Question

Cell Biology Tutorial: Molecular Mechanisms of Immunology

Answer 1

\({\bf{Basics~of~Immunology:}}\)
- an effective immune response will involve destroying pathogens and cells that harbor them

Three layers:
- mechanical/chemical, ex. skin, low pH, enzymatic activity like lysozymes
- innate: fast-acting, uses cells that are already present; ex. macrophages, dendritic cells, neutrophil, NK cell, complement cascade
- adaptive immunity: specific to antigen, takes a while to develop; ex. B Cells, T Cells

Other Terminology:
- antigen: substance that causes immune response
- antibody: binds to antigen and induces opposing response to antigen
- complement: serum protein that binds to antigen, activating a cascade resulting in cell death/lysis --> activates MAC (membrane attack complex)
- antigen-presenting cells (APCs): digest antigen and incorporate their components into their membranes to induce immune response; ex. macrophages, neutrophils, dendritic cells

Three pathways of Complement Activation
- classical pathway: antibodies bind antigens to surface
- mannonse-binding lectin pathway: lectin binds to mannose and activates lectin-associated proteases MASP-1 and MASP-2
- alternative pathway: cascade that includes B,P,D factors in blood plasma
> all three pathways result in C3 activation, C3 activates protein cascade with C-5 to C-9, forming MAC and pore ormation --> cell lysis/death

Answer 2

\({\bf{Basics~of~the~Lymphatic~System:}}\)

lymphocyte: white blood cell
lymph: fluid containing lymphocytes, enters blood through lymphatic system
> two forms, soluble antigen and antigen-laden

primary lymphoid components:
-bone marrow (where B cells mature and T-cells originate)
-thymus (where T cells mature)

secondary lymphoid components:
- lymph node: where lymph is filtered
- spleen: lymphocyte maturation site/ filtering

\({\bf{Activation~of~Immune~System:}}\)
1. T and B cells are circulated into lymph nodes
2. lymph with soluble antigen recognized by B cells, antigen-laden dendritic cells present antigen to T cells
3. differentiation of B cells into plasma cells
4. antibody production by B cells
5. lymphatic vessels return lymph back to circulation

Answer 3

\({\bf{Basics~of~the~Inflammatory~Response:}}\)
- inflammation: immune response to injured tissue
- chemokines: chemicals that attract immune system cells
- neutrophils: respond to cytokines/chemokines, migrate to the injury/infection site, ingest pathogens, produce more cytokines/chemokines/ and produce defensins
- defensins: small antimicrobial peptides

1. inflammatory proteins cause inflammatory response and destroy bacteria, releasing antibodies
2. dendritic cells acquire antigen, migrate to lymph and activate T cells
3. T cells proliferate and activate B cells, ex. plasma cell differentiation
4. antibodies and complement system fight the infection

Answer 4

\({\bf{B~Cells~vs.~T~Cells:}}\)

B:
- humoral immune response
- primary function is to present antigens or develop into memory cells
- mature in bone marrow
- clonal expansion: after coming across the antigen it will divide, amplifying the immune response, each carrying specific antigen
- somatic recombination to generate light/heavy chain genes
- affinity maturation: activated B cells produce antibodies with increased affinity for the antigen during the immune response
- may undergo deamination + point mutations, C - T most common, affinity increasing mutations may give B cells adaptive advantage

T:
- cell mediated immune response
- have special receptor (TCR)
- mature in thymus
- two subtypes:
> cytotoxic T (CD8), class I MHC, eliminate pathogens
> helper T (CD4): class II MHC, assist in B-cell differentiation

\({\bf{Immunoglobulins:}}\)
- two heavy chains, two light chains H2L2
- light chains: k, lambda
- heavy chain: mu, delta, gamma, alpha, epsilon
- Ig domains; M, D, G, A, E
M: activates complement cascade
A: protect against enviornment
G: neutralize viruses

- Ig domains: immunoglobulin fold: domain characterized by hydrophobic residues pointing in wards and hydrophilic residues pointing outward
- two beta sheets stabilized by disulfide bond

- variable region of the heavy chain (VH) contains the residues that distinguish different types of heavy chains, light chain also has variable region
- hypervariable region: contains antigen binding site
- epitope: region on the antigen that bonds with the antibody

Answer 5

\({\bf{Toll~Like~Receptors:}}\)
- present on macrophages, neutrophils, dendritic cells
- detect pathogen markers like cell wall components or nulceic acids with unmethylated cpG
- leucine rich repeats
- TIR domains associate with myddosome
- myddosome: contain 6 MyD88 adaptor proteins, 4 IRAK4 kinases, 4 IRAK2 kinases

\({\bf{Inflammasome:}}\)
- activated by pathogens/pathogenic signals
- form from NALP proteins/IPAF proteins
- activate capsas-1 which cleaves the pro-IL-1beta domain into active form, causing the inflammatory response

Answer 6

Anyway, that's the end of my tutorial, I hope it was a helpful resource. Source material is Chapter 23 of Molecular Cell Biology, Eighth Edition, Lodish, et. al.