Host defense Flashcards
What are the 2 defense systems? Which one is specific?
Innate defense: properties of the normal host, non-specific defenses
Adaptive defenses: induced by the infection, specific to the pathogen (based on antigens)
Name first barriers defenses, from which system are they?
INNATE DEFENSES
- Removal of particles from mouth
- Skin
- Stomach acidity
- Normal flora of intestine
- Flushing of urinary tract
- Lyzosyme
- Mucus, cilia lingin trachea
- Mucus and phagocytes from lung
- Blood and lymph proteins
- Rapid pH change
- Normal flora
How does the mucous membrane from intestinal track defend itself ?
Normal microbiome competes for attachment sites and nutrients. Also secretes BACTERIOCIN
What are defense mecanisms/tools of skin and mucous membranes?
- Normal microbiome
- Antimicrobial substances
- Skin
- Mucous membrane itself
What are the antimicrobial substances secreted by mucous membrane or skin?
Fatty acids
Lysozymes
Antimicrobial peptides (AMPs)
Antibodies (if the host is immune)
How does the mucous membrame participate in host defense?
secrete mucous
mucous will trap bacteria, pathogens
(in case of trachea, cilitated cells remove mucus and trapped bacteria, and dumps it in oesophagus)
What happens if the pathogen overcomes the first line of defense (skin, mucosa)?
It will encounter a second line of defense
What is the second line of defense composed of?
Complement proteins
Phagocytes
Inflammation
What is the complement system?
Set of blood prots- also present in tissues- known as complement because they complement the action of antibodies. Prots: ca-2-3-4-5-6-7-8-9
They will create pores in pathogen membrane and induce lysis
What are the prots that participate more in activation of the complement (innate defense)?
C1-2-3-4
What are the prots that participate more in formation of complex (innate defense)?
C5-6-7-8-9
What are the 2 activation pathwys of complements?
Classical pathway: antibodies
Alternative pathway: Microbial cell wall components (polysaccharides, LPS)
What will activation of complements result in?
formation of a membrane attack complex, that will cause lysis of some GRAM-NEGATIVES
What prots are part of MAC
C5-6-7-8-9
What is MAC?
Membrane attack complex
MAC complex (innate defense system) will cause lysis of Gram____ bacteria
Negative
Because they have outer membrane!
Complements affect membranes!
Will MAC complex cause lysis in all cases?
No, will not affect gram-neg bacteria that have capsule…
What is a test to know if a pathogen is sensitive to complements?
Serum sensitivity test
Exposing pathogens to serum (blood without red blood cells)
If pathogen is killed, it is sensitive
Bone marrow cell can differenciate in _ and _
Myeloid precursor
Lymphoid precursor
Myeloid precursor can differenciate into
Granulocytes
Monocytes
Granulocytes include…
Neutrophils and Mast cells
Monocytes can differenciate into
Dendritic cell
Macrophage
What cell participates mostly in inflammation?
Dendritic cells
What cell can do phagocytosis
Macrophages
Neutrophils
What cell is responsible for allergies?
Mast cells
When B cells are active, they can differenciate in
Plasma cells
Replicate into more B cells
What cells are considered white blood cells?
Monocytes
Granulocytes
Lymphocytes
What are characteristics of monocytes?
- Circulate in the blood stream
- They are attracted to inflamed tirrues
- Differenciate into macrophages in tissues
- PHAGOCYTIC
- They are fixed macrophages in tissues
What are characteristics of granulates?
- Their cytoplasm contains granules
- Include (Eosinophils, basophils) Neutrophils, Mast cells
- Neutrophils are PHAGOCYTES
What is another name for Neutrophils?
POlymorphonuclear leucocytes (PMN’s)
Characteristics of Lymphocytes?
B Cells: antibodies
T cells: T helper cells, cytotoxic T cells
What are the 4 steps of phagocytosis?
- ATTACHMENT of the organism to the membrane of the phagocyte
- INGESTION : the organism become enclosed in a PHAGOSOME
- a) Granules (endosomes, lysosymes) containing HYDROLYTIC ENZYMES fuse with the phagosome, leading to formation of the PHAGOLYSOSOMES
b) Oxidative burst : production of reactive oxygen species (ROS: Super oxides, peroxides, hypochlorides)
4. Killing and digestion of the microorganism.
What are the characteristic signs of inflammation?
Redness
Heat
Swelling
Pain
Redness and heat in inflammation are mainly due to…
enlargement of the blood vessels
Swelling in inflammation is due to…
Passage of fluid (plasma) from blood vessels to the tissues => increased VASCULAR PERMEABILITY (vasodilatation)
Plasma contains antimicrobial prots
What is the function of inflammation?
Allows recruitment of immune cells to the site of infection (vascular permeability) and an increase concentration of molecules (complement subunits and antibodies).
What signaling molecule causes fever?
interleukin-1 (Il-1)
What is a synonym of fever-producing?
pyrogen
What odes Il-1 do?
- It acts on a thermoregulatory center of the brain, which in turn causes the body temperature to increase
- It also activates phagocytes and other cells of the immune system
- Also cause inflammation
What does the innate system include?
- Complements
- Antimicrobial proteins
- Phagocytes (neutrophils, macrophages)
- Inflammation (and fever)
When does adaptive defense will be called up?
When infection is prolonged
On what does adaptive defense rely on?
on the detection and response to FOREIGN ANTIGENS
What are foreign antigens?
molecules of the microorganisms that can be recognized by the immune system
What cells are part of the adaptive immune system?
- B cells
- T cells
- Antigen presenting cells (APCs: macrophages, dendritic cells, which are important for activation of the adaptive defenses)
What are the 3 important features of T and B cells?
Specificity
Memory
Tolerance
Determine specificity of adaptive immune cells
Immune cells recognizes and react with individual molecules (antigens ) via direct molecular interactions
Each cell is specific to ONE antigen
Explain memory of adaptive immune cells
If the immune cells have been exposed to the antigen once, they will grow and dived into more antigen-reactive cells, so that at another exposure, the immune response to a specific antigen will be faster and stronger.
Explain tolerance
Immune cells are not able to react with self antigen. Self reactive cells are destroyed during development of the immune response.
It’s like a sacrifice… cells that recognize host antigen are destroyed.
What are the 2 types of T cells, and what do they do?
T helper cells (Th) : activate B cells and macrophages
Cytotoxic T cells (Tc) : Kill host cells that display foreign antigen on their surface
What does APC stand for?
Antigen presenting cells
What will happen if APCs present an antigen to a T cell?
If the T cell is specific for this antigen, the T cell will become activated and produce interleukin 2 (Il-2), which is an autocrine molecule. This will induce multiplication and differenciation into effector T cells and memory T cells
What does MHC stands for?
Major histocompatibility complex
It is an antigen-presenting molecular complex.
How many MHCs?
2 , MHC1 and MHC2
What are the differences between MHC 1 and 2?
MHC-1: expressed by all cells, present antigen that comes form inside the cell (important during infection by viruses/intracellular pathogens) REcognized by Tc.
MHC-2: expressed by APCs and B cells, present antigens processed in the phagolysosomes (from microorganisms that were phagocytosed). Recognized by Th
What MHC is recognized by Tc? By Th?
MHC1 ==> Tc
MHC2 ==> Th
What cells have MHC2?
only professional APCs (Macrophages, dendritic cells, B cells )
What does Tc do?
- Will kill cells that display foreign antigen on MHC-1 that are specific for the entigen of Tc cell.
Tc cell will release PERFORINS and GRANZYMES (granules) that will the cell
How is a macrophage activated?
Once a Th cell is activated, it can activate a macrophage that presents antigens for which the T cell is specific.
It will produce TNF-alpha (activating molecule…)
The macrophage will be activated and have increased phagocytic activity and produce much higher leels of hydrolytic enzymes. Often reffered to as “angry killer cells”
How is Activation of a macrophage by Th cell so important?
It has an important role agains bacterila pathogens, especially against intracellular pathogens of macrophages.
Macrophages can be infected with bacteria that will grow inside the macrophage.
By getting activated by TNF-alpha, the macrophage can actually be strong enough to kill the bacteria that has infected it.
What is particular about B cells?
They carry antibodies
What are the 2 parts of antibodies
Fab= variabe Fc= constant
What part of antibody will bind to receptor of macrophages? What else can this part do?
The Fc (constant) part. It can also activate complements (classical pathway)
Explain what B cells do, how they are activated.
B cells can pick up stuff. They are phagocytic-> they will display antibodies at their surface. It acts as a receptor to pick up the foreign antigen it recognizes. This antigen will be processed and displayed on its surface by MHC 2.
A pre-activated T cell specific for the antigen recognizes this complex (MHC 2 antigen), and activates the B cell by secreting Il-4.
The cells was previously activated by APC.
The B cell multiplies and differenciates into plasma cells (produce the antibody) and memory cells (waiting for the next exposure to antigen).
What are the functions of antibodies?
They function as osponins = flag on specific bacterias that will tell macrophage to phagocytose it.
Antibody will bind to bacteria and help complement bind and do its job.
Antibodies will bind to TOXINS, which prevents binding of toxin to host cells
Antibodies will bind to ADHESINS, which prevents adhesion of microorganism to host cells.
What is the role of memory cells?
They ensure that the immune response, following a second exposure to the same antigen, is faster and stronger
What are the 2 types of acquired immunity?
Active immunity: involves the production of memory cells in response to antigenic stimulus
Passive immunity: involves the acquisition of preformed antibodies
What are the 2 types of active immunity?
Natural: following and infection
Artificial: Vaccination (live, attenuated, dead agens or subunit: adhesins, capsular polysaccharide, toxoids)
What are the 2 passive immunity?
Natural: Placental transfer or COLUSTRUM
Artificial: serum from an immune animal (ex: clostridium botulinum)
What is natural immunity?
It is also called species resistance. The fact that humans are naturally resistant to many infectious diseases of lower animals and vice versa.
ex: Actinobacillus pleuropneumoniae causes pleuropneumonia in pigs but does not cause disease in humans
Salmonella typhi causes typhoid only in humans
What can explain natural immunity?
Can be explained by the absence of presence of the appropriate receptors in the animal for the adhesins expressed by the pathogens.
