Host Defense and the Immune Response Flashcards
What are the three levels of hierarchy of host defense?
Barriers (skin, membranes)
Cells & chemicals / cytokines
Specific defenses
What is immunity?
Immunity comprises all mechanisms by which the body protects itself against foreign agents.
How many arms of the immune system are there?
Two
What are the two arms of the immune system?
Innate immunity
Acquired (adaptive) immunity
What is innate immunity?
This is the immunity that you are born with
It is fast acting
It is made up of barriers, cells, and serum proteins
What is acquired (adaptive) immunity comprised of?
This immunity imroves with time
Slower acting
Cell-mediated (B cells and T cells)
What does the big picture of host immune response look like?
1) Infection - Pathogen evades barriers
2) Innate response
a) Neutrophils & Macrophages
- Toll-like receptors recognize microbes (LPS, teichoic acid, etc)
- Imflammatory cytokines / Compliment activation or Mannose-binding lectin
b) Inflammation
c) Antigen processing by antigen presenting cells, dendritic cells, and macrophages
3) Antigen presenting cells are the bridge between innate and adaptive responses
4) Specific adaptive responses
a) Th cells
- Th1 (Cytotoxic & inflammation) and Th2 (humoral)
b) Cytotoxicity and / or antibodies
What is the first hierarchy of defense?
Barriers
Skin and mucous membranes
What is the 2nd hierarchy of defense?
Non-specific cells and the chemicals / proteins that they produce.
What are specific features of the 2nd line of defense?
Phagocytosis
Complement activation
Inflammation
Fever
NK cells
What does phagocytosis mean?
This is engulfing and destroying infected / damaged cells.
Performed by Neutrophils and monocytes / macrophages
What does compliment activation lead to?
Infected cell lysis, inflammation and opsonization
What does inflammation lead to?
Heat (Calor)
Pain (Dolor)
Redness (Rubor)
Fever (Tumor)
Caused by natural killer (NK) cells
What steps must occur in order for a phagocyet to operate?
1) Chemotaxis
2) Recognition of pathogen / infected cell
3) Ingestion
4) Digestion
Image of phagocytosis.
What is complement?
Complement is the major effector of humoral immunity
Made up of 30 different proteins
When activated, a cascade of events occurs that leads to cell lysis, opsonization, and/or inflammation
- The activation of one molecule results in an enzyme-like activity to activate the next molecule and so on…
Most of the proetins are made in the liver but some are made in white blood cells
- These effectors circulate in an inactive state
What are the three arms of compliment?
Classical pathway
Lectin pathway
Alternative pathway
What compound do all three compliment pathways activate?
C3b
How does the classical compliment pathway activate?
Antibody binds to specific antigen on the surface of a pathogen.
What does the classical pathway ultimately lead to?
Recruitment of inflammatory cells and pathogen death.
What are the steps of classical pathway activation?
1) Antigen - antibody complexes on pathogen surface
2) C1q, C1r, C1s, C4, C2
3) C3 convertase (C3b)
4) C3a, C5a (From C3b)
5) Recruitment of inflammatory cells; phagocyte recruitment
Image of classical compliment pathway.
What are the steps of the mannose-binding lectin pathway?
1) Mannose binding lectin binds to mannose on pathogen surface
2) MBL, MASP-1, MASP-2. C4, C2
3) C3 convertase
4) C3b
5) Binds to complement receptors on phagocytes
6) Opsonization of pathogens
7) Removal of immune complexes
Mannose binding lectin pathway image.
What does the alternative pathway lead to?
Pathogen surface itself creates a local environment that is conducive to complement activation.
Complement activation.
C3b activation
Perforation of pathogen cell membrane
What are the steps of alternative pathway activation?
1) Pathogen surface
2) C3, Fcator B, Factor D
3) C3 convertase
4) C3b
5) Membrane attack complex (C5b6789)
6) Lysis of certain pathogens and cells
Alternative pathway image.
Overall scheme of complement activation.
What are the effector functions of complement activation?
1) Cell lysis via the membrane attack complex (C5b thru C9)
2) Opsonization of the antigen - Aids in removal
3) Removal of immune complexes
4) Inflammatory mediation - Complement products bind to complement receptors on various cells. This results in a relase of histamine and other inflammatory mediators.
What are cytokines?
Cytokines are chemical mediaters of the immune system.
What are interferons?
Interferons are a type of cytokine
Three types:
IFN alpha, IFN beta, and IFN gamma
How are IFN alpha and IFN beta produced and what do they do?
IFN alpha and beta are produced by most virally infected cells
They have direct anti-viral effects
Where is IFN gamma produced and what does it do?
IFN gamma is produced by T cells and NK cells
Important for immune system activation
Helps in the recognition and destruction of virally infected cells
What do NK cells do?
NK cells are part of the innate defenses
Kill altered “self” cells and virus-infected and tumor cells
Activated by IFN gamma
What are the steps of the inflammatory response?
1) Wound leads to tissue injury
2) Histamine release causes capillaries to leak. This releases phagocytes and clotting factors into the wound.
3) Phagocytes engulf bacteria, dead cells and debris.
4) Platelets move out of the capillaries to seal the wounded area.
Image of inflammatory response.
What is an inflammatory reaction?
This is a mechanism where host defense cells are recruited to an area of damage / infection
The signs of inflammation are heat (calor), pain (dolor), redness (rubor) and fever (tumor)
What are some of the cytokines and chemicals that are responsible for inflammation?
IL1
IL6
TNF alpha
Histamine
Why is having acquired immunity important?
Innate immunity limits most infections
However, microbes that evade innate defenses must be recognized and destroyed
Acquired immunity is tailor made and lymphocytes (and their genes) determine this
Acquired immunity improves over time