Lecture 26 Innate Immunity Flashcards
Immune system
name used to describe the tissues, cells, and molecules involved in adaptive immunity or sometimes the totality of host defense mechanisms.
Where do all cellular elements of the blood and immune system arise from?
- Pluripotent stem cells in the bone marrow
Lymphatic system
- move pathogens throughout the body wherever they may be encountered into the lymph nodes where specific adaptive immune responses take place
Peyers pathches
- small intestine
- main factory for amounting immune response for pathogens we might ingest
Spleen
-recycles blood cells
jenner
- Father of immunology
- Cow pox individuals immune to small pox
- inoculated boy with cow pox pus (1st vaccination)
When did small pox get eradicate?
15-20 years post vaccination
Categories of disease-causing microorganisms
- Viruses
- Bacteria
- Pathogenic fungi
- Parasites
Do disease come from DNA or RNA?
Both DNA/ RNA based virus genome
Small pox, herpes, chicken pox
DNA based
Red measles (rubeola) german measles (rubella)
RNA based
Would you treat smallpox and measles the same?
No because they have different bases
Where do shingles come from?
Reactivated chicken pox
What do the early phase of the immune response depend on ?
innate immunity
innate immunity
variety of innate resistance mechanisms recognize and respond to the presence of a pathogen
What type of receptors do innate immunity utilize?
- invariant (non specific)
Features of innate immunity
- Present in all individuals at all times
- Does not increase with repeated exposure to a given pathogen
- Discriminates between a group of related pathogens
Adaptive immune response
-response of antigen-specific lymphocytes to antigen, including the development of immunological memory
How are adaptive immune responses generated?
- by clonal selection of lymphocytes
How are adaptive immune responses distinct from innate and nonadaptive phases of immunity?
- clonal selection of antigen specific lymphocytes
What are adaptive immune responses also know as?
- Acquired immune responses
Immunologic memory of adaptive respnse
- confers lifelong protective immunity to reinfection by the same pathogen
What immune system would respond in the first few hours?
- innate immune system
- non specific broad response that removes infectious agent
What response would be from 4-96 hours?
- early induced innate response.
Early induced innate responde
- recognition of microbial-associated molecular patterns
- inflammation recruitment and activation of effector cells
- removal of infectious agent
what response would occur after 96 hours?
Adaptive immune response
Adaptive immune response
- Transport of antigen to lymphoid organs
- Recognition by naive B and T cells
- Clonal expansion and differentiation to effector cells
- Removal of infectious agents
(takes time to transport antigen to lymphoid and expand)
Major cells of the innate immunity
- Macrophage
- Granulocytes (basophil, neutrophil, eosinophil, monocyte)
- mast cells
- Dendritic cells
- Natural killer cells
Adaptive immunity cells
- B cell
- T cell
- NK cell
- mature Dendritic cells
Macrophage
- Phagocytosis and activation of bactericidal mechanisms
- Present in almost all tissues
- most mature form of monocytes
- general scavenger
- orchestrate immune response and induce inflammation
- secrete signaling proteins that activate other immune cells
- number of receptors
Macrohage receptors
- binding of any one of receptors will activate macrophage to phagocytose
- mannose, LPS, TLR-4, Scavenger, TLR-2 receptors
neutrophils
- Most numerous of the phagocytic cells
- most important in innate immune response
- Polymorphinucleus
Eosinophils
- killing of antibody-coated parasites
Basophils
- parasites
- unknown function
Mast cells
- contain histamine and other active agents
- Fluid/swelling @ site of infection
Dendritic cells
- Antigen uptake in peripheral sites
- Antigen presentation
- Transport cells through the lymph system
Natural killer cells
- non specific
- lytic granules that kill pathogens
How does infection triggers an immune response?
- Bacteria trigger macrophages to release cytokines and chemokines
- Vasodilation and increased vascular permeability cause redness, heat, and swelling
- Inflammatory cells migrate into tissue, releasing inflammatory mediators that cause pain
How do dendritic cells initiate adaptive immune responses?
- immature dendritic cells reside in peripheral tissues
- Dendritic cells uptake macrosome
- Dendritic cells transport via lymphatic vessels to lymph nodes
- Mature dendritic cells activate naive T cells in lymphoid organs such as lymph nodes
Infection
- infectious agents must overcome innate host defenses in order to establish an infection
- infectious disease is generally quite infrequent
- The epithelial surfaces (physical barrier) form the first barrier against most microorganisms and have rapid repair mechanisms if injured
Routes of infection for pathogens
- Airway (inhaled droplet or spore)
- Gastrointestinal tract ( contaminated water or food)
- Reproductive tract (physical contact)
Coronavirus (COVID19)
- liquid droplets in air
- can exist on surface for several days
How does the coronavirus get into cells?
- binds to human ACE2
Innate immune system with covid
- induces inflammatory response and fluid accumulation in the lungs
External routes of infection for pathogens
- External surface (physical contact)
- Wounds and abrasions (cuts/punctures/ infected animals)
- Insect bites (lyme disease/ticks)
Physical barriers and mechanisms as first line of defense against infection
- Mechanical
- Chemical
- Microbiological
Bactericidal agents produced/released by phagocytes
- Acidification (PH around 3.5 -4.0)
- Toxic oxygen -derived products (oxygen radicals)
- Toxic nitrogen oxides
- Antimicrobial peptides ( defensins and cationic proteins)
- Enzymes (lysozyme) & acid hydrolases
- Competitors
Gut mucosa barrier
- rich in antimicrobial activity
Goblet cells
- produce gel forming muscin (epithelial layer)
- glycoproteins released
Paneth cells
- produce antimicrobial peptides, lectins, and cytokines
inner mucus layer
- relatively sterile
- rich in antimicrobial molecules
- thicker
Outer mucus layer
- non-sterline
- bacterial pathogens can penetrate outer layer
- degrading mucus
- microbes utilize mucin carbohydrates for energy
Large intestine
- outer loose mucus layer (bacterial habitat)
- inner layer (intact dense mucus layer helps fight bacteria in GI tract) firmly attached
small intestine
-loose mucus layer (not dense)
complement
- can be activated early in infection in the absence of antibodies
- complement first evolved as part of the innate immune system, where it plays an important role in coating pathogens and facilitating their destruction
