Innate Immunity

  • Phagocytes (neutrophils, monocytes, macrophages)

  • NKs

  • Complement proteins, cytokines, phase proteins

**innate immunity does increase with repeated exposure



Immunogens vs. antigens

  • Immunogens - any substance that can activate an immune response against the substance (all immunogens are antigens), large proteins are most potent

  • Antigen - product of immune activation (self vs non-self, complex, size)



Antigen recognition by innate immune cells

  • Receptors on surface, can recognize diversified microbes

  • Microbe/Pathogen associated molecular pattern (peptidoglycan, LPS, flagellin)

  • Damage associated molecular pattern - alarmins, signals released by stress, damage, dying cells

  • Pathogen associated molecular patterns

  • Pattern recognition receptors - recognition of non-self (unique to itself and not recognized) or missing self

Phagocytic PRRs are expressed during phagocytosis

Secreted PRRs secreted by macrophages to activate complement, function as an accessory for PAMP recognition

PRR has immune signals with toll like (membrane bound)/NOD like/RIG like receptors

  • TLR - can recognize the specific molecule, transcription activator



Major processes in innate immunity responses

  • epithelial cells are sealed by tight junctions and produce defensins, cathelicidins to kill microbes

  • Intraepithelial lymphocytes → integrated into epithelial cells

  • Flora can release pathogens, compete for space, compete for nutrients, inhibit pathogens by stimulating host defenses

  • Antagonistic interaction - contact in/dependent 

Phagocytosis

  • Mononuclear phagocytes come from bone marrow

  • Recognition → activate macrophages → phagocytosis

Antigen presentation

  • Macrophages, after phagocytosis, will present antigen to lymphocytes

  • The APCs present antigens on their surface 

  • Classic APC: dendritic cells, migrate towards lymphocytes, activated with B7

  • Macrophages primarily eat, and could present if near a lymphocyte

  • B-cell - occasionally endocytose and then present antigens on surface

Inflammation

Non-Specific Immune Responses

  • Inflammation - host response to tissue injury to defend against antigens

Release of histamines → release of histamine by mast cells → vasoconstriction → arterial vasodilation → increased blood flow → increased phagocytes → walling off area

Inflammasome - combination of molecules involved in inflammatory response



Interferons - group of proteins that defend against viruses

  • Target host and viral factors, 3 classes

  • Class 1 (alpha, beta) - secreted by dendritic cells, macrophages, fibroblasts, induce resistance to virus replication, increase expression of ligands, activate NKs

  • Class 2 (gamma) - secreted by NKs, T cells

  • Class 3 (lambda) 



Granuloma formation

  • Eosinophils, basophils and mast cells undergo degranulation

  • Creates a boundary by macrophages (also called epithelioid/langhans giant cells)in response to a chronic stimulus/foreign object, the outer ring is CD4 helper T cells

  • Caseating - centre with necrosis, cheese-like/solidified centre

  • Noncaseating -  no central region of necrosis 

  • Encapsulated foreign material, CD4 lymphocytes will secrete cytokines after identifying cytokines from macrophages



NK cells in cell cytotoxicity 

  • Innate immune cells 

  • Protect against virus and cancer cells

  • After it gets into contact with viruses or cancer cells, it gets activated

  • Released cytolytic/cytotoxic granules/chemicals

  • NK cell - does not need antigen presentation

  • NKT cells need antigen presentation from non-MHC peptides

  • Can activate macrophages, can identify ligands on macrophages, secretes chemicals to help with phagocytosis

  • Inhibitory receptor for class 1 MHC, if engaged, will not work

Antibody-Dependent Cell Cytotoxicity - Antigens on a target cell will get attached by immunoglobulins, which can be recognized by NKs CD16 receptor, activating the cytotoxic molecules



Complement system + complement fixation pathways

  • Fragmented proteins can bind to the surface of microbes that can be recognized easily

  • System of plasma proteins

  • C1 - C4 (early), C5 - C9 (late)

  • In the activation phase response is the activation of the complement pathway

  • Alternative pathway + lectin pathway - do not need adaptive immune response 

  • classical pathway needs immunoglobulins

  • Know the difference between alternative, classic and lectin pathways



MAC 1

  • Proteasomes can help with degrading pathogens and processing

  • Presented to particular lymphocytes: B-lymphocyte, CD8 cytotoxic T cells



MAC 2

  • Proteins are simplified, epitopes are channelized to the ER and get expressed on the surface 

  • Presented to helper CD4 T lymphocytes