Overview Of Pathogens And Immunity

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Immunity

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a. All mechanisms used by the body as protection against foreign agents

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Antigens

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a. Biochemical components such as proteins and carbohydrates that alert the immune system to their presence within the body

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Innate immunity

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a. Includes all host defenses that are present and functional at birth
b. Can discriminate self from non-self
c. Responds to broad groups of foreign agents
d. Present and functional at birth
e. Rapid response (minutes)
f. No memory
g. Not enhanced by vaccination

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Adaptive immunity

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a. Develops slowly in response to host contact with a specific antigen
b. Can discriminate self from non-self
c. Exquisite specificity
d. Slow response (days)
e. Memory/anamnestic response
f. Improved by vaccination

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Adaptive immunity cells

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a. B and T lymphocytes
b. Antibodies/immunoglobulins

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Foreign agents

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a. Bacteria, viruses, fungi, parasites, allergens, chemicals, tumors, foreign tissue grafts

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Pathogens

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a. Immune system evolved primarily to protect the host from pathogenic infectious agents

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Prion

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a. Simplest pathogen
b. Do not stimulate an immune response in the human host

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Viruses

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a. Obligate intracellular microorganisms with DNA or RNA genomes

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Intracellular bacteria

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a. Single-celled prokaryotes that live inside host cells

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Extracellular bacteria

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a. Single-celled prokaryotes that live in the extracellular space

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Protozoans

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a. Single-celled eukaryotes
b. There are intracellular and extracellular species

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Helminths

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a. Multicellular nematodes, trematodes, cestodes

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Fungi

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a. Single-celled yeasts and multicellular filamentous molds
b. Intracellular and extracellular

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Interferon

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i. Inhibits synthesis of viral proteins and causes degradation of viral mRNA

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NK cells

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i. Kill infected host cells, thus halting viral spread to other cells

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Tc cells

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i. Kill infected host cells, thus halting viral spread to other cells

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Extracellular bacterial infection elimination

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a. Phagocytes
b. Antibodies
c. Complement
d. C-reactive protein

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Opsonin

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a. Substances that bind to foreign particles and microorganisms
b. Makes foreign particles easier to recognize by phagocytes
c. Especially important in the elimination of encapsulated bacteria
d. Capsule becomes coated with one or more opsonins, capsule is negated
e. Antibodies, complement, and C-reactive protein

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Helminthic infection elimination

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a. IgE antibodies
b. Eosinophils

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T cell deficiency

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a. Enhance susceptibility to viral and fungal infections and to cancer

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Antibody, complement, or neutrophil deficiencies

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a. Suffer from repeated bacterial infections such as otitis media, sinusitis, and bacterial pneumonia

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21. Fungal infection susceptibility

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a. Patients rendered neutropenic by chemotherapy

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CBC

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a. Will reveal whether a patient has a normal absolute number of WBCs
b. 5,000-10,000/mcL normal for adults

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Leukocytosis

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i. Higher than normal count of leukocytes
ii. Indicates
1. Infection
2. Inflammatory disease
3. Leukemia
4. Tissue trauma

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Leukopenia

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i. Lower than normal absolute WBC count
ii. <3,500/mcL
iii. Indicates a bone marrow failure due to certain infections, radiation exposure, or chemotherapeutic drug use

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Differential WBC count

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a. Will reveal whether a patient’s circulating white blood cells are present in normal percentages

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Lymphocytosis

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i. Leukocytosis in which increase in WBC is chiefly in lymphocytes
1. T, B, NK
ii. Indicates an acute viral infection or certain chronic intracellular bacterial infections →tuberculosis or brucellosis

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Neutrophilia

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i. Leukocytosis in which the increase in WBC is chiefly in neutrophils
ii. Indicates an acute bacterial infection
iii. Left shift
1. May be due to an increase in band/stabs (immature neutrophils)

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Eosinophilia

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i. Leukocytosis in which the increase in WBC is chiefly in eosinophils
ii. Usually indicates a worm infection or an allergy

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Normal differential WBC

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i. Neutrophils → 40-60%
ii. Lymphocytes→ 20-40%
iii. Monocytes→ 2-8%
iv. Eosinophils→ 1-4%
v. Basophils → .5-1%
vi. Bands/stabs→ 0-3%

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Cells of the immune system

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a. Originate in the bone marrow, multipotent hematopoietic stem cells that differentiate along two lineages:

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Myeloid lineage

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1. Erythrocytes
2. Megakaryocytes→ platelets/thrombocytes
3. Myeloid leukocytes
a. PMN granulocytes→ neutrophils, basophils, eosinophils
b. Mononuclear phagocytes→ macrophages, monocytes
c. Dendritic cells

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Lymphoid lineage

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1. B cells
2. T cells
3. NK cells

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Differentiation of lineage

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i. Driven by colony-stimulating factors (CSFs) and interleukins (ILs)→ secreted by mature leukocytes in bone marrow
ii. Can be used clinically to restore leukocyte populations in patients undergoing chemotherapy

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EPO

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i. EPO
ii. Reverse anemia→ renal failure

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Granulocyte colony-stimulating factor

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i. G-CSF
ii. Filgrastim
iii. Recovery of bone marrow (PMNs)

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IL-11

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i. Oprelvekin
ii. Reverse thrombocytopenia (platelets)

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Thrombopoietin

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i. TPO
ii. Reverse thrombocytopenia (platelets)

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Cells of lymphoid lineage

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i. Average adult body contain 10^12
B lymphocytes
antibodies
Plasma cells
Memory B cells
T lymphocytes
NK cells

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B lymphocytes

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1. Antibody secretion-humoral immunity
2. CD19, CD20, CD21
3. Bone marrow (differentiation)
4. Display surface immunoglobulin/antibody (slg)→ B cell antigen receptor

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Antibodies

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1. Glycoproteins
2. Neutralize microorganisms and toxins→interfere with their adherence to receptors on host cells
3. Opsonize pathogens for phagocytosis
4. Activate complement→ cell lysis

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Classes of antibodies

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a. IgG
b. IgE
c. IgD
d. IgM
e. IgA

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Clonal selection

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a. Antigen binds to slg on B cell
b. B cell undergoes clonal selection and proliferation
c. Within two weeks, there is an army of identical B cells responding to the antigen

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Plasma cells

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a. B cells may differentiate into plasma cells→ secrete large amount of antibodies

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Memory B cells

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a. B cells may differentiate into memory B cells that can survive 20 years or more in the absence of antigen
b. Secondary activation→ memory cells proliferate rapidly and begin active antibody secretion→ “Anamnestic immune response”

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T-lymphocytes

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1. Mature in thymus
2. Possess T cell receptor (TCR) for antigen
3. Helper→
4. CD3, CD4→ complex of polypeptides involved in transmembrane signal transduction
5. Th, Tc, and Treg
6. Promote immunity through cytokine secretion

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CD4+Th cells

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a. Control the immune response through cytokine secretion

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Th1 cells

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a. Promote cell-mediated immunity → IFNy, IL-2, and TNFB

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IFNy

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activates marcohpages
i. Enhances ability to phagocytize and kill ingested microbes

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IL-2

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proliferation and activation of Tc and Nk cells for enhanced killing of infected or neoplastic host cells

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TNFB

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tumor necrosis facor-beta→ cytostatic or cytolytic for tumor cells
i. Activates neutrophils and promotes wound healing by fibroblasts

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TH2 cells

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a. Promote humoral immunity, especially against helminths and allergens

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IL-4 and IL-3

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promote IgE synthesis by B cells

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IL-5

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promotes IgA synthesis by B cells and induces eosinophil activation

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Th17 cells

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a. Control infections by extracellular fungi and bacteria
b. Secrete IL-17→ stimulates production of antimicrobial substances by neutrophils and epithelial cells

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CD4 (T reg)

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a. Prevents autoimmune reactions by producing IL-10 and TGFB→ cytokines that inhibit the functions of other T cell subsets, macrophages, and dendritic cells

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CD8 cells

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a. Cytotoxic for host cells infected by viruses or intracellular bacteria, tumor cells, and foreign tissue grafts

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NK cells

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a. Elimination of infected or neoplastic host cells
b. Participate in antibody-dependent cell-mediated cytotoxicity (ADCC)
c. All NK cells express CD56→form of NCAM (neural cell adhesion molecule)

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Anitbody-dependent cell-mediated cytotoxicity (ADCC)

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i. C16 on NK cell binds to the Fc fragment of IgG
ii. IgG in turn binds to the surface of a damaged/infected host cell
iii. IgG acts as a bridge for NK cell attachment to infected/damaged host cell
iv. NK cells kill host by release of toxic substances

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Regulatory T cells

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1. CD3, CD4, CD25
2. Prevent autoimmunity

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Cytotoxic T

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1. CD3, CD4, CD25
2. Prevent autoimmunity

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NK cell markers

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1. CD16, CD56
2. Kill infected cells, tumors, and graft cells

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Mononuclear phagocytes

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i. 10-18 um diameter
ii. Circulating monocyte and tissue-fixed macrophage
iii. Macrophages can live years
iv. Functions→ phagocytosis and antigen presentation

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Phagocytosis

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1. Phagocyte attracted by bacterial fMet-Leu-Phe
2. Recognizes microbe by receptor-ligand interactions, especially fi microbe is coated by opsonins
3. Extension of pseudopodia to form phagosome
4. Fusion of phagosome with lysosome=phagolysosome
5. Lysosome, etc. break down peptidoglycan
6. Respiratory burst→ oxygen and NO radicals

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Mononuclear phagocyte system

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1. Composed of tissue-fixed macrophages
2. RES (reticuloendothelial system)→ filterin system for antigen removal from blood and lymph

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Neutrophils

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a. Functions:
i. Phagocytosis and inflammation
b. Multilobed nucleus and purple-staining granules
i. Primary
1. Acid hydrolases, lysosome, myeloperoxidase, defensins
ii. Secondary
1. Lysosome and lactoferring
c. Rapid production (7 million/min)
d. Survive 2-3 days in circulation
e. 40-60% of blood leukocytes in healthy persons

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Eosinophils

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a. Possess low affinity Fc receptors for IgE
b. Fight parasitic infections
c. Important in allergic responses/immediate hypersensitivity reactions

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Basophils (and mast cells)

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a. Least prevalent of leukocytes
b. Possess high affinity Fc receptors for IgE (FceRI)
c. Release the chemical mediators of immediate hypersensitivity/allergy

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Dendritic cells

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1. Myeloid dendritic cells are found under the epithelia and in most organs
2. Langerhans cells
a. Dendritic cells in the skin
3. Most efficient antigen-presenting cells (APCs)

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Antigen presentation I

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a. Antigen taken up by dendritic cell by pinocytosis or RM endocytosis→ antigen in vacuole=endosome
b. Endosome fuses with lysosome, antigen is digested into small fragments
c. Pairs with MHC proteins produced in ER of dendritic cell

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Antigen presentation II

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d. MHC complex+antigen transported to outer surface of APC→ presented to T cells
i. Class I MHC→ CD8 Tc cells
ii. Class II MHC→ CD4 TH cells
e. T cells cannot recognize or respond to antigens unless the antigens have been processed and presented by MHC/APC

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Megakaryocyte

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1. Large cell
2. Lobulated nucleus
3. Bone marrow
4. Gives rise to platelets

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Platelets/thrombocytes

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1. Anucleate cells
2. Promote blood clotting and inflammation
3. Normal→ 150,000-400,000/ul of blood