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
What is the 3rd hiearchy of immune defense?
Adaptive response
What does the adaptive response refer to?
Activation of B and T cells
What do B lymphocytes (B cells) do?
Recognize cell-bound or soluble antigen
Generate antibody
Ultimately responsible for humoral mediated immunity (antibody mediated)
What do T lymphocytes (T cells) do?
T cells recognize cell-bound antigen
They produce cytokines that direct other cells
Responsible for cell-mediated immunity
What does opsonization refer to?
Antibody opsonization is the process by which a pathogen is marked for ingestion and destruction by a phagocyte.
Opsonization involves the binding of an opsonin, e.g., antibody, to an epitope on an antigen.After opsonin binds to the membrane, phagocytes are attracted to the pathogen.
The Fab portion of the antibody binds to the antigen, whereas the Fc portion of the antibody binds to an Fc receptor on the phagocyte, facilitating phagocytosis.
What are the characteristics of innate immunity?
Rapid response (Hours)
Fixed
Limited number of specificities
Constant during response
What are the characteristics of adaptive immunity?
Slow (Days to weeks)
Variable
Numerous, highly selective specificities
Improves with time
What does hematopoiesis?
This is the process of forming blood and blood components.
What are the cell types in the blood?
Erythroid
- RBCs
- Platelets
Myeloid
- Granulocytes
a) Neutrophils
b) Eosinophils
c) Basophils - Monocytes / macrophages
- Dendritic cells
- Mast cells
Lymphoid
- Lymphocytes
- NK cells
What are neutrophils?
These are phagocytic cells and are the most abundant phagocytic cells in the body.
What are eosinophils?
These phagocytes ingest parasitic worms and are involved with allergic responses.
What are basophils?
These are inflammatory mediaters.
What are monocytes?
These are phagocytic antigen presenting cells
What are dedritic cells?
These are phagocytoic antigen presenting cells
What are mast cells?
These are inflammatory cells that release histamine.
What are lymphocytes?
These are B and T cells.
True or false: NK cells are antigen specific.
False; NK cells are NOT antigen specific.
What are the percentages of white blood celles in peripheral blood?
Neutrophils 40 - 75%
Eosinophils 1 - 6 %
Basophils < 1%
Monocytes 2 - 10%
Lymphocyte 20 - 50%
What are the organs of the immune system?
Primary lymphoid organs
- Bone marrow and thymus
- Sites of development of immune cells
Secondary lymphoid organs
- Peripheral
- Sites where immune response is generated (Recognition of antigen)
- Lymph node, spleen, blood, lymphatics, and Gut-associated lymphoid tissues (GALT)
What is the adaptive immune response due to?
B cells and T cells.
What are the major properties of the adaptive immune response?
Recognition of self vs. non-self
Specificity
Heterogenous / Adaptable
Memory allows it to work better and faster
What is the significance of the recognition of self vs. non-self?
Self-reactive cells should be destroyed early in the development of B and T cells
Those that are not destroyed undergo antigenic tolerance
What is antigenic tolerance?
This is a state of unresponsiveness of the immune system to substances or tissue that have the capacity to elicit an immune response.
Where does B cell maturation occur?
Bone marrow; self reactive B cells must be destroyed in the bone marrow
Where does T cell maturation occur?
Thymus and bone marrow; these cells must be able to determine self from non-self MHC.
Destroyed in thymus if they cannot recognize self vs non-self
What is autoimmunity?
This is a condition that arises when an individuals immune system attacks self.
How is the specificity of the adaptive immune response determined?
Antibodies amd T cell receptors
Antibodies are produced by B cells and T cell receptors are produced by T cells
Picture of an antibody.
Picture of antibody and T cell receptor.
What is an epitope?
An epitope is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells.
What are ‘CD’ molecules?
These are ‘Cluster of Differentiation’ molecules and are used to identify specific structures on a cell.
More than 200 different types of CD molecules
What are some of the important CD molecules?
CD4
CD8 - T cell
CD3 - T cell
TCR - T cell
CD28 - T cell
IgBeta - B cell
IgAlpha - B cell
slg - B cell
CD40 - B cell
MHC II - B cell
B7 / CD80 - B cell
True or false; The immune system must display heterogeneity.
True; The immune system must be able to recognize all antigens no matter where it is found or what form it is in.
What gives the immune system its heterogeneity?
Gene rearrangement of immunoglobulin and TCR genes.
Ig is made up of two chains; a heavy chain and light chain
TCR is made up of an a and b chain
Genes for these are rearranged to generate millions of possible combinations for antigen binding
Why are IgM and IgD expressed first?
These are the constant region sequences closest to the VDJ sequences.
How do B cells operate?
They recognize soluble antigen, usually in conformational configuration.
They are good against extracellular antigen.
Antigen can be proteins, carbohydrtaes, nucleic acids or rarely, lipids
How do T cells recognize processed antigen?
T cells recognize antigen presented by MHC (Major histocompatibility complex) molecules.
Two types of MHC molecules: MHC I and II
Good against intracellular antigens (Viral, protozoan, bacteria)
T cell antigens are usually proteins / peptides
Where are MHC I molecules found?
On all nucleated cells and are recognized by CD8 + cells
Where are MHC Class II molecules found?
Found on macrophages, B cells and dendritic cells and are recognized by CD4+ cells
What is MHC Class I?
MHC class I molecules are found on nearly every nucleated cell of the body.
Their function is to display fragments of proteins from within the cell to T cells; healthy cells will be ignored, while cells containing foreign proteins will be attacked by the immune system.
Because MHC class I molecules present peptides derived from cytosolic proteins, the pathway of MHC class I presentation is often called the cytosolic or endogenous pathway
What is MHC Class II?
MHC class II molecules are a family of molecules normally found only on antigen-presenting cells and B cell lymphocytes.
The antigens presented by class II peptides are derived from extracellular proteins and this pathway of antigen presentation is called the endocytic or exogenous pathway.
Loading of MHC class II occurs by phagocytosis; extracellular proteins are endocytosed, ingested in lysosomes, and created by the class II MHC molecule prior to the molecule’s migration to the cellular membrane.
What cells function as the bridge between the innate and adaptive immune response?
Antigen presenting cells.
Present protein antigen to T cells
T cells become active and produce cytokines
What are professional antigen presenting cells?
Macrophages, dendritic cells, and B cells
These present antigen in association with MHC Class II
What are the roles of macrophages?
Antigen presentation
T cell activation
Bacterial adhesion
Facilitated uptake
Image of MHC Class II.
MHC Class I image.
Describe the endogenous pathway.
The endogenous pathway is used to present cellular peptide fragments on the cell surface on MHC class I molecules. If a virus had infected the cell, viral peptides would also be presented, allowing the immune system to recognize and kill the infected cell.
Describe the exogenous pathway.
The exogenous pathway is utilized by specialized antigen presenting cells to present peptides derived from proteins that the cell has endocytosed. The peptides are presented on MHC class II molecules.
What are the two subsets of T cells?
Th Helper T cells (Recognize MHC II)
Tc Cytotoxic T cells (Recognize MHC I)
What do Th1 T cells do?
Produce cytokines to stimulate inflammation and cytotoxicity
Recruit macrophages and neutrophils
Activate cytotoxic T cells and NK cells
IL12 from macrophages directs Th1 cell response
IL2 and IFN gamma are the major Th1 cytokines produced
What do Th2 cells do?
These cells are important in antibody responses
Activate B cells and help them differentiate
Il4, Il5, Il6, and IL10 are the major Th2 cytokines produced
What are some of the important cytokines?
IL1
IL2
IL4
IL10
IL12
IFN gamma
TNF alpha
What are the five major types of antibodies?
IgM - Produced 1st and best at complement activation
IgG - Highest conc. in blood and highest amounts in most secondary responses, crosses placenta
IgA - Secretory, found in secretions, highest conc in body
IgE - Allergicrxns, good for worm infections
IgD - initiation of immune response
What does immunological memory refer to?
When immune cells are produced, effector cells and memory cells are produced
Memory cells allow for a quicker and better response when next recognizing the antigen
Increased affinity
What is a primary immune response?
This is the initial immune response.
What is a secondary immune response?
This is the second, memory-based response.
Leads to increased affinity upon subsequent exposure to the same antigen
What is the purpose of vaccines?
Use the immune system to protect against infectious diseases.
What are the types of vaccines?
Attenuated microbe
Heat-killed / Chemically killed microbe
Toxoids
What is passive immunity?
Immune system products from another (Mothers milk contains IgA, anti venom)
What is active immunity?
Stimulate individuals immune system to produce memory cells
