Causes aggregation of antigens and helps in early complement activation
IgA: where it is found, what does it do
Secretory antibody, found in extracellular body fluids and in mucus. Main mediators of mucosal immunity
IgE: function, characteristics
Least abundant, main function os immunity to parasites. Essential role in hypersensitivity and various allergies (food allergy)
Function of antobodies
Function as opsonins, which increase phagocytosis efficiency.
Bind to toxins , which prevents binding of toxin to host cells
Bind to adhesins, which prevents of microorganism to host cel
The role of memory cells
They ensure the immune response, following a second exposure to the same antigen, is faster and stronger
Antibodies produced during primary and secondary responses
Initial contact at day 0 initiates a primary immune response
After several days, IgM antibody is produced at detectable but low titers.
In the absence of antigen , the titer decreases with time
Another contact with the same antigen -> secondary immune response.
Antibody class switches rapidly to IgG, produced in high amounts
What is active immunity
Involves the production of memory cells in response to antogenic stimulus
Two types of active immunity
- Natural:following infection
- Artifical: vaccination (live, attenuated, dead agents or subunit: adhesins, capsular polysaccharide toxoids)
What is passive immunity
Involves the acquisition of preformed antibodies
Two types of passive immunity
- Natural: placentral transfer or colostrum (first form of milk)
- Artificial: serum from an immune animal
Why do we do vaccination
Activation of B cells might take few days, vaccination -> immediate response
What is natural immunity and its examples in animals and humans
Humans are naturally resistant to many infectious diseases of lower animals and vice versa:
Actinobacillus pleuropneumoniae causes pleuropneumoniae in pigs but does not cause diseases in humans
Salmonella typhi causes typhoid only in humans
How natural immunity can be explained
In part by the absence or presence of the appropriate receptors in the animal for the adhesins expressed by the pathogen (same rationale for toxins and other virulence factors)
