Immunology- Lymphoid structures and cellular components Flashcards
Immune system organs
1° organs:
Bone marrow—immune cell production, B cell maturation.
Thymus—T cell maturation
Immune system organs
2° organs:
Spleen, lymph nodes, tonsils, Peyer patches
Allow immune cells to interact with antigen
Lymph node
Follicle
Site of B-cell localization and proliferation. In outer cortex.
Lymph node
Medulla
Consists of medullary cords (closely packed lymphocytes and plasma cells) and medullary sinuses
Lymph node
Paracortex
Houses T cells. Region of cortex between follicles and medulla. Contains high endothelial venules through which T and B cells enter from blood.
Lymphatic drainage associations Cervical Mediastinal Hilar Axillary Celiac Superior mesenteric
- Head and neck
- Trachea and esophagus
- Lungs
- Upper limb, breast, skin above umbilicus
- Liver, stomach, spleen, pancreas, upper duodenum
- Lower duodenum, jejunum, ileum, colon to splenic flexure
Lymphatic drainage associations Inferior mesenteric Para-aortic Internal iliac Superficial inguinal Popliteal
- Colon from splenic flexure to upper rectum
- Testes, ovaries, kidneys, uterus
- Lower rectum to anal canal (above pectinate line), bladder, vaginab(middle third), cervix, prostate
- Anal canal (below pectinate line), skin below umbilicus (except popliteal area), scrotum, vulva.
- Dorsolateral foot, posterior calf
Spleen- Components
T cells are found in the periarteriolarlymphatic sheath (PALS) within the white pulp.
B cells are found in follicles within the
white pulp.
The marginal zone, in between the red pulp and white pulp, contains macrophages and specialized B cells, and is where APCs capture blood-borne antigens for recognition by lymphocytes.
Splenic dysfunction
lower IgM
lower complement activation
susceptibility to encapsulated organisms.
Postsplenectomy blood findings:
Howell-Jolly bodies (nuclear remnants) Target cells Thrombocytosis (loss of sequestration and removal) Lymphocytosis (loss of sequestration
Thymus
Thymus is derived from the Third pharyngeal pouch.
Cortex is dense with immature T cells; medulla is pale with mature T cells and Hassall corpuscles.
Normal neonatal thymus “sail-shaped” on CXR.
Thymoma
neoplasm of thymus. Associated with myasthenia gravis and superior vena cava syndrome.
Hypoplastic thymus in…
DiGeorge syndrome and severe combined immunodeficiency (SCID).
Innate immunity
COMPONENTS
Neutrophils, macrophages, monocytes, dendritic cells, natural killer (NK) cells (lymphoid origin), complement, physical epithelial barriers, secreted enzymes.
Innate immunity
KEY FEATURES IN PATHOGEN
RECOGNITION
(TLRs): (PAMPs)
Innate immunity
SECRETED PROTEINS
Lysozyme, complement, C-reactive protein (CRP), defensins.
Adaptative immunity
COMPONENTS
T cells, B cells, circulating antibodies
MHC I
- Loci
- binding
- expression
- Function
- HLA-A, HLA-B, HLA-C
- TCR and CD8
- All nucleated cells, APCs, platelets Not on RBCs
- Present endogenously synthesized antigens (eg,
viral or cytosolic proteins) to CD8+ cytotoxic T cells
MHC II
- Loci
- binding
- expression
- Function
- HLA-DP, HLA-DQ, HLA-DR
- TCR and CD4
- APCs
- Present exogenously synthesized antigens (eg,
bacterial proteins) to CD4+ helper T cells.
HLA subtypes associated with diseases
A3
Hemochromatosis
HLA subtypes associated with diseases
B27
PAIR:
Psoriatic arthritis, Ankylosing spondylitis,
IBD-associated arthritis, Reactive arthritis
HLA subtypes associated with diseases
B8
Don’t Be late(8), Dr. Addison, or else you’ll send my patient to the grave.
Addison disease, myasthenia gravis, Graves disease
HLA subtypes associated with diseases
DR2
Multiple hay pastures have dirt:
Multiple sclerosis, hay fever, SLE, Goodpasture syndrome
HLA subtypes associated with diseases
DR3
Diabetes mellitus type 1, SLE, Graves disease,
Hashimoto thyroiditis, Addison disease
DR4
Rheumatoid arthritis, diabetes mellitus type 1,
Addison disease
DR5
Hashimoto is an odd doctor (DR3, DR5):
Hashimoto thyroiditis
Rule of 8:
MHC II × CD4 = 8; MHC I × CD8 = 8.
Differentiation of T cells
Positive selection
Thymic cortex. T cells expressing TCRs capable of binding self-MHC on cortical epithelial cells survive.
Negative selection
Thymic medulla. T cells expressing TCRs with high affinity for self antigens undergo apoptosis or
become regulatory T cells.
Tissue-restricted self-antigens are expressed in the thymus due to the action of autoimmune regulator (AIRE); deficiency leads to autoimmune polyendocrine syndrome.
Th1 cell
- Secretes
- Function
- Induced by
- Supressed by
- Immunodeficency
IFN-γ
Activates macrophages and cytotoxic T cells
IFN-γ, IL-12
IL-4, IL-10
Mendelian susceptibility to mycobacterial disease
Th2 cell
- Secretes
- Function
- Induced by
- Supressed by
IL-4, IL-5, IL-6, IL-10, IL-13
Activate eosinophils and promote production of IgE.
IL-2, IL-4
IFN-γ
Th17 cell
- Secretes
- Function
- Induced by
- Supressed by
- Immunodeficency
IL-17, IL-21, IL-22 Immunity against extracellular microbes, neutrophil. TGF-β, IL-1, IL-6 IFN-γ, IL-4 Hyper-IgE syndrome
ThReg cell
- Secretes
- Function
- Induced by
- Supressed by
- Immunodeficency
TGF-ß, IL-10, IL-35 Prevent autoimmunity TGF-β, IL-2 IL-6 IPEX
IPEX
(Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked) syndrome
Genetic deficiency of FOXP3 leads to autoimmunity.
Associated with diabetes in male infants.
T-cell activation
T-cell activation (signal 1): antigen is presented on MHC II and recognized by TCR on Th (CD4+) cell. Endogenous or cross-presented antigen is presented on MHC I to Tc (CD8+) cell.
Proliferation and survival (signal 2): costimulatory signal via interaction of B7 protein (CD80/86) on dendritic cell and CD28 on naïve T cell.
B-cell activation and class switching
- Th-cell activation
- foreign antigen is presented on MHC II and recognized by TCR on Th cell.
- CD40 receptor on B cell binds CD40 ligand
(CD40L) on Th cell.
4. Th cell secretes cytokines that determine Ig class switching of B cell.