Disorders of the Immune System

innate immunity

immediate, non-specific, no memory; first line of defense = epithelia; second line of defense = leukocytes and complement proteins

adaptive immunity

specific, requires activation, has memory, humoral and cellular component

humoral adaptive immunity

B lymphocytes (bone marrow derived) response to pathogens floating around the body and differentiate into memory b and plasma cells that secrete antibodies

cellular adaptive immunity

T lymphocytes (thymus derived) include hyper and cytotoxic T cells

complement system

plasma proteins in innate and adaptive immunity; cascade activated by cleavage of C3 by C3 convertase; all pathways lead to C3 convertase splitting C3 into C3a and C3b

classic pathway of complement system

C1 attached to IgG/IgM bound to antigen

alternative pathway of complement system

C3b attaches to microbial surface

lectin pathway of complement system

mannose binding lectin activates C1

outcomes of complement system

MAC (C5b-C9) —> cell lysis

C3a, C5a —> inflammation, leukocyte recruitment

C3b, C4b —> opsonization (tagging) for phagocytosis

Helper T cells (CD4)

activate B cells and phagocytes

cytotoxic T cells (CD8)

kill infected/tumor cells, transplant rejection

memory cells

long term repsonse

regulatory cells (t cells)

shut down T-cell responses

B lymphocytes

anti-producing cells, each B cell has one specific antibody, make up 10-20% of lymphocytes in blood, mature into plasma cells and memory cells

dendritic cells

main antigen-presenting cells, activate helper t cells; immature DCs = langerhans cells, in epithelia; follicular DCs = in lymphoid tissue, capture antigen with attached antibody

macrophages

phagocytosis and antigen presentation to activate helper t cells; effector function = destroy opsonized microbes

Nature killer cells

rapid response, kill tumors/virally infected cells, do not require activation

what are cytokines

short acting mediators, 3 classes - innate, adaptive, colony-stimulating factors

innate cytokines

rapid, inflammatory, antiviral

adaptive cytokines

promote lymphocyte proliferation, differentiation, effector activation

colony-stimulating factors

stimulate hematopoiesis, increase leukocyte supply

therapeutic use of cytokines

cytokine inhibition —> decrease autoimmune inflammation

recombinant cytokines —> enhance immunity against infections/cancer

type I (immediate/allergy) hypersenstivity

dendritic cells binds antigen —> activates T-cells —> tells B cell to produce IgE —> IgE hits mast cell —> histamine release

initial effects: vasodilation, leakage, smooth muscle spasm

late effects: eosinophil infiltration, mucosal damage

type II (antibody mediated) hypersensitivity

IgG/IgM against self —> complement system activation, opsonization, MAC

ex: graves, myasthenia gravis, rheumatic fever, goodpature, pernicious anemia, autoimmune hemolytic anemia

type III (immune complex mediated) hypersensitivity

IgG/IgM antibody-antigen complex deposit in vessels after 1 week

ex: systemic lupus erythematous, post-streptococcal glomerulonephritis, polyarteritis nodosa, reactive arthritis, serum sickness

Type IV (cell-mediated) hypersensitivity

self antigens activate CD4+ T cells —> release cytokines —> inflammation and macrophage activation ; CD8+ may kill cells

delayed responses

ex: contact dermatitis, MS, type 1 diabetes, IBD, psoriasis

major histocompatibility complex (MHC)

group of genes that code for surface proteins that present antigens on a cell’s surface; barrier to transplants

mechanism of transplant rejection

t-cell and antibody mediated, recognize MHC as foreign and is attacked

hyperacute rejection

minutes-hours, preformed antibodies present in recipients circulation

acute rejection

days to years, cellular (T cell) or humoral (antibody mediated vasculitis)

Chronic rejection

progressive fibrosis, organ failure (esp. kidney), decreased/discontinued immunosuppressants

graft versus host disease (GVHD)

donor T cells attack recipients tissue; bone marrow transplant

autoimmune disorders

immune reaction against self antigens due to loss of self-tolerance; can be organ specific (type 1 diabetes) or systemic (lupus)

requirements of autoimmunity

presence of an immune reaction against self-antigens, cannot be secondary damage, absence of another cause for the disease

causes of autoimmunity

inheritance of susceptibility genes (HLA/MHC genes, HLA-B27) and environmental factors (infections, tissue damage)

Systemic Lupus Erythematosus (SLE)

type III hypersenstivity that primarily affects young women, more common in black and hispanic populations

pathogenesis of lupus

loss of tolerance, can be genetic (MHC) and environmental (UV)

injury patterns of lupus

renal - glomerulonephritis (50%)

skin - malar (butterfly) rash

joints - non-erosive synovitis

CNS - seizures, psychosis, stroke

cardiac - pericarditic, mayocarditis, valve disease

lungs - pleural effusion, interstitial fibrosis

treatment of lupus

hydroxycholorquine, prognosis greatly improved (>90% surivival)

primary (inherited) immunodeficiencies

onset: 6 months - 2 years, recurrent infections

types: x-linked agammaglobulinemia, IgA deficiency, common variable immunodeficiency, DiGeorge syndrome

secondary (acquired) immunodeficiencies

more common, secondary to underlying disease; most common = AIDS

causes: cancer, diabetes, malnutrition, chronic infection, renal disease, chemo/radiation, immunosuppressive drugs