Immunology Chapter 10: Systemic and Mucosal Immunity

Chapter 10: Systemic and Mucosal Immunity

• Systemic immunity is reactive, inflammation is common
• Mucosal immunity is proactive, inflammation is avoided.
• Mucin is a glycoprotein produced by mucosal epithelium; it protects the mucosal epithelium.
• Mucins are large collections of polypeptides, either secreted or membrane-bound.
• Membrane-bound mucins trap microorganisms, aiding pathogen removal.
• Defensins are AMPs (antimicrobial peptides) that create holes in pathogen lipid bilayers.
• Commensal organisms benefit the host but don't have a close relationship.
• Commensal organisms are one step below symbiotic relationships.
• Commensal organisms help synthesize metabolites, break down fibers, inactivate toxins, act as a barrier in the gut and stimulate secondary lymphoid tissue.
• Commensal organisms can become pathogenic if they don't stay put.

Subsets of Gut Epithelial Cells

• AMPs (antimicrobial peptides), such as defensins, disrupt pathogen membranes.
• ILCs (innate lymphoid cells) may or may not care about pathogens, depending on the context.
• Enterocytes absorb nutrients
• Goblet cells produce and secrete mucus.
• Paneth cells secrete AMPs (e.g., defensins).
• ISC (intestinal stem cells) replace gut epithelial cells.

M cells and Intraepithelial Lymphocytes

• M cells transport microbes/antigens into the intestinal tissue.
• IELs (intraepithelial lymphocytes) are essentially cytotoxic T-cells in the epithelium.
• Peyer's patches are secondary lymphoid organs in the small intestine.

Macrophages and Oral Tolerance

• Intestine macrophages don't secrete cytokines and lack a significant inflammatory response.

• Oral tolerance relates to the immune system's ability to not respond to food antigens.

Chapter 14: Hypersensitivity Reactions

• Hypersensitivity reactions are exaggerated inflammatory responses to allergens.
• Atopy is a genetic predisposition to allergy.
• Anaphylaxis is a severe hypersensitivity reaction that can cause organ damage and asphyxiation.
• Type I hypersensitivity involves immediate degranulation of mast cells when an allergen binds to IgE.

Mast Cells, Eosinophils and Basophils

• Mast cells, eosinophils, and basophils have high-affinity IgE receptors.
• Mast cells release histamine and other cytokines, causing inflammation.
• Eosinophils release cytotoxic granules, harming tissues in allergic reactions.
• Basophils cause tissue damage in allergic reactions and have regulatory roles in initiating Th2 responses

Chapter 16: Immunological Self-tolerance

• Immunological self-tolerance is a process that prevents the immune system from attacking its own tissues.
• Mechanisms include negative selection of B and T cells in the bone marrow and thymus, induction of anergy, lymphatic exclusion, and T-reg cell suppression.
• Autoimmune diseases fail to resolve because they are only managed.
• AIRE allows for presentation of non-thymus antigens to T-cells for negative selection, defects in AIRE lead to autoimmune disease.
• FOXP3 is a transcriptional repressor involved in T-reg function and autoimmunity.
• HLA is a major genetic factor for autoimmune disease susceptibility, with women more impacted than men.

Chapter 17: Oncogenesis, Metastasis, and Cancer

• Oncogenesis is the development of tumors.
• Metastasis signifies tumor spreading to other tissues.
• Proto-oncogenes are genes involved in cell growth and regulation, while oncogenes have mutations that increase proliferation.
• Tumor suppressor genes constrain cell growth and mutation.
• Malignant tumors can invade nearby tissues (metastasis).
• Benign tumors remain localized.
• The multi-hit model suggests that cancer requires multiple mutations for tumor growth.
• Neoantigens are tumor-specific antigens, allowing the immune system to recognize and eliminate tumors.
• The immune system eliminates cancer cells by presentation of antigens with MHC molecules, through cytotoxic T-cells, antibody-dependent cellular cytotoxicity, antibody-dependent phagocytosis, or TIME (tumour immune microenvironment).

Chapter 15: Transplantations

• Grafts are types of transplanted tissues or cells.

• Autograft uses self-tissue, isograft uses a identical donor, allograft uses a different donor of the same species, and xenograft uses donors of different species.

• Histocompatibility is similar between donors and recipients (no inflammation), whereas histoincompatibility shows differences that the immune system does respond to.

• ABO blood types and Rh factors must be matched for blood transfusions to avoid rejection.

Chapter 14: ABO blood incompatibility

• Different blood types have different antigens (A, B, AB, O).
• Someone with type O blood can donate blood to anyone (universal donor).
• Someone with type AB blood can receive blood from anyone (universal recipient).

Chapter 17: Tumor Immune Editing

• Tumor immunoediting refers to the process by which tumors mutate and divide to evade death and detection from the immune system.
• Tumor-treated as self, low immunogenicity, immune suppression and antigenic modulation are tumor immune escape mechanisms and strategies tumors use to evade immune responses.
• Low immunogenicity means the tumor does not stimulate immune response.
• Tumor cells treated as "self" cells are not targeted, meaning their presence is not acknowledged.
• Immune modulation involves suppressing the immune response within a physical barrier; the tumor then is not attacked.
• Antigenic modulation means the tumor loses its immunogenic antigens and is not targeted.

Chapter 17: Immunotherapy for Cancer

• Chimeric antigen receptor (CAR) T-cells, which are genetically engineered to target specific tumor antigens, can prevent activation of T-cells and thus bypass the need for MHC.
• Radio-conjugated antibodies allow for targeted delivery of radiation to cancer cells.

Explore the key concepts of systemic and mucosal immunity in this chapter. Understand the roles of mucins, antimicrobial peptides, and commensal organisms in protecting the body from pathogens. Discover how mucosal immunity operates proactively compared to systemic immunity.