29 Immune responses Flashcards
Innate vs adaptive immunity
Innate: first line of defense, nonspecific, fast acting, kills all non-self
Adaptive: acquired, specific, memory, antibodies and antigen (HUMORAL IMMUNITY)
Innate immunity: barriers
1 Epithelial cell layer: tight junctions, antimicrobial peptides (sebaceous gland, eccrine and paracrine)
2 Mucous membranes: mucins, proteins, proteases, protease inhibitors
3 Chemical environment: GI tract (hydrolytic and proteolytic enzymes), skin (pH, salt, fatty acids), GU tract (pH of vagina)
Phagocytes
1 Monocytes/macrophage
2 Granulocytes; neutrophils (intracellular vesicles), eosinophils/basophils (release granules)
3 Dendritic cells: activate T cells (APC function), regulatory cytokines
NK cells
Look for cells with specific receptors (MHC Class I) and kill with perforins and granzymes
ADCC: CD16 bind to Fc portion of antibodies
Microbial sensors
Toll-like receptors: recognize PAMPS on surface of pathogens
NOD-like receptors: intracellular (cytoplasm) receptor, activated NF-kB pathway
RIG-1 like helicases and MDA 5: cytoplasmic sensors of viral ssRNA -> IFN-1 -> inhibit viral replication
Complement system
Classical: antigen-antibody complex
Alternative: absence of antibody
Lectin: bypasses antibody (mannose binding lectin)
Complement system processes
Cytolysis (MAC: C5b, 6, 7, 8, 9)
Chemotaxis: C5a(attraction)
Opsonization: C3b
Vasodilation + vascular permeability: Anaphylatoxins (C3a, C5a) -> release histamine
Cytokines
Synthesis: macrophage, DCs, NK cells, T cells, B cells
Applications: biomarkers, immune status monitoring, therapeutic agents, targets of therapy
Other proteins
Defensins: form pore-like membrane
Collectins: garbage bags for macrophages
B lymphocytes
Plasma cells: produce antibodies
Memory B cells: proliferate in second infection
CD21: complement component
CD40: for maturation and antibody production
T-dependent: creates IgG; phagocytosed by macrophage -> APC (antigen + MHC II) -> CD4 Th cell
T-independent: creates IgM; B cell + antigen
CD4 T cells
T-helper cells
Th1: IL-2, IL-12; macrophage; B cells -> IgG
Th2: IL-4; mast cells and eosinophils; Bcells -> IgE
Th17: TGFB, IL-6,23,27,8; recruitment
Treg: TGFB, suppress responses
CD8 T cells
Effector cytotoxic cells (ETC)
Perforin
Granzyme: activate cellular caspase (apoptosis)
T cell receptor
B cell: light and heavy chain
T cell: a and B chain
MHC
Bind antigens + present to T cells
Binds to specific antigens only
HLA complex
MHC Class I: all nucleated cells, CD8
MHC Class II: B lymph, macrophage, DCs; CD4
MHC Class III
Clonal selection
Specific Bcell/Tcell proliferates after infection = immune response
Antibody (Ig)
Polyclonal: different antigenic determinants
Monoclonal: single clone, homogenous
Enhance phagocytosis (opsonization) Neutralizes viruses Neutralizes toxins Complement-mediated lysis ADCC (killer cell-Fc -> lysis)
Structure of antibodies
L and H chain: variable (antigen-binding) + constant
Fragments: Fab (antigen-binding) + Fc (complement fixation)
Classes of Ig
IgG: 2L+2H; cross placenta; opsonization; 1=most abundant, 2=against encapsulated bacteria, 3=complement, 4=no complement
IgM: first produced; 5H2L2, no cross placenta, intracellular
IgA: serum (mono) and secretions(dimer)
IgE: allergic responses
IgD: mature B lymph with no antigen
Antibody responses
1º: produces within days/weeks
2º: more rapid and higher levels; IgG, longer
Active vs passive immunity
Active: produce antibodies; infection, immunization, exposure, transplant; long-lasting, delayed
Passive: pre-formed antibodies; short-term, immediate
Methods of acquisition
Natural: no intervention; naturally acquired active (exposure), naturally acquired passive (breastfeeding)
Artificial: artificially acquired active (vaccine = live, attenuated or killed vaccine), passive (Ig/anti-toxin)
Type I hypersensitivity
IMMEDIATE HYPERSENSITIVITY
Allergy: seconds after antigen -> IgE
First exposure: form IgE antibodies
Second exposure: cross-linking -> release mediators
Atopy: have pre-existing HLA haplotypes to predispose; already high IgE
Histamine: primary mediator
Prostaglandins and leukotrienes: from arachidonic acid, LB4 (recruits leukocytes) LC4/D4 (vasodilation and vascular permeability)
Type II hypersensitivity
ANTIBODY-MEDIATED (+cell)
IgG-cells: complement mediated lysis (ABO rxns, Rh)
Antibody directed at cell (cell-cell interaction)
Penicillin: antibody-surface proteins, hemolysis
Goodpasture syndrome: antibody-BM, complement activation
Graves’ disease: antibody-TSH -> hyperthyroidism
Type III hypersensitivity
IMMUNE COMPLEX
antibody-immune complex -> damage -> inflammation and complement activation
Autoimmune disorders
Local rxn (arthus reaction): wheal formation, IgG antibodies + complement activation Systemic (post strep glomerulonephritis)
