Chapter 1: Basics Concepts in Immunology Flashcards
What are the three strategies against microbial threat?
Avoidance:
- Anatomical barriers
- Behaviors to avoid diseased animals (ex. hygiene)
Tolerance:
- Protecting tissues against toxins
- Repairing damages
Resistance:
- Activating innate and adaptive immunity
- Stimulating inflammation
What are the four phases of the immune response?
- Anatomical barriers
- Skin mucosa, epithelium, intestine
- Complement/ antimicrobial proteins
- C3, defensins, RegIIIγ
- Innate immune cells
- Macrophages, granulocytes, NK, epithelial cells
- Adaptive immunity
- B cells, antibodies, T cells
Compare the timing of the innate immune response and adaptive immune response .
Innate:
- First line of defense
- Try to prevent spread
- Fast response
Adaptive:
- Recognizes and eliminates pathogens quickly
- May take days and be too late if innate cannot reduce spread effectively
Outline the steps and purpose of the compliment system.
- Pathogen must overcome physical barriers
- Complements are a set of plasma proteins
- Can attach to pathogen so it can be more easily be identified by macrophage
- Can form pores in pathogen promoting inflammation
How is the immune system activated?
- Activation via inflammatory inducers which indicate presence of pathogens or damaged tissue
- Sensor cells detect inducers using innate recognition receptors
- Mediators then amplify immune response
What type of cells comprise most of the innate immune response?
- Myeloid lineage
What are sensor cells? What are pattern recognition receptors?
- Sensor cells initially screen for self and non self via recognition receptors
- Pattern recognition receptors (PRRs) are innate receptors that recognize pathogen-associated molecular patters (PAMPs)
- PAMPs are not present in all microorganisms, conserved in evolution, identified on cell wall
What are TLR and NOD receptors?
- They’re PRRs
- Toll-like receptors (TLR)
- Nucleotide-binding and oligomerization domain (NOD) - like receptors
Other types of receptors: Mannose, glycan, scavenger
How do sensor cells induce an inflammatory response? What is a chemokine?
- Via production of mediators such as chemokines and cytokines
- A specialized subgroup of secreted proteins that act as a chemoattractant. Neutrophils and monocytes are attracted by their chemokine receptors
- Accumulation of fluid and while blood cells causes redness, swelling, heat, and pain known as inflammation
Outline the steps involved in inflammation.
- Macrophage encounters microorganism = cytokine/chemokine release
- Response to chemokines is increase permeability and dilation of blood vessels (vasodilation) results in inflammation
- Chemokines from macrophages attract neutrophils + WBC to infection
- As epithelial adhesive properties alter, pain is caused
What is a lymphocyte? Why are they important in an immune response?
- A type of WBC usually B,T, or NK cell
- They’re important due to high variability in antigen receptors on surface
- Antigens can always be recognized due to unique antigen receptors
What happens when a Naïve B-cell encounters an antigen?
- BCR on the naïve B cell encounter an antigen, receptor binds
- B cell to proliferate and differentiate into a plasma cell as a response
- Effector form (plasma cell) will secrete antibodies (Ig)
- Antigen then becomes the target of the B cell’s progeny
What happens when a TCR on a T cell binds to an antigen?
- T cell encounters antigen, receptor binds
- T cell proliferates and differentiates into an effector T lymphocyte
- Helper T cells (CD4+)(coreceptor 4) Activates immune B cells
- Cytotoxic T-cells (CD8+)(coreceptor 8) releases cytotoxins to induce apoptosis and membrane proliferation to kill infected cells
- Regulatory T cells control immune reaction to avoid autoimmunity
What is an MHC? What is its purpose?
- Major histocompatibility complex
- Two classes
- Class I - antigen recognized by cytotoxic T cell (expressed in all nucleated cells)
- Class II - antigen recognized by T-helper cells (expressed in antigen presenting cells (dendritic, macro, B cells)
- The purpose of MHC is to bind the epitope peptide and present it to the T cell
How are lymphocytes able to have so many unique receptors?
- Antigen receptor genes are assembled by somatic gene rearrangements of incomplete gene segments
What is clonal expansion?
- When an antigen binds and activates a B cell, proliferation will create many identical progeny which develop into effector (plasma) cells which release identical antibodies
- Gene rearrangement is irreversible so progeny will have antibodies identical to surface receptors
What do helper T cells do to help B-cells?
- When a B-cell is activate, the antigen is bound to MHCII which presents the antigen to a helper T cell
- Helper T cell then activates releasing cytokines which help in the proliferation (replication)of the B-cells and differentiation (creating plasma cells)
- Helper T cells also aid in formation of B-memory cells
Outline the steps in Clonal Selection Theory.
- Each lymphocyte is unique with its own specificity
- Interaction of B-cell with antigen results in activation
- Differentiated effector cell will produce antibodies identical to parent B cell
- Lymphocytes that were self antigens are removed thus absent from mature lymphocyte inventory
What happens to self reactive lymphocytes?
- Normally eliminated or functionally inactivated
- Eventually self reactive antigens produced are eliminated before maturation (clonal deletion)
- Immature lymphocytes that receive too much or little signal removed by apoptosis
- Induction of anergy (inactivation of immature B-cells)
Where do lymphocytes mature? What are primary lymphoid organs? What are secondary lymphoid organs?
- Mature in bone marrow or thymus (T cells)
- Circulate in blood and lymph system
- Where lymphocytes develop from non functional precursors (bone marrow and thymus)
- Where mature naive lymphocytes are maintained and adaptive immune responses are carried out
- Lymph nodes, spleen, mucosal lymphoid tissue of gut, and other mucosa
Outline the steps involved in adaptive immune responses leading up to antigen presentation.
- PRR on dendritic cells bind to PAMPs on pathogen leading to engulfment
- Bacteria is engulfed by macrophage encased in vacuole
- Lysosomes fuse and digest bacteria
- Antigen from digested bacteria are presented by MHCII on the surface of the macrophage
How do dendritic cells activate naive T cells?
- Immature dendritic cell in peripheral tissue migrates via lymphatic vessels to lymph node where naive T cells are found and activated
- Surface proteins (co-stimulatory molecules) are expressed on dendritic cells and stimulate proliferation and differentiation
- Dendritic cell or other APC (antigen presenting cell) will display peptide fragment to naive T cell to activate
- Other APC can be macrophages and B cells but dendritic cells are main presenters
Why are dendritic cells important?
- They bridge innate and adaptive immunity
How can infections be detected by lymphocytes in peripheral tissue or other areas?
- Lymphocytes circulate and hen encountering a pathogen release chemokines to attract more WBC
- Free antigens circulating may also end up in lymph nodes and be picked up by APC (antigen presenting cells)
- Once lymphocyte differentiates into effector cell it will leave lymphoid organ and enter blood to reach infection
What are lymphoid organs?
- Aggregates of lymphocytes that trap antigens and APC from sites of infection to present antigens to lymphocytes which causes an adaptive response
- Spleen, lymph nodes, and mucosal-associated lymphoid tissue
What is the structure and function of a lymph node?
- Follicles made up of B-cells
- Paracortical area made of T cells (also where APC are)
- Medullary cords made of macrophages and plasma cells
- Activate B and T cells move close so T cells can carry out helper function
- B cells proliferate and differentiate creating germinal centers expanding the lymph node
What is the function of the spleen?
- Not connected to lymphatic system and relies on circulation
- Filters and detects antigens and pathogens in blood
- Filters old RBC and stores platelets
- Lymphoid tissue in white pulp, platelets in red pulp
Describe the structure of white pulp.
- Periarteriol lymphoid sheath made of T cells
- Follicles made of B cells (also form germinal center)
- Marginal zone made of Unique B cells, macrophages, dendritic cells
Describe the structure of Peyer’s patches in GALT.
- Follicle-B-cells
- T-cell dependent areas
- Subepithelial dome - T,B, dendritic cells
- Microfold (M) cells are specialized cells that collect and transport pathogens from lumen to the dome
- Tonsils, adenoids, appendix, Peyer’s patches in small intestine
What happens to lymphocytes after an infection is overcome?
- Effector cells die and antibody levels decline
- Long lived plasma cells can remain for years to lifetime
- A significant number of progeny B and T cells will remain as clonal cells which can be reactived
Compare the primary vs secondary response to a pathogen.
Primary:
- Naive B cell
- 4-7 days, peak at 7-10
- Lower antigen affinity
Secondary:
- Memory B cell
- 1-3 days, peak 3-5 days
- Higher antigen affinity
Why are vaccines so important?
- Vaccines mimic primary response for disease in which adaptive immune system may respond too late
- Most effective way to control infectious diseases
What is the significance of effector mechanisms in innate and adaptive immunity?
- For each of the four major lymphocytes there is a corresponding type of T cell with generally similar functional characteristics
What are the three effector mechanisms of immunity?
- Neutralization
- Antibodies bind to bacterial toxins/viruses and are then ingested by macrophages
- Opsonization
- Bacteria is coated with antibodies to facilitate phagocytosis
- Complement
- antibodies attach to bacteria which result in bacteria being lysed and digested
What is the function of MHC I?
- CD8 (cytotoxic) T-cells recognize MHC I
- Infected cells display antigen in the MHC I complex
- CD8 cells recognize the MHC I molecule and kill the infected cell
What is the function of MHC II?
- CD4 (helper) T-cells recognize MHC II
- Activates macrophage causing lysosomes to fuse to vesicle then kill bacteria
What do TH2 cells produce
Interleukin-4,5,13
- Recruit eosinophils activates Mast and Basophils
What does TH 17 do?
Produces Interleukin-17
- Recruit neutrophils
- Works against Bacteria and Fungi
What does TFH do?
Regulates antibody production
