Immune System

MCAT Immune System 

Anatomy 

·       Bone Marrow: All leukocyte production 

·       Spleen: Blood storage and B Cell activation 

·       Thymus: T cell maturation 

·       Lymph Nodes: Immune communication/ B cell activation 

o   Gut associate lymphoid tissue (GALT) 

o   Tonsils 

o   Adenoid (Head 

o   Peyer’s Patches (small intestine) 

o   Aggregates in appendix  

·       Skin: first line of defense 

Innate Immune System (Nonspecific) 

Skin 

Contains defensins (antibacterial enzymes) 

Respiratory Passages  

Contain mucous membranes, mucociliary elevator 

Eyes/Oral cavity  

Both contain lysozyme in tears and saliva (nonspecific antibacterial enzyme) 

GI Tract 

·       High acidity and high microbial diversity (no niche for pathogens) 

·       Antibiotics that destroy diversity lead to infection 

Complement System 

·       Proteins in blood that get activated  

·       Classical Activation (requires Abs) 

·       Alternative Activation (no Abs) 

Interferons 

·       Produced by virally infected cells 

·       Lead to decreased cell/viral protein production of nearby cells 

·       Decrease nearby cell permeability 

·       Upregulate MHC Class 1 presentation 

MHC Class Presentation 

·       Presentation of antigens on cell surface for immune surveillance of healthy vs sick cells 

·       MHC Class 1: endogenous pathway of antigen presentation (uptake of pathogen internally and present antigen externally) 

·       MHC Class 2: exogenous pathway of antigen presentation obtained from external antigens in surrounding environment  

Typically, professional antigen presenting cells like dendritic cells in skin, macrophages, some B cells, and certain epithelial cells 

Cells of Innated Immune System 

Macrophages  

·       Derived from monocytes, become macrophages once they enter tissues (resident macrophages) 

·       When bacteria enter tissues, macrophages activated 

·       Phagocytize pathogen and present antigens on MHC molecules 

·       Cytokine release for recruitment and inflammation 

Natural Killer Cells (nonspecific lymphocyte) 

·       Recognize downregulation of MHC class molecules (a pathogen defense mechanism to evade immune system) and induces apoptosis of infected cell 

·       Cancer also downregulates MHC 

Granulocytes  

·       Neutrophils 

o   Most populous leukocyte in blood (short lived) 

o   Phagocytic 

o   Target bacteria by chemotaxis  

o   Can also detect opsonized bacteria (marked with antibody from B cells) 

o   Dead neutrophils responsible for pus 

·       Eosinophils  

o   Bright red-orange granules  

o   Allergic reaction 

o   Release large amounts of histamine that vasodilate/increase leakiness of blood vessels so immune cells can move into tissues  

·       Basophils  

o   Contain large purple granules  

o   Allergic reactions; least populous leukocyte  

o   Release histamine  

o   Mast cells closely related but have smaller granules that exist in tissues, mucosa, and epithelium 

Adaptive Immune System 

Consists of mainly B/T cells  

Humoral Immunity 

·       Involves antibody production 

·       Antibodies produced by B cells 

·       B cells produced in bone marrow but activated in spleen/lymph nodes 

Antibodies (immunoglobulins) 

·       Can be displayed on cell surface or float freely 

·       When antibody binds, response depends on location  

o   Antibodies secreted in fluid and bound to antigen will: 

§  Attract other leukocytes (opsonization) 

§  Clump pathogens together (agglutination) forming large insoluble complexes for phagocytosis 

§  Neutralize pathogen by blocking its ability to invade tissues 

·       Antibodies displayed on cell surface and antigen bound will cause activation/proliferation of that specific B cell (generates plasma and memory cells) 

·       Antibodies displayed on mast cells and bound to antigen trigger degranulation (exocytosis of granuels) releasing histamine and cause inflammatory allergic reaction 

Antibody Structure 

·       Two identical heavy chains 

·       Two identical light chains 

·       Held together by disulfide bonds and noncovalent interactions  

·       Variable region: antigen binding region  

o   B-cell undergoes hypermutation to switch this region around, only B cells that make the highest affinity binding region activate and proliferate (reason why it takes so long to mount immune response) 

o   This process called clonal selection (generates specificity) 

·       Constant Region: part where macrophages, NKs, monocytes, and eosinophils have receptors for and can initiate complement cascade  

o   Each B cell can only have one type of antibody  

o   (IgM/D/G/E/A) are the different isotypes (different types for different responses/purpose)  

o   Cells can change the isotype they produce when stimulated by specific cytokines (isotype switching) 

·       Naive B cells: cells that wait in lymph nodes and haven't been activated, once activated can either become plasma cells (produce antibodies) or memory B cells 

o   Primary Response: initial activation of B cell (takes ten days) 

o   Secondary response: more rapid/robust (reason for vaccination) 

Cytotoxic Immunity 

T cells mature in thymus where they undergo positive and negative selection 

·       Positive Selection: Only allows maturation of cells that can responds to MHC antigen presentation (if not, undergoes apoptosis) 

·       Negative Selection: Undergoes apoptosis of self-reactive cells  

·       Maturation facilitated by thymosin peptide hormone  

·       Once T cell has left thymus, it is mature but naive  

·       Upon antigen exposure, undergoes clonal selection to proliferate only cells with highest affinity 

T cell Types 

Helper T Cells (CD4): coordinate immune response by releasing lymphokines that recruit immune cells, including cytotoxic T cells and increase their activity 

·       Loss of these cells occur in HIV 

o   Respond to MHC Class 2 antigen presentation (exogenous) so best against bacterial, fungal, and parasitic infection 

·       Cytotoxic T Cells (CD8 T Cells): capable of directly killing virally infected cells through toxic injection because best against MHC Class 1 (endogenous) presentation (also intracellular bacteria/fungal infection) 

·       Suppressor T cells (Tregs): also express CD4 but different because also express Foxp3 and function to tamp down immune response and turn off self-reactive lymphocytes to prevent autoimmune diseases (self-tolerance) 

·       Memory T Cells: exactly what it means 

Pathway of Immune Activation 

Laceration → Macrophages/APCs engulf bacteria/release inflammatory cytokines → bacteria also digested and presented →  cytokines attract inflammatory cells (neutrophils and more macrophages) → mast cells activate and degranulate (release histamine) → immune cells leave blood into tissue → dendritic cells leave tissue and travel to lymph node (presents to B cell, correct B cell proliferate) → Abs travel through tissue to pathogen → dendritic cells present to T cells (Th1 T cells release IGNγ for macrophage activation/ Th2 activate B cells-common in parasitic infection)→ pathogen eliminated and memory kept 

Recognition of Self/Non self 

·       Body can attack self-antigens (autoimmunity) 

·       Immune system can be sensitive to non-threatening antigens (hypersensitivity reactions) 

·       Most autoimmune diseases treated with glucocorticoids (modified versions of cortisol), which are highly immunosuppressive  

Immunization 

Passive Immunity: Acquire antibodies from someone else

·       Antibodies can cross placenta and breast milk 

Active Immunity: Immune system was stimulated to produce its own antibodies  

·       Can be natural or artificial  

Lymphatic System 

·       Type of circulatory system 

·       One-way vessels that carry lymphatic fluid and most join to form thoracic duct, which then delivers fluid to subclavian veins 

·       Lymph nodes are small ben shaped structures along the vessels that contain a lymphatic channel, plus an artery and vein 

·       Involved in pathogen exposure 

·       Helps absorb excess fluid in tissue left behind at venule end of capillary due to decreasing hydrostatic pressure (blockage in duct = edema/swelling) 

·       Transports fats from digestive system 

·       B cells also proliferate and mature in lymph node collections known as germinal centers 

·       Lacteals: small lymphatic vessels located in center of each villus in small intestine and absorb/transport packaged chylomicrons